Embolization with or without portal vein stenting for bleeding ectopic jejunal varices in hepatopetal portal collaterals due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery.

PURPOSE: To evaluate the efficacy and safety of embolization with or without portal vein stenting for bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery. MATERIALS AND METHODS: This study included consecutive patients who underwent embolization for bleeding ectopic jejunal varices in the hepatopetal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery between September 2012 and December 2020. The safety, technical and clinical success rates (no re-bleeding within 1 month) and re-bleeding-free survival after the first therapy and overall survival were assessed. RESULTS: Fourteen sessions in 11 patients were included. Four patients (7 sessions) underwent variceal embolization only, and the remaining seven patients (7 sessions) underwent portal vein stenting and variceal embolization. Technical success was achieved in all 14 sessions (100%). Clinical success was achieved in 13 of 14 sessions (92.9%). No treatment-related serious complications including liver failure were observed. One-year and 2-year re-bleeding-free survival rate after the first endovascular therapy in all 11 patients was 90.9 and 60.6%, respectively. Two patients who experienced re-bleeding had repeat embolization treatment. There was no significant difference in re-bleeding-free survival after endovascular therapy between the combination with stenting and embolization group and the embolization-only group (p = 0.13). CONCLUSION: Embolization with or without portal vein stenting of bleeding ectopic jejunal varices in the hepatopetal portal collateral due to extrahepatic portal vein occlusion or stenosis after hepatobiliary and pancreatic surgery can be considered a safe, effective, and repeatable therapy for long-term hemostasis of uncontrollable bleeding.

Low-CO2-inducible bestrophins outside the pyrenoid sustain high photosynthetic efficacy in diatoms.

Anion transporters sustain a variety of physiological states in cells. Bestrophins (BSTs) belong to a Cl- and/or HCO3- transporter family conserved in bacteria, animals, algae, and plants. Recently, putative BSTs were found in the green alga Chlamydomonas reinhardtii, where they are upregulated under low CO2 (LC) conditions and play an essential role in the CO2-concentrating mechanism (CCM). The putative BST orthologs are also conserved in diatoms, secondary endosymbiotic algae harboring red-type plastids, but their physiological functions are unknown. Here, we characterized the subcellular localization and expression profile of BSTs in the marine diatoms Phaeodactylum tricornutum (PtBST1 to 4) and Thalassiosira pseudonana (TpBST1 and 2). PtBST1, PtBST2, and PtBST4 were localized at the stroma thylakoid membrane outside of the pyrenoid, and PtBST3 was localized in the pyrenoid. Contrarily, TpBST1 and TpBST2 were both localized in the pyrenoid. These BST proteins accumulated in cells grown in LC but not in 1% CO2 (high CO2 [HC]). To assess the physiological functions, we generated knockout mutants for the PtBST1 gene by genome editing. The lack of PtBST1 decreased photosynthetic affinity for dissolved inorganic carbon to the level comparable with the HC-grown wild type. Furthermore, non-photochemical quenching in LC-grown cells was 1.5 to 2.0 times higher in the mutants than in the wild type. These data suggest that HCO3- transport at the stroma thylakoid membranes by PtBST1 is a critical part of the CO2-evolving machinery of the pyrenoid in the fully induced CCM and that PtBST1 may modulate photoprotection under CO2-limited environments in P. tricornutum.

Impact of frailty on long-term outcomes after liver resection for hepatocellular carcinoma in elderly patients: A prospective study.

