Genomic analysis of familial pancreatic cancers and intraductal papillary mucinous neoplasms: A cross-sectional study.

Environmental and genetic factors play a critical role in the pathogenesis of pancreatic cancer, which is likely to follow a multistep process that includes intraductal papillary mucinous neoplasm. The pathogenesis of familial pancreatic cancer has been reported; however, epidemiological characteristics and causative genes remain unclear. This study aimed to determine the relationship between the family history of pancreatic cancer and tumor malignancy and identify novel susceptible germline variants of pancreatic cancer. We performed an epidemiologic study at our institute on a cohort of 668 patients with intraductal papillary mucinous neoplasm and 242 with pancreatic cancer but without associated intraductal papillary mucinous neoplasm stratified by family history of pancreatic cancer. Whole-exome sequencing was conducted for 10 patients from seven families with familial pancreatic cancer and intraductal papillary mucinous neoplasm. We found that patients who had intraductal papillary mucinous neoplasm with positive family history of pancreatic cancer within first-degree relatives were more likely to develop malignancy in a shorter period than those without family history. Duplicate frameshift variants in TET2 c.3180dupG (p.Pro1061fs) and ASXL1 c.1934dupG (p.Gly646fs) in one family and POLN c.1194dupT (p.Glu399fs) in another were identified as pathogenic truncating germline variants which were previously recognised susceptibility genes. Moreover, PDIA2 c.1403C>T (p.Pro468Leu) and DPYSL4 c.926C>A (p.Pro309Gln) were shared in four and two patients, respectively. In particular, PDIA2 was identified as a novel candidate for one of the deleterious variants of familial pancreatic cancer.

Reconsideration of operative indications in pancreatic neuroendocrine neoplasms.

BACKGROUND: The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS: In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS: Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION: Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata.

BACKGROUND/OBJECTIVES: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. METHODS: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. RESULTS: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). CONCLUSIONS: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

Clinical Impact of Portal Vein Distance on Computed Tomography for Postoperative Pancreatic Fistula after Pancreatoduodenectomy.

BACKGROUND: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area. METHODS: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011-2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus. RESULTS: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830). CONCLUSIONS: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting.

Hereditary pancreatic cancer.

Pancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

Novel toxicity of tris(1,3-dichloro-2-propyl) phosphate in adult male rats.

The widespread use of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar-Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti-androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen-dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP-treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP-treated rats, but mean corpuscular volume, total iron-binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti-androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti-androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound.

Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report.

BACKGROUND: Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis. CASE PRESENTATION: Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary. CONCLUSIONS: Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression.

Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature.

PURPOSE: Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. METHODS: We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. RESULTS: Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. CONCLUSIONS: Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.

Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer.

Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.

Technical note: Calving prediction in dairy cattle based on continuous measurements of ventral tail base skin temperature using supervised machine learning.

In this study, we developed a calving prediction model based on continuous measurements of ventral tail base skin temperature (ST) with supervised machine learning and evaluated the predictive ability of the model in 2 dairy farms with distinct cattle management practices. The ST data were collected at 2- or 10-min intervals from 105 and 33 pregnant cattle (mean ± standard deviation: 2.2 ± 1.8 parities) reared in farms A (freestall barn, in a temperate climate) and B (tiestall barn, in a subarctic climate), respectively. After extracting maximum hourly ST, the change in values was expressed as residual ST (rST = actual hourly ST - mean ST for the same hour on the previous 3 d) and analyzed. In both farms, rST decreased in a biphasic manner before calving. Briefly, an ambient temperature-independent gradual decrease occurred from around 36 to 16 h before calving, and an ambient temperature-dependent sharp decrease occurred from around 6 h before until calving. To make a universal calving prediction model, training data were prepared from pregnant cattle under different ambient temperatures (10 data sets were randomly selected from each of the 3 ambient temperature groups: <15°C, ≥15°C to <25°C, and ≥25°C in farm A). An hourly calving prediction model was then constructed with the training data by support vector machine based on 15 features extracted from sensing data (indicative of pre-calving rST changes) and 1 feature from non-sensor-based data (days to expected calving date). When the prediction model was applied to the data that were not part of the training process, calving within the next 24 h was predicted with sensitivities and precisions of 85.3% and 71.9% in farm A (n = 75), and 81.8% and 67.5% in farm B (n = 33), respectively. No differences were observed in means and variances of intervals from the calving alerts to actual calving between farms (12.7 ± 5.8 and 13.0 ± 5.6 h in farms A and B, respectively). Above all, a calving prediction model based on continuous measurement of ST with supervised machine learning has the potential to achieve effective calving prediction, irrespective of the rearing condition in dairy cattle.

