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Objective: The aim of the present study was to investigate which treatment, neoadjuvant chemoradiotherapy (NAC‐RT) with S‐1 or combination neoadjuvant chemotherapy with gemcitabine and S‐1 (NAC‐GS), is more promising as neoadjuvant treatment (NAT) for resectable pancreatic cancer in terms of effectiveness and safety. Methods: In the NAC‐RT with S‐1 group, the patients received a total radiation dose of 50.4 Gy in 28 fractions with oral S‐1. In the NAC‐GS group, the patients received intravenous gemcitabine at a dose of 1000 mg/m2 with oral S‐1 for two cycles. The primary endpoint was the 2‐year progression‐free survival (PFS) rate. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 to April 2017, a total of 103 patients were enrolled. After exclusion of one patient because of ineligibility, 51 patients were included in the NAC‐RT with S‐1 group, and 51 patients were included in the NAC‐GS group in the intention‐to‐treat analysis. The 2‐year PFS rate was 45.0% (90% confidence interval [CI]: 33.3%–56.0%) in the NAC‐RT with S‐1 group and 54.9% (42.8%–65.5%) in the NAC‐GS group (p =.350). The 2‐year overall survival rate was 66.7% in the NAC‐RT with S‐1 group and 72.4% in the NAC‐GS group (p =.300). Although leukopenia and neutropenia rates were significantly higher in the NAC‐GS group than in the NAC‐RT with S‐1 group (p =.023 and p <.001), other adverse events of NAT and postoperative complications were comparable between the two groups. Conclusion: Both NAC‐RT with S‐1 and NAC‐GS are considered promising treatments for resectable pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: The exfoliative cell analyzer, LC‐1000, is medical device that utilizes the principles of flow cytometry, and might provide digital diagnostic information for cytology using a different approach from conventional cytomorphology. In this study, wae examined the usefulness of the LC‐1000 as a diagnostic support system for intraoperative peritoneal lavage cytology and its prognostic impact for pancreatic (PC) and biliary tract cancer (BTC). Methods: Patients with PC and BTC who underwent surgical treatment were included. First, we identified useful indicators of LC‐1000 and established cutoff values to discriminate positive cytology. Next, we verified the validity of these cutoff values. Results: In the test set (n = 48), of the LC‐1000 indicators examined, only MR‐CPIx was significantly different between the negative and positive cytology groups, yielding a cutoff value of 0.86. In the validation set (n = 52), the sensitivity, specificity, positive and negative predictive value of the LC‐1000 for cytology results was 1.0, 0.49, 0.11 and 1.0, respectively. In patients who had undergone radical resection, recurrence‐free survival rate was significantly higher in the LC‐1000 negative group than in the positive group in PC, but not in BTC. Conclusion: The LC‐1000 was useful as digital support system for peritoneal cytology, and it might have potential as a prognostic factor for PC. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic ultrasonography (EUS) findings of the pancreatic parenchyma, such as hyperechoic foci/stranding and lobularity, may be associated with the severity of chronic pancreatitis (CP). However, the correlation between parenchymal EUS findings and histology remains unclear. We designed a large‐scale retrospective study analyzing over 200 surgical specimens to elucidate the association between parenchymal EUS findings and histological features. Methods: Clinical data of 221 patients with pancreatobiliary tumors who underwent preoperative EUS and pancreatic surgery between January 2010 and November 2020 were reviewed to investigate the association between parenchymal EUS findings and histological features at the pancreatic body. None of these patients met the definition of CP. Results: Of the 221 patients, 87 (39.4%), 89 (40.2%), and 45 (20.4%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. In the multivariate analyses, parenchymal EUS findings significantly correlated with histological CP findings of fibrosis, inflammation, and atrophy (hyperechoic foci/stranding without lobularity vs hyperechoic foci/stranding with lobularity, odds ratio [95% confidence interval]: 4.1 [2.2–7.9] vs 31.3 [9.3–105.6], Ptrend < 0.001; 3.9 [1.9–8.2] vs 21.8 [8.0–59.4], Ptrend < 0.001; and 4.0 [2.0–7.8] vs 22.9 [7.0–74.5], Ptrend < 0.001, respectively). Further, a trend toward higher histological grade was observed in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Conclusions: Endoscopic ultrasonography findings of the pancreatic parenchyma may be associated with the histological conditions in CP, such as pancreatic fibrosis, inflammation, and atrophy. Lobularity reflects more severe histological conditions than does hyperechoic foci/stranding. [ABSTRACT FROM AUTHOR]

