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Recent advances in the development of chemotherapies have helped improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). However, predicting factors for the outcomes of chemotherapies (either gemcitabine or S-1) have not yet been established. We analyzed the expression of 4 major epithelial-to-mesenchymal transition-inducing transcription factors in 38 PDAC patients who received adjuvant chemotherapy after radical resection to examine the association with patients’ prognoses. The TWIST1-positive group showed a significantly poorer prognosis than the TWIST1-negative group for both the relapse‐free survival (median survival time [MST] of 8.9 vs. 18.5 months, P = 0.016) and the overall survival (MST of 15.2 vs. 33.4 months, P = 0.023). A multivariate analysis revealed that TWIST1 positivity was an independent prognostic factor for a poor response to adjuvant chemotherapies (hazard ratio 2.61; 95% confidence interval 1.10–6.79; P = 0.029). These results suggest that TWIST1 can be utilized as an important poor prognostic factor for radically resected PDAC patients with adjuvant chemotherapy, potentially including neoadjuvant therapy using these agents.

To elucidate the prognostic impact of sarcopenia before and after neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC).We retrospectively studied 75 consecutive PC patients who underwent neoadjuvant gemcitabine plus S-1 combination therapy followed by pancreatectomy between 2008 and 2016. According to the skeletal muscle volume index (SMI), the patients were divided into the muscle attenuation group (MAG) and normal group (NG) before or after NAC. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards models.The MAG showed significantly poorer OS than the NG before and after NAC. Pre-NAC, median OS was 20.0 months in the MAG versus 49.0 months in the NG (p = 0.006). Post-NAC, median OS was 21.3 months in the MAG versus 48.8 months in the NG (p = 0.014). Multivariate analysis, excluding muscle attenuation after NAC because of confounding factors and lower hazard ratio (2.08, 95% confidence interval: 1.14-3.78, p = 0.016) than that before NAC (2.14, 1.23-3.70, p = 0.007) by univariate analysis, revealed the following independent prognostic factors: muscle attenuation pre-NAC (2.25, 1.26-4.05, p = 0.007); borderline resectability (1.96, 1.04-3.69, p = 0.038); operative blood loss (2.60, 1.38-4.88, p = 0.003); and distant metastasis (3.31, 1.40-7.82, p = 0.006).Sarcopenia before and after NAC for PC is suggested to be a poor prognostic factor, with a stronger impact before than after NAC.

and purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).Of 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).The current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.

Metachronous tumors arising in the remnant bile duct after surgical resection for primary biliary tract cancers (BTCs) are rarely treated surgically and have not been well documented. This study aimed to clarify the clinicopathological and genomic features of metachronous tumors arising in the remnant bile duct. Consecutive 12 patients who underwent resection for metachronous BTCs arising in the remnant bile duct after primary surgical resection between 2008 and 2020 were enrolled. Clinicopathological analysis and genomic analysis using targeted amplicon sequencing for 31 biliary tract cancer-related genes, including TP53, APC, ARID1A, ARID2, BAP1, CDKN2A, CTNNB1, ELF3, ERBB2, GNAS, IDH1, KRAS, and SMAD4, and immunohistochemistry for p53, p16, SMAD4, ARID1A, and β-catenin, were performed on 12 matched pair of primary and metachronous BTCs. In the 12 patients, 7 metachronous tumors developed antegradely in the lower portion of the biliary tree, and the remaining 5 metachronous tumors developed retrogradely in the upper portion, with negative bile duct margin at the initial operations. Molecular analysis revealed mutations and copy number alterations in TP53 (87.5%), APC (20.8%), CTNNB1 (20.8%), KRAS (12.5%), GNAS (8.3%), and RNF43 (8.3%). In comparison analysis, the matched primary and metachronous tumors shared identical genomic features in 10 cases, except in 2 cases showing metachronous perihilar and distal bile duct carcinomas after gallbladder cancer resection. Seven patients survived without recurrence, 5 showed postoperative local recurrences, and 2 died. Nine patients achieved 5-year overall survival after primary surgery. In conclusion, among the 12 patients with subsequent metachronous BTCs, 10 originated from neoplastic clones of the primary carcinoma, indicating recurrence due to intramural metastases or intraductal disseminations. Repeated surgical approach for metachronous BTCs may provide definitive local control and potentially prolong survival in these patients.

