Gut microbiota and metabolites in patients with COVID-19 are altered by the type of SARS-CoV-2 variant.

Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19. Materials and methods: We conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants. Results: Twenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p < 0.05). Conclusion: The intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.

The diagnostic accuracy of endoscopic ultrasound-shear wave elastography in multiple pancreatic regions for chronic pancreatitis based on the Rosemont criteria.

PURPOSE: Although endoscopic ultrasound (EUS) has been widely used for diagnosing chronic pancreatitis (CP), the assessment of fibrosis using the Rosemont criteria (RC) is generally subjective. Shear wave elastography using EUS (EUS-SWE) has been advocated as an objective approach to evaluating pancreatic fibrosis; however, it is unknown which pancreatic region should be selected for measurement. This study aims to compare the diagnostic accuracy in diagnosing CP by measurement site. METHODS: Fifty patients with CP or suspected CP who underwent EUS-SWE were retrospectively analyzed. As per the RC, they were classified into two groups: CP and non-CP. Pancreatic stiffness was evaluated by measuring the velocities of the shear wave (Vs) in addition to determining the relevant cutoff value of Vs for diagnosing CP. The correlation between Vs and RC, and the RC factors affecting pancreatic stiffness were evaluated. RESULTS: In the CP group, the Vs were notably higher in all regions (P < 0.001). The Vs for diagnostic accuracy of CP were highest in the body [area under the curve (AUC): 0.87]. A significant correlation was seen between the number of RC and Vs in all regions, with the correlation coefficient being highest in the pancreatic body (rs = 0.55). Multivariate analysis revealed that lobularity with honeycombing was an independent factor for pancreatic stiffness (P = 0.02). CONCLUSION: The pancreatic body is a suitable region for assessing pancreatic stiffness using EUS-SWE. Additionally, quantifying Vs is a valuable objective indicator for diagnosing CP.

Sex-based differences in metabolic protection by the ANP genetic variant rs5068 in the general population.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are produced in the heart and secreted into the circulation. As hormones, both peptides activate the guanylyl cyclase receptor A (GC-A), playing a role in blood pressure (BP) regulation. A significant role for ANP and BNP includes favorable actions in metabolic homeostasis. Sex-based high prevalence of risk factors for cardiovascular disease in males compared with females is well established, but sex-based differences on cardiometabolic protection have not been investigated in relation to ANP (NPPA) and BNP (NPPB) gene variants. We included 1,146 subjects in the general population from Olmsted County, Minnesota. Subjects were genotyped for the ANP gene variant rs5068 and BNP gene variant rs198389. Cardiometabolic parameters and medical records were reviewed. In the presence of the minor allele of rs5068, diastolic BP, creatinine, body mass index (BMI), waist measurement, insulin, and prevalence of obesity and metabolic syndrome were lower, whereas HDL was higher in males with only trends observed in females. We observed no associations of the minor allele with echocardiographic parameters in either males or females. Regarding rs198389 genotype, the minor allele was not associated with any BP, metabolic, renal, or echocardiographic parameters in either sex. In the general community, the minor allele of the ANP gene variant rs5068 is associated with a favorable metabolic phenotype in males. No associations were observed with the BNP gene variant rs198389. These studies support a protective role of the ANP pathway on metabolic function and underscore the importance of sex in relationship to natriuretic peptide responses.NEW & NOTEWORTHY Males are characterized by lower ANP and BNP with greater prevalence of cardiometabolic disease. The ANP genetic variant rs5068 was associated with less metabolic dysfunction in males, whereas no metabolic profile was related to the BNP genetic variant rs198389 in the general population. ANP may play a more biological role in metabolic homeostasis compared with BNP in the general population with greater physiological metabolic actions in males compared with females.

Impact of S-1 adjuvant chemotherapy longer than 6 months on survival in patients with resected pancreatic cancer: a nationwide survey by the Japan Pancreas Society based on real-world data.

BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.

Self-assessment scale for the community-based and emergency practice.

