title: SARS-CoV-2 Omicron variant

text: On 29 November, a positive case was recorded in Darwin, Australia. The person arrived in Darwin on a repatriation flight from Johannesburg, South Africa on 25 November, and was taken to a quarantine facility, where the positive test was recorded. Two more people who travelled to Sydney from southern Africa via Singapore tested positive. Portugal reported 13 Omicron cases, all of them members of a soccer club. Sweden also confirmed their first case on 29 November, as did Spain, when a traveler came from South Africa.


title: SARS-CoV-2 Omicron variant

text: On 30 November, the Netherlands reported that Omicron cases had been detected in two samples dating back as early as 19 November. A positive case was recorded in Sydney from a traveller who had visited southern Africa before travel restrictions were imposed, and was subsequently active in the community. Japan also confirmed its first case. Two Israeli doctors tested positive and entered isolation. Both of them had received three shots of the Pfizer vaccine prior to testing positive. In Brazil, three cases of the Omicron variant were confirmed in São Paulo. Another five are under suspicion. A person in Leipzig, Germany with no travel history nor contact with travellers tested positive for Omicron.


title: SARS-CoV-2 Omicron variant

text: On 1 December, the Omicron variant was detected in three samples in Nigeria that had been collected from travelers from South Africa within the last week. On the same day, public health authorities in the United States announced the country's first confirmed Omicron case. A resident of San Francisco who had been vaccinated returned from South Africa on 22 November, began showing mild symptoms on 25 November and was confirmed to have a mild case of COVID-19 on 29 November. Ireland and South Korea also reported their first cases. South Korea reported its cases from five travelers arriving in South Korea from Nigeria.


title: SARS-CoV-2 Omicron variant

text: On 2 December, Dutch health authorities confirmed that all 14 passengers with confirmed Omicron infection on 26 November had been previously vaccinated. The same day, the Norwegian Institute of Public Health confirmed that 50 attendees of a company Christmas party held at a restaurant in Norway's capital, Oslo, were infected with the Omicron variant. France has confirmed only 25 cases of the new Omicron variant but officials say the number could jump significantly in the coming weeks.


title: SARS-CoV-2 Omicron variant

text: By 6 December, Malaysia confirmed its first case of the variant. The case was a South African student entering to study at a private university. In Namibia, 18 cases out of 19 positive COVID-19 samples that had been collected between 11 and 26 November were found to be Omicron, indicating a high level of prevalence in the country. Fiji also confirmed two positive cases of the variant. They travelled from Nigeria arriving in Fiji on November 25.


title: SARS-CoV-2 Omicron variant

text: On 9 December, Richard Mihigo, coordinator of the World Health Organisation's Immunisation and Vaccine Development Programme for Africa, announced that Africa accounted for 46% of reported cases of the Omicron variant globally.


title: SARS-CoV-2 Omicron variant

text: On 16 December, New Zealand confirmed its first case of the Omicron variant, an individual who had traveled from Germany via Dubai.


title: SARS-CoV-2 Omicron variant

text: The first death of a person with Omicron was reported in Germany on 23 December and in Australia on 27 December.


title: SARS-CoV-2 Omicron variant

text: On 3 January 2022, South Korea reported the first two deaths of people who tested positive post mortem for Omicron.


title: SARS-CoV-2 Omicron variant

text: As of May 2022, BA.2.12.1 was spreading in the US and two new subvariants of Omicron named BA.4 and BA.5, first detected in January 2022, spread in South Africa. All 3 subvariants have spike protein mutations of L452 and elude immunity from prior BA1 infection.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021, BioNTech said it would know in two weeks whether the current vaccine is effective against the variant and that an updated vaccine could be shipped in 100 days if necessary. AstraZeneca, Moderna and Johnson & Johnson were also studying the variant's impact on the effectiveness of their vaccines. On the same day, Novavax stated that it was developing an updated vaccine requiring two doses for the Omicron variant, which the company expected to be ready for testing and manufacturing within a few weeks. On 29 November 2021, The Gamaleya Institute said that Sputnik Light should be effective against the variant, that it would begin adapting Sputnik V, and that a modified version could be ready for mass production in 45 days. Sinovac said it could quickly mass-produce an inactivated vaccine against the variant and that it was monitoring studies and collecting samples of the variant to determine if a new vaccine is needed.


title: SARS-CoV-2 Omicron variant

text: On 7 December 2021, at a symposium in Brazil with its partner Instituto Butantan, Sinovac said it would update its vaccine to the new variant and make it available in three months. On 2 December, the Finlay Institute was already developing a version of Soberana Plus against the variant. Pfizer hoped to have a vaccine targeted to immunize against Omicron ready by March 2022.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021, the WHO asked nations to enhance surveillance and sequencing efforts, submit complete genome sequences and associated metadata to a publicly available database, such as GISAID, report initial cases/clusters associated with virus-of-concern infection to WHO through the IHR mechanism, where capacity exists and in coordination with the international community, perform field investigations and laboratory assessments to improve understanding of the potential impacts of the virus of concern on COVID-19 epidemiology, severity, and the effectiveness of public health and social measures, diagnostic methods, immune responses, antibody neutralization, or other relevant characteristics.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021, WHO advised countries not to impose new restrictions on travel, instead recommending a "risk-based and scientific" approach to travel measures. On the same day, the European Centre for Disease Prevention and Control (ECDC) reported modeling indicating that strict travel restrictions would delay the variant's impact on European countries by two weeks, possibly allowing countries to prepare for it.


title: SARS-CoV-2 Omicron variant

text: As with other variants, the WHO recommended that people continue to keep enclosed spaces well ventilated, avoid crowding and close contact, wear well-fitting masks, clean hands frequently, and get vaccinated. On 29 November 2021, the WHO said cases and infections were expected among those vaccinated, albeit in a small and predictable proportion.


title: SARS-CoV-2 Omicron variant

text: After the WHO announcement, on the same day, several countries announced travel bans from southern Africa in response to the identification of the variant, including the United States, which banned travel from eight African countries, although as of 30 November 2011 it notably did not ban travel from any European countries, Israel, Canada, or Australia where cases were also detected at the time the bans were announced. Other countries that also implemented travel bans include Japan, Canada, the European Union, Israel, Australia, the United Kingdom, Singapore, Malaysia, Indonesia, Morocco, and New Zealand.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021 the Brazilian Health Regulatory Agency recommended flight restrictions regarding the new variant. The state of New York declared a state of emergency ahead of a potential Omicron spike, although no cases had yet been detected in the state or the rest of the United States. On 27 November 2021, Switzerland introduced obligatory tests and quarantine for all visitors arriving from countries where the variant was detected, which originally included Belgium and Israel.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021 South African Minister of Health Joe Phaahla defended his country's handling of the pandemic and said that travel bans went against the "norms and standards" of the World Health Organization.


title: SARS-CoV-2 Omicron variant

text: Some speculated that travel bans could have a significant impact on South Africa's economy by limiting tourism and could lead to other countries with economies that are reliant on tourism to hide the discovery of new variants of concern. Low vaccine coverage in less-developed nations could create opportunities for the emergence of new variants, and these nations also were struggling to gain intellectual property to develop and produce vaccines locally. At the same time, inoculation had slowed in South Africa due to vaccine hesitancy and apathy, with a nationwide vaccination rate of only 35% as of November 24, 2021.


title: SARS-CoV-2 Omicron variant

text: On 29 November 2021, the WHO warned countries that the variant poses a very high global risk with severe consequences and that they should prepare by accelerating vaccination of high-priority groups and strengthening health systems. WHO director-general Tedros Adhanom described the global situation as dangerous and precarious and called for a new agreement on the handling of pandemics, as the <q>current system disincentivizes countries from alerting others to threats that will inevitably land on their shores.</q> CEPI CEO Richard Hatchett said that the variant fulfilled predictions that transmission of the virus in low-vaccination areas would accelerate its evolution.


title: SARS-CoV-2 Omicron variant

text: In preparation for the Omicron variant arriving in the United States, President Joe Biden stated that the variant is "cause for concern, not panic", reiterated that the government was prepared for the variant and would have it under control and that large-scale lockdowns, similar to the ones in 2020 near the beginning of the pandemic, were "off the table for now."


title: SARS-CoV-2 Omicron variant

text: In mid-December 2021, multiple Canadian provinces reinstated restrictions on gatherings and events such as sports tournaments, and tightened enforcement of proof of vaccination orders. British Columbia expressly prohibited any non-seated "organized New Year's Eve event", while Quebec announced a partial lockdown on 20 December 2021, ordering the closure of all bars, casinos, gyms, schools, and theatres, as well as imposing restrictions on the capacity and operating hours of restaurants, and the prohibition of spectators at professional sporting events.


title: SARS-CoV-2 Omicron variant

text: On 18 December 2021, the Netherlands government announced a lockdown intended to prevent spread of the variant during the holiday period.


title: SARS-CoV-2 Omicron variant

text: In late December 2021, some countries shortened the typical six-month interval for a booster dose of the vaccine to prepare for a wave of Omicron, as two doses are not enough to stop the infection. UK, South Korea and Thailand reduced to three months; Belgium, four months; France, Singapore, Taiwan, Italy and Australia, five months. Finland reduced it to three months for risk groups. Other countries continued with a six-month booster schedule. While antibody levels begin to drop at four months, a longer interval usually allows time for the immune system's response to mature.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021, worry about the potential economic impact of the Omicron variant led to a drop in global markets, including the worst drop of the Dow Jones Industrial Average in 2021, led by travel-related stocks. The price of Brent Crude and West Texas Intermediate oil fell 10% and 11.7%, respectively Cryptocurrency markets were also routed. and the South African rand also hit an all-time low for 2021, trading at over 16 rand to the dollar, losing 6% of its value in November.


title: SARS-CoV-2 Omicron variant

text: In early December 2021, Jerome Powell, the chairman of the Federal Reserve, testified before the U.S. Senate Committee on Banking that "The recent rise in COVID-19 cases and the emergence of the Omicron variant pose downside risks to employment and economic activity and increased uncertainty for inflation."