BACKGROUND: sFrailty affects short-term outcomes after liver resection in elderly patients. However, frailty's effects on long-term outcomes after liver resection in elderly patients with hepatocellular carcinoma (HCC) are unknown. METHODS: This prospective, single-center study included 81 independently living patients aged ≥65 years scheduled to undergo liver resection for initial HCC. Frailty was evaluated according to the Kihon Checklist, a phenotypic frailty index." We investigated and compared postoperative long-term outcomes after liver resection between patients with and without frailty. RESULTS: Of the 81 patients, 25 (30.9%) were frail. The proportion of patients with cirrhosis, high serum alpha-fetoprotein level (≥200 ng/mL), and poorly differentiated HCC was higher in the frail group than in the nonfrail group (n = 56). Among the patients with postoperative recurrence, the incidence of extrahepatic recurrence was higher in the frail group than in the nonfrail group (30.8% vs. 3.6%, P = 0.028). Moreover, the proportion of patients who underwent repeat liver resection and ablation for recurrence who met the Milan criteria tended to be lower in the frail group than in the nonfrail group. Although there was no difference in disease-free survival between the two groups, the overall survival rate in the frail group was significantly worse than that in the nonfrail group (5-year overall survival: 42.7% vs. 77.2%, P = 0.005). Results of the multivariate analysis indicated that frailty and blood loss were independent prognostic factors for postoperative survival. CONCLUSION: Frailty is associated with unfavorable long-term outcomes after liver resection in elderly patients with HCC.

Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.

BACKGROUND: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. METHODS: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. RESULTS: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. CONCLUSION: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.

Pancreaticoduodenectomy with celiac artery resection (PD-CAR) for unresctable locally advanced pancreatic ductal adenocarcinoma.

PURPOSE: Locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) involving the celiac artery (CeA), the common hepatic artery and the gastroduodenal artery (GDA) is considered unresectable. We developed the novel procedure of pancreaticoduodenectomy with celiac artery resection (PD-CAR) for such LA-PDACs. METHODS: From 2015 to 2018, we performed curative pancreatectomy with major arterial resection for 13 LA-PDACs as a clinical study (UMIN000029501). Of those, four patients with pancreatic neck cancer involving the CeA and GDA were candidates for PD-CAR. Prior to surgery, blood flow alterations were performed to unify the blood flow to the liver, stomach, and pancreas, resulting in feeding from the cancer-free artery. During PD-CAR, arterial reconstruction of the unified artery was performed as needed. Based on the records of PD-CAR cases, we retrospectively analyzed the validity of the operation. RESULTS: R0 resection was achieved in all patients. Arterial reconstruction was performed in three patients. In another patient, the hepatic arterial flow was maintained by preserving of the left gastric artery. The mean operative time was 669 min, and the mean blood loss was 1003 ml. Although Clavien-Dindo classification III-IV postoperative morbidities occurred in three patients, no reoperations nor mortalities occurred. Although two patients died of cancer recurrence, one patient survived for 26 months without recurrence (died of cerebral infarction), and another is alive at 76 months without recurrence. CONCLUSION: PD-CAR, which enabled R0 resection and preservation of the residual stomach, pancreas, and spleen, provided acceptable postoperative outcomes.

Tumor-infiltrating lymphocytes and macrophages as a significant prognostic factor in biliary tract cancer.

BACKGROUND: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME). METHODS: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining. RESULTS: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively). CONCLUSIONS: High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS.

Non-atrophic gastric mucosa is an independently associated factor for superficial non-ampullary duodenal epithelial tumors: a multicenter, matched, case-control study.

BACKGROUND/AIMS: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. METHODS: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. RESULTS: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). CONCLUSION: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

Proposal of nomograms to predict clinical outcomes in patients with ampulla of Vater cancer based on the Korea-Japan collaborative study.

BACKGROUND: In this study, we aimed to develop and validate a nomogram to predict overall survival (OS) and recurrence-free survival (RFS) in patients who underwent curative resection of ampulla of Vater (AOV) cancer. This is the first study for nomograms in AOV cancer patients using retrospective data based on an international multicenter study. METHODS: A total of 2007 patients with AOV adenocarcinoma who received operative therapy between 2002 January and 2015 December in Korea and Japan were retrospectively assessed to develop a prediction model. Nomograms for 5-year OS and 3-year RFS were constructed by dividing the patients who received and who did not receive adjuvant therapy after surgery, respectively. Significant risk factors were identified by univariate and multivariate Cox analyses. Performance assessment of the four prediction models was conducted by the Harrell's concordance index (C-index) and calibration curves using bootstrapping. RESULTS: A total of 2007 and 1873 patients were collected for nomogram construction to predict 5-year OS and 3-year RFS. We developed four types of nomograms, including models for 5-year OS and 3-year RFS in patients who did not receive postoperative adjuvant therapy, and 5-year OS and 3-year RFS in patients who received postoperative adjuvant therapy. The C-indices of these nomograms were 0.795 (95% confidence interval [CI]: 0.766-0.823), 0.712 (95% CI: 0.674-0.750), 0.804 (95% CI: 0.7778-0.829), and 0.703 (95% CI: 0.669-0.737), respectively. CONCLUSIONS: This predictive model could help clinicians to choose optimal treatment and precisely predict prognosis in AOV cancer patients.