BACKGROUND: For current medical education, community-based primary care for the elderly is an essential topic. This study aimed to establish a scale of community-based assessment for clinical and emergency practice (C-CEP). METHODS: A self-assessment scale for C-CEP was developed according to four steps. Initially, we reviewed publications from the societies of the United States, British, and Japan regarding educational goals. In addition, we searched MEDLINE for educational goals regarding attitude, skills, and knowledge. Getting together, we established 23 items as the educational goals of the C-CEP. Second, we collected responses for these 23 items from 5th-grade medical students (n = 195). Third, we conducted an exploratory factor analysis (EFA) using their responses to determine the fundamental structure of the self-assessment scale. Finally, a confirmatory factor analysis (CFA) was performed to assess the fitness of the self-assessment scale developing the EFA, resulting in modification of the items. RESULTS: In EFA and CFA results, C-CEP Scale consisted of four factors with 15 items: "Attitude and communication in emergency care," Basic clinical skills," "Knowledge of community healthcare," and "Knowledge of evidence-based medicine perseverance." The model fit indices were acceptable (Goodness of Fix Index = 0.928, Adjusted Goodness of Fit Index = 0.900, Comparative Fit Index = 0.979, and Root Mean Square Error of Approximation = 0.045). The values of McDonald's omega as an estimate of scale reliability were more than 0.7 in all four factors. As for test-retest reliability, the intraclass correlation coefficients were ≥ 0.58 for all factors. All four factors of the C-CEP Scale correlated positively with the Medical Professionalism Evaluation Scale subscales. CONCLUSIONS: We developed a valid and reliable self-assessment scale to assess student competence.

Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. Materials and methods: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. Results: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. Discussion: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.

Natriuretic Peptide-Based Novel Therapeutics: Long Journeys of Drug Developments Optimized for Disease States.

The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin-angiotensin-aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.

Larger Volume and Higher Fat Content of the Pancreatic Head Are Predictive Factors for Postendoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVES: Acute pancreatitis is the most critical complication of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we investigated the association between the volume/fat content of the pancreatic head and the incidence of post-ERCP pancreatitis (PEP). METHODS: We retrospectively enrolled 157 patients who underwent ERCP. The volume and fat content of the pancreas were calculated by multislice computed tomographic imaging by using a volume analyzer. Multivariate analysis was performed to identify risk factors for PEP. RESULTS: The mean volumes of the whole pancreas and pancreatic head were significantly larger, and the fat content of the pancreatic head was significantly higher in the PEP group (P < 0.01). There were no significant differences in the mean volume and fat content of the pancreatic body and tail in the PEP group. Multivariate analysis revealed that the pancreatic guidewire placement (odds ratio [OR], 12.4; P < 0.01), pancreatic head volume (OR, 5.3; P < 0.01), and the pancreatic head fat content (OR, 4.8; P < 0.01) were independent risk factors for PEP. CONCLUSIONS: The pancreatic head volume and fat content were independent predicting factors of PEP. Quantitative assessment of the pancreas may contribute to the prediction of PEP onset.

Estimated tumor blood flow as a predictive imaging indicator of therapeutic response in pancreatic ductal adenocarcinoma: use of three-phase contrast-enhanced computed tomography.

BACKGROUND: Preoperative chemotherapy or chemoradiotherapy is a common strategy for treating pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the association between the therapeutic response in PDAC and tumor blood circulation. METHODS: The medical records of patients who underwent chemotherapy or chemoradiotherapy prior to pancreatectomy for PDAC were reviewed. Of these, patient data that included three-phase contrast-enhanced computed tomography (CECT) findings before treatments were used in this study. We evaluated the estimated tumor blood flow (eTBF) using CECT. According to the therapeutic histopathological response defined by the Evans classification, patients were divided into poor (grade I/IIa) and good (grade IIb/III/IV) responder groups. The variables, including eTBF, were compared between the two groups. RESULTS: Thirty patients were enrolled in this study. Of these, 13 (43.3%) (grade IIB/III/IV: 8/4/1 patients) were categorized into the good responder group and 17 patients (56.7%) (grade I/IIA: 4/13 patients) were categorized into the poor responder group. eTBF was significantly higher in the good responder group (0.39 s-1 vs. 0.32 s-1, p = 0.007). An eTBF ≥ 0.36 s-1 was found to be an independent predictive factor for the destruction of over 50% of tumor cells (p = 0.036; odds ratio, 9.71; 95% confidence interval, 1.16-81.30). CONCLUSIONS: eTBF can be used to predict the therapeutic histopathological response in PDAC prior to treatment.

The clinical efficacy of azathioprine as maintenance treatment for autoimmune pancreatitis: a systematic review and meta-analysis.

