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Background: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. Methods: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. Results: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. Conclusions: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) is performed for pancreatic neuroendocrine tumor (PanNEN) liver metastases; however, the safety and efficacy of TACE procedures, especially for patients who have undergone previous pancreatic surgery, have not been established. We reviewed 48 TACE procedures (1–6 procedures/patient) performed on 11 patients with PanNEN liver metastases, including 16 TACE procedures (4–6 procedures/patient) for 3 patients with a history of biliary-enteric anastomosis. The overall tumor objective response rate was 94%. The incidence of Clavien‒Dindo grade ≥ 2 complications was 1/16 (6%) and 1/32 (3%), and the median time to untreatable progression was 31 (14–41) and 27 (2–60) months among patients with and without a history of biliary-enteric anastomosis, respectively. Although validation is needed in future studies, our experiences have shown that TACE treatment is a viable treatment option for PanNEN liver metastases, even after biliary-enteric anastomosis with experienced teams and careful patient follow-up. [ABSTRACT FROM AUTHOR]

Background: Postoperative cholangitis is a common complication of pancreaticoduodenectomy. Frequent cholangitis impairs patients' quality of life after pancreaticoduodenectomy. However, the risk factors for recurrence of cholangitis remain unclear. Hence, this retrospective study aimed to identify risk factors for recurrence of cholangitis after pancreaticoduodenectomy. Methods: The medical records of patients who underwent pancreaticoduodenectomy between 2015 and 2019 in our institution were retrospectively reviewed. At least two episodes of cholangitis a year after pancreaticoduodenectomy were defined as 'recurrence of cholangitis' in the present study. Univariate and multivariate analyses were performed. Results: The recurrence of cholangitis occurred in 40 of 207 patients (19.3%). Multivariate analysis revealed that internal stent (external, RR: 2.16, P = 0.026; none, RR: 4.76, P = 0.011), firm pancreas (RR: 2.61, P = 0.021), constipation (RR: 3.49, P = 0.008), and postoperative total bilirubin>1.7 mg/dL (RR: 2.94, P = 0.006) were risk factors of recurrence of cholangitis. Among patients with internal stents (n = 54), those with remnant stents beyond 5 months had more frequent recurrence of cholangitis (≥5 months, 75%; <5 months, 30%). Conclusions: Internal stents, firm pancreas, constipation, and postoperative high bilirubin levels are risk factors for cholangitis recurrence after pancreaticoduodenectomy. In addition, the long-term implantation of internal stents may trigger cholangitis recurrence. [ABSTRACT FROM AUTHOR]

Stapling is the standard method for pancreatic transection during laparoscopic distal pancreatectomy. Although most surgeons use a 60 mm cartridge stapler, space limitations created by laparoscopic surgery make the instrument difficult to handle, especially during pancreatic transection at the neck. Therefore, we currently use a 45 mm cartridge stapler for laparoscopic pancreatic transection at the neck. Between October 2019 and December 2020, we performed pancreatic transection using a 45 mm cartridge stapler in 27 patients. Fifteen patients experienced biochemical leakage, but no patients developed clinically relevant pancreatic fistula. The compactness of the 45 mm cartridge has several benefits: (1) less space is required for flexing, opening, and closing the device; (2) it enables easy insertion of the lower jaw behind the pancreas, even if the dissected space behind the pancreas is narrow; (3) less obstruction of the surgeons' view prevents accidental injury to the surrounding tissues and vessels. These benefits may enable safe pancreatic transection. [ABSTRACT FROM AUTHOR]

Background: Effects of pancreatectomy on glucose tolerance have not been clarified, and evidence regarding the difference in postoperative glucose tolerance between pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is lacking.Study Design: This prospective, single-center observational study analyzed 40 patients undergoing PD and 29 patients undergoing DP (Clinical trial registry number UMIN000008122). Glucose tolerance, including insulin secretion (Δ C-peptide immunoreactivity, ΔCPR) and insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) were assessed before and 1 month after pancreatectomy using the oral glucose tolerance test (OGTT) and glucagon stimulation test. We assessed long-term hemoglobin A1c (HbA1c) levels in patients, with a follow-up time of 3 years.Results: Percentages of patients diagnosed with abnormal OGTT decreased after PD (from 12 [30%] to 7 [17.5%] of 40 patients, p = 0.096); however, they increased after DP (from 4 [13.8%] to 8 [27.6%] of 29 patients, p = 0.103), although the changes were not statistically significant. ΔCPR decreased after both PD (from 3.2 to 1.0 ng/mL, p < 0.001) and DP (from 3.3 to 1.8 ng/mL, p < 0.001). HOMA-IR decreased after PD (from 1.10 to 0.68, p < 0.001), but did not change after DP (1.10 and 1.07, p = 0.42). Median HbA1c level was higher after DP than after PD for up to 3 years, but the differences were not statistically significant.Conclusions: In comparisons of pre- and 1 month post-pancreatectomy data, glucose tolerance showed improvement after PD, whereas it worsened after DP. Insulin secretion decreased after both PD and DP. Insulin resistance improved after PD, but did not change after DP. Further studies are warranted to clarify mechanisms of improved insulin resistance after PD. [ABSTRACT FROM AUTHOR]

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Correction to: Surgery Today https://doi.org/10.1007/s00595-022-02540-5 In the original publication, the name of third author was incorrectly published as: Sadaki Asdari. [Extracted from the article]

After immunization with T cell-dependent antigens, the high-affinity B cells selected in germinal centers differentiate into memory B cells or long-lived antibody-forming cells. However, a role for germinal centers in development of these B lineage cells is still controversial. We show here that Bcl6-deficient B cells, which cannot develop germinal centers, differentiated into IgM and IgG1 memory B cells in the spleen but barely differentiated into long-lived IgG1 antibody-forming cells in the bone marrow. Mutation in the V-heavy gene was null in these memory B cells. Therefore, Bcl6 and germinal center formation are essential for somatic hypermutation, and generation of memory B cells can occur independently of germinal center formation, somatic hypermutation, and Ig class switching. [Copyright &y& Elsevier]

Introduction: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. Methods: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. Results: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P =.04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR:.57, 95% CI:.33-.97, P =.03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. Discussion: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection. [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.