Comparison of clinicopathological characteristics between resected ampullary carcinoma and carcinoma of the second portion of the duodenum.

BACKGROUND: Few studies compared the oncological and biological characteristics between ampullary carcinoma (AC) and cancer of the second portion of the duodenum (DC-II), although both tumors arise from anatomically close locations. AIM: To elucidate differences in clinicopathological characteristics, especially the patterns of lymph node metastasis (LNM), between AC and DC-II. METHODS: This was a retrospective cohort study of 80 patients with AC and 27 patients with DC-II who underwent pancreaticoduodenectomy between January 1998 and December 2018 in two institutions. Clinicopathological factors, LNM patterns, and prognosis were compared between the two groups. RESULTS: The patients with AC and DC-II did not exhibit significant differences in 5-year overall survival (66.0% and 67.1%, respectively) and 5-year relapse-free survival (63.5% and 62.2%, respectively). Compared to the patients with DC-II, the rate of preoperative biliary drainage was higher (P = 0.042) and the rates of digestive symptoms (P = 0.0158), ulcerative-type cancer (P < 0.0001), large tumor diameter (P < 0.0001), and advanced tumor stage (P = 0.0019) were lower in the patients with AC. The LNM rates were 27.5% and 40.7% in patients with AC and DC-II, respectively, without significant difference (P = 0.23). The rates of LNM to hepatic nodes (N-He) and pyloric nodes (N-Py) were significantly higher in patients with DC-II than in those with AC (metastasis to N-HE: 18.5% and 5% in patients with DC-II and AC, respectively; P = 0.0432; metastasis to N-Py: 11.1% and 0% in patients with DC-II and AC, respectively; P = 0.0186). CONCLUSION: Although there were no significant differences in the prognosis and recurrence rates between the two groups, metastases to N-He and N-Py were more frequent in patients with DC-II than in those with AC.

Interleukin-8 produced from cancer-associated fibroblasts suppresses proliferation of the OCUCh-LM1 cancer cell line.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play an important role in cancer growth by interacting with cancer cells, but their effects differ depending on the type of cancer. This study investigated the role of CAFs in biliary tract cancers (BTCs), compared with pancreatic ductal adenocarcinoma (PDAC) as a comparison cohort. METHODS: We retrospectively evaluated alpha-smooth muscle actin (αSMA) expression in CAFs from 114 cases of PDAC and 154 cases of BTCs who underwent surgical treatment at our institution from 1996 to 2017. CAFs were isolated from resected specimens of BTC and PDAC, and tested for the effects of their supernatants and cytokines on cancer cell proliferation. RESULTS: PDAC patients with positive αSMA expression showed significantly shorter overall survival and recurrence-free survival than αSMA-negative patients (p = 0.003, p = 0.009, respectively). BTC patients with positive αSMA expression showed better recurrence-free survival than αSMA-negative patients (p = 0.03). CAF-conditioned medium suppressed the proliferation of cancer cells for only OCUCh-LM1 cells and not PDAC cells. Blockage of Interleukin-8 (IL-8) or its receptor C-X-C motif chemokine receptor 2 (CXCR2) by antibodies canceled the suppressive effect of the IL-8. CONCLUSIONS: CAFs are a good prognostic factor in BTC, but not for PDAC. Moreover, CAF-produced Interleukin-8 suppresses the proliferation of OCUCh-LM1 cell lines.

Laparoscopic liver resection reduces postoperative infection in patients with hepatocellular carcinoma: a propensity score-based analysis.

