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Background/purpose Aeromonas hydrophila can cause lethal infectious complications after surgery. There have been no large cohort studies of this specific to the hepato-biliary-pancreatic (HBP) field. We investigate the postoperative influence of A hydrophila infection after HBP surgery. Methods We retrospectively reviewed patients who underwent HBP surgery between 2008 and 2017 at eight university hospitals. Patients with A hydrophila isolation during perioperative management were extracted, and their postoperative courses were investigated. Results Bacterial culture examination of 10 074 patients was performed as perioperative management. Among them, 76 patients (0.75%) had A hydrophila isolation, most of whom underwent pancreatoduodenectomy (n = 38) or hepatectomy with biliary reconstruction (n = 14). There were seven mortalities after these two procedures (13.5%), five within 3 days after the onset of infection. Bile (n = 48) and abdominal drainage fluid (n = 29) were major sites of A hydrophila isolation. Typical prophylactic antibiotics, cefazolin or flomoxef, were mostly resistant. There was no mortality among patients that received sensitive antibiotics prophylactically. Conclusions Isolation of A hydrophila was low in our cases of HBP surgery, but the condition of some patients deteriorated rapidly by this infection. Although there could be several bacterial infections during management of HBP surgery, A hydrophila should not be overlooked. Preparation of appropriate prophylactic antibiotics may prevent or reduce mortality.

The prognostic impact of radiographic splenic vessel involvement in pancreatic cancer remains unclear. We evaluate its oncological significance in resectable pancreatic body/tail cancer. 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. 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

BackgroundRhabdomyolysis may develop into acute kidney injury (AKI), a life-threatening complication. Obese people are at risk for rhabdomyolysis due to prolonged immobilization. However, there are only a few reports of rhabdomyolysis-induced AKI due to prolonged immobilization after falls in morbidly obese people. Myoglobin is a causative compound for rhabdomyolysis-induced AKI, but the lack of treatments targeting its mechanism is a problem.Case presentationTwo morbidly obese women (body mass index > 40.0 kg/m2) who fell on the floor at home and remained in the same posture for more than 12 h developed rhabdomyolysis-induced AKI. Both patients received aggressive fluid resuscitation but required hemodialysis because of persistent oliguria. They underwent 11 and 2 intermittent hemodialysis (HD) sessions with a conventional polymethylmethacrylate (PMMA) high-flux dialyzer, respectively, and their renal functions returned to baseline after withdrawal of HD.ConclusionsWe should be aware that morbidly obese people are at risk for rhabdomyolysis-induced AKI due to prolonged immobilization, such as after falls. At present, prophylactic renal replacement therapy (RRT) is not recommended for rhabdomyolysis. We need to reevaluate whether RRT using the appropriate membranes to effectively remove myoglobin including the PMMA membrane can improve the renal outcome in patients with rhabdomyolysis-induced AKI.

Diabetes mellitus (DM) is now recognized as one of the risk factors for Alzheimer's disease (AD), and the disease‐modifying effects of anti‐diabetic drugs on AD have recently been attracting great attention. Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of anti‐diabetic drugs targeting the SGLT2/solute carrier family 5 member 2 (SLC5A2) protein, which is known to localize exclusively in the brush border membrane of early proximal tubules in the kidney. However, recent data suggest that it is also expressed in other tissues. In the present study, we investigated the expression of SGLT2/SLC5A2 in human and mouse brains. Immunohistochemical staining of paraffin sections from autopsied human brains and C3H/He mouse brains revealed granular cytoplasmic immunoreactivity in choroid plexus epithelial cells and ependymal cells. Immunoblot analysis of the membrane fraction of mouse choroid plexus showed distinct immunoreactive bands at 70 and 26 kDa. Band patterns around 70 kDa in the membrane fraction of the choroid plexus were different from those in the kidney. Reverse transcription‐polymerase chain reaction analysis confirmed the expression of Slc5a2 mRNA in the mouse choroid plexus. Our results provide in vivo evidence that SGLT2/SLC5A2 is expressed in cells facing the cerebrospinal fluid, in addition to early proximal tubular epithelial cells. These findings suggest that SGLT2 inhibitors may have another site of action in the brain. The effects of SGLT2 inhibitors on brain function and AD progression merit further investigation to develop better treatment options for DM patients.