This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. Methods: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. Results: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. Conclusions: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis. [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]

Introduction: The usefulness of gadolinium-ethoxybenzyl diethylenetriamine pentaacetate acid-enhanced magnetic resonance imaging (EOB-MRI) in assessing the functional future remnant liver volume (fFRLV) to predict post-hepatectomy liver failure (PHLF) has been previously reported. Herein, we evaluated the efficacy of this technique in patients with hepatocellular carcinoma (HCC) with a major portal vein tumor thrombus (PVTT). Methods: This study included 21 patients with PVTT in the ipsilateral first-order branch (Vp3) and 30 patients with PVTT in the main trunk/contralateral branch (Vp4). To evaluate fFRLV, the signal intensity (SI) of the remnant liver was determined on T1-weighted images, using both conventional and newly developed methods. The fFRLV was calculated using the SI of the remnant liver and muscle, remnant liver volume, and body surface area. Preoperative factors predicting PHLF (≥grade B) in HCC patients with Vp3/4 PVTT were evaluated. Results: In the Vp3 group, we found fFRLV area under the receiver-operating characteristic curves (AUCs) above 0.70 (AUC = 0.875, 0.750) using EOB-MRI results calculated using either the plot or whole method. None of the parameters in the Vp4 group had an AUC greater than 0.70. Conclusion: The fFRLV calculated by EOB-MRI using the whole method can be as useful as the conventional method in predicting PHLF (≥grade B) for HCC patients with Vp3 PVTT. [ABSTRACT FROM AUTHOR]

The Global Leadership Initiative on Malnutrition (GLIM), comprising several of the major global clinical nutrition societies, suggested the world's first criteria for diagnosis of the severity of malnutrition. However, the impact of the resulting diagnosis on patient outcomes for those with hepatocellular carcinoma (HCC) following liver resection (LR) has not been investigated. A retrospective analysis of 293 patients with HCC who underwent LR between January 2011 and December 2018 was performed. We compared overall survival (OS) and recurrence-free survival (RFS) and evaluated prognostic factors after LR using Cox proportional hazards regression models. Preoperative patient nutritional status, n (%), was classified as follows: normal, 130 (44%), moderate malnutrition, 116 (40%), and severe malnutrition, 47 (16%). The median OS (129 vs. 43 months, p < 0.001) and median RFS (54 vs. 20 months, p = 0.001) were significantly greater in the normal group than in the severe malnutrition group. Multivariate analysis showed that severe malnutrition was a significant risk factor for OS (p = 0.006) and RFS (p = 0.010) after initial LR. Severe malnutrition, as diagnosed by the GLIM criteria, is a significant prognostic factor for survival and recurrence in patients with HCC after LR. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes and prognostic factors of proton radiotherapy for locally advanced pancreatic cancer (LAPC) in the body and tail are still unknown. The aim of this study was to determine the prognostic factors after proton radiotherapy in a large group of patients with LAPC in the body and tail. Methods: The medical records of 200 patients with LAPC in the body and tail who underwent proton radiotherapy between February 2009 and January 2021 at the Hyogo Ion Beam Medical Center were retrospectively reviewed to identify prognostic factors that contribute to long-term survival. Results: The overall survival rate at 1- and 2-year after PT was 69.6% and 35.4% with a median overall survival of 18.4 months. The 1- and 2-year local progression-free, and progression-free survival rates were 84.3% and 68.0%, and 44.3% and 19.4%, respectively. In multivariate analysis, superior mesenteric artery (SMA) invasion (SMA only invasion vs. celiac artery only invasion; P = 0.049: SMA and celiac artery invasion vs. celiac artery only invasion; P = 0.017), carbohydrate antigen 19-9 (CA 19-9) level ≥ 231.9 U/mL (P = 0.001), anterior peripancreatic invasion (P = 0.006), and incomplete scheduled concurrent chemotherapy (P = 0.009) were statistically significant prognostic factors for overall survival. There was no significant difference in local progression-free survival; however, distant metastasis-free survival was statistically worse in patients with prognostic factors than in those without. Conclusions: Proton radiotherapy for LAPC in the body and tail may be a valuable multidisciplinary treatment option. Patients with SMA invasion, higher pre-proton radiotherapy serum CA 19-9 level, anterior peripancreatic invasion, or incomplete scheduled concurrent chemotherapy had worse overall survival because of worse distant metastasis-free survival, suggesting that distant metastases have a significant impact on overall survival in such patients. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of laparoscopic liver resection (LLR) have been reported worldwide. However, those of LLR for tumors located in Couinaud's segment 8 are not sufficiently investigated. Methods: We retrospectively analyzed 108 patients who underwent liver resection for hepatocellular carcinoma (HCC) in segment 8 at Kobe University Hospital and Hyogo Cancer Center between January 2010 and December 2021. The patients were categorized in LLR and open liver resection (OLR) groups, and 1:1 propensity score matching (PSM) was performed to compare surgical outcomes between the groups. Results: Forty-seven and 61 patients underwent LLR and OLR, respectively. After PSM, each group contained 34 patients. There was no significant difference in operation time between the groups (331 min vs. 330 min, P = 0.844). Patients in the LLR group had significantly less blood loss (30 mL vs. 468 mL, P < 0.001) and shorter length of postoperative hospital stay (10 days vs. 12 days, P = 0.015) than those in the OLR group. There was no significant difference in the occurrence of postoperative complications between the groups (12% vs. 9%, P = 0.690). Further, the 1-year cumulative incidence of recurrence was not significantly different between the groups (16% vs. 19%, P = 0.734). Conclusions: The surgical outcomes and short-term prognosis of LLR were similar or better than those of OLR. LLR could be an effective and safe procedure, even for lesions located in segment 8, which is considered a difficult anatomical location for LLR. [ABSTRACT FROM AUTHOR]