title: SARS-CoV-2 Omicron variant

text: As of June 2022, Omicron (BA.1) had about 50 mutations, which is more than any previous SARS-CoV-2 variant, 32 of which pertained to the spike protein, which most vaccines target to neutralise the virus. As of December 2021, many mutations were novel and not found in previous variants. As of April 2022 the variant was characterised by 30 amino acid changes, three small deletions, and one small insertion in the spike protein compared with the original virus, of which 15 are located in the receptor-binding domain (residues 319–541). As of December 2022 the virus carried a number of changes and deletions in other genomic regions, for example three mutations at the furin cleavage site, which facilitates its transmission.


title: SARS-CoV-2 Omicron variant

text: Researchers have detected several subvariants of Omicron and new ones continue to emerge. There are 310 Pango lineages currently associated with the Omicron variant. The 'standard' sublineage is now referred to as BA.1 (or B.1.1.529.1), and the two other sublineages are known as BA.2 (or B.1.1.529.2) and BA.3 (or B.1.1.529.3). In mid-2022, BA.4 (or B.1.1.529.4) and BA.5 (or B.1.1.529.5) were detected in several countries.


title: SARS-CoV-2 Omicron variant

text: They share many mutations, but also significantly differ. In general, BA.1 and BA.2 share 32 mutations, but differ by 28. BA.1 has itself been divided in two, the original BA.1 and BA.1.1 (or B.1.1.529.1.1) where the main difference is that the latter has a R346K mutation.


title: SARS-CoV-2 Omicron variant

text: Standard PCR and rapid tests continue to detect all Omicron subvariants as COVID-19, but further tests are necessary to distinguish the subvariants from each other and from other COVID-19 variants.


title: SARS-CoV-2 Omicron variant

text: A laboratory study on hamsters and mice in Japan published as a non-peer-reviewed preprint in mid-February 2022 suggested that BA.2, is not only more transmissible than BA.1, but may cause more severe disease. This was later disproven by a study in late-October 2022, that found BA.2 actually caused less severe disease relative to the original omicron variant (which in turn, caused less severe disease compared to the delta variant). Therapeutic monoclonal antibodies used to treat people infected with COVID-19 did not have much effect on BA.2, which was "almost completely resistant" to casirivimab and imdevimab, and 35 times more resistant to sotrovimab than the original BA.1 subvariant.


title: SARS-CoV-2 Omicron variant

text: The first known sequence of BA.2 was in a sample from 15 November 2021. As of 17 January 2022, BA.2 had been detected in at least 40 countries and in all continents except Antarctica. By 31 January, it had been detected in at least 57 countries. In global samples collected from 4 February to 5 March and uploaded to GISAID, BA.2 accounted for c. 34%, compared to 41% for BA.1.1, 25% for BA.1 and less than 1% for BA.3. In a review two weeks later, covering 16 February to 17 March, BA.2 had become the most frequent. However, the data is geographically skewed due to sequencing rate and speed; for example, among the 205,000 COVID-19 sequences from March that had been uploaded to GISAID as of 22 March, United Kingdom and Denmark accounted for more than , and most of the remaining were from other European countries, Australia, Canada and the United States (altogether, 6,000 were from Africa, Asia and Latin America). Based on GISAID uploads, BA.1 peaked in early January 2022, after which it was overtaken by both BA.1.1 and BA.2. In North America, parts of Europe and parts of Asia, BA.1 was first outcompeted by BA.1.1. For example, in the United States, France and Japan, BA.1.1 became the dominant subvariant in January 2022.


title: SARS-CoV-2 Omicron variant

text: By late December 2021/early January 2022, BA.2 appeared to have become dominant in at least parts of India (already making up almost 80 percent in Kolkata in late December 2021) and the Philippines, had become frequent in Scandinavia, South Africa and Singapore, and was showing signs of growth in Germany and the United Kingdom. In Japan, which has quarantine and detailed screening of all international travellers, as of 24 January, the vast majority of BA.2 had been detected in people that had arrived from India or the Philippines with cases going back at least to 1 December 2021 (far fewer BA.1 or other variants were detected among arrivals from the two countries in that period), but small numbers had also been detected in people arriving from other countries.


title: SARS-CoV-2 Omicron variant

text: In Denmark, the first BA.2 was in a sample collected on 5 December 2021 and extremely few were found in the directly following period. By week fifty (13–19 December) it had started to increase, with BA.2 being at around 2 percent of sequenced cases compared to 46 percent BA.1 (remaining Delta). The frequency of both Omicron subvariants continued to increase throughout the last half of December; in week fifty-two (27 December–2 January), BA.2 had reached 20 percent and BA.1 peaked at 72 percent. In January 2022, BA.1 began decreasing, whereas BA.2 continued its increase. By the second week (10–16 January) of 2022, the frequency of the two was almost equal, both being near 50 percent (around one percent was the rapidly disappearing Delta). In the following week, BA.2 became clearly dominant in Denmark with 65 percent of new cases being the BA.2 subvariant. Trends from the other Scandinavian countries, India, South Africa and the United Kingdom also showed that BA.2 was increasing in proportion to the original BA.1. In early February 2022, it had become the dominant subvariant in South Africa, in late February it had become dominant in Germany and in early March it had become dominant in the United Kingdom. In early March, BA.1.1 was still heavily dominant in the United States (having overtaken BA.1 in January), but BA.2 was increasing in frequency, later becoming dominant in the US by 29 March.


title: SARS-CoV-2 Omicron variant

text: A new BA.1–BA.2 recombinant isolated from the UK in January 2022, dubbed the "XE" recombinant, was found by the WHO to be potentially 10% more transmissible than BA.2, making it about 43% to 76% to more transmissible than BA.1, and making the XE recombinant the most contagious variant identified.


title: SARS-CoV-2 Omicron variant

text: There were two new BA.2 subvariants detected in the US state of New York, which are BA.2.12 (or B.1.1.529.2.12) and BA.2.12.1 (or B.1.1.529.2.12.1), both of which have a significant growth advantage of 23–27% over BA.2 and contributing to a rise in infections in central New York, centred on Syracuse and Lake Ontario, which later became dominant by May 24 in the US.


title: SARS-CoV-2 Omicron variant

text: The subvariant BA.2.75 (or B.1.1.529.2.75, nicknamed "Centaurus" by the media), first detected in India in May 2022, has been classified as variant under monitoring by the WHO. Additional newer mutations in this line (like BA.2.75.2 aka B.1.1.529.2.75.2 or "Chiron") may be capable of escape neutralizing antibodies.


title: SARS-CoV-2 Omicron variant

text: XBB, a recombinant of the BA.2.10.1 and BA.2.75 sublineages, is an Omicron subvariant first detected in August 2022. Described as "immune-evasive", it has caused a small surge of cases in countries including Singapore and Bangladesh.


title: SARS-CoV-2 Omicron variant

text: On 20 October 2022, the chief scientist of the World Health Organization (WHO), Soumya Swaminathan, warned that the XBB subvariant of Omicron may cause infections in some countries while the severity of the new variants is not yet known.


title: SARS-CoV-2 Omicron variant

text: Early observations from Singapore indicated the possibility of XBB being less severe compared to the omicron BA.5 variant, with data from the first two weeks in October 2022 indicating that the XBB variant had a 30% lower hospitalisation risk. However, this could also be due to high levels of population immunity from vaccination and previous waves.


title: SARS-CoV-2 Omicron variant

text: The third Omicron sublineage, BA.3, is very rare. It has the same S-gene target failure (SGTF) deletion (Δ69-70) as BA.1.


title: SARS-CoV-2 Omicron variant

text: In April 2022, the WHO announced it was tracking the BA.4 and BA.5 subvariants with BA.4 having been detected in South Africa, Botswana, Denmark, Scotland and England. Early indications from data collected in South Africa suggested BA.4 and BA.5 have a significant growth advantage over BA.2, which by 12 May earned the status Variant of Concern by the European Centre for Disease Prevention and Control, and, by 20 May, by the UK Health Security Agency. BA.5 was dominant in Portugal by 25 May, accounting for two-thirds of all new cases there. By 24 June, BA.4 and BA.5 together had become dominant variants in the UK and Germany. These two subvariants became dominant in the United States by 28 June. By late June, BA.5 became the dominant subvariant in France, with 59% of new cases linked to it.


title: SARS-CoV-2 Omicron variant

text: On 10 May 2022, a case of a new subvariant BA.5.2.1 was reported in California. On 10 July, the city of Shanghai reported its first case of BA.5.2.1, in a man who had flown in from Uganda, sparking a new wave of testing. On 22 July, the province of Ontario, Canada announced that subvariant BA.5.2.1 overtook BA.2.12.1 as the main variant in circulation in Ontario around 2 July. Regeneron is reporting that BA.5.2.1 is the main variant in Australia, Belgium, Brunei, Greece and Iceland. The government of Canada is also reporting that in late June and July, of the travelers arriving by air who test positive for COVID-19, a substantial proportion are BA.5.2.1.


title: SARS-CoV-2 Omicron variant

text: Since October 2022, BQ.1 (or B.1.1.529.5.3.1.1.1.1.1, nicknamed "Typhon" by the media) and BQ.1.1 (or B.1.1.529.5.3.1.1.1.1.1.1, nicknamed "Cerberus") which are subvariants of BA.5 have been found. They have been more prevalent in France than any other European country, As of 17 November, 93% of sequences in France were Omicron sub-lineage BA.5 and among the BA.5 sub-lineages, BQ.1.1 continued to rise (32% vs 25% in the prior week). according to Nextclade even 55%. they were reported in the US to have become dominant, accounting for 44% of new infections, up from 33% the previous week. Early laboratory tests found that these subvariants were better at escaping first and booster vaccines than previous variants; however, no new treatments appeared to be in development. Virologist Andy Pekosz said that "the mutations have pretty much eliminated every single monoclonal antibody on the market right now in terms of their efficacy".


title: SARS-CoV-2 Omicron variant

text: In January 2022, William Schaffner, professor of infectious diseases at Vanderbilt University Medical Center, compared the contagiousness of the Omicron variant to that of the measles.


