Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Double Negativity of MRI-Detected and Pathologically-Diagnosed Extramural Venous Invasion is a Favorable Prognostic Factor for Rectal Cancer.

BACKGROUND: Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. PATIENTS AND METHODS: Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. RESULTS: Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity (p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. CONCLUSIONS: Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

Neoadjuvant Triplet Chemotherapy with Docetaxel, Cisplatin plus 5-Fluorouracil versus Docetaxel, Cisplatin plus S-1 for Advanced Esophageal Squamous cell Carcinoma: Propensity Score Matched Analysis.

INTRODUCTION: This study examines whether neoadjuvant docetaxel, cisplatin plus S-1 (DCS) therapy is superior to docetaxel, cisplatin plus 5-fluorouracil (DCF) therapy for resectable advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients diagnosed with resectable advanced ESCC at our hospital between January 2010 and December 2019 underwent either neoadjuvant DCF therapy or DCS therapy, followed by radical esophagectomy. Prior to August 2014, we usually used neoadjuvant DCF therapy; we then completely transitioned to using neoadjuvant DCS therapy. RESULTS: A total of 144 patients received one of these triplet regimens as neoadjuvant chemotherapy: DCF therapy to 67 patients and DCS therapy to 77 patients. After propensity score matching, 55 patients in each group were selected as matched cohorts. There was no significant difference between the groups in complete response (DCF = 7.3%, DCS = 9.1%) or in partial response (DCF = 45.4%, DCS = 52.7%). The pathological response rate was 23.8% for grade 2 and 18.2% for grade 3 in the DCF group, compared with 30.9% and 14.5% in the DCS group. Independent predictive factors for recurrence-free survival were poor clinical response and pathological response ≤1b. Independent prognostic factors for overall survival were poor clinical response, anastomotic leakage, and pathological response ≤1b. Duration of hospital stays in the DCS group was significantly shorter than those of the DCF group (6.0 vs. 15.0 days, p < 0.001). Expenses of drug and hospitalization for the neoadjuvant chemotherapy in the DCS group were also significantly lower than those of the DCF group (265.7 vs. 550.3 USD, p < 0.001). CONCLUSIONS: Neoadjuvant DCS therapy for resectable advanced ESCC did not result in significantly higher clinical and pathological response than neoadjuvant DCF therapy. However, neoadjuvant DCS therapy for resectable ESCC required comparatively shorter hospital stays and incurred lower costs, making it an attractive therapeutic option.

Impact of sarcopenia on recurrent biliary obstruction after EUS-guided biliary drainage in patients with malignant biliary obstruction.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). METHODS: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. RESULTS: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. CONCLUSION: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer: A Multicenter Study.

OBJECTIVE: The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear. METHODS: In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42). RESULTS: Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery ( P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups. CONCLUSION: PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.

Response Prediction Model of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Retrospective Study.