BACKGROUND: This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR). METHODS: This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups. RESULTS: An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P < 0.001 in the matched cohort; 120 vs. 320 mL, P < 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P < 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P < 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI). CONCLUSIONS: Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

Optimal Organ for Patient-derived Xenograft Model in Pancreatic Cancer and Microenvironment that Contributes to Success.

BACKGROUND: We aimed to investigate the difference in engraftment rates depending on the transplant site for a patient-derived xenograft (PDX) of pancreatic ductal adenocarcinoma (PDAC) and the effects of the microenvironment on engraftment. MATERIALS AND METHODS: Frozen cancer tissues from PDAC tumors were used, and tumor fragments were directly implanted into the subcutaneous, orthotopic pancreas, peritoneum, and liver of X-linked severe combined immunodeficiency (XSCID) rats. We assessed the success of engraftment in each organ. Additionally, to evaluate the effect of the microenvironment in each organ, we performed immunohistochemical analysis. RESULTS: Subcutaneous transplantation was successful in 8 of 10 PDAC cases (16 of 30 rats). This was a higher rate than for other organ transplants. The vascular endothelial cells in the stroma were replaced with those from rats instead of humans. Vascular endothelial growth factor-A (VEGF-A) and cluster of differentiation-31 (CD31) was significantly more strongly expressed in the subcutaneous transplantation model (VEGF-A: p<0.001, CD31: p=0.0036). CONCLUSION: The engraftment rate was significantly higher for the subcutaneous PDX model than for the orthotopic pancreatic, peritoneal, and liver PDX models. Blood vessels of the PDX stroma had been replaced by rat-derived vessels instead of the original human vessels, suggesting that angiogenesis in the PDX microenvironment may be a major factor in engraftment.

CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma.

BACKGROUND: We reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA. MATERIALS AND METHODS: Two human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features. RESULTS: CXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival. CONCLUSION: CXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.

Clinical Implication of Preoperative C-Reactive Protein/Albumin Ratio in Malignant Transformation of Intraductal Papillary Mucinous Neoplasm: A Propensity Score Analysis.

BACKGROUND: Inflammation-based scoring has been reported to be useful for predicting the recurrence and prognosis of various carcinomas. This study retrospectively investigated the relationship between inflammation-based score and intraductal papillary mucinous neoplasms (IPMNs). METHODS: Between January 2013 and October 2018, we enrolled 417 consecutive patients with pancreatic tumors who received surgical resections at our hospital. The main outcome was the association between the preoperative inflammation-based score and their accuracy in predicting malignant transformation of IPMN. RESULTS: Seventy six patients were eligible. Pathological findings indicated that 35 patients had low-grade dysplasia, 18 had high-grade dysplasia, and 23 had invasive carcinomas. As the C-reactive protein albumin ratio (CAR) was higher, malignant transformation of IPMNs also increased (p = 0.007). In comparing CARhigh and CARlow using cutoff value, the results using a propensity score analysis showed that the CARhigh group predicted malignant transformation of IPMNs (odds ratio, 4.18; 95% confidence interval, 1.37-12.8; p = 0.01). In the CARhigh group, disease-free survival (DFS) was significantly shorter (p = 0.04). In the worrisome features, the AUC for the accuracy of malignant transformation with CARhigh was 0.84 when combining with the MPD findings. CONCLUSIONS: Preoperative CAR could be a predictive marker of malignant transformation of IPMNs.

Indications of Laparoscopic Repeat Liver Resection for Recurrent Hepatocellular Carcinoma.

AIM: This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. METHODS: One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low- or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). RESULTS: In the low- or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. CONCLUSION: LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR.

Superiority of laparoscopic liver resection to open liver resection in obese individuals with hepatocellular carcinoma: A retrospective study.