Although hyperuricemia has been shown to be associated with the progression of cardiovascular disorder and chronic kidney disease (CKD), there is conflicting evidence as to whether xanthine oxidase (XO) inhibitors confer organ protection besides lowering serum urate levels. In this study, we addressed the cardio-renal effects of XO inhibition in rodent CKD model with hyperuricemia. Sprague-Dawley rats underwent 5/6 nephrectomy and received a uricase inhibitor oxonic acid for 8 weeks (RK + HUA rats). In some rats, a XO inhibitor febuxostat was administered orally. Compared with control group, RK + HUA group showed a significant increase in albuminuria and renal injury. Febuxostat reduced serum uric acid as well as urinary albumin levels. Histological and immunohistochemical analysis of the kidney revealed that febuxostat alleviated glomerular, tubulointerstitial, and arteriolar injury in RK + HUA rats. Moreover, in the heart, RK + HUA showed individual myofiber hypertrophy and cardiac fibrosis, which was significantly attenuated by febuxostat. We found that renal injury and the indices of cardiac changes were well correlated, confirming the cardio-renal interaction in this model. Finally, NF-E2-related factor 2 (Nrf2) and the downstream target heme oxygenase-1 (HO-1) protein levels were increased both in the heart and in the kidney in RK + HUA rats, and these changes were alleviated by febuxostat, suggesting that tissue oxidative stress burden was attenuated by the treatment. These data demonstrate that febuxostat protects against cardiac and renal injury in RK + HUA rats, and underscore the pathological importance of XO in the cardio-renal interaction.

The presence of Barrett’s mucosa in the esophageal remnant is a result of post-esophagectomy anastomotic site exposure to gastric acid and is regarded as a human model of Barrett’s esophagus onset. Here, we attempted to clarify the relationship between duodenogastric reflux and formation of columnar epithelium by following the changes over time after esophagectomy. A total of 96 patients underwent esophagectomy due to superficial cancer from April 2000 to March 2018 were included in this study. Cases were divided into two groups according to the reconstruction technique after esophagectomy as either the gastric pull-up (Ga) group and ileocolonic interposition (Ic) group. Previously obtained endoscopic pictures of the cases were reviewed retrospectively and chronologically. There were 24 cases of columnar epithelium in the Ga group (42%) and 1 in the Ic group (2.6%) (P

Background: Anastomotic leakage (AL) is arguably the most troublesome complication of anterior resection (AR). In recent years, however, indocyanine green (ICG) fluorescence imaging has been recent...

Na-K-2Cl cotransporter 2 (NKCC2) in thick ascending limb (TAL) in the kidney plays a central role in tubuloglomerular feedback (TGF) system by sensing NaCl delivery to the distal tubules. Although accumulating data indicate that dysregulated TGF contributes to the progression of diabetic complications, the regulation of NKCC2 in diabetes mellitus (DM) remains unclear. We here show that NKCC2 is overactivated via a vasopressin receptor 2 (V2R)-dependent mechanism in db/db mice, a mouse model of obese DM. Compared with db/+ mice, we found that both aquaporin 2 and NKCC2 levels were significantly increased in the kidney in db/db mice. Immunohistochemical analysis of V2R and NKCC2 in the kidney demonstrated that V2R is present in the TAL, as well as in the collecting duct. Moreover, the administration of tolvaptan, a selective V2R antagonist, sharply decreased aquaporin 2 and NKCC2 in db/db mice, confirming the causal role of V2R signaling in NKCC2 induction in this model. Although tolvaptan reduced aquaporin 2 abundance also in db/+ mice, its effect on NKCC2 was modest compared with db/db mice. In total kidney lysates, uromodulin expression was not altered between db/+ and db/db mice, suggesting that V2R signaling alters NKCC2 without altering uromodulin levels. These data implicate the dysregulation of NKCC2 in the pathophysiology of type 2 DM, and underscore the complex nature of fluid volume disorders in diabetic kidney disease.