title: SARS-CoV-2 Omicron variant

text: It was not known in November 2021 how Omicron would spread in populations with high levels of immunity or if it causes a milder or more severe disease. On 15 December 2021, Jenny Harries, head of the UK Health Security Agency, told a parliamentary committee that the doubling time of COVID-19 in most regions of the UK was now less than two days despite the country's high vaccination rate. She said that the Omicron variant of COVID-19 is "probably the most significant threat since the start of the pandemic", and that the number of cases in the next few days would be "quite staggering compared to the rate of growth that we've seen in cases for previous variants".


title: SARS-CoV-2 Omicron variant

text: Relating to naturally acquired immunity, Anne von Gottberg, an expert at the South African National Institute for Communicable Diseases, believed at the beginning of December 2021 that immunity granted by previous variants would not protect against Omicron.


title: SARS-CoV-2 Omicron variant

text: A study suggests that mutations that promote breakthrough infections or antibody-resistance "like those in Omicron" could be a new mechanism for viral evolution success of SARS-CoV-2 and that such may become a dominating mechanism of its evolution. A preprint supports such an explanation of Omicron's spread, suggesting that it "primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility". Studies showed the variant to escape the majority of existing SARS-CoV-2 neutralizing antibodies, including those in sera from vaccinated and convalescent individuals. Nevertheless, current vaccines are expected to protect against severe illness, hospitalizations, and deaths due to Omicron and, on an individual level, the Omicron variant is milder than earlier variants that evolved when the antibody/vaccination share was lower than it was when Omicron emerged.


title: SARS-CoV-2 Omicron variant

text: In contrast to other investigated variants, Omicron showed substantial, population-level, evasion of immunity from prior infection as well as a higher ability to evade immunity induced by vaccines.


title: SARS-CoV-2 Omicron variant

text: In February 2022, the first confirmed case infecting a wild animal was confirmed by researchers at Pennsylvania State University in white-tailed deer in Staten Island, N.Y.


title: SARS-CoV-2 Omicron variant

text: Although transmission via fomites is rare, preliminary data indicate that the variant lasts for 194 hours on plastic surfaces and 21 hours on skin, compared with just 56 and 7 hours, respectively, for the original strain.


title: SARS-CoV-2 Omicron variant

text: Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) mRNA Vaccines offer less protection against the omicron variant. In January 2022, results from Israel suggested that a fourth dose is only partially effective against Omicron. Many cases of infection broke through, albeit "a bit less than in the control group", even though trial participants had higher antibody levels after the fourth dose.


title: SARS-CoV-2 Omicron variant

text: In December, studies, some of which using large nationwide datasets from either Israel and Denmark, found that vaccine effectiveness of multiple common two-dosed COVID-19 vaccines is substantially lower against the Omicron variant than for other common variants including the Delta variant, and that a new (often a third) dose – a booster dose – is needed and effective, as it substantially reduces deaths from the disease compared to cohorts who received no booster but two doses. On 7 December 2021, preliminary results from a laboratory test conducted at the Africa Health Research Institute in Durban with 12 people who received the Pfizer-BioNTech vaccine found a 41-fold reduction in neutralizing antibody activity against the variant in some of the samples. This is a significant reduction, but it does not mean that the variant can escape vaccines completely, so vaccination with current vaccines is still recommended. Neutralizing antibody activity against the variant was greater in those fully vaccinated after being infected about a year earlier. Effectiveness estimates will likely change as more data is collected, as antibodies generated by vaccination vary widely between individuals and the sample was small. On 8 December 2021, Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide a similar level of neutralizing antibodies against the variant as seen against other variants after two doses.


title: SARS-CoV-2 Omicron variant

text: On 10 December 2021, the UK Health Security Agency reported that early data indicated a 20- to 40-fold reduction in neutralizing activity for Omicron by sera from Pfizer 2-dose vaccinees relative to earlier strains and a 20-fold reduction relative to Delta. The reduction was greater in sera from AstraZeneca 2-dose vaccinees, falling below the detectable threshold. An mRNA booster dose produced a similar increase in neutralising activity regardless of the vaccine used for primary vaccination. After a booster dose (usually with an mRNA vaccine), vaccine effectiveness against symptomatic disease was at , and the effectiveness against severe disease was expected to be higher.


title: SARS-CoV-2 Omicron variant

text: Many of the mutations to the spike protein are present in other variants of concern and are related to increased infectivity and antibody evasion. Computational modeling suggests that the variant may also escape cell-mediated immunity.


title: SARS-CoV-2 Omicron variant

text: Vaccines continue to be recommended for BA.1. Professor Paul Morgan, immunologist at Cardiff University said, "I think a blunting rather than a complete loss [of immunity] is the most likely outcome. The virus can't possibly lose every single epitope on its surface, because if it did that spike protein couldn't work any more. So, while some of the antibodies and T cell clones made against earlier versions of the virus, or against the vaccines may not be effective, there will be others, which will remain effective. (...) If half, or two-thirds, or whatever it is, of the immune response is not going to be effective, and you're left with the residual half, then the more boosted that is the better."


title: SARS-CoV-2 Omicron variant

text: Professor Francois Balloux of the Genetics Institute at University College London said, "From what we have learned so far, we can be fairly confident that – compared with other variants – Omicron tends to be better able to reinfect people who have been previously infected and received some protection against COVID-19. That is pretty clear and was anticipated from the mutational changes we have pinpointed in its protein structure. These make it more difficult for antibodies to neutralise the virus."


title: SARS-CoV-2 Omicron variant

text: On 23 December 2021, "Nature" indicates that, though Omicron likely weakens vaccine protection, reasonable effectiveness against Omicron (BA.1) may be maintained with currently available vaccination and boosting approaches.


title: SARS-CoV-2 Omicron variant

text: In May 2022, a preprint indicated Omicron subvariants BA.4 and BA.5 could cause a large share of COVID-19-reinfections, beyond the increase of reinfections caused by the Omicron lineage, even for people who were infected by Omicron BA.1 due to increases in immune evasion, especially for the unvaccinated. However, the observed escape of BA.4 and BA.5 from immunity by a BA.1 infection is more moderate than of BA.1 against studied prior cases of immunity (such as immunity from specific vaccines).


title: SARS-CoV-2 Omicron variant

text: Immunity from an Omicron infection for unvaccinated and previously uninfected was found to be weak "against non-Omicron variants", albeit at the time Omicron is, by a large margin, the dominant variant in sequenced human cases.


title: SARS-CoV-2 Omicron variant

text: better at escaping first and booster vaccines than previous variants, and "to have pretty much eliminated every single monoclonal antibody on the market right now in terms of their efficacy".


title: SARS-CoV-2 Omicron variant

text: As of June 2022, researchers, health organizations and regulators are discussing, investigating (including with preliminary laboratory studies and trials) and partly recommending COVID-19 vaccine boosters that mix the original vaccine formulation with Omicron-adjusted parts – such as spike proteins of a specific Omicron subvariant – to better prepare the immune system to recognize a wide variety of variants amid substantial and ongoing immune evasion by Omicron.


title: SARS-CoV-2 Omicron variant

text: Loss of taste and smell seem to be uncommon compared to other strains. A unique reported symptom of the Omicron variant is night sweats, particularly with the BA.5 subvariant. A study performed between 1 and 7 December 2021 by the Center for Disease Control found that: "The most commonly reported symptoms [were] cough, fatigue, and congestion or runny nose" making it difficult to distinguish from a less damaging variant or another virus. Research published in London on 25 December 2021 suggested the most frequent symptoms stated by users of the Zoe Covid app were "a runny nose, headaches, fatigue, sneezing and sore throats."<ref name="theguardian.com/world/2021/dec/24">Omicron's cold-like symptoms mean UK guidance 'needs urgent update' "The Guardian"</ref>


title: SARS-CoV-2 Omicron variant

text: A British omicron case-control observational study until March 2022 showed a reduction in odds of long COVID with the omicron variant versus the delta variant of 0·24–0·5 depending on age and time since vaccination.


title: SARS-CoV-2 Omicron variant

text: As of 28 November 2021 the World Health Organization stated that no information suggested that symptoms associated with Omicron were different from other variants, but it was not yet clear whether Omicron was more virulent, causing more severe disease. Increased rates of hospitalization in South Africa at the time could be due to a higher number of cases, rather than any specific feature.


title: SARS-CoV-2 Omicron variant

text: On 4 December 2021, the South African Medical Research Council reported that from 14 to 29 November 2021 at a hospital complex in Tshwane, inpatients were younger than in previous waves and the ICU and oxygen therapy rates were lower than in earlier waves, but observations were not definitive and subject to change over the following two weeks. in the week of 28 November 2021 excess deaths nearly doubled suggesting under-reporting, but the level was much lower than that seen in the second wave in mid-January 2021.


title: SARS-CoV-2 Omicron variant

text: On 12 December 2021, director-general of the World Health Organization Tedros Adhanom said that it was <q>wrong for people to consider Omicron as mild</q>, as high exposure to previous infections in South Africa was likely to affect the clinical course of the new infections.


title: SARS-CoV-2 Omicron variant

text: On 20 December 2021, a report by the Imperial College COVID-19 Response Team, based on data from England, found that <q>hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta.</q> On 22 December 2021, the team reported an about lower risk of a hospitalization requiring a stay of at least 1 night compared to the Delta variant, and that the data suggested that recipients of 2 doses of the Pfizer–BioNTech, the Moderna or the Oxford–AstraZeneca vaccine were substantially protected from hospitalization.


title: SARS-CoV-2 Omicron variant

text: As of 6 January 2022, Omicron BA.1 multiplied around 70 times faster than the Delta variant in the bronchi (lung airways) but evidence suggested it is less severe than previous variants, especially compared to Delta, since it might be less able to penetrate deep lung tissue. As of January 2022, in southern California infections were 91 percent less fatal than the delta variant, with 51 percent less risk of hospitalization. However, the estimated difference in the intrinsic risk of hospitalization in England largely decreased to 0–30 percent, when reinfections were excluded.