INTRODUCTION: Atezolizumab plus bevacizumab (ATZ+BV) treatment has become the first-line regimen for unresectable hepatocellular carcinoma (u-HCC). Prediction of response to it might be clinically beneficial. Using peripheral blood parameters, we aimed to construct a prediction model for ATZ+BV treatment. METHODS: Clinical records of 119 patients with u-HCC treated by ATZ+BV were retrospectively analyzed. The primary outcome measurement was defined as any-size reduction at the initial image evaluation. Using baseline values of peripheral blood parameters, a prediction model was constructed by univariate and multivariate logistic regression analysis. Validation was performed internally by bootstrap method. RESULTS: The primary outcome was achieved in 46 patients. Univariate analysis showed that C-reactive protein (CRP), alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were possible predictors. CRP and DCP, and NLR and PLR had correlation (correlation coefficient >0.3), so we used CRP and NLR as representative factors, respectively. Multivariate analysis constructed the following prediction model: Logit = 1.62-0.61×[CRP] -0.38×[Log10AFP] -0.37×[NLR]. Bootstrapped median (95% confidence interval) of coefficients of CRP, Log10AFP, NLR were -0.64 (-1.46 ∼ -0.11), -0.40 (-0.82 ∼ -0.03), and -0.38 (-0.74 ∼ -0.05), respectively. The area under the receiver operating characteristic curve (95% confidence interval) was 0.73 (0.60-0.80). Median overall survival of the favorably and unfavorably predicted groups were 17.0 and 11.0 months (p = 0.03), respectively. DISCUSSION: In patients with u-HCC treated by ATZ+BEV, a prediction model constructed using baseline values of CRP, AFP, and NLR had impact on any-size reduction at the initial image evaluation and on prognosis.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for prediction of pathological response after neoadjuvant chemotherapy in patients with pancreatic cancer.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) plays an important role in the diagnosis of pancreatic lesions. The aim of this study was to evaluate whether CH-EUS is useful for predicting the treatment efficacy of neoadjuvant chemotherapy (NAC) determined by pathological response. METHODS: Patients who underwent CH-EUS before chemotherapy and surgical resection were divided into two groups according to poor (group-P) or rich tumor vascularity (group-R) determined by enhancement pattern on early- and late-phase CH-EUS. The pathological response to chemotherapy was categorized according to Evans' classification. Pathological analysis showing tumor cell destruction (>50 %) defined a good response. RESULTS: Early-phase CH-EUS classified 44 patients into group-R and 50 into group-P, whereas late-phase CH-EUS classified 10 into group-R and 84 into group-P. Early-phase CH-EUS classification resulted in significantly higher numbers of patients with a good response in the rich group (n = 19) than in the poor group (n = 4; P = 0.0015). Multivariate analysis showed that assignment to the rich group was the strongest independent factor associated with chemosensitivity (P = 0.006, hazard ratio = 5.66, 95 % confidence interval: 1.17-19.27). In resectable patients, the enhancement pattern was the only independent factor associated with chemosensitivity (group-P vs. group-R, P = 0.003; HR [95 % CI], 14.59 [1.38-154.38]). Late-phase CH-EUS did not reveal a significant difference between group-P and group-R. CONCLUSIONS: Evaluation of vascular pattern on CH-EUS could be useful for predicting the efficacy of NAC in patients with pancreatic cancer. The enhancement pattern on CH-EUS could be a one of the useful features for determining NAC indications in resectable pancreatic cancer patients.

Impact of zero anastomotic leakage after esophagectomy followed by whole stomach reconstruction for esophageal cancer: prospective cohort study.

PURPOSE: The stomach is the most common organ which is used for reconstruction after esophagectomy for esophageal cancer. It is controversial which is better narrow gastric tube reconstruction or whole stomach reconstruction to prevent anastomotic leakage. METHODS: From August 2022 to March 2023, we started a prospective cohort study of whole stomach reconstruction after esophagectomy. Until then (from January 2018 to July 2022), narrow gastric tube reconstruction was performed as a standard reconstruction. RESULTS: Narrow gastric tube reconstruction and whole stomach reconstruction were performed in 183 patients and 20 patients, respectively. The patient's characteristics were not significantly different between the narrow gastric tube group and the whole stomach group. In particular, for all patients in the whole stomach reconstruction group, retrosternal route and esophagogastrostomy by hand sewn were applied. There were no occurrences of AL through the continuous 20 cases in the whole stomach group, otherwise 42 (22.9%) patients in the narrow gastric group (P = 0.016). Postoperative hospital stays were significantly shorter in the whole stomach group than in the narrow gastric group (21 days vs. 28 days, P < .001). Blood perfusions were evaluated by indocyanine green for all cases, which had very good blood perfusion in all cases. Additionally, quantitative blood perfusion was examined by SPY-QP (Stryker, USA) for one case. Even the edge of the fornix showed more than 90% blood perfusion levels when the antrum was fixed as the reference point. CONCLUSION: Whole stomach reconstruction with excellent blood perfusion is considered to be safe and has the possibility to prevent from occurring AL after esophagectomy for esophageal cancer patients.

Laparoscopic reconstruction in McKeown esophagectomy is a risk factor for postoperative diaphragmatic hernia.