AIM: This study aimed to elucidate the effects of laparoscopic liver resection (LLR) vs open liver resection (OLR) for major complications (Clavien-Dindo classification grade ≥ IIIa) in obese individuals with hepatocellular carcinoma (HCC). METHODS: The clinical records of 339 and 733 patients who underwent LLR and OLR, respectively, for HCC between 2000 and 2019 were retrospectively reviewed. Body mass index (BMI) groups were classified according to the definitions of the World Health Organization: underweight group, BMI ≤ 18.4 kg/m2 (LLR vs OLR: 27 vs 47); normal weight, BMI 18.5-24.9 kg/m2 (211 vs 483); overweight, BMI 25.0-29.9 kg/m2 (85 vs 181); and obese, BMI ≥ 30.0 kg/m2 (16 vs 22). The effects of obesity on major complications after LLR and OLR were investigated. RESULTS: In total, 18 (5.3%) and 127 (17.3%) patients presented with major complications after LLR and OLR, respectively. There was no significant difference in the incidence of major complications after OLR in the four BMI groups. However, a stepwise decrease in the incidence of major complications after LLR was observed from the underweight to the obese group. In addition, a multivariate analysis revealed that increased BMI was an independent preventive factor for major complications after LLR (P = .026, odds ratio: 0.84). The estimated adjusted risk of major postoperative complications decreased with increased BMI in the LLR group, while the risk did not decrease in the OLR group (P for interaction = .048). CONCLUSION: Laparoscopic liver resection is beneficial for obese patients and is superior to OLR.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Influence of a biliary stent in patients with advanced pancreatic cancer treated with modified FOLFIRINOX.

Endoscopic biliary drainage is the recommended 1st-line treatment for malignant biliary obstruction. Although a high incidence of febrile neutropenia has been reported in patients treated with FOLFIRINOX and a biliary stent, it remains unknown whether the biliary stent contributes to patient survival. Thus, we aimed to elucidate the effects of biliary stents on the survival of patients with advanced pancreatic cancer treated with modified FOLFIRINOX (mFFX). We retrospectively reviewed medical charts of patients with advanced pancreatic cancer treated with mFFX between January 2014 and April 2020. We compared the overall survival (OS) of patients with and without biliary stent during mFFX treatment and examined the independent effect on mortality using propensity score matching. Overall, we included 89 patients (stent group, n = 24; non-stent group, n = 65). The proportion of patients with pancreatic head cancer was significantly higher in the stent group than in the non-stent group (P < .01). Stratification analysis in patients with pancreatic head cancer revealed that OS was significantly shorter in the stent group than in the non-stent group (P = .03). After propensity score matching, 19 pairs of patients in each group were analyzed. The stent group revealed a significantly shorter survival than the non-stent group (median OS, 10.3 vs 24.9 months; P < .01). The incidences of febrile neutropenia (P = .01) and biliary tract-related events that required biliary stenting or stent replacement (P < .01) were significantly higher in the stent group than in the non-stent group. Stent insertion was an independent risk factor for overall mortality. Biliary stents may reduce survival in patients with advanced pancreatic cancer. The rate of febrile neutropenia was higher in the stent group than in the non-stent group. There is a need to assess the patient's condition with discretion and develop a treatment strategy with short prognosis in mind after stent insertion.

Development of gallbladder cancer during follow-up of pancreaticobiliary maljunction: a report of two cases.

Pancreaticobiliary maljunction (PBM) is a congenital malformation. The reflux of pancreatic juice into the biliary tract caused by PBM plays a significant role in the development of biliary tract cancers (BTCs), such as gallbladder cancer and cholangiocarcinoma. Previous studies have demonstrated a high incidence of BTC in patients with PBM. However, there are only a few reports of patients who developed BTC after a diagnosis of PBM. We report the cases of two patients who developed gallbladder cancer after being diagnosed with PBM. They had refused treatment and were being managed with follow-up observation alone after the diagnosis of PBM and developed gallbladder cancer after several years of observation. Thus, surgical treatment should be recommended for all patients with PBM in order to prevent the development of BTC. Moreover, long-term, close, regular follow-up is necessary to facilitate the early diagnosis of subsequent BTC in patients with untreated PBM.

The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size.

INTRODUCTION: The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). METHODS: A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. RESULTS: In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. CONCLUSIONS: Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.