Background Probiotics have been reported to be beneficial for the prevention of postoperative complications and are often used during the perioperative period. Among the probiotic-related adverse events, bacteremia is rare. Here, we report two cases of probiotic-related bacteremia after major hepatectomy for biliary cancer. Case presentation 1 A 74-year-old man was referred to our hospital to be treated for gallbladder cancer. Neoadjuvant chemotherapy, two courses of gemcitabine plus S-1 combination therapy, was administered. Extended right hepatectomy with caudate lobectomy, extrahepatic bile duct resection and biliary reconstruction were performed 3 weeks after chemotherapy. Probiotics, Clostridium butyricum (C. butyricum) MIYAIRI 588, were administered 6 days before surgery and continued after surgery. Sepsis of unknown origin occurred 17 days after surgery and developed into septic shock. C. butyricum was detected in blood cultures at postoperative day 26 and 45. After stopping the probiotic agent, C. butyricum was undetectable in the blood cultures. The patient died due to an uncontrollable sepsis 66 days after surgery. Case presentation 2 A 63-year-old man with diabetes mellitus whose past history included total colectomy, papillectomy, and Frey’s operation at the age of 19, 34 and 48, respectively, was referred to our hospital to be treated for perihilar cholangiocarcinoma. Extended left hepatectomy with caudate lobectomy, extrahepatic bile duct resection and reconstruction of bile duct were performed. Probiotics were administered during the perioperative period. Combined probiotics that included lactomin, amylolytic bacillus and C. butyricum, were given before surgery. C. butyricum MIYAIRI 588 was given after surgery. Sepsis occurred 16 days after surgery and developed to respiratory failure 8 days later. Blood culture at postoperative day 25 revealed Enterococcus faecalis and C. butyricum. After the probiotics were stopped at postoperative day 27, C. butyricum was not detected in the blood culture. The general condition improved with intensive care. The patient was transferred to another hospital for rehabilitation at postoperative day 156. Conclusion It should be noted that the administration of probiotics in severe postoperative complications can lead to probiotic-related bacteremia.

Aim Cancer patients with personal/family histories of pancreatic/breast/ovarian/prostate cancer are associated with a higher likelihood of harboring DNA damage repair (DDR)‐related germline mutations. Here, we aimed to obtain a better understanding of DDR‐related germline mutations in Japanese pancreatic ductal adenocarcinoma (PDAC) patients with personal and/or family histories of BRCA‐related cancers of the pancreas, breast, ovary, and prostate. Methods We performed next‐generation sequencing (NGS) and evaluated germline mutations in nine DDR‐related genes (BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, and PMS2) in PDAC patients with personal and/or family histories. Results Of 196 patients with PDAC, 39 (19.9%) fulfilled the criteria for at least one family history of pancreatic/breast/ovarian/prostate cancer in first‐degree relatives (sibling–sibling or parent‐child) or the personal history of these malignancies. Targeted NGS revealed that four (10.2%) of 39 patients with personal/family histories harbored deleterious germline mutations—two in BRCA2, one in ATM, and one in MLH1. Both the BRCA2 variants showed frameshift mutations due to short insertion/deletions. In the 39 patients undergoing NGS, a similar distribution of the clinicopathological characteristics was observed between those with deleterious mutations/variants of unknown significance (VUSs) and with benign/wild types. Patients with deleterious germline mutations/VUSs in DDR‐related genes showed a significantly more favorable prognosis than those with benign mutations/wild‐type genes (hazard ratio: 0.160, P = .040). Conclusions A significant fraction of PDAC patients with personal/family histories of BRCA‐related cancers harbored deleterious germline mutations in DDR‐related genes. DDR‐related germline gene mutations might be a favorable prognostic factor in patients with pancreatic cancer., A significant fraction of pancreatic cancer patients with personal and/or family histories of BRCA‐related cancers, such as pancreatic, breast, ovarian, and prostate cancers, harbored deleterious germline mutations in DNA damage repair‐related genes.