title: SARS-CoV-2 Omicron variant

text: As of 21 January 2022 the risk of hospitalization was the same in BA.1 and BA.2 based on reviews from Denmark, India, South Africa and the United Kingdom. Norwegian studies showed that the amount of virus in the upper airways was similar in those infected with BA.1 and BA.2.


title: SARS-CoV-2 Omicron variant

text: As of 22 February 2022 studies from Denmark and Qatar found that after an infection with BA.1, the vast majority of people were well-protected against a BA.2 infection, and that antibodies for BA.1 generally protect against BA.2. although it was unknown how long this protection would last. In Denmark, preliminary data found breakthrough rates in vaccinated people were similar to the breakthrough rates seen for BA.1. A January 2022 study by the UK Health Security Agency found that vaccines afforded similar levels of protection against symptomatic disease by BA.1 and BA.2, and in both it was considerably higher after two doses and a booster than two doses without booster, though because of the gradually waning effect of vaccines, further booster vaccination may later be necessary.


title: SARS-CoV-2 Omicron variant

text: As of November 2021, the chance of detecting an Omicron case particularly depended on a country's sequencing rate, with South Africa sequencing far more samples than any other country in Africa, but at a considerably lower rate than most Western nations. Furthermore, it could take up to two weeks to return a viral sequence in places with the technical capability, hence solid statistics on confirmed cases have lagged the actual situation.


title: SARS-CoV-2 Omicron variant

text: In December 2021, the US FDA published guidelines on how PCR tests would be affected by Omicron. Tests that detect multiple gene targets were to continue to identify the testee as positive for COVID-19. S-gene dropout or target failure was proposed as a shorthand way of differentiating Omicron from Delta. besides sequencing and genotyping.


title: SARS-CoV-2 Omicron variant

text: As of December 2021, Denmark and Norway have regarded cases found by their variant qPCR test, which is relatively fast and checks several genes, as sufficient for counting it as Omicron, before full sequencing.


title: SARS-CoV-2 Omicron variant

text: As of 7 December 2021 it was known that BA.2 -unlike Ba1- lacks the characteristic S-gene target failure (SGTF) causing deletion (Δ69-70), by which many qPCR tests have been able to rapidly detect a case as an Omicron (or Alpha) variant, from the previously dominant Delta variant. Thus, countries which primarily rely on SGTF for detection may overlook BA.2, and British authorities consider SGTF alone as insufficient for monitoring the spread of Omicron. This has resulted in it having been nicknamed 'Stealth Omicron', but because BA.2 still can be separated from other variants through normal full sequencing, or checks of certain other mutations, the nickname is not quite accurate. As of January 2022, some countries, such as Denmark and Japan, have been using a variant qPCR which tests for several mutations, including L452R. It can also distinguish Delta, which has L452R, and all Omicron subvariants, which do not have L452R. As Omicron became dominant and the Delta variant became rare in early 2022, the SGTF mutation that had made Delta and BA.2 similar in qPCR tests was found to be useful for separating BA.1 and BA.2 from each other.


title: SARS-CoV-2 Omicron variant

text: In January 2022 the medicine and therapeutic regulatory agency Therapeutic Goods Administration (TGA) of the Australian Government found that only one of their 23 approved COVID-19 rapid antigen tests (RAT) stated that it detected Omicron.


title: SARS-CoV-2 Omicron variant

text: In June 2022, the German federal Paul-Ehrlich-Institute published their findings, that most RATs detected the Omicron Variant.


title: SARS-CoV-2 Omicron variant

text: As of 28 November 2021, Corticosteroids such as dexamethasone and IL6 receptor blockers such as tocilizumab (Actemra) were known to be effective for managing patients with the earlier strains of severe COVID-19 but the impact on the effectiveness of other treatments was being assessed.


title: SARS-CoV-2 Omicron variant

text: Relating to monoclonal antibodies (mAbs) treatments, similar testing and research is ongoing. Preclinical data on in vitro pseudotyped virus data demonstrate that some mAbs designed to use highly conserved epitopes retain neutralizing activity against key mutations of Omicron substitutions.


title: SARS-CoV-2 Omicron variant

text: Similar results are confirmed by cryo-electron microscopy and X-ray data, also providing the structural approach and molecular basis for the evasion of humoral immunity exhibited by Omicron antigenic shift as well as the importance of targeting conserved epitopes for vaccine and therapeutics design. While 7 clinical mAbs or mAb cocktails experienced loss of neutralizing activity of 1-2 orders of magnitude or greater relative to the prototypic virus, the S309 mAb, the parent mAb of sotrovimab, neutralized Omicron with only 2-3-fold reduced potency.


title: SARS-CoV-2 Omicron variant

text: As of December 2021, most monoclonal antibodies had lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs examined in another study retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab (VIR-7831), S2X259 and S2H97. However, sotrovimab was not fully active against the BA.2 Omicron sublineage, and in March2022 the office of the U.S. ASPR stopped distributing the antibody treatment to states where BA.2 was dominant.


title: SARS-CoV-2 Omicron variant

text: February 2022 data suggested Omicron caused significant humoral immune evasion, while neutralizing antibodies targeting the sarbecovirus conserved region remained most effective.


title: SARS-CoV-2 Omicron variant

text: On 26 November 2021, the South African National Institute for Communicable Diseases announced that 30,904 COVID-19-tests (in one day) detected 2,828 new COVID-19 infections (a 9.2% positivity rate).


title: SARS-CoV-2 Omicron variant

text: One week later, on 3 December 2021, the NICD announced that 65,990 COVID-19 tests had found 16,055 new infections (5.7 times as many as seven days before; positive rate 24.3%) and that 72 percent of them were found in Gauteng.


title: SARS-CoV-2 Omicron variant

text: This province of South Africa is densely populated at about 850 inhabitants per km. Gauteng's capital Johannesburg is a megacity (about 5.5 million inhabitants in the city itself plus 9.5 million in the urban region).


title: SARS-CoV-2 Omicron variant

text: In November 2021, the transmissibility of the Omicron variant, as compared to the Delta variant or other variants of the COVID-19 virus, was still uncertain. Omicron is frequently able to infect previously COVID-19-positive people.


title: SARS-CoV-2 Omicron variant

text: It has been estimated the Omicron variant diverged in late September or early October 2021, based on Omicron genome comparisons.


title: SARS-CoV-2 Omicron variant

text: Sequencing data suggests that Omicron had become the dominant variant in South Africa by November 2021, the same month where it had been first identified in the country.


title: SARS-CoV-2 Omicron variant

text: Phylogeny suggests a recent emergence. Data from South Africa suggests that Omicron has a pronounced growth advantage there. However, this may be due to transmissibility or immune escape related, or both." Also the serial interval plays a role in the growth.


title: SARS-CoV-2 Omicron variant

text: Detectable changes in levels of COVID-19 in wastewater samples from South Africa's Gauteng province were seen as early as 17–23 October (week 42). The National Institute for Communicable Diseases reports that children under the age of 2 make up 10% of total hospital admissions in the Omicron point of discovery Tshwane in South Africa. Data on the S gene target failure (SGTF) of sampled cases in South Africa indicates a growth of 21% per day relative to Delta, generating an increased reproduction number by a factor of 2.4. Omicron became the majority strain in South Africa around 10 November. Another analysis showed 32% growth per day in Gauteng, South Africa, having become dominant there around 6 November.


title: SARS-CoV-2 Omicron variant

text: In the UK, the logarithmic growth rate of Omicron-associated S gene target failure (SGTF) cases over S gene target positive (SGTP) cases was estimated at 0.37 per day, which is exceptionally high. Furthermore, by 14 December it appears to have become the most dominant strain. Without presuming behavior change in response to the variant, a million infections per day by 24 December are projected for a 2.5 days doubling time. In Denmark, the growth rate has been roughly similar with a doubling time of about 2–3 days, it having become the most prevalent strain on 17 December. Switzerland is not far behind. In Germany Omicron became the most prevalent variant on 1 January. In Scotland, Omicron apparently became the most prevalent variant on 17 December. In the Canadian province of Ontario it became the most prevalent strain on 13 December. In the US, the variant appears to have become the most prevalent strain on 18 December, growing at 0.24 per day. In Portugal, Omicron had reached 61.5% of cases on 22 December. In Belgium, the strain has become the most prevalent on 25 December, and in the Netherlands on 28 December. In Italy, it had reached 28% of cases on 20 December and was doubling every two days, while it became the dominant variant in Norway on 25 December. In France, it made up about 15% of COVID-19 cases in mid-December, but around 27 December it had increased to more than 60%. Researchers recommend sampling at least 5% of COVID-19 patient samples in order to detect Omicron or other emerging variants.


title: SARS-CoV-2 Omicron variant

text: During January 2022, in Denmark the BA.2 variant grew at ~0.10 per day (+11% per day) as a ratio to BA.1 (the legacy Omicron variant), and became the dominant strain in week 2, 2022. In the United Kingdom, the BA.2 variant was growing at ~0.11 per day (+12% per day) as a ratio to BA.1.


title: SARS-CoV-2 Omicron variant

text: On 13 January 2022, the BBC reported that the hospitalization rate was higher in the US and Canada than in Europe and South Africa. This was attributed to a combination of a greater number of elderly people than in South Africa, greater prevalence of comorbidities such as hypertension and obesity than in Europe, higher indoor transmission due to the winter, lower vaccination rate in the US than in Europe and Canada, and a possible still high prevalence of the Delta variant, which more often leads to hospitalization.


title: Pancreatic cancer

text: Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancreatic cancer are known.


title: Pancreatic cancer

text: The most common, pancreatic adenocarcinoma, accounts for about 90% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells. About 1–2% of cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma.


title: Pancreatic cancer

text: Signs and symptoms of the most-common form of pancreatic cancer may include yellow skin, abdominal or back pain, unexplained weight loss, light-colored stools, dark urine, and loss of appetite. Usually, no symptoms are seen in the disease's early stages, and symptoms that are specific enough to suggest pancreatic cancer typically do not develop until the disease has reached an advanced stage. By the time of diagnosis, pancreatic cancer has often spread to other parts of the body.