Percutaneous endoscopic gastrostomy (PEG) is a minimally invasive procedure providing nutritional benefits to malnourished patients. Although a past history of celiotomy is not a contradiction for PEG construction, this procedure is rarely undertaken in post-esophagectomy patients, for two reasons: anatomically limited gastric spaces and high susceptibility to pulmonary aspiration. To overcome these limitations, we developed an original method of introducing PEG with jejunal extension for esophagectomized patients with retrosternal gastric pull-up reconstruction. The procedures were as follows: (1) confirmation of endoscopic transillumination of the antrum; (2) test puncture of the antral wall and subsequent gastropexy using a double-needle device; (3) insertion of a needle jejunostomy catheter into the antrum; (4) direct catheter cannulation to the pylorus and introduction of a feeding tube into the jejunum. We successfully carried out this procedure in three male patients (70-78 years old): two suffering from repetitive aspiration pneumonia and one with extensive recurrence of esophageal carcinoma. The operative times ranged 15-50 min. There were no PEG-associated complications. Of note, none of the patients experienced aspiration pneumonia after PEG construction. Our novel method appears to be a promising approach to managing esophagectomized patients because of its feasibility and the potential to prevent postoperative pulmonary aspiration.

Recurrent esophageal cancer after radical therapy usually is thought to be incurable and treated with palliative-intent systemic therapy. However, it is empirically known that surgical resection may be effective for selected patients, although no consensus exists on the efficacy of surgery for recurrent esophageal cancer. This study sought to identify a group of patients for whom surgical resection is considered effective. The study enrolled 206 patients at a single center who had recurrence after radical therapy for esophageal cancer. Prognostic factors after recurrence were identified, and efficacy of surgery was analyzed according to whether the recurrent lesions were oligometastases (i.e., ≤ 5 lesions in a single domain) or not. In the multivariate analysis, oligometastatic presentation was the only factor associated with survival after recurrence (hazard ratio 6.29; 95% confidence interval, 4.10–9.71). The actuarial survival rates for the patients with oligometastases were 59.5% at 3 years and 51.7% at 5 years. The survival rates at 3 and 5 years were significantly higher for the patients who underwent resection (64.3% and 55.6%, respectively) than for those who did not (both 100%) and for the patients with multiple metastases (9.8% and 0%, respectively). The survival rates for the patients who had oligometastases without resection were comparably lower than for the patients with multiple metastases. Oligometastatic presentation at recurrence was associated with better survival outcomes for the patients who experienced recurrence after radical treatment for esophageal cancer, and surgical resection could be a choice of treatment for this group of patients.

Constrictive pericarditis is a rare condition characterized by clinical signs of right heart failure subsequent to the loss of pericardial compliance. We report a case of constrictive pericarditis due to pericardial metastasis in a patient with a history of esophageal squamous cell carcinoma that had a pathological complete response (pCR) to preoperative chemoradiotherapy. A 66-year-old woman was referred to our division for the treatment of advanced esophageal cancer. Video-assisted thoracoscopic surgery esophagectomy (VATSE) with 3-field lymphadenectomy was performed after neoadjuvant chemoradiotherapy (NAC-CRT). Pathological examination revealed no residual tumor, lymph node metastasis, lymphatic invasion, or vessel invasion. The histological treatment effect of the chemoradiotherapy was pathological complete response (pCR). Five months after surgery, the patient was admitted to a nearby hospital for the treatment of acute pericarditis. However, a month after admission, acute pericarditis progressed to constrictive pericarditis, and she was referred to our hospital for further management. Subsequently, urgent pericardiectomy was performed through a lower half sternotomy incision. After surgery, heart failure improved for a while but worsened again. The patient died 7 days after the surgery. Pathological examination of the resected pericardium revealed evidence of metastasis from squamous cell carcinoma of the esophagus. An autopsy revealed the spread of esophageal cancer to the bilateral pleura, right lung, pericardium, diaphragm, soft tissue surrounding the tracheal bifurcation, and bilateral hilar lymph nodes. Similarly, tumor cells were found in the lymphatic vessels of the pericardium and pleura. Even if pCR is achieved with NAC-CRT, as in our case, esophageal cancer may metastasize and present as constrictive pericarditis within a short period; therefore, careful patient follow-up is essential.