Background: Spacer placement surgery is useful in particle therapy (PT) for patients with abdominopelvic malignant tumors located adjacent to the gastrointestinal tract. This study aimed to assess the safety, efficacy, and long-term outcomes of spacer placement surgery using an expanded polytetrafluoroethylene (ePTFE) spacer. Methods: This study included 131 patients who underwent ePTFE spacer placement surgery and subsequent PT between September 2006 and June 2019. The overall survival (OS) and local control (LC) rates were calculated using Kaplan-Meier method. Spacer-related complications were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Results: The median follow-up period after spacer placement surgery was 36.8 months. The 3-year estimated OS and LC rates were 60.5% and 76.5%, respectively. A total of 130 patients (99.2%) were able to complete PT. Spacer-related complications of ≥ grade 3 were observed in four patients (3.1%) in the acute phase and 13 patients (9.9%) in the late phase. Ten patients (7.6%) required removal of the ePTFE spacer. Conclusions: Spacer placement surgery using an ePTFE spacer for abdominopelvic malignant tumors is technically feasible and acceptable for subsequent PT. However, severe spacer-related late complications were observed in some patients. Since long-term placement of a non-absorbable ePTFE spacer is associated with risks for morbidity and infection, careful long-term follow-up and prompt therapeutic intervention are essential when complications associated with the ePTFE spacer occur. Trial registration: retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. Methods: We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC. The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis. Results: Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41–12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08–4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59–3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36–5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34–6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). Conclusions: Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Long-term outcomes and prognostic factors of proton radiotherapy for locally advanced pancreatic cancer (LAPC) in the body and tail are still unknown. The aim of this study was to determine the prognostic factors after proton radiotherapy in a large group of patients with LAPC in the body and tail. Methods: The medical records of 200 patients with LAPC in the body and tail who underwent proton radiotherapy between February 2009 and January 2021 at the Hyogo Ion Beam Medical Center were retrospectively reviewed to identify prognostic factors that contribute to long-term survival. Results: The overall survival rate at 1- and 2-year after PT was 69.6% and 35.4% with a median overall survival of 18.4 months. The 1- and 2-year local progression-free, and progression-free survival rates were 84.3% and 68.0%, and 44.3% and 19.4%, respectively. In multivariate analysis, superior mesenteric artery (SMA) invasion (SMA only invasion vs. celiac artery only invasion; P = 0.049: SMA and celiac artery invasion vs. celiac artery only invasion; P = 0.017), carbohydrate antigen 19-9 (CA 19-9) level ≥ 231.9 U/mL (P = 0.001), anterior peripancreatic invasion (P = 0.006), and incomplete scheduled concurrent chemotherapy (P = 0.009) were statistically significant prognostic factors for overall survival. There was no significant difference in local progression-free survival; however, distant metastasis-free survival was statistically worse in patients with prognostic factors than in those without. Conclusions: Proton radiotherapy for LAPC in the body and tail may be a valuable multidisciplinary treatment option. Patients with SMA invasion, higher pre-proton radiotherapy serum CA 19-9 level, anterior peripancreatic invasion, or incomplete scheduled concurrent chemotherapy had worse overall survival because of worse distant metastasis-free survival, suggesting that distant metastases have a significant impact on overall survival in such patients. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Less intra-abdominal adhesions are expected following laparoscopic surgery. Although an initial laparoscopic approach for primary liver tumors may have advantages in patients who require repeat hepatectomies for recurrent liver tumors, this has not been sufficiently investigated. Methods: Patients who underwent repeat hepatectomies for recurrent liver tumors at our hospital between 2010 and 2022 were retrospectively analyzed. Of 127 patients, 76 underwent laparoscopic repeat hepatectomy (LRH), of whom 34 patients initially underwent laparoscopic hepatectomy (L-LRH) and 42, open hepatectomy (O-LRH). Fifty-one patients underwent open hepatectomy as both the initial and second operation (O-ORH). We analyzed surgical outcomes between L-LRH and O-LRH groups and between L-LRH and O-ORH groups using propensity-matching analysis for each pattern. Results: Twenty-one patients each were included in L-LRH and O-LRH propensity-matched cohorts. The L-LRH group had a lower rate of postoperative complications than the O-LRH group (0 vs 19%, P = 0.036). When we compared surgical outcomes between L-LRH and O-ORH groups in another matched cohort with 18 patients in each group, in addition to the lower rate of postoperative complications, the L-LRH group had additional favorable surgical outcomes including shorter operation time and lower blood loss volume than the O-ORH group (291 vs 368 min, P = 0.037 and 10 vs 485 mL, P < 0.0001). Conclusions: An initial laparoscopic approach would be favorable for patients undergoing repeat hepatectomies, as it leads to lower risk of postoperative complications. Compared with O-ORH, the advantage of the laparoscopic approach may be enhanced when it is repeatedly adopted. [ABSTRACT FROM AUTHOR]

Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0–7.3], with lobularity: 6.5 [1.9–22.5], Ptrend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1–8.2], with lobularity: 9.7 [2.6–36.3], Ptrend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8–5.8], with lobularity: 3.2 [1.0–10.2], Ptrend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions. [ABSTRACT FROM AUTHOR]

• Post-transplant weight control is an important factor affecting long-term outcomes. • Younger patients and those with a body mass index <25 were at risk of post-transplant weight gain. • Education on post-transplant weight control is necessary for good outcomes. • This is important for improving long-term prognosis after liver transplantation. Post-transplantation weight control is important for long-term outcomes; however, few reports have examined postoperative weight change. This study aimed to identify perioperative factors contributing to post-transplantation weight change. Twenty-nine patients who underwent liver transplantation between 2015 and 2019 with an overall survival of >3 years were analyzed. The median age, model for end-stage liver disease score, and preoperative body mass index (BMI) of the recipients were 57, 25, and 23.7, respectively. Although all but one recipient lost weight, the percentage of recipients who gained weight increased to 55% (1 month), 72% (6 months), and 83% (12 months). Among perioperative factors, recipient age ≤50 years and BMI ≤25 were identified as risk factors for weight gain within 12 months (P <.05), and patients with age ≤50 years or BMI ≤25 recipients gained weight more rapidly (P <.05). The recovery time of serum albumin level ≥4.0 mg/dL was not statistically different between the 2 groups. The weight change during the first 3 years after discharge was represented by an approximately straight line, with 18 and 11 recipients showing a positive and negative slope, respectively. Body mass index ≤23 was identified as a risk factor for a positive slope of weight gain (P <.05). Although postoperative weight gain implies recovery after transplantation, recipients with a lower preoperative BMI should strictly manage body weight as they may be at higher risk of rapid weight increase. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Tertiary lymphoid structure (TLS) reflects an intense immune response against cancer, which correlates with favorable patient survival. However, the association of TLS with tumor-infiltrating lymphocytes (TILs) and clinical outcomes has not been investigated comprehensively in pancreatic ductal adenocarcinoma (PDAC). Methods: We utilized an integrative molecular pathological epidemiology database on 162 cases with resected PDAC, and examined TLS in relation to levels of TILs, patient survival, and treatment response. In whole-section slides, we assessed the formation of TLS and conducted immunohistochemistry for tumor-infiltrating T cells (CD4, CD8, CD45RO, and FOXP3). As confounding factors, we assessed alterations of four main driver genes (KRAS, TP53, CDKN2A [p16], and SMAD4) using next-generation sequencing and immunohistochemistry, and tumor CD274 (PD-L1) expression assessed by immunohistochemistry. Results: TLSs were found in 112 patients with PDAC (69.1%). TLS was associated with high levels of CD4+ TILs (multivariable odds ratio [OR], 3.50; 95% confidence interval [CI] 1.65–7.80; P = 0.0002), CD8+ TILs (multivariable OR, 11.0; 95% CI 4.57–29.7, P < 0.0001) and CD45RO+ TILs (multivariable OR, 2.65; 95% CI 1.25–5.80, P = 0.01), but not with levels of FOXP3+ TILs. TLS was associated with longer pancreatic cancer-specific survival (multivariable hazard ratio, 0.37; 95% CI 0.25–0.56, P < 0.0001) and favorable outcomes of adjuvant S-1-treatment. TLS was not associated with driver gene alterations but tumor CD274 negative expression. Conclusions: Our comprehensive data supports the surrogacy of TLS for vigorous anti-tumor immune response characterized by high levels of helper and cytotoxic T cells and their prognostic role. [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 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]

Bile leakage is a major complication after liver transplantation and remains as a significant source of morbidity and mortality. In 2011, the International Study Group of Liver Surgery (ISGLS) defined bile leakage as a drain/serum bilirubin ratio ≥3. However, to our knowledge there is no literature assessing serum and drain bilirubin concentrations after liver transplantation. The aim of this study was to describe the natural postoperative changes in serum and drain fluid bilirubin concentrations in patients after liver transplantation. We included 32 patients who underwent liver transplantation at Kobe University Hospital from January 2007 to December 2020. We enrolled 34 living donors who had no complications as the control group. The recipient serum total/direct bilirubin concentration were higher compared with the donors from postoperative day (POD) 1 to 5 with a statistical difference (P <.05). The recipient drain/serum total bilirubin ratio was lower than donors on POD 3 (0.89 ± 0.07 vs 1.53 ± 0.07: P <.0001), which was also confirmed by the recipient drain/serum direct bilirubin ratio (0.64 ± 0.10 vs 1.18 ± 0.09: P <.0001). On POD 3, the drain fluid volume (647.38 ± 89.47 vs 113.43 ± 86.8 mL: P <.001) and serum total bilirubin concentration (6.73 ± 0.61 vs 1.23 ± 0.60 mg/dL: P <.001) was higher in the recipients than in donors. Categorized in 2 groups, the higher drain fluid volume and bilirubin concentration recipients showed lower drain/serum total bilirubin ratio compared with the other group (P =.03) The drain/serum bilirubin ratio in the transplanted patients could be calculated lower compared with the hepatectomy patients because of high drain fluid volume and hyperbilirubinemia. Great care should be taken when assessing the bile leakage in liver transplant recipients using the ISGLS definition. [ABSTRACT FROM AUTHOR]