Diaphragmatic hernia is a very rare but high-risk complication after esophagectomy. Although there are many studies on the Ivor Lewis esophagectomy procedure for diaphragmatic hernia, there are fewer studies on the McKeown procedure. The present study aimed to estimate the incidence of diaphragmatic hernia after esophagectomy, describing its presentation and management with the McKeown procedure. We retrospectively evaluated the 622 patients who underwent radical esophagectomy between January 2002 and December 2020 at the Wakayama Medical University Hospital. Statistical analyses were performed to evaluate risk factors for diaphragmatic hernia. Emergency surgery for postoperative diaphragmatic hernia was performed in nine of 622 patients (1.45%). Of these nine patients, one developed prolapse of the small intestine into the mediastinum (11.1%). The other eight patients underwent posterior mediastinal route reconstructions (88.9%), one of whom developed prolapse of the gastric conduit, and seven of whom developed transverse colon via the diaphragmatic hiatus. Laparoscopic surgery was identified in multivariate analysis as the only independent risk factor for diaphragmatic hernia (odd's ratio [OR] = 9.802, p = 0.034). In all seven cases of transverse colon prolapse into the thoracic cavity, the prolapsed organ had herniated from the left anterior part of gastric conduit. Laparoscopic surgery for esophageal cancer is a risk factor for diaphragmatic hernia. The left anterior surface of gastric conduit and diaphragmatic hiatus should be fixed firmly without compromising blood flow to the gastric conduit.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

Contrast-enhanced harmonic endoscopic ultrasonography for predicting the efficacy of first-line gemcitabine and nab-paclitaxel chemotherapy in pancreatic cancer.

BACKGROUND AND AIMS: The purpose of this study was to assess prognosis with different intratumoral vascularity on contrast-enhanced endoscopic harmonic ultrasonography (CH-EUS) in pancreatic cancer patients receiving chemotherapy. METHODS: Patients with unresectable pancreatic cancer who underwent CH-EUS before first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX) therapy were classified into four groups according to vascularity on the early and late phases of contrast enhancement: "Group A″, poor on both phases; "Group B″, rich and poor on the early and late phases, respectively; "Group C″, poor and rich on the early and late phases; "Group D″, rich on both phases. Subgroups were compared in terms of progression-free survival (PFS) and overall survival (OS). We also assessed whether the results with CH-EUS correlate with those of contrast-enhanced computed tomography (CE-CT). RESULTS: On CH-EUS, 57, 64, 0, and 24 patients were classified into Groups A, B, C, and D, respectively. The median PFS of patients in groups A, B, and D was 3.9, 7.6, and 10.8 months, respectively, and the median OS were 9.5, 13.1, and 18.6 months, respectively. Both PFS and OS were longest in Group D (p < 0.001 and p < 0.001, respectively). The results of CE-CT were consistent with those of CH-EUS, and there was a correlation between CE-CT and CH-EUS. CONCLUSIONS: Evaluation of intratumoral vascularity by CH-EUS may be useful for predicting the efficacy of chemotherapy in patients with pancreatic cancer. A better response to GEM and nab-PTX can be expected in patients showing rich vascularity at both the early and late phases.

Impact of sarcopenia on prediction of progression-free survival and overall survival of patients with pancreatic ductal adenocarcinoma receiving first-line gemcitabine and nab-paclitaxel chemotherapy.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. Here, we assessed the effects of sarcopenia on progression-free survival (PFS) and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent treatment with first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX). METHODS: The study enrolled patients with unresectable PDAC who underwent chemotherapy between April 2016 and May 2020. The skeletal muscle index (SMI) at the third lumbar spine level (L3) was calculated from computed tomography (CT) images. Propensity score analysis was used to compare PFS and OS in the sarcopenia and non-sarcopenia groups. Univariate and multivariate analyses were performed to determine variables significantly associated with prognosis. RESULTS: Of the 176 patients who received first-line GEM and nab-PTX, 84 were selected and divided into two groups of 42 (the sarcopenia and the non-sarcopenia groups) by propensity score matching. The median PFS of the sarcopenia and the non-sarcopenia groups was 5.0 and 8.0 months, respectively (p = 0.004). The median OS was 10.3 and 18.1 months, respectively (p = 0.001). Multivariate analyses revealed that sarcopenia was an independent prognostic factor for PFS and OS (p = 0.004, p = 0.001, respectively). The rates of major grade 3 or 4 AEs were significantly higher in the sarcopenia group (p = 0.008). CONCLUSIONS: Sarcopenia is an independent indicator of a poor prognosis in patients with PDAC treated with first-line GEM and nab-PTX.

Radiographic Splenic Artery Involvement Is a Poor Prognostic Factor in Upfront Surgery for Patients with Resectable Pancreatic Body and Tail Cancer.