Background: Gadoxetic acid‐enhanced magnetic resonance imaging (MRI) is useful in detecting liver metastases from pancreatic ductal adenocarcinoma (PDAC). However, the long examination time limits its utility in the initial workup of patients with PDAC. Purpose: To evaluate the incremental value of an abbreviated gadoxetic acid‐enhanced MRI for the detection of liver metastases in patients with PDAC. Study Type: Retrospective. Population: Patients (N = 130) with potentially resectable PDAC (women, 58 [44.6%]). Field Strength/Sequence: 1.5 T and 3 T; gradient dual‐echo T1‐weighted (in‐phase and opposed‐phase), fat‐suppressed fast spin‐echo T2‐weighted, single‐shot echo‐planar diffusion‐weighted, and three‐dimensional fat‐suppressed T1‐weighted gradient‐echo dynamic contrast‐enhanced and hepatobiliary phase sequences, as well as contrast‐enhanced computed tomography (CECT). Assessment: Three radiologists independently reviewed three different image sets to detect liver metastases: set 1, CECT alone; set 2, CECT and abbreviated MRI comprising fat‐suppressed T2‐weighted, diffusion‐weighted, and hepatobiliary phase images; and set 3, CECT and standard gadoxetic acid‐enhanced MRI. Statistical Tests: Figure of merit (FOM) was compared using the jackknife alternative free‐response receiver operating characteristics, and other per‐lesion and per‐patient diagnostic parameters for each image set were compared using McNemar's and Fisher's test. P < 0.05 was considered statistically significant. Results: A total of 43 liver metastases were identified in 13 patients. Reader‐averaged FOM to detect liver metastases were significantly higher for sets 2 (0.884) and 3 (0.886) than for set 1 (0.609), while they were comparable between sets 2 and 3 (P = 0.96). The mean per‐patient sensitivities, negative predictive values, and accuracies were significantly higher for sets 2 and 3 than for set 1, while those between sets 2 and 3 were not significantly different (not applicable, P > 0.99, and P > 0.99, respectively). Data Conclusion: Gadoxetic acid‐enhanced MRI combined with CECT had higher diagnostic performance than CECT alone for the detection of liver metastases in patients with PDAC. The incremental values were comparable for the abbreviated MRI and standard MRI. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

The article presents a case study of a nine year-old boy with trisomy 21 who developed L-asparaginase-induced acute necrotizing pancreatitis during chemotherapy for B-cell precursor acute lymphoblastic leukemia (BCP-ALL). It is reported that four weeks later, an acute necrotic collection transformed into a massive walled-off necrosis (WON) with a maximum diameter of 21 cm, causing symptoms such as vomiting and abdominal pain.

Aim: With the increased use of particle therapy for liver cancer, local recurrence after particle therapy increased. Salvage hepatectomy is an acceptable treatment option for local recurrence following particle therapy; however, its safety and effectiveness remain unclear. Therefore, this multi‐center study aimed to verify the feasibility and efficacy of salvage hepatectomy and assess clinical issues associated with its application. Methods: We retrospectively assessed the perioperative outcomes, prognosis, and pathological characteristics of 15 patients who underwent salvage hepatectomy for local recurrence after particle therapy between 2006 and 2019. Results: Hepatocellular carcinoma and metastatic liver tumors were noted in eight and seven patients, respectively. The mean total dose and number of fractions were 66.5 Gy and 12, respectively, and the mean interval between particle therapy and surgery was 30.1 months. Major hepatectomy was performed in seven cases. Moreover, the mortality rate was 0%, and surgical complications of Clavien‐Dindo grade IIIa or higher were observed in four cases (27%)—two bile leakages, one pleural effusion, and one refractory skin fistula. The median overall survival time and 5‐year overall survival rate after salvage hepatectomy were 29.9 months and 43.1%, respectively. Histological examination of the irradiated liver tissue surrounding the tumor showed sinusoidal dilatation, loss of hepatocyte, and fibrosis in most cases. Conclusion: Salvage hepatectomy after particle therapy is a feasible therapy; however, the risk of refractory complications associated with particle therapy is relatively high. Therefore, the first‐line treatment for resectable liver cancer should be carefully determined considering second‐line treatment after local recurrence. [ABSTRACT FROM AUTHOR]