Background: Resecting liver tumors located in Couinaud's segment VII is challenging; the efficacy and safety of laparoscopic liver resection for segment VII lesions compared to open liver resection remain unclear. Methods: Medical records of 84 patients who underwent liver resection of segment VII at Kobe University Hospital and Hyogo Cancer Center between 2010 and 2021 were retrospectively analyzed. Surgical outcomes were compared between laparoscopic liver resection and open liver resection groups using propensity matching analysis. Results: Thirty-one and 53 patients underwent laparoscopic liver resection and open liver resection, respectively. After propensity matching, 29 patients were included in each group. The laparoscopic liver resection group had a significantly longer operation time (407 vs. 305 min, P = 0.002), lower blood loss (100 vs. 230 mL, P = 0.004), and higher postoperative alanine aminotransferase levels (436 vs. 252 IU/L, P = 0.008) than the open liver resection group. In patients with liver cirrhosis, the proportion of patients with postoperative liver-specific complications was higher in the laparoscopic liver resection group than in the open liver resection group (57% vs 11%, P = 0.049), although there was no significant difference in postoperative liver-specific complication rates between the groups in patients without liver cirrhosis. Conclusions: For liver resection of segment VII, laparoscopic liver resection led to higher postoperative liver damage than open liver resection. Open liver resection may be better for patients with liver cirrhosis to avoid postoperative liver-specific complications. Laparoscopic liver resection could be an acceptable procedure for patients without liver cirrhosis, with some merits such as less blood loss. [ABSTRACT FROM AUTHOR]

Background: Anatomic liver resection (ALR) has been established to eliminate the tumor-bearing hepatic region with preservation of the remnant liver volume for liver malignancies. Recently, laparoscopic ALR has been widely applied; however, there are few reports on laparoscopic segmentectomy 2. This study aimed to present the standardization of laparoscopic segmentectomy 2 with surgical outcomes. Methods: This study included seven patients who underwent pure laparoscopic segmentectomy 2 by the Glissonean approach from January 2020 to December 2021. Four of them had hepatocellular carcinoma, two had colorectal liver metastasis, and one had hepatic angiomyolipoma, which was preoperatively diagnosed with hepatocellular carcinoma. In all patients, preoperative three-dimensional (3D) simulation images from dynamic CT were reconstructed using a 3D workstation. The layer between the hepatic parenchyma and the Glissonean pedicle of segment 2 (G2) was dissected to encircle the root of G2. After clamping or ligation of the G2, 2.5 mg of indocyanine green was injected intravenously to identify the boundaries between segments 2 and 3 with a negative staining method under near-infrared light. Parenchymal transection was performed from the caudal side to the cranial side according to the demarcation on the liver surface, and the left hepatic vein was exposed on the cut surface if possible. Results: The mean operative time for all patients was 281 min. The mean blood loss was 37 mL, and no transfusion was necessary. Estimated liver resection volumes significantly correlated with actual liver resection volumes (r = 0.61, P = 0.035). After the operation, one patient presented with asymptomatic deep venous and pulmonary thrombosis, which was treated with anticoagulant therapy. The mean length of hospital stay was 8.9 days. Conclusion: Laparoscopic segmentectomy 2 by the Glissonean approach is a feasible and safe procedure with the preservation of the nontumor-bearing segment 3 for liver tumors in segment 2. [ABSTRACT FROM AUTHOR]

Purpose: The therapeutic strategy for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) has remained unestablished because the preoperative prognostic factors have not been determined. Methods: One hundred eighty-four consecutive PDAC patients who underwent upfront surgery with a curative resection between January 2000 and June 2013 at Kobe University Hospital were retrospectively studied. The PDAC patients were stratified into resectable (R)-PDAC ( n = 147) and BR-PDAC patients ( n = 37). We evaluated the independent prognostic significance of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) in the BR-PDAC patients. Results: BR-PDAC patient survival was significantly worse than R-PDAC patient survival (median survival time: 22.1 months vs. 24.3 months; 5-year survival rate 6 vs. 21 %; P = 0.042). The median survival in BR-PDAC patients with a preoperative NLR of >3 ( n = 12) was 10.2 months, while that in patients with preoperative NLR of ≤3 ( n = 25) was 24.9 months ( P = 0.002). Moreover, the median survival in BR-PDAC patients with a preoperative PLR of >225 ( n = 8) was 10.2 months, while that in patients with a preoperative PLR of ≤225 ( n = 29) was 24.7 months ( P = 0.003). Preoperative NLR >3 (HR = 2.980, 95 % CI 1.251-6.920; P = 0.015) and PLR >225 (HR = 3.050, 95 % CI 1.169-7.468; P = 0.024) were independent prognostic factors in BR-PDAC patients. Conclusions: Higher preoperative NLR and PLR can be independent predictive risk factors in BR-PDAC patients following curative resection. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year-old male with severe type 1 diabetes with chronic renal failure who received simultaneous PKT from a female donor. Diarrhea developed on postoperative day (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin rashes appeared with pain and itching on his trunk and extremities on POD 40. As pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD because skin biopsies revealed the XX chromosome signal in a fluorescence in situ hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5 days. Although every symptom was temporarily improved, on POD 156, the patient expired from the septic pneumonia without any effects of antibiotics. Clinician should be aware that PKT has the potential to induce aGVHD. [ABSTRACT FROM AUTHOR]