PURPOSE: The prognostic impact of radiographic splenic vessel involvement in pancreatic cancer remains unclear. We evaluate its oncological significance in resectable pancreatic body/tail cancer. PATIENTS AND METHODS: We retrospectively review 102 cases of resectable pancreatic cancer and 51 of borderline resectable pancreatic cancer (BRPC) who underwent pancreatectomy for pancreatic body/tail cancer. Resectable pancreatic body/tail cancer was classified into one of three categories based on radiographic splenic vessel involvement. RESULTS: Among 102 cases of resectable pancreatic cancer, 37 (36.3%), 35 (34.3%), and 30 cases (29.4%) were classified as no splenic vessel involvement (Rnone), splenic vein involvement (RV), and splenic artery involvement (RA), respectively. Disease-free survival (DFS) among patients with Rnone, RV, RA, and BRPC was 58.5, 18.4, 10.8, and 9.2 months, respectively. Patients with RV and RA had significantly poorer DFS than patients with Rnone (P = 0.010, P < 0.001, respectively). Median survival among Rnone, RV, RA, and BRPC was 80.6, 23.4, 15.1, and 21.3 months, respectively. Patients with RV and RA had significantly poorer survival than patients with Rnone (P = 0.001, P < 0.001, respectively) and had short survival similar to that of those with BRPC. Multivariate Cox proportional hazard analysis detected preoperative CA19-9 ≥ 37 IU/L, radiologic splenic vein involvement, radiologic splenic artery involvement, intraoperative bleeding ≥ 500 ml, transfusion, positive washing cytology, and noncompletion of adjuvant therapy as independent prognostic factors. CONCLUSIONS: Radiographic splenic artery involvement is a poor prognostic factor in resectable pancreatic body/tail cancer and may have a role in stratification of treatment strategy.

Division of the pancreas at the neck reduces postoperative pancreatic fistula in laparoscopic distal pancreatectomy: Comparison of pancreatic division at the body.

BACKGROUND: objectives: During laparoscopic distal pancreatectomy (LDP), the optimal site for pancreatic division with consideration of postoperative pancreatic fistula (POPF) is unclear. We evaluate which site of pancreatic division, neck or body, has better outcomes after LDP. METHODS: This was a retrospective, observational study. LDP was performed in 102 consecutive patients between December 2009 and May 2020. After excluding 14 patients with pancreatic division at tail, 88 patients (pancreatic division at neck n = 46, at body n = 42) were included in this study. Short- and long-term outcomes after LDP were compared between pancreatic division at neck and body. RESULTS: The pancreatic transection site was thicker at body than at neck (17.5 vs. 11.9 mm, P < 0.001), although there were no significant differences of pancreatic texture and pancreatic duct size. The Grade B/C POPF rate was significantly higher when the pancreas was divided at body than when divided at neck (21.4 vs. 6.5%, P = 0.042). We found no significant differences between pancreatic division at neck and body in residual pancreatic volume (34.0 vs. 34.8 ml, P = 0.855), incidence of new-onset or worsening diabetes mellitus more than six months after LDP (P = 0.218), or body weight change (six-month: P = 0.116, one-year: P = 0.108, two-year: P = 0.195, tree-year: P = 0.131, four-year: P = 0.608, five-year: P = 0.408). CONCLUSION: This study suggests that the pancreatic division at neck might reduce the Grade B/C POPF incidence after LDP, compared to division at body. A potential reason is that the pancreas at body is thicker than that at neck. However, further large-scale studies are necessary to confirm our results.

Value of contrast-enhanced harmonic endoscopic ultrasound for diagnosing hepatic metastases of pancreatic cancer: A prospective study.

BACKGROUND AND AIMS: This study aimed to compare contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) with fundamental B-mode endoscopic ultrasonography (EUS) and contrast-enhanced computed tomography (CE-CT) for the diagnosis of left hepatic lobe metastases of pancreatic adenocarcinoma. METHODS: In this single-center prospective study, CE-CT, EUS, and CH-EUS were performed to detect left hepatic lobe metastases in patients with pancreatic adenocarcinoma, and the detection rates were compared between EUS plus CH-EUS and the other two modalities. Subgroup comparisons of between-modality detection rate were performed in patients with only metastases of <10 mm. The number of pancreatic adenocarcinoma patients whose clinical stage and treatment strategy were changed because of EUS plus CH-EUS findings was also assessed. RESULTS: Thirty-one patients were diagnosed with left hepatic lobe metastases. For overall detection of left hepatic lobe metastases, EUS plus CH-EUS had significantly higher accuracy (94.3%) than CE-CT (86.7%) and EUS alone (87.6%) (P = 0.021 and P = 0.020, respectively). For detection of left hepatic lobe metastases < 10 mm, EUS plus CH-EUS (93.3%) was significantly superior to CE-CT (84.4%) and EUS alone (85.6%) (P = 0.021 and P = 0.020, respectively). In five of the 11 patients in whom only CH-EUS allowed detection of hepatic metastases, the stage and/or treatment strategy of the pancreatic adenocarcinoma was changed after CH-EUS. CONCLUSION: This study demonstrated that EUS plus CH-EUS has advantages over CE-CT and EUS alone with regard to the accuracy of detecting left hepatic lobe metastases, particularly small hepatic metastases and accurate staging.