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse‐free survival (odds ratio = 2.37; P =.033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT. [ABSTRACT FROM AUTHOR]

The bifid pancreas is a rare anatomical variation of the pancreatic duct in which double main pancreatic ducts in the body and tail of the pancreas join at the pancreas head and drain through the major papilla. When pancreaticoduodenectomies are carried out on bifid pancreases, close attention must be paid to the reconstruction because of the possibility that there may be two pancreatic ducts that need to be reconstructed. We present a case of pancreaticoduodenectomy for the bifid pancreas and a novel technique named the 'two‐in‐one' method for double pancreatic duct to jejunum anastomosis. Using the two‐in‐one method, we anastomosed one jejunal hole to a double pancreatic duct. Pancreatic texture was normal and postoperative volumes of pancreatic juice from the two external pancreatic duct stents were 250 mL and 100 mL/day, respectively. Postoperative recovery went well although the patient needed a slightly longer hospital stay as a result of surgical site infection. This novel anastomotic technique was as simple to carry out as a normal pancreaticojejunostomy and may be useful for reconstruction of the bifid pancreas. [ABSTRACT FROM AUTHOR]

Background: Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods: Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results: Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90‐day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion: LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy. [ABSTRACT FROM AUTHOR]

The high expression of human equilibrative nucleoside transporter‐1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5‐fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S‐1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S‐1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S‐1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S‐1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S‐1 arm. [ABSTRACT FROM AUTHOR]

Background: Acute cholecystitis (AC) after cardiovascular surgery (CS) tends to have a serious postoperative course; however, there are few reports of AC after CS. In this study, we investigated the clinical features of AC after CS. Method: Of 26 patients who underwent surgery for AC after CS between 2001 and 2018 were investigated. Of these patients, the severity of AC, onset time, surgical outcomes, and postoperative pathological findings were evaluated. Results: Grade III accounted for 46% (12/26) of the AC after CS patients. Gallbladder drainage did not produce sufficient outcomes in all CS cases. The postoperative hospital days of AC after CS were extended (31/21 days, P = 0.07) and the postoperative pathologic findings revealed a higher rate of gangrenous cholecystitis (88/41%, P < 0.01) than the control group. With regard to the incidence of postoperative complications, there were no differences between CS and the control group (23/24%). The mortality rate of AC after CS was 12%. Conclusion: Because more than 80% of CS cases involved pathologically gangrenous cholecystitis, it may be necessary to perform early surgery for AC after CS, even when the severity of AC is Grade III. [ABSTRACT FROM AUTHOR]

Background and Aim: Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatic calcification is a characteristic of chronic pancreatitis; however, its significance for intraductal papillary mucinous neoplasm (IPMN) oncogenesis remains unknown. Therefore, we investigated the relationship between pancreatic calcification and invasive IPMN. Methods: This study included 157 patients who underwent resection for IPMN between April 2001 and October 2016 (intraductal papillary mucinous adenoma, n = 76; noninvasive intraductal papillary mucinous carcinoma [IPMC], n = 32; and invasive IPMC, n = 49). We divided the subjects on the basis of the presence/absence of pancreatic calcification on preoperative computed tomography (CT). The factors associated with pancreatic calcification were investigated in univariate analyses. Then, multivariate logistic regression analyses of the relationship between pancreatic calcification and invasive IPMC (after adjusting for clinical or imaging characteristics) were conducted. Results: Preoperative CT revealed pancreatic calcification in 17.2% (27/157) of the resected IPMN. In the univariate analyses, jaundice, high serum carbohydrate antigen 19‐9 levels, and invasive IPMC were significantly associated with pancreatic calcification (4/27 [14.8%] vs 4/130 [3.1%], 0.01; 12/27 [44.4%] vs 31/130 [23.8%], 0.03; and 15/27 [55.6%] vs 34/130 [26.2%], 0.001, respectively). Pancreatic calcification was significantly associated with invasive IPMC (multivariate odds ratio = 2.88, 95% confidence interval [95% CI] = 1.15–7.21, 0.03, adjusted for clinical characteristics; odds ratio = 5.50, 95% CI = 1.98–15.3, 0.001, adjusted for imaging characteristics). Conclusions: Pancreatic calcification on CT is associated with invasive IPMC. Pancreatic calcification might be a predictor of invasive IPMC. [ABSTRACT FROM AUTHOR]