Urgent distal pancreatectomy for intraperitoneal hemorrhage due to the spontaneous rupture of a pancreatic metastatic tumor from synovial sarcoma: a case report.

BACKGROUND: Synovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy. CASE PRESENTATION: A 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery. CONCLUSIONS: While the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.

The Efficacy of PTGBD for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

BACKGROUNDS: We usually performed percutaneous transhepatic gallbladder drainage (PTGBD) for moderate and severe acute cholecystitis (AC) prior to cholecystectomy. But, the validity of preoperative drainage for AC is still controversial. The aim of this study is to evaluate the efficacy and safety of PTGBD for moderate and severe AC, based on the Tokyo Guidelines 2018. MATERIALS: Total of 146 AC patients from 2012 to 2017 were enrolled. Patients were classified in the grade of severity according to TG18, compared with PTGBD and non-PTGBD group. We retrospectively reviewed clinical backgrounds and laboratory data at admission. We evaluated surgical performances as the primary outcomes and recovery periods based on guidelines. RESULTS: A total of 61 cases were moderate, and 18 cases were severe AC, and PTGBD were performed in 34 cases. For moderate AC, age, DM rate and ASA in PTGBD group were significantly higher than those in non-PTGBD group. Also, serum albumin and hemoglobin at admission were significantly lower in the PTGBD group. However, surgical outcomes were almost the same. For severe AC patients, laparoscopic cholecystectomy was performed safely in all of pre-operating drainage cases, while almost all of non-PTGBD cases underwent open laparotomy and needed transfusion for massive bleeding. CONCLUSIONS: Preoperative PTGBD is a useful and safe procedure for AC patients with comorbidities, especially in severe AC cases. Treatment flowchart in TG18 can be feasible to make accurate prediction for surgically high-risk patients in AC.

Resection of chronic expanding hematoma within the liver cyst difficult to differentiate from liver cystadenocarcinoma: A case report.

Liver cysts are common benign lesions with rare malignancy potential. Distinguishing between benign and malignant tumors within liver cysts is challenging. We present the case of a patient with a chronically expanding hematoma within a liver cyst that was resected under suspicion of liver cystadenocarcinoma. A 73-year-old female patient presented with elevated hepatobiliary enzyme levels, no viral hepatitis, elevated tumor marker levels, and preserved liver capacity (Child-Pugh grade A). Abdominal ultrasonography revealed a large cyst (>10 cm) occupying the right lobe and a 25-mm mass lesion with mixed echogenicity inside the cyst. Contrast-enhanced computed tomography showed atrophy of the parenchyma of the right lobe and dilation of the right intrahepatic bile duct due to the large cyst. Moreover, in the arterial phase, a point-like high-density area was observed inside the nodule, which increased from 25 to 35 mm over 3 months. Diffusion-weighted magnetic resonance imaging revealed a high-intensity signal within the nodule; however, positron emission tomography did not show an increased accumulation of fluorodeoxyglucose in the same area. Considering the risk of peritoneal dissemination if the cyst was punctured and found to be malignant, we performed a right hepatectomy. Pathological findings revealed a brownish fluid-filled cyst containing a dark reddish nodule diffusely filled with hematoma, confirming the absence of a malignancy. To date, the patient has not experienced recurrence. We encountered a case of a chronic, expanding hematoma originating from a liver cyst that was difficult to distinguish preoperatively from a liver cystadenocarcinoma.

Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm.

OBJECTIVES: Some intraductal papillary mucinous neoplasms (IPMNs) have malignant potential and can become pancreatic cancer. The mechanism behind the malignant progression of IPMN remains unknown. We aimed to identify the risk factors and interactions between backgrounds for IPMN. METHODS: We retrospectively enrolled 980 patients of pancreatic cancer or suspected IPMN (sIPMN) who underwent endoscopic ultrasound or retrograde cholangiopancreatography. We classified them into pancreatic cancer, high-risk sIPMN, and low-risk sIPMN, and investigated the risk factors for high-risk sIPMN. RESULTS: Smoking habits (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.04-6.85; P < 0.001), serum carbohydrate antigen 19-9 ≥37 U/mL (OR, 6.30; 95% CI, 2.88-13.80; P < 0.001), and family history of cancers (OR, 2.38; 95% CI, 1.30-4.37; P = 0.005) were independent risk factors for high-risk suspected IPMN. Odds ratios of diabetes and neutrophil-to-lymphocyte ratio of 2.45 or greater were significantly higher in patients with a family history of cancer than those without a family history of cancer (OR, 3.28; 95% CI, 0.52-20.80 vs 1.85; 95% CI, 0.78-4.41; OR, 2.44; 95% CI, 0.81-7.34 vs 1.24; 95% CI, 0.67-2.30, respectively). CONCLUSIONS: Understanding the interactions between background factors can effectively prevent IPMNs' malignant transformation.