Background and study aimsTreatment of superficial cancer in the remnant esophagus after esophagectomy is highly invasive, and early detection and minimally invasive treatment are considered necessary. We performed endoscopic submucosal dissection (ESD) for superficial cancer in the remnant esophagus and evaluated its safety and efficacy.Patients and methodsThis study involved 28 patients (33 lesions) who underwent ESD for superficial esophageal cancer in the remnant esophagus after esophagectomy from January 2007 to December 2018. The safety and efficacy of ESD were evaluated retrospectively.ResultsThe average age of all 28 cases (24 men and 4 women) was 69.6 ± 5.3 years. The average duration of ESD from esophagectomy was 2826 ± 2197 days. Twenty-six of the 28 cases were treated under general anesthesia. All 33 lesions were resected en bloc. The complete resection rate was 81.8% (27/33). There were no serious adverse events such as perforation, intraoperative bleeding, postoperative bleeding, and pneumonia. The overall survival rate was 78.6% (22/28) with a mean observation period post-ESD of 1793 ± 1148 days. There was no local recurrence, lymph node metastasis, or distant metastasis.ConclusionsThe ESD procedure for superficial cancer of the remnant esophagus was performed with high rate of complete resection without serious complications. In addition, there was no local recurrence and lymph node metastasis, and so ESD for superficial cancer of the remnant esophagus can be considered a safe and effective treatment.

Background Patients with esophageal cancer often have depressed mood and fear of metastasis and death. Esophagectomy is an invasive procedure with a high incidence of complications. The objective of this study was to examine the association between stress-coping style and psychological distress at different points in the treatment of esophageal cancer. Methods Of 152 consecutive patients treated for esophageal cancer at the outpatient clinic at Toranomon Hospital between April 2017 and April 2019, 102 met the eligibility criteria for this study. Questionnaires designed to identify psychological distress and stress-coping styles were longitudinally administered at 5 time points, from the initial outpatient consultation to 3 months after esophagectomy. Results The coping styles ‘fighting spirit’ (OR 0.836, 95% CI 0.762–0.918; p

This study aims to clarify the risk factors of clinically relevant pancreatic fistula after early drain removal with higher drain fluid amylase after pancreaticoduodenectomy. Clinical evaluation of early drain removal with a higher drain fluid amylase after pancreaticoduodenectomy has been controversial. The safety and effectiveness have not been sufficiently examined.Between 2015 and 2020, prophylactic surgical drains were prospectively removed on postoperative day 4 regardless of drain fluid amylase level in 364 study-eligible patients who underwent pancreaticoduodenectomy. Patients were classified according to drain fluid amylase on postoperative day 1: 281 patients with drain fluid amylase4,000 U/L, and 83 patients with drain fluid amylase ≥4,000 U/L.Clinically relevant pancreatic fistula occurred in 40 of 364 enrolled patients (11.0%). In the entire cohort, male, positive postoperative day 1 drain fluid culture, and postoperative day 1 drain fluid amylase ≥4,000 U/L were independent risk factors for clinically relevant pancreatic fistula after early drain removal. When stratifying by 4,000 U/L of postoperative day 1 drain fluid amylase, the rate of clinically relevant pancreatic fistula in postoperative day 1 drain fluid amylase4,000 U/L was significantly lower than that in postoperative day 1 drain fluid amylase ≥4,000 U/L (4% vs 35%, P.001) after early drain removal. Moreover, in postoperative day 1 drain fluid amylase4,000 U/L, positive postoperative day 1 drain fluid culture did not develop clinically relevant pancreatic fistula after early drain removal. However, in postoperative day 1 drain fluid amylase ≥4,000 U/L, multivariate analysis clarified that positive postoperative day 1 drain fluid culture was the only independent risk factor of clinically relevant pancreatic fistula after early drain removal (odds ratio 26.27, 95% confidence interval 5.59-123.56, P = .001).Positive drain fluid culture on postoperative day 1 might predict clinically relevant pancreatic fistula in early drain removal with a higher drain fluid amylase.