Computed tomography findings for predicting the future occurrence of pancreatic cancer: value of pancreatic volumetry.

BACKGROUND: The features of pancreatic parenchyma that tend to progress towards pancreatic cancer (PC) are unknown. We performed volumetry of the pancreas in PC patients using computed tomography (CT) scans acquired before detection of PC, and investigated whether CT findings of pancreatic parenchyma could predict the future occurrence of PC. METHODS: Between April 2009 and March 2017, a total of 3769 patients underwent abdominal contrast-enhanced CT, the scans of which were archived as digital images. Among them, 15 PC patients underwent abdominal CT 6-120 months before diagnosis of PC. This retrospective study compared the 15 PC patients (PC group) with 15 propensity score-matched subjects without PC (non-PC group). Pancreatic volumetry and radiological findings were compared between the two groups. RESULTS: There were significant differences between the PC and non-PC groups in the volume of the main pancreatic duct (MPD) plus any cystic lesion (P = 0.007), volume of the MPD plus any cystic lesion/body surface area (BSA; P = 0.009), MPD diameter (P = 0.011), and MPD diameter/BSA (P = 0.013). Univariate analysis revealed volume of MPD plus any cystic lesion/BSA ≥ 0.53 mL/m2 (odds ratio [OR] 38.50, P = 0.002), volume of pancreatic parenchyma/BSA < 27.0 mL/m2 (OR 12.25, P = 0.030), and MPD diameter/BSA ≥ 1.0 mm/m2 (OR 13.00, P = 0.006) as significant risk factors for PC. CONCLUSIONS: Quantification of the volume of MPD plus any cystic lesion/BSA, volume of pancreatic parenchyma/BSA, and MPD diameter/BSA on pre-diagnosis CT were useful for predicting the future occurrence of PC.

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

OBJECTIVES: This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). METHODS: Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. RESULTS: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. CONCLUSIONS: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Prognostic Analysis of Hepatocellular Carcinoma With Hepatitis C Virus Infection Using Epithelial-Mesenchymal Transition Gene Profiles.

BACKGROUND: Epithelial-mesenchymal transition genes have prognostic influence on hepatocellular carcinoma (HCC). Previously, the following four epithelial-mesenchymal transition-related genes were considered to be significantly influential: E-cadherin (CDH1), inhibitor of DNA binding 2 (ID2), matrix metalloproteinase 9 (MMP9), and transcription factor 3 (TCF3). A prognostic prediction model, NRISK4 = (-0.333 × [CDH1] - 0.400 × [ID2] + 0.339 × [MMP9] + 0.387 × [TCF3]) was constructed, but from patients with HCC with predominantly hepatitis B virus infection. We therefore aim to validate if this model also fits patients with HCC and hepatitis C virus (HCV) infection. METHODS: We collected HCC tissue samples from 67 patients with HCV infection. Discrimination of the NRISK4 was re-estimated using receiver operating curve analysis and we redefined the appropriate cutoff value. Using this cutoff value, patients were divided into two groups (high/low risk patients) and we compared their clinicopathological factors and prognosis. RESULTS: Area under the curve of NRISK4 prediction was 0.70 and an appropriate cutoff value was 3.19 in this cohort. Patients were divided into high- (n = 25) and low-risk (n = 42) patients for prognosis. There were no significant differences in tumor factors between the two groups. Cancer-specific survival rates at 5 y after surgery on high- and low-risk patients were 45% and 68%, respectively (P = 0.02). At 2 y after surgery, recurrence rates were 68% and 37% among high- and low-risk patients, respectively (P = 0.01). Aggressive recurrences were highly observed in the high-risk patients (P = 0.01). CONCLUSIONS: NRISK4 model could also successfully validate prognosis of patients with HCC with HCV infection similarly to in the previous report of patients with hepatitis B virus infection, especially in the early period after surgery.