The significance of surgical resection in pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal cytology (PPC) is controversial. This study aimed to evaluate whether preceding chemotherapy could be beneficial for patients with PDAC with PPC. Between 2017 and 2019, 34 consecutive PDAC patients diagnosed with PPC without distant metastasis were retrospectively reviewed. Twenty-three patients did not receive neoadjuvant treatment (NAT) and 11 received NAT. All patients received systemic chemotherapy after PPC was confirmed, and they underwent surgical resection if PPC turned negative. The treatment course, ratio of conversion surgery (CS), and prognosis were evaluated. Moreover, the prognosis of PPC patients who underwent up-front surgery without NAT between 2003 and 2016 was analyzed as a comparative cohort. The median survival time (MST) of the patients without NAT was 31.4 months. CS was performed in 52.2% of the patients. Patients who underwent CS had better prognoses than those who did not undergo CS (p = 0.005). The CS rate was significantly higher in resectable PDAC (78.5%) than in borderline/unresectable PDAC (11.1%) (p = 0.002). The prognosis of patients with resectable PDAC was improved with preceding chemotherapy compared with up-front surgery (MST 13.0 months; p = 0.016). After NAT, the CS rate was low (27.3%), and the MST was only 14.1 months. As an initial treatment for PDAC patients with PPC, chemotherapy may lead to a favorable prognosis. Especially, resectable PDAC is associated with a greater chance of improved prognosis. Future studies are required to ascertain whether up-front surgery or preceding chemotherapy should be performed for these patients.

An 83-year-old man without specific symptoms was referred to our hospital for further evaluation and treatment of apparent double primary tumors of the cystic duct and common bile duct. Computed tomography showed contrast-enhanced solid tumors in the cystic duct and common bile duct. Magnetic resonance imaging showed that the bile duct tumor was isointense on T1-weighted images and had low intensity on T2-weighted images. In addition, the bile duct tumor showed high intensity on diffusion-weighted images. Endoscopic ultrasonography revealed the tumor of the common bile duct and endoscopic retrograde cholangiopancreatography demonstrated a filling defect in the bile duct. The cystic duct was not identified on endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography. Transpapillary biopsy of the bile duct tumor showed adenocarcinoma. The patient was diagnosed with double primary tumors of the cystic duct and the common bile duct and underwent subtotal stomach-preserving pancreaticoduodenectomy. Microscopic examination with molecular profiling of the tumors revealed a high-grade noninvasive intracholecystic papillary neoplasm of the cystic duct extending into the common bile duct and forming a tubulopapillary neoplasm with invasion of the common bile duct.

Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications.A total of 3787 patients who underwent LDP for benign or low-grade malignant pancreatic disease in 92 centers across Korea and Japan were included in this retrospective study. Postoperative infectious complications and other complications were compared between LDP with splenectomy (LDPS) and LDP with spleen preservation (LSPDP) by propensity score matching (PSM) analysis.After PSM, the LSPDP group had a lower rate of overall infectious complications (P = .079) and a significantly lower rate of intra-abdominal abscess (P = .014) compared with the LDPS group. Within the LSPDP group, the vessel preservation subgroup had a significantly higher rate of infectious complications (P = .002) compared with the vessel resection subgroup. Low-volume centers had a higher rate of intra-abdominal abscess than high-volume centers in the LSPDP group (P = .001) and the splenic vessel preservation subgroup (P = .003).Spleen preservation in LDP for benign or borderline malignant pancreatic diseases was advantageous in lowering the risk of infectious complications, specifically intra-abdominal abscess. However, the risk of intra-abdominal abscess may differ according to the level of surgeon's experience.

Background To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.

Minimally invasive surgery (MIS) is the optimal treatment for congenital biliary dilatation (CBD), but few studies on adults have been reported. We compared the postoperative outcomes of MIS with those of open surgery (OS) in adult patients with CBD.The subjects of this retrospective study were 36 adult patients who underwent surgery for CBD. We compared the postoperative outcomes of 20 patients who underwent laparoscopic (n = 15) or robotic (n = 5) surgery with those of 16 patients who underwent OS.MIS was associated with a significantly higher rate of type I (p 0.001), significantly less blood loss (p 0.001), a significantly lower rate of internal stents (p = 0.048), significantly longer operation times (p = 0.009), and a significantly shorter postoperative hospital stay (p = 0.007) than OS. The postoperative outcomes of MIS for type I CBD were similar to those of the whole cohort. There were no significant differences in late complications between the groups. The robotic procedure had a significantly shorter operative time than laparoscopic surgery for hepaticojejunostomy (HJ; p = 0.029).MIS achieved favorable short-term outcomes without compromising mid-term outcomes compared to OS and is appropriate for adult patients with CBD. Robotic HJ may be more ideal than its laparoscopic counterpart.