Tremelimumab plus durvalumab (Dur/Tre) is the first-line treatment for advanced hepatocellular carcinoma (HCC) worldwide. The present report describes the case of a 68-year-old man diagnosed with advanced HCC and a bile duct tumor thrombus (BDTT) who achieved a complete response to Dur/Tre therapy. The BDTT progressed to the bifurcation of the left and right hepatic ducts. Over time, both the tumors and BDTT progressively decreased in size, and a complete response was confirmed using the Response Evaluation Criteria in Solid Tumors (version 1.1.) 6 months after treatment administration. Subsequently, immune-related adverse events, including type 1 diabetes mellitus and diabetic ketoacidosis, emerged, leading to treatment discontinuation. The patient was undergoing outpatient follow-up in a drug-free state with no signs of recurrence 290 days after the initial administration of Dur/Tre. Although long-term and meticulous observations are required, the present findings could influence the choice of systemic chemotherapy for advanced HCC. [ABSTRACT FROM AUTHOR]

Objectives: Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Methods: We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro. Results: Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression. Conclusion: Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC. [ABSTRACT FROM AUTHOR]

Introduction: Although the relationship between systemic inflammatory responses and prognosis has been known in various cancers, it remains unclear which scores are most valuable for determining the prognosis of extrahepatic cholangiocarcinoma. We aimed to verify the usefulness of various inflammation-based scores as prognostic factors in patients with resected extrahepatic cholangiocarcinoma. Methods: We analyzed consecutive patients undergoing surgical resection for extrahepatic cholangiocarcinoma at our institution between January 2000 and December 2019. The usefulness of the following inflammation-based scores as prognostic factor was investigated: glasgow prognostic score (GPS), modified GPS, neutrophil-to-lymphocyte ratio, platelet to lymphocyte ratio, lymphocyte-to-monocyte ratio, prognostic nutrition index, C-reactive protein to albumin ratio (CAR), controlling nutritional status (CONUT), and prognostic index. Results: A total of 169 patients were enrolled in this study. Of the nine scores, CAR and CONUT indicated prognostic value. Furthermore, multivariate analysis for overall survival revealed that high CAR (>0.23) was an independent prognostic factor (hazard ratio: 1.816, 95% confidence interval: 1.135–2.906, p = 0.0129), along with lymph node metastasis and curability. There was no difference in tumor staging and short-term outcomes between the low CAR (≤0.23) and high CAR groups. Conclusions: CAR was the most valuable prognostic score in patients with resected extrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Optimal treatment strategies for advanced hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) remain controversial. Therefore, this study aimed to assess the impact and predictive factors of hepatectomy for HCC with macroscopic PVTT. Methods: This study included 100 patients who presented with intraoperatively confirmed PVTT extending to the first portal branch (Vp3), main portal trunk, or opposite-side portal branch (Vp4) between June 2000 and December 2019. Their postoperative outcomes and predictive factors for survival were evaluated. Results: Of the 100 patients, 37 (37%) and 63 (63%) had Vp3 and Vp4 PVTTs, respectively. Moreover, 42 (42%) and 58 (58%) patients underwent R0/1 and R2 hepatectomies, respectively. The median survival time (MST) of all patients with Vp3/4 PVTT was 14.5 months; the 1- and 3-year overall survival rates were 59.6 and 16.8%, respectively. The MSTs of patients with Vp3 and Vp4 PVTTs were 16.1 and 14.3 months, respectively (P = 0.7098). The MSTs of patients who underwent R0/1 and R2 hepatectomies were 14.3 and 14.9 months, respectively (P = 0.3831). All assessed tumor factors (including the Vp status [Vp3 or Vp4], type of resection [R0/1 or R2], intrahepatic maximal tumor size, intrahepatic tumor number, and the existence of extrahepatic metastasis) did not influence the overall survival significantly. Conclusions: Tumor factors, such as the presence of a Vp3/4 PVTT, have a strong impact on survival; however, other multiple tumor factors have a limited impact. Hepatectomy can be an effective treatment option for HCC with Vp3/4 PVTT, and its indications should be considered. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic performance of the extracellular volume (ECV) fraction in multiphasic contrast-enhanced computed tomography (CE-CT) for estimating histologic pancreatic fibrosis and predicting postoperative pancreatic fistula (POPF). Methods: Eighty-five patients (49 men; mean age, 69 years) who underwent multiphasic CE-CT followed by pancreaticoduodenectomy with pancreaticojejunal anastomosis between January 2012 and December 2018 were retrospectively included. The ECV fraction was calculated from absolute enhancements of the pancreas and aorta between the precontrast and equilibrium-phase images, followed by comparisons among histologic pancreatic fibrosis grades (F0‒F3). The diagnostic performance of the ECV fraction in advanced fibrosis (F2‒F3) was evaluated using receiver operating characteristic curve analysis. Multivariate logistic regression analysis was used to evaluate the associations of the risk of POPF development with patient characteristics, histologic findings, and CT imaging parameters. Results: The mean ECV fraction of the pancreas was 34.4% ± 9.5, with an excellent intrareader agreement of 0.811 and a moderate positive correlation with pancreatic fibrosis (r = 0.476; p < 0.001). The mean ECV fraction in advanced fibrosis was significantly higher than that in no/mild fibrosis (44.4% ± 10.8 vs. 31.7% ± 6.7; p < 0.001), and the area under the receiver operating characteristic curve for the diagnosis of advanced fibrosis was 0.837. Twenty-two patients (25.9%) developed clinically relevant POPF. Multivariate logistic regression analysis demonstrated that the ECV fraction was a significant predictor of POPF. Conclusions: The ECV fraction can offer quantitative information for assessing pancreatic fibrosis and POPF after pancreaticojejunal anastomosis. Key Points: • There was a moderate positive correlation of the extracellular volume (ECV) fraction of the pancreas in contrast-enhanced CT with the histologic grade of pancreatic fibrosis (r = 0.476; p < 0.001). • The ECV fraction was higher in advanced fibrosis (F2‒F3) than in no/mild fibrosis (F0‒F1) (p < 0.001), with an AUC of 0.837 for detecting advanced fibrosis. • The ECV fraction was an independent risk factor for predicting subclinical (odds ratio, 0.81) and clinical (odds ratio, 0.80) postoperative pancreatic fistula. [ABSTRACT FROM AUTHOR]