Background: Lactate production is exacerbated by surgical stress. We sought to determine whether branched-chain amino acid (BCAA) supplementation could decrease blood lactate levels in patients undergoing hepatectomy.Methods: A total of 275 consecutive patients who underwent hepatectomy of ≥2 segments were retrospectively reviewed. Blood lactate levels in patients treated with BCAA supplementation before hepatectomy (December 2011 to December 2016) were compared with levels in patients who were not pretreated (January 2008 to November 2011).Results: Postoperative lactate levels were significantly lower in patients who received preoperative BCAA supplementation than in those who did not (2.6 vs 3.4 mmol/L; P < .001). Intraoperative blood lactate levels, which were evaluated after induction of general anesthesia, were also lower in those who received BCAA supplementation than in those who did not (1.1 vs 1.5 mmol/L, respectively; P < .001). A multiple regression analysis revealed that preoperative BCAA supplementation was independently associated with decreased postoperative and intraoperative lactate levels (P = .030 and P < .001, respectively).Conclusion: Preoperative BCAA supplementation decreased intraoperative and postoperative blood lactate levels in patients undergoing major hepatectomy. [ABSTRACT FROM AUTHOR]

We report a case of an internal hernia through a transverse mesocolon defect after laparoscopic distal pancreatectomy. The patient was a 58-year-old man with an intraductal papillary mucinous neoplasm of the pancreatic body who underwent laparoscopic distal pancreatectomy. During surgery, an approximately 5-cm defect in the transverse mesocolon was inadvertently made. The defect was not closed as it was thought to be large enough to preclude incarceration. However, the patient developed a bowel obstruction 2 months postoperatively. Laparotomy revealed that a loop of the proximal jejunum herniated through the defect and was adherent to the stapled pancreatic stump. An additional loop of the jejunum was herniated through the narrowed mesenteric defect. To our knowledge, this is the first case of an internal hernia through a transverse mesocolon defect after laparoscopic distal pancreatectomy. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic distal pancreatectomy has been shown to be associated with favorable postoperative outcomes using meta‐analysis. However, there have been no randomized controlled studies yet. This study aimed to compare laparoscopic and open distal pancreatectomy using propensity score‐matching. Methods: We retrospectively collected perioperative data of 2,266 patients who underwent distal pancreatectomy in 69 institutes from 2006–2013 in Japan. Among them, 2,010 patients were enrolled in this study and divided into two groups, laparoscopic distal pancreatectomy and open distal pancreatectomy. Perioperative outcomes were compared between the groups using unmatched and propensity matched analysis. Results: After propensity score‐matching, laparoscopic distal pancreatectomy was associated with favorable perioperative outcomes compared with open distal pancreatectomy, including higher rate of preservation of spleen and splenic vessels (P < 0.001); lower rates of intraoperative transfusion (P = 0.020), clinical grade of pancreatic fistula (International Study Group on Pancreatic Fistula grade B and C; P < 0.001), and morbidity (P < 0.001); and shorter hospital stay (P = 0.001), but a longer operative time (P < 0.001). Conclusions: Laparoscopic distal pancreatectomy was associated with more favorable perioperative outcomes than open distal pancreatectomy. Highlight Nakamura and colleagues conducted the largest multicenter propensity score matched study to date comparing laparoscopic and open distal pancreatectomy, based on data from 2,266 patients. The laparoscopic procedure was associated with significantly more favorable short‐term postoperative outcomes than open surgery, particularly in terms of morbidity and development of pancreatic fistulas. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy.Ninety‐five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non‐simple nodular (non‐SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes.Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non‐SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non‐SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non‐SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non‐SN lesions underwent sequential local therapy.Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non‐SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non‐SN lesions. [ABSTRACT FROM AUTHOR]