To investigate the impact of early postoperative drainage fluid culture positivity on the development of clinically relevant postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD). We assessed the positive prevalence, distribution, and drug sensitivity of microorganisms in drainage fluid collected on postoperative day (POD) 1 after PD from 465 patients. Culture results were positive in pancreaticojejunostomy (PJ) drainage fluid from 26.0% of patients. Similar distributions of microorganisms were observed in the bile juice and PJ/hepaticojejunostomy (HJ) drainage fluid from these patients. PJ drain culture positivity was associated with an elevated drainage amylase level and with preoperative biliary drainage. No associations were seen between HJ drainage culture positivity and the drainage amylase and bilirubin levels. PJ drainage culture positivity was found to be an independent predictor of grade B/C POPF. According to the antibiogram, the bacteria identified were likely to be resistant to prophylactic antibiotics. PJ drainage culture positivity on POD 1 in combination with an elevated drainage amylase level is an early predictor of grade B/C POPF. PJ drainage culture positivity may be attributable to bile juice contamination caused by intraoperative spillage and early postoperative leakage from the PJ anastomotic sites.

We introduced a superior approach and a unique technique to retract the stomach, called the “stomach roll-up technique”, to standardize laparoscopic distal pancreatectomy and increase educational effectiveness. The aim of this study was to evaluate the clinical outcomes of these procedures. Forty-five patients who underwent laparoscopic distal pancreatectomy by surgeons-in-training between January 2015 and December 2018 were included. Twenty laparoscopic distal pancreatectomies were performed using the inferior approach, and 25 procedures were performed using the superior approach. The stomach roll-up technique was used in all cases. The perioperative outcomes were retrospectively analyzed. Compared with the inferior approach, the superior approach was associated with a significantly shorter operation time (p

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, mainly because of its invasive and metastatic characteristics. Pancreatic intraepithelial neoplasia (PanIN) is one of the major precursor lesions of PDAC. Although epithelial‐to‐mesenchymal transition (EMT) is known to play an important role for these malignant behaviors, the association between PanIN and EMT has not been clearly understood. Therefore, we explored possible molecules for regulation of EMT immunohistochemically. Using surgically resected specimens from 71 PDAC patients, expressions of SNAIL, SLUG, TWIST1, and ZEB1 were investigated in high‐grade PanIN (HG‐PanIN) and PDAC. Results demonstrated that PDAC accompanied by SNAIL‐positive HG‐PanIN showed a significantly better relapse‐free survival (RFS) (median survival time (MST) of 11.3 months vs 4.4 months, P

Objectives The aim of this study was to evaluate the diagnostic and prognostic impact of systemic inflammatory markers for IPMN with high-grade dysplasia (HGD)/invasive carcinoma. Methods Neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio were compared across the different histological grades of 205 IPMN cases. We also tested the diagnostic performance for IPMN with HGD/invasive carcinoma. Results The median (interquartile range) preoperative NLR was higher in IPMN with HGD/invasive carcinoma (2.03 [1.48-2.93]) than IPMN with low-grade dysplasia (1.74 [1.42-2.24], P = 0.0137). The C-reactive protein-to-albumin ratio and derived NLR values were also significant higher in cases with HGD/invasive carcinoma. A combination assay of NLR, carcinoembryonic antigen, and carbohydrate antigen 19-9 revealed a 58.8% sensitivity and 76.8% specificity. Among the cases with worrisome features, the high NLR values increased the positive predictive value (68.8%) compared with low values (31.8%). In IPMN cases with the associated invasive carcinoma, high NLR values showed association with the deeper vertical invasion and shorter survival periods. Conclusions Preoperative NLR, combined with tumor markers and image findings, can be a useful predictive marker for the presence of HGD/invasive carcinoma in IPMNs. Preoperative NLR also predicts the long-term outcomes in IPMN cases with invasive carcinoma.

Purpose To elucidate the effectiveness of circulating tumor DNA (ctDNA) for predicting occult metastases in patients with pancreatic cancer without apparent metastases. Methods Circulating tumor DNA was obtained from plasma samples of 165 patients with pancreatic cancer and analyzed using droplet digital PCR. The prevalence and allele frequencies of ctDNA were compared across different patterns and degrees of metastatic spread. Results Of the 142 patients without apparent metastases who underwent abdominal exploration, 39 (27.5%) harbored occult metastases including positive peritoneal lavage cytology. The prevalence of ctDNA was significantly higher in patients with occult metastases than in those without (41.0% vs 14.6%, P = .001). A markedly high prevalence of ctDNA was observed in patients with radiographically visible metastases (78.3%). ctDNA was found to be an independent predictor of the presence of occult metastases (odds ratio: 3.113, P = .039), and its diagnostic performance in combination with tumor markers had a sensitivity of 66.7% and a specificity of 81.6%. In 62 treatment-naive patients without metastases, multivariate analysis identified the presence of ctDNA as an independent prognostic factor (hazard ratio: 6.311, P = .001). Conclusion Circulating tumor DNA can help predict the presence of occult metastases in pancreatic cancer patients with radiographically non-metastatic disease.