Pro108Ser mutation of SARS-CoV-2 3CLpro reduces the enzyme activity and ameliorates the clinical severity of COVID-19.

Recently, an international randomized controlled clinical trial showed that patients with SARS-CoV-2 infection treated orally with the 3-chymotrypsin-like protease (3CLpro) inhibitor PF-07321332 within three days of symptom onset showed an 89% lower risk of COVID-19-related hospital admission/ death from any cause as compared with the patients who received placebo. Lending support to this critically important result of the aforementioned trial, we demonstrated in our study that patients infected with a SARS-Cov-2 sub-lineage (B.1.1.284) carrying the Pro108Ser mutation in 3CLpro tended to have a comparatively milder clinical course (i.e., a smaller proportion of patients required oxygen supplementation during the clinical course) than patients infected with the same sub-lineage of virus not carrying the mutation. Characterization of the mutant 3CLpro revealed that the Kcat/Km of the 3CLpro enzyme containing Ser108 was 58% lower than that of Pro108 3CLpro. Hydrogen/deuterium-exchange mass spectrometry (HDX-MS) revealed that the reduced activity was associated with structural perturbation surrounding the substrate-binding region of the enzyme, which is positioned behind and distant from the 108th amino acid residue. Our findings of the attenuated clinical course of COVID-19 in patients infected with SARS-CoV-2 strains with reduced 3CLpro enzymatic activity greatly endorses the promising result of the aforementioned clinical trial of the 3CLpro inhibitor.

Multiple introductions of SARS-CoV-2 B.1.1.214 lineages from mainland Japan preceded the third wave of the COVID-19 epidemic in Hokkaido.

BACKGROUND: The third wave of the COVID-19 epidemic in the island of Hokkaido, the second largest island in Japan, began abruptly in October 2020. METHODS: We conducted a phylodynamic analysis of the SARS-CoV-2 genome sequences obtained from tertiary medical centers in the Greater Tokyo Area and Sapporo, the largest city in the island of Hokkaido, and genome sequences published by GISAID, an international SARS-CoV-2 genome database. We also analyzed the statistics on the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 versus 2020. RESULTS: At least eight sub-lineages belonging to the B.1.1.214 lineage were introduced to the island of Hokkaido from the island of Honshu, the mainland of Japan from late July to November 2020, during the governmental travel promotion program. Five of the eight sub-lineages originated from the Greater Tokyo Area. Comparison of the monthly ratios of the person-nights of travelers in the island of Hokkaido from the Greater Tokyo Area in 2019 and 2020 revealed that the highest value occurred in October 2020. CONCLUSION: We contend that the Japanese governmental travel promotion program contributed to the introduction of the B.1.1.214 sub-lineages from the main island of Honshu to the island of Hokkaido, and drove the third wave in Hokkaido, even if we are unable to establish the causality.

Identification of B.1.346 Lineage of SARS-CoV-2 in Japan: Genomic Evidence of Re-entry of Clade 20C.

SARS-CoV-2 whole-genome sequencing of samples from COVID-19 patients is useful for informing infection control. Datasets of these genomes assembled from multiple hospitals can give critical clues to regional or national trends in infection. Herein, we report a lineage summary based on data collected from hospitals located in the Tokyo metropolitan area. We performed SARS-CoV-2 whole-genome sequencing of specimens from 198 patients with COVID-19 at 13 collaborating hospitals located in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions were performed to differentiate and classify the viral lineages. More than 90% of the identified strains belonged to Clade 20B, which has been prevalent in European countries since March 2020. Only two lineages (B.1.1.284 and B.1.1.214) were found to be predominant in Japan. However, one sample from a COVID-19 patient admitted to a hospital in the Kanto region in November 2020 belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in the western United States since November 2020. The patient had no history of overseas travel or any known contact with anyone who had travelled abroad. Consequently, the Clade 20C strain belonging to the B.1.346 lineage appeared likely to have been imported from the western United States to Japan across the strict quarantine barrier. B.1.1.284 and B.1.1.214 lineages were found to be predominant in the Kanto region, but a single case of the B.1.346 lineage of clade 20C, probably imported from the western United States, was also identified. These results illustrate that a decentralized network of hospitals offers significant advantages as a highly responsive system for monitoring regional molecular epidemiologic trends.