BACKGROUND: First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODS: In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTS: A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P

This study aimed to determine the risk factors for severe postoperative complications in patients undergoing pure laparoscopic liver resection (LLR) for tumors in the right posterosuperior (PS) segments.The study included 289 patients who underwent parenchyma-sparing pure LLR for tumors in the right PS segments at eight treatment centers between January 2009 and December 2019.Multivariate analysis revealed tumor size ≥3 cm (P = .016), segmentectomy (P = .044), and liver cirrhosis (P = .029) as independent risk factors for severe postoperative complications. The severe complication rates (2.7% vs 12.1%, P = .0025), median intraoperative blood loss (100 mL vs 150 mL, P = .001), and median operation time (248 minutes vs 299.5 minutes, P = .0013) were lower in the patients without all these three risk factors than those with at least one risk factor. The median length of postoperative hospital stay was shorter in patients with no risk factors than those with at least one risk factor (9 days vs. 10 days, P = .001).Tumor size ≥3 cm, segmentectomy, and liver cirrhosis were the risk factors for severe postoperative complications after parenchyma-sparing pure LLR for tumors in the right PS segments. Patients without these three risk factors would be appropriate candidates for safely performing parenchyma-sparing pure LLR in the right PS segments at the outset.

Background: Non-invasive biomarkers detected preoperatively are still inadequate for treatment decision making for patients with intrahepatic cholangiocarcinoma (ICC). In this study, we analyzed preoperative findings to establish a novel preoperative staging system (PRE-Stage) for patients with ICC. Methods: The clinical data of 227 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals were analyzed. Results: Cox proportional hazards regression analysis of survival revealed that a CRP–albumin–lymphocyte index < 3, central tumor location, and CA19-9 level > 40 U/mL were prognostic factors among the preoperatively obtained clinical findings (hazard ratios (HRs) of all three factors for disease-specific survival (DSS) and disease-free survival (DFS: 2.4–3.3 and 1.7–2.9; all p < 0.05). The PRE-Stage was developed using these three prognostic factors, and it was able to significantly predict DSS and DFS when the patients were stratified into four stages (p < 0.05). In addition, the PRE-Stage resulted in similar HRs as those of the Liver Cancer Study Group of Japan (LCSGJ) stage (HRs for DSS: PRE-Stage, 1.985; LCSGJ stage, 1.923; HRs for DFS: LCSGJ stage, 1.909, and PRE-Stage, 1.623, all p < 0.05). Conclusion: The PRE-Stage demonstrated similar accuracy in predicting the prognosis of ICC as that of the LCSGJ stage, which is based on postoperative findings. The PRE-Stage may contribute to appropriate treatment decision making.