Background: Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC.Methods: The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes.Results: The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P < 0.001). LAPCs with anterior peripancreatic invasion had more peritoneal recurrence within 6 months after GTP than those without anterior peripancreatic invasion (P = 0.039).Conclusions: GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion. [ABSTRACT FROM AUTHOR]

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of “sequential particle radiotherapy,” consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) with major portal vein tumor thrombus (Vp4 PVTT) is an extremely advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option, and atezolizumab plus bevacizumab has recently emerged as a first-line treatment option.Case Presentation: We describe the case of an 82-year-old man with unresectable advanced HCC with Vp4 PVTT who achieved a significant response to atezolizumab plus bevacizumab treatment. A single administration of atezolizumab plus bevacizumab ensured significant anti-tumor effects (regression in the tumor size and PVTT, portal vein recanalization, and serum alfa-fetoprotein levels decreased from 90,770 to 89 ng/mL). The patient continued with atezolizumab monotherapy, and after nine consecutive regimens, there was no apparent sign of residual tumor.Conclusions: This case demonstrates the powerful anti-tumor effect of atezolizumab plus bevacizumab treatment for advanced HCC with Vp4 PVTT, suggesting that these agents can be a promising treatment option for such refractory tumors. [ABSTRACT FROM AUTHOR]

Although liver transplantation is widely accepted as the therapeutic strategy for end-stage liver failure, complication of hepatic venous outflow obstruction remains lethal. Currently, ensuring a single wide orifice in both the graft and recipient inferior vena cava has been proposed to avoid hepatic venous outflow obstruction with no theoretical concept. We herein report a standardization technique for the reconstruction of the hepatic vein based on the causal analysis. During the put-in process, the graft must be positioned in contact with the recipient diaphragm and slightly pushed to the cranial direction to simulate the state after abdominal closure. Because there is no extra space between the graft and diaphragm, the graft could not rotate about the anastomotic site of the inferior vena cava toward the diaphragm after abdominal closure as the intestinal pressure increases, and accordingly hepatic venous outflow obstruction does not develop. With this concept, all transplant surgeons can successfully and easily perform hepatic vein reconstruction without total clamping of the inferior vena cava and without outflow block. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatogenic diabetes after pancreatectomy is of growing importance due to the increasing life expectancy of pancreatectomized patients. Although reduction of pancreatic volume is thought to affect glucose metabolism, a consistent relationship has yet to be determined. This study aimed to investigate functional consequences of distal pancreatectomy (DP) in preoperatively non-diabetic patients. Methods: This study included 61 non-diabetic patients who underwent DP. Clinical data were obtained, and the percent resected volume (PRV) of each pancreas was determined via multi-detector row computed tomography volumetry. Results: During the follow-up period (median 26 months), 22 patients (36 %) developed new-onset diabetes within a median onset time of 8 months (range 0.5-42 months) postoperatively. The remaining 39 patients also showed impaired glucose metabolism. Multivariate analysis identified preoperative hemoglobin A1c ≥ 5.7 % (odds ratio 15.6, p = 0.001) and PRV > 44 % (odds ratio 11.3, p = 0.004) as independent risk factors for new-onset diabetes. Conclusions: Key determinants of postoperative glycemic control include preoperative functional reserve of the endocrine pancreas and the volume reduction of pancreatic parenchyma. Our findings enable reliable preoperative evaluation of the risk of postoperative diabetes and appropriate postoperative surveillance, which is helpful for early intervention in high risk patients. [ABSTRACT FROM AUTHOR]

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucin production and cystic dilatation of the pancreatic ducts. The clinical presentation often involves recurrent episodes of pancreatitis associated with the temporal obstruction of the main pancreatic duct caused by the hypersecretion of mucin. We herein describe a case in which the patient repeatedly experienced the occurrence of idiopathic acute pancreatitis in the head of the pancreas over a 9-year period, and who was ultimately was cured by distal pancreatectomy for IPMNs in the pancreatic tail. This case illustrates the potential pitfalls in the diagnosis of IPMNs owing to a discrepancy between the site of pancreatitis and that of the IPMN. The possible mechanisms linking acute pancreatitis with the formation of IPMNs are also reviewed. [ABSTRACT FROM AUTHOR]

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach.Methods/design: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival.Discussion: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view.Trial Registration: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020. [ABSTRACT FROM AUTHOR]