The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.

Diagnosing Biliary Strictures: Distinguishing IgG4-Related Sclerosing Cholangitis From Cholangiocarcinoma and Primary Sclerosing Cholangitis.

Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography-related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary SC.

Dilemma of physician-mothers faced with an increased home burden and clinical duties in the hospital during the COVID-19 pandemic.

PURPOSE: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world. During the pandemic, physicians in our hospital have had to respond both to the issue of treating the patients and the increasing domestic burden associated with social disruption. The purpose of this study was to assess how much the burden on our doctors, especially female doctors, was increasing. MATERIAL AND METHODS: The Physicians' Career Support Committee in Sapporo Medical University conducted a questionnaire survey. The questionnaire inquired about a wide range of subjects with regard to working style and family life during the first and second waves of the COVID-19 pandemic, and was sent to all medical/dental physicians working in Sapporo Medical University. RESULTS: A total of 266 (42.7%) physicians in our hospital responded to our questionnaire and the data for 264 data were analyzed. The total numbers of males, females, and others, including those who did not want to specify, were 178 (67.4%), 82 (31.0%), and 4 (1.5%), respectively. Among them, 62 (23.5%) and 23 (8.7%) answered that their domestic burden was slightly or markedly increased. The increase in the domestic burden showed a significant difference between genders (p = 0.04). Even after correction for background differences using multivariate analysis, being female (p<0.001), having child dependents (p<0.001), and treating COVID-19 patients (p = 0.03) were significantly related to an increased domestic burden. Regarding family style, 58.1% of the physician-fathers were from two-income families (i.e., families with both parents in employment), and they answered that their partner mainly cared for the children. In contrast, 97.3% of physician-mothers were from two-income families, and 94.6% of the physician-mothers had to take care of children by themselves. CONCLUSION: Physician-mothers are caught in a dilemma between an increased home burden and clinical duties in the hospital, with a significantly higher ratio than physician-fathers during the pandemic. As we showed, female doctors could have not continued their careers and take responsible positions in the same way as male doctors. This is a social risk in the timing of a crisis, such as a pandemic.

Reducing the risk of developing walled-off necrosis in patients with acute necrotic collection using recombinant human soluble thrombomodulin.

BACKGROUND/PURPOSE: The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS: In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS: Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P < .01]. Severity on admission and imaging costs for follow-up in ANC patients were significantly higher than those in APFC (P < .01). However, regarding mortality, there was no significant difference between patients with ANC and APFC (P = .41). Adjusting severity, it was revealed that rTM administration significantly reduced the risk of ANC developed WON (OR = 0.23, P = .01). CONCLUSIONS: While ANC had a higher clinical impact than that of APFC, we found that early administration of rTM may reduce the impact.

Fatal Immune Checkpoint Inhibitor-related Pancreatitis.

We herein report a case of fatal pancreatitis induced by an immune checkpoint inhibitor. A 62-year-old man with cancer of unknown primary was treated with pembrolizumab. After 12 cycles, immune-related pneumonitis developed and was treated with prednisolone. Three months later, pancreatitis developed, which was successfully treated with hydration and protease inhibitors. Eight months later, another attack of pancreatitis occurred, which did not respond to therapy, including high-dose corticosteroids, and he eventually died. This is the first report describing fatal immune checkpoint inhibitor-related pancreatitis. Despite the rarity of this complication, attention should be paid to its potential severity and treatment.

Non-compliance to practice guidelines still exist in the early management of acute pancreatitis: Time for reappraisal?

INTRODUCTION: Earlier national surveys on the management of acute pancreatitis (AP) had reported non-compliance to practice guidelines. In the past decade, several guidelines were revised based on new evidence. In this multicenter international survey, we aimed to evaluate the practice patterns of early management of AP and compliance to the revised treatment guidelines across different disciplines and practice environments. METHODS: A structured questionnaire was sent via email to a target population of 654 that constituted of medical and surgical gastroenterologists, physicians and general surgeons, paediatricians from academic and non-academic centres across 30 countries. Other than demographic variables, the questionnaire contained items pertaining to early management of AP, such as, assessment at admissions and within first 72 h s, details regarding analgesics, IV hydration, oral/enteral feeding and antibiotic use. RESULTS: The response rate was 46.2% and after exclusions, a total of 297 participant's responses were analysed. Majority of the participants were from Asia, followed by Europe and the Americas. 181 (60.9%) claimed to follow practice guidelines, out of which 59 (32.6%) followed more than one. On further probing, only 41.9% were actually compliant to feeding and 59.7% to antibiotic guidelines. Even though participants opted for aggressive hydration, early feeding and avoidance of prophylactic antibiotics, there were non-compliance and discrepancies in titration of fluid therapy, indications of feeding and antibiotic use. DISCUSSION: Discrepancies and non-compliance still appear to exist in the early management of AP due to lack of strong evidence. We discuss ways that could improve compliance to the existing guidelines until stronger evidence comes to the fore.