title: Pancreatic cancer

text: Pancreatic cancer rarely occurs before the age of 40, and more than half of cases of pancreatic adenocarcinoma occur in those over 70. Risk factors for pancreatic cancer include tobacco smoking, obesity, diabetes, and certain rare genetic conditions. About 25% of cases are linked to smoking, and 5–10% are linked to inherited genes. Pancreatic cancer is usually diagnosed by a combination of medical imaging techniques such as ultrasound or computed tomography, blood tests, and examination of tissue samples (biopsy). The disease is divided into stages, from early (stage I) to late (stage IV). Screening the general population has not been found to be effective.


title: Pancreatic cancer

text: The risk of developing pancreatic cancer is lower among nonsmokers, and people who maintain a healthy weight and limit their consumption of red or processed meat; however, the risk is greater for men, especially at very high levels of red meat consumption. Smokers' chances of developing the disease decrease if they stop smoking and almost return to that of the rest of the population after 20 years. Pancreatic cancer can be treated with surgery, radiotherapy, chemotherapy, palliative care, or a combination of these. Treatment options are partly based on the cancer stage. Surgery is the only treatment that can cure pancreatic adenocarcinoma, and may also be done to improve quality of life without the potential for cure. Pain management and medications to improve digestion are sometimes needed. Early palliative care is recommended even for those receiving treatment that aims for a cure.


title: Pancreatic cancer

text: In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. Pancreatic cancer is the fifth-most-common cause of death from cancer in the United Kingdom, and the third most-common in the United States. The disease occurs most often in the developed world, where about 70% of the new cases in 2012 originated. Pancreatic adenocarcinoma typically has a very poor prognosis; after diagnosis, 25% of people survive one year and 5% live for five years. For cancers diagnosed early, the five-year survival rate rises to about 20%. Neuroendocrine cancers have better outcomes; at five years from diagnosis, 65% of those diagnosed are living, though survival considerably varies depending on the type of tumor.


title: Pancreatic cancer

text: The many types of pancreatic cancer can be divided into two general groups. The vast majority of cases (about 95%) occur in the part of the pancreas that produces digestive enzymes, known as the exocrine component. Several subtypes of exocrine pancreatic cancers are described, but their diagnosis and treatment have much in common. The small minority of cancers that arise in the hormone-producing (endocrine) tissue of the pancreas have different clinical characteristics and are called pancreatic neuroendocrine tumors, sometimes abbreviated as "PanNETs". Both groups occur mainly (but not exclusively) in people over 40, and are slightly more common in men, but some rare subtypes mainly occur in women or children.


title: Pancreatic cancer

text: The exocrine group is dominated by pancreatic adenocarcinoma (variations of this name may add "invasive" and "ductal"), which is by far the most common type, representing about 85% of all pancreatic cancers. Nearly all these start in the ducts of the pancreas, as pancreatic ductal adenocarcinoma (PDAC). This is despite the fact that the tissue from which it arises – the pancreatic ductal epithelium – represents less than 10% of the pancreas by cell volume, because it constitutes only the ducts (an extensive but capillary-like duct-system fanning out) within the pancreas. This cancer originates in the ducts that carry secretions (such as enzymes and bicarbonate) away from the pancreas. About 60–70% of adenocarcinomas occur in the head of the pancreas.


title: Pancreatic cancer

text: The next-most common type, acinar cell carcinoma of the pancreas, arises in the clusters of cells that produce these enzymes, and represents 5% of exocrine pancreas cancers. Like the 'functioning' endocrine cancers described below, acinar cell carcinomas may cause over-production of certain molecules, in this case digestive enzymes, which may cause symptoms such as skin rashes and joint pain.


title: Pancreatic cancer

text: Cystadenocarcinomas account for 1% of pancreatic cancers, and they have a better prognosis than the other exocrine types.


title: Pancreatic cancer

text: Pancreatoblastoma is a rare form, mostly occurring in childhood, and with a relatively good prognosis. Other exocrine cancers include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells. Solid pseudopapillary tumor is a rare low-grade neoplasm that mainly affects younger women, and generally has a very good prognosis.


title: Pancreatic cancer

text: Pancreatic mucinous cystic neoplasms are a broad group of pancreas tumors that have varying malignant potential. They are being detected at a greatly increased rate as CT scans become more powerful and common, and discussion continues as how best to assess and treat them, given that many are benign.


title: Pancreatic cancer

text: The small minority of tumors that arise elsewhere in the pancreas are mainly pancreatic neuroendocrine tumors (PanNETs). Neuroendocrine tumors (NETs) are a diverse group of benign or malignant tumors that arise from the body's neuroendocrine cells, which are responsible for integrating the nervous and endocrine systems. NETs can start in most organs of the body, including the pancreas, where the various malignant types are all considered to be rare. PanNETs are grouped into 'functioning' and 'nonfunctioning' types, depending on the degree to which they produce hormones. The functioning types secrete hormones such as insulin, gastrin, and glucagon into the bloodstream, often in large quantities, giving rise to serious symptoms such as low blood sugar, but also favoring relatively early detection. The most common functioning PanNETs are insulinomas and gastrinomas, named after the hormones they secrete. The nonfunctioning types do not secrete hormones in a sufficient quantity to give rise to overt clinical symptoms, so nonfunctioning PanNETs are often diagnosed only after the cancer has spread to other parts of the body.


title: Pancreatic cancer

text: As with other neuroendocrine tumors, the history of the terminology and classification of PanNETs is complex. PanNETs are sometimes called "islet cell cancers", though they are now known to not actually arise from islet cells as previously thought.


title: Pancreatic cancer

text: Since pancreatic cancer usually does not cause recognizable symptoms in its early stages, the disease is typically not diagnosed until it has spread beyond the pancreas itself. This is one of the main reasons for the generally poor survival rates. Exceptions to this are the functioning PanNETs, where over-production of various active hormones can give rise to symptoms (which depend on the type of hormone).


title: Pancreatic cancer

text: Bearing in mind that the disease is rarely diagnosed before the age of 40, common symptoms of pancreatic adenocarcinoma occurring before diagnosis include:


title: Pancreatic cancer

text: Other common manifestations of the disease include weakness and tiring easily, dry mouth, sleep problems, and a palpable abdominal mass.


title: Pancreatic cancer

text: The spread of pancreatic cancer to other organs (metastasis) may also cause symptoms. Typically, pancreatic adenocarcinoma first spreads to nearby lymph nodes, and later to the liver or to the peritoneal cavity, large intestine, or lungs. Uncommonly, it spreads to the bones or brain.


title: Pancreatic cancer

text: Cancers in the pancreas may also be secondary cancers that have spread from other parts of the body. This is uncommon, found in only about 2% of cases of pancreatic cancer. Kidney cancer is by far the most common cancer to spread to the pancreas, followed by colorectal cancer, and then cancers of the skin, breast, and lung. Surgery may be performed on the pancreas in such cases, whether in hope of a cure or to alleviate symptoms.


title: Pancreatic cancer

text: Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, but considerable research has failed to firmly establish alcohol consumption as a direct risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association, with smoking a strong confounding factor. The evidence is stronger for a link with heavy drinking, of at least six drinks per day.


title: Pancreatic cancer

text: Exocrine cancers are thought to arise from several types of precancerous lesions within the pancreas, but these lesions do not always progress to cancer, and the increased numbers detected as a byproduct of the increasing use of CT scans for other reasons are not all treated. Apart from pancreatic serous cystadenomas, which are almost always benign, four types of precancerous lesion are recognized.


title: Pancreatic cancer

text: The first is pancreatic intraepithelial neoplasia (PanIN). These lesions are microscopic abnormalities in the pancreas and are often found in autopsies of people with no diagnosed cancer. These lesions may progress from low to high grade and then to a tumor. More than 90% of cases at all grades carry a faulty "KRAS" gene, while in grades 2 and 3, damage to three further genes – "CDKN2A" ("p16"), "p53", and "SMAD4" – are increasingly often found.


title: Pancreatic cancer

text: A second type is the intraductal papillary mucinous neoplasm (IPMN). These are macroscopic lesions, which are found in about 2% of all adults. This rate rises to about 10% by age 70. These lesions have about a 25% risk of developing into invasive cancer. They may have "KRAS" gene mutations (40–65% of cases) and in the GNAS Gs alpha subunit and RNF43, affecting the Wnt signaling pathway. Even if removed surgically, a considerably increased risk remains of pancreatic cancer developing subsequently.


title: Pancreatic cancer

text: The third type, pancreatic mucinous cystic neoplasm (MCN), mainly occurs in women, and may remain benign or progress to cancer. If these lesions become large, cause symptoms, or have suspicious features, they can usually be successfully removed by surgery.


title: Pancreatic cancer

text: A fourth type of cancer that arises in the pancreas is the intraductal tubulopapillary neoplasm. This type was recognised by the WHO in 2010 and constitutes about 1–3% of all pancreatic neoplasms. Mean age at diagnosis is 61 years (range 35–78 years). About 50% of these lesions become invasive. Diagnosis depends on histology, as these lesions are very difficult to differentiate from other lesions on either clinical or radiological grounds.


title: Pancreatic cancer

text: The genetic events found in ductal adenocarcinoma have been well characterized, and complete exome sequencing has been done for the common types of tumor. Four genes have each been found to be mutated in the majority of adenocarcinomas: "KRAS" (in 95% of cases), "CDKN2A" (also in 95%), "TP53" (75%), and "SMAD4" (55%). The last of these is especially associated with a poor prognosis. "SWI/SNF" mutations/deletions occur in about 10–15% of the adenocarcinomas. The genetic alterations in several other types of pancreatic cancer and precancerous lesions have also been researched. Transcriptomics analyses and mRNA sequencing for the common forms of pancreatic cancer have found that 75% of human genes are expressed in the tumors, with some 200 genes more specifically expressed in pancreatic cancer as compared to other tumor types.