Background: We compared surgical outcomes, with a focus on tumor characteristics, of laparoscopic repeat hepatectomy (LRH) and open repeat hepatectomy (ORH) to identify recurrent hepatocellular carcinoma (HCC) cases where the LRH procedure would be more favorable than ORH.Methods: Eighty-one HCC patients who underwent repeat hepatectomy in our hospital from 2008 to 2019 were retrospectively analyzed in this study. Of these patients, 30 and 51 patients underwent LRH and ORH, respectively. We analyzed surgical outcomes of LRH and ORH, focusing on tumor characteristics such as tumor size, location, distance from major vessels, and contralateral or ipsilateral tumor recurrence to determine what factors could affect surgical outcomes. Subsequently, using a propensity-matched cohort, we compared the impact of those factors on LRH and ORH outcomes.Results: In the entire cohort, the LRH operation time was significantly shorter in contralateral recurrent HCC cases than in ipsilateral recurrent HCC cases (252 vs. 398 min, P = 0.008); however, such a difference was not observed in the ORH operation time. We subsequently compared the surgical outcomes, in terms of the location of tumor recurrence, between the LRH and ORH groups in a propensity-matched cohort. In total, 23 patients were included in each of these groups. We found that the LRH procedure had significantly shorter operative time than the ORH procedure in the contralateral recurrent HCC cases (253 vs. 391 min, P = 0.018); however, we did not observe such a difference in the ipsilateral recurrent HCC cases (372 vs. 333 min, P = 0.669). LRH had lower blood loss, similar postoperative complications and shorter hospital stay than ORH in both contralateral and ipsilateral recurrent HCC cases.Conclusions: LRH is likely considered a more favorable approach than ORH in treating patients with contralateral recurrent HCC. [ABSTRACT FROM AUTHOR]

Background: Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.Methods: Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.Results: Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy.Conclusions: Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. Methods: We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m2, nab-paclitaxel 90 mg/m2, S-1 60/80/100 mg/day (< 1.25 m2/1.25–1.50 m2/ > 1.5 m2)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned. Results: From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m2, nab-paclitaxel 90 mg/m2, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response. Conclusion: We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007). [ABSTRACT FROM AUTHOR]

The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC). The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients. Of the study subjects, 37 patients had Child–Pugh class A (CPA) liver function, and 14 patients had Child–Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1–2 months, or 2–3 months (p = 0.2368, 0.9368, and 0.9293). The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy. Methods: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study. Results: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size <100 mm and intrahepatic tumor number ≤2 were 39.0 months and 51.9%, respectively. Conclusions: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size <100 mm, irrespective of vascular invasion. [ABSTRACT FROM AUTHOR]

Introduction and Background: Autoimmune pancreatitis (AIP) is a rare disease that closely mimics pancreatic cancer (PC) in its presentation. It is very important for clinicians to distinguish one from the other because their treatment and prognosis are vastly different. Typical radiological imaging findings, in particular observation of diffusely or segmentally narrowed main pancreatic duct (MPD) with an irregular wall by endoscopic retrograde cholangiopancreatography (ERCP), are essential for making the diagnosis of AIP. On the other hand, MPD obstruction is one of the most frequent features on ERCP.Case Report: We report a rare case of a patient with focal mass-forming AIP strongly suspected of being PC because of MPD obstruction on ERCP.Conclusion: It was difficult to distinguish PC from AIP with current diagnostic modalities. We will continue to make an effort to distinguish between the two disorders to prevent unnecessary surgery. [ABSTRACT FROM AUTHOR]

• Space-making particle therapy provides a rational combination treatment. • Effectiveness of space-making particle therapy has been demonstrated. The primary definitive treatment for abdominopelvic sarcomas (APSs) is resection, although incomplete resection has a negative prognostic impact. Although the effectiveness of particle therapy (PT) as a treatment for APS has already been demonstrated, its application for tumors adjacent to the gastrointestinal tract is frequently restricted, due to extremely low tolerance. Space-making PT, consisting of surgical spacer placement and subsequent PT, has been developed to overcome this limitation. Between June 2006 and June 2018, a total of 75 patients with 12 types of APS underwent space-making PT. The 3-year local control rate of all patients was 90.3%. Fourteen surgery-related complications were observed in 12 patients (16%), and complications of Grade 3b or higher were observed in 3 patients. Ninety-five PT-related complications were seen in 66 patients (88.0%), and 13 patients (17.3%) had complications of Grade 3 or higher. The median V95% (volume irradiated with 95% of the treatment planning dose) of the gross tumor volume and clinical target volume were 99.9% and 99.5%, respectively. The median D95% (dose intensity covering 95% of the target volume) of the gross tumor volume/planned dose and clinical target volume/planned dose were 99.4%, and 99.1%, respectively. The feasibility and effectiveness of space-making PT have been demonstrated via dosimetric evaluation, and our results indicate that this new strategy may potentially provide an effective and innovative treatment option for advanced APS. [ABSTRACT FROM AUTHOR]

The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients. We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score. Multivariate analysis indicated that recipient age (P =.003), donor age (P =.003), ALBI score ≥ −1.28 (P =.002), and ALBI grade III (P =.004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P =.023, P =.005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P =.031) and infection (P =.020). ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases. • An albumin-bilirubin score predicts recipient survival after living-donor transplantation. • An albumin-bilirubin score is more useful than Model for End-Stage Liver Disease score. • An albumin-bilirubin score of ≥ −1.28 is independently associated with worth survival. • A high albumin-bilirubin score predicts an incidence of infection and graft dysfunction. [ABSTRACT FROM AUTHOR]