Measurement Device for Ambient Carbonyl Sulfide by Means of Catalytic Reduction Followed by Wet Scrubbing/Fluorescence Detection.

A portable chemical analysis system for monitoring ambient carbonyl sulfide (COS) was investigated for the first time. COS is paid attention to from the perspectives of photosynthesis tracer, breath diagnosis marker, and new process-use in the manufacture of semiconductors. Recently, the threshold level value of COS was settled at 5 ppm in volume ratio (ppmv) for workplace safety management. In this work, COS was converted to H2S by a small column packed with alumina catalyzer at 65 °C. Then, the H2S produced was collected in a small channel scrubber to react with fluorescein mercuric acetate (FMA), and the resulting fluorescence quenching was monitored using an LED/photodiode-based miniature detector. The miniature channel scrubber was re-examined to determine its robustness and easy fabrication, and conditions of the catalyzer were optimized. When the FMA concentration used was 1 µM, the limit of detection and dynamic range, which were both proportional to the FMA concentration, were 0.07 and 25 ppbv, respectively. Ambient COS in the background level and even contaminated COS in the nitrogen gas cylinder could be detected. If necessary, H2S was removed selectively by reproducible adsorbent columns. COS concentrations of engine exhaust were measured by the proposed method and by cryo-trap-gas chromatography-flame photometric detection, and the results obtained (0.5-5.9 ppbv) by the two methods agreed well (R 2 = 0.945, n = 19). COS in ambient air and exhaust gases was successfully measured without any batchwise pretreatment.

High risk pathogens and risk factors for postoperative pancreatic fistula after pancreatectomy; a retrospective case-controlled study.

BACKGROUND: Although the rates of surgical site infection are decreasing, surgical site infection after pancreatectomy remains frequent because of postoperative pancreatic fistula. Recent studies suggested a relationship between postoperative pancreatic fistula and pathogens cultured from drainage fluids after pancreatectomy. This study aimed to assess and evaluate high-risk pathogens cultured from postoperative drainage fluids for postoperative pancreatic fistulas or severe postoperative complications after pancreatectomy. MATERIALS AND METHODS: We retrospectively enrolled patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2012 and 2019. We assessed clinical characteristics and microbiological results of drainage cultures of pancreaticoduodenectomy or distal pancreatectomy patients, and we investigated the risk factors for clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status using univariate and multivariate analyses. Finally, we detected high-risk pathogens from drainage cultures and analyzed the correlation between these pathogens and the severity of clinically relevant postoperative pancreatic fistula or Clavien-Dindo status. RESULTS: Four hundred and twenty-nine patients were enrolled: 257 underwent pancreaticoduodenectomy and 172 underwent distal pancreatectomy. Clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status ≥ III were more frequently seen in pancreaticoduodenectomy patients than in distal pancreatectomy patients, namely grade C postoperative pancreatic fistula, which was observed in 19 pancreaticoduodenectomy patients. The most common pathogen found from drainage cultures was Enterococcus species, followed by Enterobacter species and Candida species. All pathogens were associated with clinically relevant postoperative pancreatic fistulas; however, Candida species was a dominant microorganism of clinically relevant postoperative pancreatic fistulas grade C, Clavien-Dindo status ≥ IV, and hemorrhage due to pseudoaneurysm. CONCLUSION: The presence of Candida species in the drainage fluid culture after pancreaticoduodenectomy can be a predictive factor of severe infectious complications, including postoperative pancreatic fistulas; thus, we should regularly collect cultures from drainage fluids and monitor for Candida infection.

Clinical Utility of SARS-CoV-2 Whole Genome Sequencing in Deciphering Source of Infection.

COVID-19 caused by SARS-CoV-2 is a worldwide problem. From the standpoint of hospital infection control, determining the source of infection is critical. We conducted the present study to evaluate the efficacy of using whole genome sequencing to determine the source of infection in hospitalized patients who do not have a clear infectious contact history. Recently, we encountered two seemingly separate COVID-19 clusters in a tertiary hospital. Whole viral genome sequencing distinguished the two clusters according to the viral haplotype. However, the source of infection was unclear in 14 patients with COVID-19 who were clinically unlinked to clusters #1 or #2. These patients, who had no clear history of infectious contact within the hospital ("undetermined source of infection"), had haplotypes similar to those in cluster #2 but did not have two of the mutations used to characterize cluster #2, suggesting that these 14 cases of "undetermined source of infection" were not derived from cluster #2. Whole viral genome sequencing can be useful for confirming that sporadic COVID-19 cases with an undetermined source of infection are indeed not part of clusters at the institutional level.