title: Pancreatic cancer

text: The genes often found mutated in PanNETs are different from those in exocrine pancreatic cancer. For example, "KRAS" mutation is normally absent. Instead, hereditary "MEN1" gene mutations give risk to MEN1 syndrome, in which primary tumors occur in two or more endocrine glands. About 40–70% of people born with a "MEN1" mutation eventually develop a PanNet. Other genes that are frequently mutated include "DAXX", "mTOR", and "ATRX".


title: Pancreatic cancer

text: The symptoms of pancreatic adenocarcinoma do not usually appear in the disease's early stages, and they are not individually distinctive to the disease. The symptoms at diagnosis vary according to the location of the cancer in the pancreas, which anatomists divide (from left to right on most diagrams) into the thick head, the neck, and the tapering body, ending in the tail.


title: Pancreatic cancer

text: Regardless of a tumor's location, the most common symptom is unexplained weight loss, which may be considerable. A large minority (between 35% and 47%) of people diagnosed with the disease will have had nausea, vomiting, or a feeling of weakness. Tumors in the head of the pancreas typically also cause jaundice, pain, loss of appetite, dark urine, and light-colored stools. Tumors in the body and tail typically also cause pain.


title: Pancreatic cancer

text: People sometimes have recent onset of atypical type 2 diabetes that is difficult to control, a history of recent but unexplained blood vessel inflammation caused by blood clots (thrombophlebitis) known as Trousseau sign, or a previous attack of pancreatitis. A doctor may suspect pancreatic cancer when the onset of diabetes in someone over 50 years old is accompanied by typical symptoms such as unexplained weight loss, persistent abdominal or back pain, indigestion, vomiting, or fatty feces. Jaundice accompanied by a painlessly swollen gallbladder (known as Courvoisier's sign) may also raise suspicion, and can help differentiate pancreatic cancer from gallstones.


title: Pancreatic cancer

text: Medical imaging techniques, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) are used both to confirm the diagnosis and to help decide whether the tumor can be surgically removed (its "resectability"). On contrast CT scan, pancreatic cancer typically shows a gradually increasing radiocontrast uptake, rather than a fast washout as seen in a normal pancreas or a delayed washout as seen in chronic pancreatitis. Magnetic resonance imaging and positron emission tomography may also be used, and magnetic resonance cholangiopancreatography may be useful in some cases. Abdominal ultrasound is less sensitive and will miss small tumors, but can identify cancers that have spread to the liver and build-up of fluid in the peritoneal cavity (ascites). It may be used for a quick and cheap first examination before other techniques.


title: Pancreatic cancer

text: A biopsy by fine needle aspiration, often guided by endoscopic ultrasound, may be used where there is uncertainty over the diagnosis, but a histologic diagnosis is not usually required for removal of the tumor by surgery to go ahead.


title: Pancreatic cancer

text: Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity, not least because 5% of people lack the Lewis (a) antigen and cannot produce CA19-9. It has a sensitivity of 80% and specificity of 73% in detecting pancreatic adenocarcinoma, and is used for following known cases rather than diagnosis.


title: Pancreatic cancer

text: The most common form of pancreatic cancer (adenocarcinoma) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. There is typically considerable desmoplasia or formation of a dense fibrous stroma or structural tissue consisting of a range of cell types (including myofibroblasts, macrophages, lymphocytes and mast cells) and deposited material (such as type I collagen and hyaluronic acid). This creates a tumor microenvironment that is short of blood vessels (hypovascular) and so of oxygen (tumor hypoxia). It is thought that this prevents many chemotherapy drugs from reaching the tumor, as one factor making the cancer especially hard to treat.


title: Pancreatic cancer

text: Pancreatic cancer is usually staged following a CT scan. The most widely used cancer staging system for pancreatic cancer is the one formulated by the American Joint Committee on Cancer (AJCC) together with the Union for International Cancer Control (UICC). The AJCC-UICC staging system designates four main overall stages, ranging from early to advanced disease, based on TNM classification of Tumor size, spread to lymph Nodes, and Metastasis.


title: Pancreatic cancer

text: To help decide treatment, the tumors are also divided into three broader categories based on whether surgical removal seems possible: in this way, tumors are judged to be "resectable", "borderline resectable", or "unresectable". When the disease is still in an early stage (AJCC-UICC stages I and II), without spread to large blood vessels or distant organs such as the liver or lungs, surgical resection of the tumor can normally be performed, if the patient is willing to undergo this major operation and is thought to be sufficiently fit.


title: Pancreatic cancer

text: The AJCC-UICC staging system allows distinction between stage III tumors that are judged to be "borderline resectable" (where surgery is technically feasible because the celiac axis and superior mesenteric artery are still free) and those that are "unresectable" (due to more locally advanced disease); in terms of the more detailed TNM classification, these two groups correspond to T3 and T4 respectively.


title: Pancreatic cancer

text: Locally advanced adenocarcinomas have spread into neighboring organs, which may be any of the following (in roughly decreasing order of frequency): the duodenum, stomach, transverse colon, spleen, adrenal gland, or kidney. Very often they also spread to the important blood or lymphatic vessels and nerves that run close to the pancreas, making surgery far more difficult. Typical sites for metastatic spread (stage IV disease) are the liver, peritoneal cavity and lungs, all of which occur in 50% or more of fully advanced cases.


title: Pancreatic cancer

text: The 2010 WHO classification of tumors of the digestive system grades all the pancreatic neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society.


title: Pancreatic cancer

text: Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.


title: Pancreatic cancer

text: In the general population, screening of large groups is not considered effective and may be harmful as of 2019, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.


title: Pancreatic cancer

text: A key assessment that is made after diagnosis is whether surgical removal of the tumor is possible (see Staging), as this is the only cure for this cancer. Whether or not surgical resection can be offered depends on how much the cancer has spread. The exact location of the tumor is also a significant factor, and CT can show how it relates to the major blood vessels passing close to the pancreas. The general health of the person must also be assessed, though age in itself is not an obstacle to surgery.


title: Pancreatic cancer

text: Chemotherapy and, to a lesser extent, radiotherapy are likely to be offered to most people, whether or not surgery is possible. Specialists advise that the management of pancreatic cancer should be in the hands of a multidisciplinary team including specialists in several aspects of oncology, and is, therefore, best conducted in larger centers.


title: Pancreatic cancer

text: Surgery with the intention of a cure is only possible in around one-fifth (20%) of new cases. Although CT scans help, in practice it can be difficult to determine whether the tumor can be fully removed (its "resectability"), and it may only become apparent during surgery that it is not possible to successfully remove the tumor without damaging other vital tissues. Whether or not surgical resection can be offered depends on various factors, including the precise extent of local anatomical adjacency to, or involvement of, the venous or arterial blood vessels, as well as surgical expertise and a careful consideration of projected post-operative recovery. The age of the person is not in itself a reason not to operate, but their general performance status needs to be adequate for a major operation.


title: Pancreatic cancer

text: One particular feature that is evaluated is the encouraging presence, or discouraging absence, of a clear layer or plane of fat creating a barrier between the tumor and the vessels. Traditionally, an assessment is made of the tumor's proximity to major venous or arterial vessels, in terms of "abutment" (defined as the tumor touching no more than half a blood vessel's circumference without any fat to separate it), "encasement" (when the tumor encloses most of the vessel's circumference), or full vessel involvement. A resection that includes encased sections of blood vessels may be possible in some cases, particularly if preliminary neoadjuvant therapy is feasible, using chemotherapy and/or radiotherapy.


title: Pancreatic cancer

text: Even when the operation appears to have been successful, cancerous cells are often found around the edges ("margins") of the removed tissue, when a pathologist examines them microscopically (this will always be done), indicating the cancer has not been entirely removed. Furthermore, cancer stem cells are usually not evident microscopically, and if they are present they may continue to develop and spread. An exploratory laparoscopy (a small, camera-guided surgical procedure) may therefore be performed to gain a clearer idea of the outcome of a full operation.


title: Pancreatic cancer

text: For cancers involving the head of the pancreas, the Whipple procedure is the most commonly attempted curative surgical treatment. This is a major operation which involves removing the pancreatic head and the curve of the duodenum together ("pancreato-duodenectomy"), making a bypass for food from the stomach to the jejunum ("gastro-jejunostomy") and attaching a loop of jejunum to the cystic duct to drain bile ("cholecysto-jejunostomy"). It can be performed only if the person is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can, therefore, be performed only in a minority of cases. Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy, which often also entails removal of the spleen. Nowadays, this can often be done using minimally invasive surgery.


title: Pancreatic cancer

text: Although curative surgery no longer entails the very high death rates that occurred until the 1980s, a high proportion of people (about 30–45%) still have to be treated for a post-operative sickness that is not caused by the cancer itself. The most common complication of surgery is difficulty in emptying the stomach. Certain more limited surgical procedures may also be used to ease symptoms (see Palliative care): for instance, if the cancer is invading or compressing the duodenum or colon. In such cases, bypass surgery might overcome the obstruction and improve quality of life but is not intended as a cure.


title: Pancreatic cancer

text: After surgery, adjuvant chemotherapy with gemcitabine or 5-FU can be offered if the person is sufficiently fit, after a recovery period of one to two months. In people not suitable for curative surgery, chemotherapy may be used to extend life or improve its quality. Before surgery, neoadjuvant chemotherapy or chemoradiotherapy may be used in cases that are considered to be "borderline resectable" (see Staging) in order to reduce the cancer to a level where surgery could be beneficial. In other cases neoadjuvant therapy remains controversial, because it delays surgery.


title: Pancreatic cancer

text: Gemcitabine was approved by the United States Food and Drug Administration (FDA) in 1997, after a clinical trial reported improvements in quality of life and a five-week improvement in median survival duration in people with advanced pancreatic cancer. This was the first chemotherapy drug approved by the FDA primarily for a nonsurvival clinical trial endpoint. Chemotherapy using gemcitabine alone was the standard for about a decade, as a number of trials testing it in combination with other drugs failed to demonstrate significantly better outcomes. However, the combination of gemcitabine with erlotinib was found to increase survival modestly, and erlotinib was licensed by the FDA for use in pancreatic cancer in 2005.