Utility and safety of a new uneven double-lumen sphincterotome in cases of difficult biliary cannulation.

BACKGROUND: We investigated the utility and safety of a new uneven double-lumen sphincterotome in biliary cannulation in comparison with the conventional pancreatic guidewire (PGW) method. METHODS: We retrospectively evaluated 119 patients who required PGW placement because of difficult biliary cannulation. Endoscopic retrograde cholangiopancreatography (ERCP) was performed using a conventional ERCP catheter or a new uneven double-lumen sphincterotome. The success rate of bile duct cannulation, the operation time of bile duct cannulation, and the incidence of post-ERCP pancreatitis (PEP) were evaluated. RESULTS: Forty-four patients were treated with a new double-lumen sphincterotome (the new sphincterotome group) and 75 patients underwent conventional PGW placement (the conventional group). The success rate of bile duct cannulation was 39/44 (88.6%) in the new sphincterotome group and 63/75 (84.0%) in the conventional group (not significant). The total biliary cannulation time (from the reach to the papilla to the finish of biliary cannulation) was 16.0 (6.5-78) min in the new sphincterotome group and 26.0 (5-80) min in the conventional group (P < 0.01). The time from PGW placement to bile duct cannulation was 3.5 (0.3-57) min in the magictome group and 12.0 (1-65) min in the conventional group (P < 0.01). Hyperamylasemia was observed in 13/44 (29.5%) and 17/75 (22.7%), respectively (not significant). Five of 44 (11.3%) of the new sphincterotome group and 14/75 (18.7%) of the conventional group were diagnosed with PEP (not significant). CONCLUSION: A new double-lumen sphincterotome allows selective bile duct cannulation to be performed in a shorter time than the conventional PGW method.

Optimal Treatment for Octogenarians With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study.

OBJECTIVES: The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society. METHODS: Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis. RESULTS: Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group. CONCLUSIONS: Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.

Prognostic importance of peritoneal washing cytology in patients with otherwise resectable pancreatic ductal adenocarcinoma who underwent pancreatectomy: A nationwide, cancer registry-based study from the Japan Pancreas Society.

BACKGROUND: The importance of peritoneal washing cytology status both as a sign of irresectability and as a prognostic factor for pancreatic ductal adenocarcinoma remains controversial. The purpose of this nationwide, cancer registry-based study was to clarify the clinical implications of operative resection in patients who had positive cytology status. METHODS: Clinical data from 1,970 patients who underwent tumor resection were collected from the Pancreatic Cancer Registry in Japan. Clinicopathologic factors and overall survival curves were analyzed, and multivariate Cox proportional hazard models were evaluated. RESULTS: Among the 1,970 patients analyzed, positive cytology status was found in 106 patients and negative cytology status was found in 1,864 patients. The positive cytology status group had a greater frequency of pancreatic body and tail cancer and greater preoperative serum carbohydrate antigen 19-9 levels than the negative cytology status group (P < .001 each). The ratio of peritoneal recurrence tended to be greater in the positive cytology status group (14% vs 43%; P < .001). Overall median survival times were less in the positive cytology status group (17.5 months vs 29.4 months; P < .001). The 5-year survival rates were 13.7% and 31.1% in the positive cytology status and negative cytology status groups, respectively. Multivariate analysis of positive cytology status patients revealed that adjuvant chemotherapy was an independent prognostic factor. CONCLUSION: Positive cytology status was an adverse prognostic factor in patients who underwent resection for pancreatic ductal adenocarcinoma but did not preclude attempted curative resection. Curative resection followed by adjuvant chemotherapy may contribute to long-term prognosis in patients with positive cytology status.