Stomatin‑like protein 2 (SLP‑2) is associated with poor prognosis in several types of cancer, including pancreatic cancer (PC); however, the molecular mechanism of its involvement remains elusive. The present study aimed to elucidate the role of this protein in the development of PC. Human PC cell lines AsPC‑1 and PANC‑1 were transfected by a vector expressing SLP‑2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were conducted, while a mouse xenograft model was used to evaluate the functional role of SLP‑2 in PC. Immunohistochemical analysis was retrospectively performed on human tissue samples to compare expression between the primary site (n=279) and the liver metastatic site (n=22). Furthermore, microarray analysis was conducted to identify the genes correlated with SLP‑2. In vitro analysis demonstrated that cells in which SLP‑2 was suppressed exhibited reduced cell motility and glucose uptake, while in vivo analysis revealed a marked decrease in the number of liver metastases. Immunohistochemistry revealed that SLP‑2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutamine‑fructose‑6‑phosphate transaminase 2 (GFPT2), a rate‑limiting enzyme of the hexosamine biosynthesis pathway. SLP‑2 contributed to the malignant character of PC by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway through the expression of GFPT2. The present study revealed a new mechanism of liver metastasis and indicated that SLP‑2 and its downstream pathway could provide novel therapeutic targets for PC.

The collagen gel droplet-embedded drug sensitivity test (CD-DST) was revealed to be useful for predicting the effect of S-1 adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC). However, collection of an adequate number of PDAC cells is difficult due to the surrounding fibroblasts. Thus, the aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results. Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC–MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC. Among the 2696 proteins extracted by LC–MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. The double-positive group was associated with significantly prolonged RFS compared to the no adjuvant chemotherapy group. C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.

A 64-year-old woman was referred to our hospital for treatment of pancreatic head cancer with acute pancreatitis due to iatrogenic injury of the pancreatic duct during endoscopic retrograde cholangiopancreatography. In addition to a 28 mm pancreatic head tumor, soft tissue shadow and fluid collection surrounding the superior mesenteric artery(SMA)due to pancreatitis were observed in the abdominal CT scan. The tumor was histologically diagnosed as adenocarcinoma by endoscopic ultrasound-guided fine needle aspiration. Neoadjuvant chemotherapy with gemcitabine and S-1 was performed to control the progression of the pancreatic cancer and improve the inflammatory changes for reduction of the operative risk. After 2 courses of neoadjuvant chemotherapy, abdominal CT scan revealed stable disease according to the Response Evaluation Criteria in Solid Tumors and attenuation of the inflammatory changes surrounding the SMA. Then, subtotal stomach- preserving pancreaticoduodenectomy was performed without the difficulty of peeling around the SMA in spite of the old inflammatory changes. Histological examination of the resected specimen showed R0 resection. The patient was discharged 18 days after surgery without any complications and is surviving 9 months postoperatively without any recurrence. Neoadjuvant chemotherapy was helpful for disease control and improvement of the inflammatory changes.

The neoadjuvant therapy against locally advanced pancreatic cancer(LAPC)have been developed by combining radiation with chemotherapy. We experienced a case of LAPC performed R0 resection and obtained high histopathological effect by carbon-ion radiotherapy with gemcitabine(GEM).A 65-year-old male with epigastric and back pain was suspected as pancreas cancer by FDG-PET/CT scan, and was referred to our hospital. CT scan revealed a tumor in pancreatic body with poor contrast effect and with invasion to celiac artery, common hepatic artery and portal vein, and diagnosed as pancreatic adenocarcinoma by endoscopic ultrasound-fine needle aspiration(EUS-FNA). Therefore we diagnosed the tumor as pancreatic body cancer, cT4, cN1a, cM0, cStage Ⅲ, UR-LA. GEM plus nab-paclitaxel(GnP)were administered for 4 months followed by carbon-ion radiotherapy with GEM at other hospital. Distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed 3 months after irradiation. High therapeutic effect was obtained histopathologically( Evans grade Ⅲ), and lesions outside the pancreas disappeared except for metastasis to one lymph node (ypT1c, ypN1a, ycM0, ypStage ⅡB), and R0 resection was performed.Carbon-ion radiotherapy with chemotherapy for LAPC may improve curative resection rate.