title: Pancreatic cancer

text: The FOLFIRINOX chemotherapy regimen using four drugs was found more effective than gemcitabine, but with substantial side effects, and is thus only suitable for people with good performance status. This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine in pancreas cancer. By the end of 2013, both FOLFIRINOX and nab-paclitaxel with gemcitabine were regarded as good choices for those able to tolerate the side-effects, and gemcitabine remained an effective option for those who were not. A head-to-head trial between the two new options is awaited, and trials investigating other variations continue. However, the changes of the last few years have only increased survival times by a few months. Clinical trials are often conducted for novel adjuvant therapies.


title: Pancreatic cancer

text: The role of radiotherapy as an auxiliary (adjuvant) treatment after potentially curative surgery has been controversial since the 1980s. In the early 2000s the European Study Group for Pancreatic Cancer Research (ESPAC) showed prognostic superiority of adjuvant chemotherapy over chemoradiotherapy. The European Society for Medical Oncology recommends that adjuvant radiotherapy should only be used for people enrolled in clinical trials. However, there is a continuing tendency for clinicians in the US to be more ready to use adjuvant radiotherapy than those in Europe. Many clinical trials have tested a variety of treatment combinations since the 1980s, but have failed to settle the matter conclusively.


title: Pancreatic cancer

text: Radiotherapy may form part of treatment to attempt to shrink a tumor to a resectable state, but its use on unresectable tumors remains controversial as there are conflicting results from clinical trials. The preliminary results of one trial, presented in 2013, "markedly reduced enthusiasm" for its use on locally advanced tumors.


title: Pancreatic cancer

text: Treatment of PanNETs, including the less common malignant types, may include a number of approaches. Some small tumors of less than 1 cm. that are identified incidentally, for example on a CT scan performed for other purposes, may be followed by watchful waiting. This depends on the assessed risk of surgery which is influenced by the site of the tumor and the presence of other medical problems. Tumors within the pancreas only (localized tumors), or with limited metastases, for example to the liver, may be removed by surgery. The type of surgery depends on the tumor location, and the degree of spread to lymph nodes.


title: Pancreatic cancer

text: For localized tumors, the surgical procedure may be much less extensive than the types of surgery used to treat pancreatic adenocarcinoma described above, but otherwise surgical procedures are similar to those for exocrine tumors. The range of possible outcomes varies greatly; some types have a very high survival rate after surgery while others have a poor outlook. As all this group are rare, guidelines emphasize that treatment should be undertaken in a specialized center. Use of liver transplantation may be considered in certain cases of liver metastasis.


title: Pancreatic cancer

text: For functioning tumors, the somatostatin analog class of medications, such as octreotide, can reduce the excessive production of hormones. Lanreotide can slow tumor growth. If the tumor is not amenable to surgical removal and is causing symptoms, targeted therapy with everolimus or sunitinib can reduce symptoms and slow progression of the disease. Standard cytotoxic chemotherapy is generally not very effective for PanNETs, but may be used when other drug treatments fail to prevent the disease from progressing, or in poorly differentiated PanNET cancers.


title: Pancreatic cancer

text: Radiation therapy is occasionally used if there is pain due to anatomic extension, such as metastasis to bone. Some PanNETs absorb specific peptides or hormones, and these PanNETs may respond to nuclear medicine therapy with radiolabeled peptides or hormones such as iobenguane (iodine-131-MIBG). Radiofrequency ablation (RFA), cryoablation, and hepatic artery embolization may also be used.


title: Pancreatic cancer

text: Palliative care is medical care which focuses on treatment of symptoms from serious illness, such as cancer, and improving quality of life. Because pancreatic adenocarcinoma is usually diagnosed after it has progressed to an advanced stage, palliative care as a treatment of symptoms is often the only treatment possible.


title: Pancreatic cancer

text: Palliative care focuses not on treating the underlying cancer, but on treating symptoms such as pain or nausea, and can assist in decision-making, including when or if hospice care will be beneficial. Pain can be managed with medications such as opioids or through procedural intervention, by a nerve block on the celiac plexus (CPB). This alters or, depending on the technique used, destroys the nerves that transmit pain from the abdomen. CPB is a safe and effective way to reduce the pain, which generally reduces the need to use opioid painkillers, which have significant negative side effects.


title: Pancreatic cancer

text: Other symptoms or complications that can be treated with palliative surgery are obstruction by the tumor of the intestines or bile ducts. For the latter, which occurs in well over half of cases, a small metal tube called a stent may be inserted by endoscope to keep the ducts draining. Palliative care can also help treat depression that often comes with the diagnosis of pancreatic cancer.


title: Pancreatic cancer

text: Both surgery and advanced inoperable tumors often lead to digestive system disorders from a lack of the exocrine products of the pancreas (exocrine insufficiency). These can be treated by taking pancreatin which contains manufactured pancreatic enzymes, and is best taken with food. Difficulty in emptying the stomach (delayed gastric emptying) is common and can be a serious problem, involving hospitalization. Treatment may involve a variety of approaches, including draining the stomach by nasogastric aspiration and drugs called proton-pump inhibitors or H antagonists, which both reduce production of gastric acid. Medications like metoclopramide can also be used to clear stomach contents.


title: Pancreatic cancer

text: Pancreatic adenocarcinoma and the other less common exocrine cancers have a very poor prognosis, as they are normally diagnosed at a late stage when the cancer is already locally advanced or has spread to other parts of the body. Outcomes are much better for PanNETs: Many are benign and completely without clinical symptoms, and even those cases not treatable with surgery have an average five-year survival rate of 16%, although the outlook varies considerably according to the type.


title: Pancreatic cancer

text: For locally advanced and metastatic pancreatic adenocarcinomas, which together represent over 80% of cases, numerous trials comparing chemotherapy regimes have shown increased survival times, but not to more than one year. Overall five-year survival for pancreatic cancer in the US has improved from 2% in cases diagnosed in 1975–1977, and 4% in 1987–1989 diagnoses, to 6% in 2003–2009. In the less than 20% of cases of pancreatic adenocarcinoma with a diagnosis of a localized and small cancerous growth (less than 2 cm in Stage T1), about 20% of Americans survive to five years.


title: Pancreatic cancer

text: About 1500 genes are linked to outcomes in pancreatic adenocarcinoma. These include both unfavorable genes, where high expression is related to poor outcome, for example C-Met and MUC-1, and favorable genes where high expression is associated with better survival, for example the transcription factor PELP1.


title: Pancreatic cancer

text: In 2015, pancreatic cancers of all types resulted in 411,600 deaths globally. In 2014, an estimated 46,000 people in the US are expected to be diagnosed with pancreatic cancer and 40,000 to die of it. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year. It is the seventh highest cause of death from cancer worldwide. Pancreatic cancer is the fifth most common cause of death from cancer in the United Kingdom, and the third most common in the United States.


title: Pancreatic cancer

text: Globally pancreatic cancer is the 11th most common cancer in women and the 12th most common in men. The majority of recorded cases occur in developed countries. People from the United States have an average lifetime risk of about 1 in 67 (or 1.5%) of developing the disease, slightly higher than the figure for the UK. The disease is more common in men than women, though the difference in rates has narrowed over recent decades, probably reflecting earlier increases in female smoking. In the United States the risk for African Americans is over 50% greater than for whites, but the rates in Africa and East Asia are much lower than those in North America or Europe. The United States, Central, and eastern Europe, and Argentina and Uruguay all have high rates.


title: Pancreatic cancer

text: The annual incidence of clinically recognized PanNETs is low (about 5 per one million person-years) and is dominated by the non-functioning types. Somewhere between 45% and 90% of PanNETs are thought to be of the non-functioning types. Studies of autopsies have uncovered small PanNETs rather frequently, suggesting that the prevalence of tumors that remain inert and asymptomatic may be relatively high. Overall PanNETs are thought to account for about 1 to 2% of all pancreatic tumors. The definition and classification of PanNETs has changed over time, affecting what is known about their epidemiology and clinical relevance.


title: Pancreatic cancer

text: The earliest recognition of pancreatic cancer has been attributed to the 18th-century Italian scientist Giovanni Battista Morgagni, the historical father of modern-day anatomic pathology, who claimed to have traced several cases of cancer in the pancreas. Many 18th and 19th-century physicians were skeptical about the existence of the disease, given the similar appearance of pancreatitis. Some case reports were published in the 1820s and 1830s, and a genuine histopathologic diagnosis was eventually recorded by the American clinician Jacob Mendes Da Costa, who also doubted the reliability of Morgagni's interpretations. By the start of the 20th century, cancer of the head of the pancreas had become a well-established diagnosis.


title: Pancreatic cancer

text: Regarding the recognition of PanNETs, the possibility of cancer of the islet cells was initially suggested in 1888. The first case of hyperinsulinism due to a tumor of this type was reported in 1927. Recognition of a non-insulin-secreting type of PanNET is generally ascribed to the American surgeons, R. M. Zollinger and E. H. Ellison, who gave their names to Zollinger–Ellison syndrome, after postulating the existence of a gastrin-secreting pancreatic tumor in a report of two cases of unusually severe peptic ulcers published in 1955. In 2010, the WHO recommended that PanNETs be referred to as "neuroendocrine" rather than "endocrine" tumors.


title: Pancreatic cancer

text: Small precancerous neoplasms for many pancreatic cancers are being detected at greatly increased rates by modern medical imaging. One type, the intraductal papillary mucinous neoplasm (IPMN) was first described by Japanese researchers in 1982. It was noted in 2010 that: "For the next decade, little attention was paid to this report; however, over the subsequent 15 years, there has been a virtual explosion in the recognition of this tumor."


title: Pancreatic cancer

text: The first reported partial pancreaticoduodenectomy was performed by the Italian surgeon Alessandro Codivilla in 1898, but the patient only survived 18 days before succumbing to complications. Early operations were compromised partly because of mistaken beliefs that people would die if their duodenum were removed, and also, at first, if the flow of pancreatic juices stopped. Later it was thought, also mistakenly, that the pancreatic duct could simply be tied up without serious adverse effects; in fact, it will very often leak later on. In 1907–1908, after some more unsuccessful operations by other surgeons, experimental procedures were tried on corpses by French surgeons.


title: Pancreatic cancer

text: In 1912 the German surgeon Walther Kausch was the first to remove large parts of the duodenum and pancreas together ("en bloc"). This was in Breslau, now Wrocław, in Poland. In 1918 it was demonstrated, in operations on dogs, that it is possible to survive even after complete removal of the duodenum, but no such result was reported in human surgery until 1935, when the American surgeon Allen Oldfather Whipple published the results of a series of three operations at Columbia Presbyterian Hospital in New York. Only one of the patients had the duodenum entirely removed, but he survived for two years before dying of metastasis to the liver.


title: Pancreatic cancer

text: The first operation was unplanned, as cancer was only discovered in the operating theater. Whipple's success showed the way for the future, but the operation remained a difficult and dangerous one until recent decades. He published several refinements to his procedure, including the first total removal of the duodenum in 1940, but he only performed a total of 37 operations.


title: Pancreatic cancer

text: The discovery in the late 1930s that vitamin K prevented bleeding with jaundice, and the development of blood transfusion as an everyday process, both improved post-operative survival, but about 25% of people never left hospital alive as late as the 1970s. In the 1970s a group of American surgeons wrote urging that the procedure was too dangerous and should be abandoned. Since then outcomes in larger centers have improved considerably, and mortality from the operation is often less than 4%.


title: Pancreatic cancer

text: In 2006 a report was published of a series of 1,000 consecutive pancreatico-duodenectomies performed by a single surgeon from Johns Hopkins Hospital between 1969 and 2003. The rate of these operations had increased steadily over this period, with only three of them before 1980, and the median operating time reduced from 8.8 hours in the 1970s to 5.5 hours in the 2000s, and mortality within 30 days or in hospital was only 1%. Another series of 2,050 operations at the Massachusetts General Hospital between 1941 and 2011 showed a similar picture of improvement.


title: Pancreatic cancer

text: Early-stage research on pancreatic cancer includes studies of genetics and early detection, treatment at different cancer stages, surgical strategies, and targeted therapies, such as inhibition of growth factors, immune therapies, and vaccines. Bile acids may have a role in the carcinogenesis of pancreatic cancer.


title: Pancreatic cancer

text: A key question is the timing of events as the disease develops and progresses – particularly the role of diabetes, and how and when the disease spreads. The knowledge that new onset of diabetes can be an early sign of the disease could facilitate timely diagnosis and prevention if a workable screening strategy can be developed. The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) trial is aiming to determine whether regular screening is appropriate for people with a family history of the disease.


title: Pancreatic cancer

text: Keyhole surgery (laparoscopy) rather than Whipple's procedure, particularly in terms of recovery time, is being evaluated. Irreversible electroporation is a relatively novel ablation technique with potential for downstaging and prolonging survival in persons with locally advanced disease, especially for tumors in proximity to peri-pancreatic vessels without risk of vascular trauma.


title: Pancreatic cancer

text: Efforts are underway to develop new drugs, including those targeting molecular mechanisms for cancer onset, stem cells, and cell proliferation. A further approach involves the use of immunotherapy, such as oncolytic viruses. Galectin-specific mechanisms of the tumor microenvironment are under study.


The 2022 Pennsylvania gubernatorial election was held on November 8, 2022, to elect the governor of Pennsylvania and lieutenant governor of Pennsylvania. Democratic state attorney general Josh Shapiro easily defeated Republican state senator Doug Mastriano to succeed term-limited incumbent Democratic governor Tom Wolf. Primaries were held on May 17, 2022. Shapiro won the Democratic nomination after running unopposed and Mastriano won the Republican nomination with 44% of the vote. Mastriano's nomination drew attention due to his far-right political views.


title: 2022 Pennsylvania gubernatorial election

text: Shapiro defeated Mastriano by almost 15 points, a margin consistent with most polls. Shapiro scored the largest margin for a non-incumbent candidate for governor since 1946, and his victory marked the first time since 1844 that the Democratic Party won three consecutive gubernatorial elections in Pennsylvania. Shapiro also made history by earning the most votes of any gubernatorial candidate in the state's history, garnering just over three million votes. Austin Davis was elected Lieutenant Governor, and became the second African-American elected to statewide office in the state's history, following Timothy DeFoor in 2020.


text: Shapiro's large margin of victory has been widely credited with helping down-ballot Democrats in concurrent elections.


text: Pennsylvania Attorney General Josh Shapiro ran unopposed and was described as the Democratic Party's presumptive nominee by "The Philadelphia Inquirer" and the "Pennsylvania Capital-Star" early in the campaign, with the "Capital-Star" reporting that efforts to recruit a primary challenger to the left of Shapiro (who is considered a progressive by the paper) had failed.


text: In the Republican primary, leading candidates included former Congressman Lou Barletta, Montgomery County Commissioner Joe Gale, political strategist Charlie Gerow, former U.S. Attorney William McSwain, State Senator Doug Mastriano and former Delaware County Councilmember Dave White.


text: Several key issues, such as school choice, natural gas exploration in PA, and tax reform, were early themes in the Pennsylvania GOP debates before the primary election, while voting laws in the Commonwealth were a later topic of debate.


text: Due to his support for overturning the results of the 2020 presidential election and his role in the January 6 U.S. Capitol attack, many Republicans expressed concern about Mastriano's ability to win the general election. As a result, the party encouraged other candidates to drop out to allow for an alternative to Mastriano to gain traction.


text: On May 12, president pro tempore of the Pennsylvania Senate Jake Corman dropped out and endorsed Barletta. On May 14, former President Donald Trump endorsed Mastriano. On May 12, "The Philadelphia Inquirer" reported that former U.S. Representative Melissa Hart would also drop out and endorse Barletta. Mastriano won the primary anyway with almost 44% of the vote, defeating his nearest competitor, Barletta, by over 23 points.


text: "The New York Times" reported in mid-June that Mastriano had been aided in the primary by the Pennsylvania Democratic Party and Shapiro's campaign with an ad equating him to Trump. Shapiro defended the move, saying the ad demonstrated the contrast between him and Mastriano as part of the general election campaign. The "Times" saw it as part of a nationwide strategy to gain easier opponents in November.


text: Attorney General Josh Shapiro ran a progressive campaign emphasized on protecting abortion rights, voter rights, and raising the state's minimum wage to $15 an hour. On criminal justice issues, Shapiro promised to sign a bill abolishing the death penalty (after previously supporting it), but has also faced criticism from some left-wing voters for adopting a "tough on crime" image. In addition, he has openly feuded with Philadelphia District Attorney Larry Krasner, likely to court moderate and swing voters.


text: State Senator Doug Mastriano positioned himself as a staunch ally of former President Donald Trump, promoting conspiracy theories about the 2020 election, defense of Confederate monuments, arming school teachers with firearms, and to disobey COVID-19 safety protocols. Mastriano also drew accusations of antisemitism and for using anti-semitic dogwhistles against Shapiro (who is Jewish). One of Mastriano's most vocal supporters was Andrew Torba, the CEO of far-right social media website Gab, which was the same website where the perpetrator of the Tree of Life Synagogue shooting posted before committing the massacre. Torba donated $500 to the Mastriano campaign, and Mastriano himself told the Gab founder in an interview, "Thank god for what you've done."


text: No debate was held during the general election, as Shapiro and Mastriano were unable to come to an agreement on how to debate. In addition, Mastriano did not release his first general election ads until October, while the more well-funded Shapiro had already spent $18.6 million in television broadcasting by that time. These factors, combined with Mastriano's refusal to talk to major media outlets and decision to ban journalists from campaign rallies, severely limited his voter outreach.


text: Josh Shapiro defeated Doug Mastriano by 14.8%. While this marked a 2.73% Republican swing from 2018, it was still 13.18% larger than Joe Biden's win in the presidential race in Pennsylvania two years earlier, and 9.86% larger than Shapiro's reelection for Attorney General that same year. All counties in the Keystone State voted the exact same way they did in 2018, with Shapiro doing best in heavily populated Southeastern Pennsylvania, which is made up of Philadelphia and its suburbs, Berks County (Reading), the Lehigh Valley (Allentown, Bethlehem, and Easton), the Wyoming Valley (Scranton, Wilkes-Barre, and Hazelton), the Susquehanna Valley (Harrisburg and Carlisle), Erie County in the northwest corner, and finally, Greater Pittsburgh in the southwest.


text: Doug Mastriano, meanwhile, piled up large margins in Pennsylvania's rural counties, but also won some populous places like Butler, Washington, and Westmoreland counties near Pittsburgh. He also carried Lancaster, including the counties contained (either fully or partially) within his State Senate district, namely Adams, Franklin and York. Except for Adams and Franklin counties, Lancaster and York were once again carried by single digits by the Republican gubernatorial candidate just like 2018, as Mastriano's extremist views likely turned off moderate Republicans in these areas.


text: Voter demographic data for 2022 was collected by CNN. The voter survey is based on exit polls completed by 2,657 voters in person as well as by phone.


title: Nazi concentration camps

text: From 1933 to 1945, Nazi Germany operated more than a thousand concentration camps on its own territory and in parts of German-occupied Europe.


title: Nazi concentration camps

text: The first camps were established in March 1933 immediately after Adolf Hitler became Chancellor of Germany. Following the 1934 purge of the SA, the concentration camps were run exclusively by the SS via the Concentration Camps Inspectorate and later the SS Main Economic and Administrative Office. Initially, most prisoners were members of the Communist Party of Germany, but as time went on different groups were arrested, including "habitual criminals", "asocials", and Jews. After the beginning of World War II, people from German-occupied Europe were imprisoned in the concentration camps. Following Allied military victories, the camps were gradually liberated in 1944 and 1945, although hundreds of thousands of prisoners died in the death marches.


title: Nazi concentration camps

text: More than 1,000 concentration camps (including subcamps) were established during the history of Nazi Germany and around 1.65 million people were registered prisoners in the camps at one point. Around a million died during their imprisonment. Many of the former camps have been turned into museums commemorating the victims of the Nazi regime, while the camp system has become a symbol of violence and terror.