Background The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the recurrence predictive ability of such markers after curative resection in patients with these neoplasms.Methods Circulating/systemic neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet-white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan–Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals.Results Univariate analysis demonstrated that preoperative neutrophil-lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil-lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil-lymphocyte ratio (HR=3.49 95% CI 1.05-11.7; P=0.042) and 2017 World Health Organization classification (HR=8.81, 95% CI 1.46-168.2; P=0.015) were independent recurrence predictors.Conclusions The circulating/systemic neutrophil-lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

Background The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the ability to predict the recurrence of such markers after curative resection in patients with these neoplasms. Methods Circulating/systemic neutrophil–lymphocyte, monocyte–lymphocyte, platelet–lymphocyte, and platelet–white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan–Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals. Results Univariate analysis demonstrated that preoperative neutrophil–lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil–lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil–lymphocyte ratio (HR = 3.49 95% CI 1.05–11.7; P = 0.042) and 2017 World Health Organization classification (HR = 8.81, 95% CI 1.46–168.2; P = 0.015) were independent recurrence predictors. Conclusions The circulating/systemic neutrophil–lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

Pancreatic cystic neoplasms (PCNs) are a heterogeneous group with varying risks of malignancy. To explore the clinical utility of liquid biopsy in cyst type classification, we analyzed the GNAS/KRAS mutations in circulating cell-free DNA (cfDNA) obtained from 57 patients with histologically diagnosed PCNs, including 34 with intraductal papillary mucinous neoplasms (IPMNs) and compared the mutant allele prevalence and variant patterns with the paired resected specimens using next-generation sequencing. The positive prevalence of GNAS mutations in cfDNA of patients with IPMN (n = 11, 32%) was significantly higher than that in those with other PCNs (0%, P = 0.002). Conversely, KRAS mutations were detected in cfDNA of only 2 (6%) IPMN patients. The paired-sample comparison revealed highly concordance between the GNAS mutation status of cfDNA and resected IPMN specimens. Similar distributions of GNAS mutation positivity in cfDNA were observed across the different histological grades, whereas IPMNs with intestinal subtype showed a significantly higher prevalence of GNAS mutations than other subtypes (P = 0.030). GNAS mutation positivity in cfDNA was significantly associated with the acellular mucin pool of histological findings in primary IPMN lesions (P = 0.017). Detection of GNAS mutation in cfDNA can serve as a novel biomarker for cyst type classification and differentiation of intestinal subtype IPMN from the other PCNs.

Some presumed resectable pancreatic cancer patients harbor radiographically occult metastases that are incidentally identified at the time of abdominal exploration. This study aims to identify novel diagnostic or predictive microRNA (miRNA) markers for subclinical peritoneal dissemination in patients with pancreatic cancer undergoing abdominal exploration. Peritoneal lavage fluid samples were harvested from 74 patients with pancreatic cancer at the time of staging laparoscopy. Microarray analysis was performed using peritoneal lavage fluids with positive and negative cytology. Candidate microRNA expression was quantified and validated by droplet-digital PCR assays. In the miRNA array analysis, miR-593-3p showed significant upregulation in peritoneal lavage fluids with positive cytology. Of the 74 patients validated, peritoneal lavage fluids with positive cytology had significantly higher expression of miR-593-3p than those with negative cytology (P

The aims of this study were to compare the perioperative outcomes after hepatectomy with prior bilioenteric anastomosis to those without prior anastomosis, and to elucidate the mechanisms and preventative measures of its characteristic complications. The demographic data and perioperative outcomes of 525 hepatectomies performed between January 2007 and December 2018, including 40 hepatectomies with prior bilioenteric anastomosis, were retrospectively analyzed. A propensity score matching analysis demonstrated that hepatectomies with prior bilioenteric anastomosis were associated with a higher frequency of major complications (p = 0.015), surgical site infection (p = 0.005), organ/space surgical site infection (p = 0.003), and bile leakage (p = 0.007) compared to those without. A multivariate analysis also elucidated that prior bilioenteric anastomosis was one of the independent risk factors of organ/space surgical site infection. In the patients with prior bilioenteric anastomosis, bile leakage was associated with organ/space surgical site infection at a significantly higher rate than those without prior bilioenteric anastomosis (p

Background Neoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT. Methods Between 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses. Results The postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively). Conclusions CY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.