Background The effects of therapeutic hypothermia (TH) on renal function are not widely reported, especially in longer-term animal models. The hypothesis of this study was that TH of the kidneys of hypoxic-ischemic newborn piglets would reduce pathological renal fibrosis. Methods Twenty-five newborn piglets obtained within 24 h of birth were classified into a Control group (n = 5), hypoxic insult with normothermia (HI-NT) group (n = 12), and hypoxic insult with TH (HI-TH) group (33.5°C ± 0.5°C for 24 h; n = 8). Five days after the insult, all piglets were sacrificed under deep anesthesia by isoflurane inhalation. The kidneys were perfused with phosphate-buffered paraformaldehyde and immersed in formalin buffer. Territory fibrosis was studied and scored in the renal medulla using Azan staining. Results Fibrosis area scores (mean ± standard deviation) based on Azan staining were 1.00 ± 0.46 in the Control group, 2.85 ± 0.93 in the HI-NT group, and 3.58 ± 1.14 in the HI-TH group. The fibrosis area of the HI-NT and HI-TH groups was larger than that of the Control. The HI-NT and HI-TH groups were not statistically different. Conclusion Renal fibrosis is affected by perinatal asphyxia and cannot be prevented by TH, based on histopathological findings.

Simple Summary For 657 cases of segment or less repeat liver resection with results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery, the indicators were compared before and after surgery. There were 268 open repeat after open and 224 cases laparoscopic repeat after laparoscopic liver resection. The background factors and liver functional indicators before and after surgery, and the changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Though laparoscopic group had poorer performance status and liver function, changes of the values and overall survivals were similar between both groups. Plasma levels of albumin and bilirubin and ALBI score could be the liver functional indicators for liver functional deterioration after liver resection. The laparoscopic group with poorer conditions showed a similar deterioration of liver function and overall survival to the open group. Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.

Indocyanine green (ICG) fluorescence angiography is being increasingly performed intraoperatively to detect restricted blood flow intraoperatively for the prevention of postoperative organ ischemia and anastomotic leakage. This is the first case report of simultaneous laparoscopic distal gastrectomy (LDG) and spleen-preserving distal pancreatectomy (LSPDP) involving ICG angiography use to avoid the remnant stomach ischemia.A 55-year-old man was diagnosed with early cancer of the stomach body and intraductal papillary mucinous neoplasms of the pancreatic tail. We performed simultaneous LDG with D2 dissection and LSPDP to conserve the gastrosplenic ligament and preserve blood supply to the remnant stomach. Intraoperatively, blood flow to the remnant stomach was visualized using ICG fluorescence angiography, after which Roux-en-Y reconstruction was performed. There was no perioperative remnant stomach ischemia.Despite the preserved splenic artery and vein, complete splenic infarction occurs after LSPDP possibly due to thrombus formation during surgical procedures. In this patient, we conserved the gastrosplenic ligament for the short gastric artery, which supplied blood to the remnant stomach; however, remnant stomach ischemia may occur. Therefore, we performed ICG fluorescence angiography during this operation to ensure that sufficient blood supply to the remnant stomach was maintained.Our experience demonstrates that ICG angiography may be useful for the prevention of remnant stomach ischemia.

We aimed to clarify the association between frailty evaluated using the clinical frailty scale (CFS) and outcomes in elderly patients with esophageal squamous cell carcinoma.We retrospectively included 67 patients (aged ≥ 75 years) diagnosed with esophageal squamous cell carcinoma (tumor depth ≥ m3) between 2011 and 2016. The patients were retrospectively evaluated and categorized according to their CFS scores (1-7) and divided into non-frailty (scores 1-2) and frailty groups (scores 3-7). Postoperative complications, 5 year survival rate, and prognostic risk factors were analyzed.Significant differences in performance status, American Society of Anesthesiologists-Physical Status score, Charlson comorbidity index, and treatment type were observed between the two groups. Thirty-six patients underwent surgery, and morbidities with Clavien-Dindo grades ≥ II and ≥ IIIa were found in 72.2 and 47.2% of the patients, respectively. The remaining 31 patients underwent endoscopic resection and/or chemo (radio) therapy. The morbidity rate did not differ between the two groups. The 5 year survival rate was 75.3% overall and 92.7 and 60.8% in patients in the non-frailty and frailty groups, respectively (p = 0.007). Multivariate analysis revealed that frailty and cStage ≥ II were independent risk factors of overall survival (p = 0.005 and p = 0.013, respectively) and disease-specific survival (p = 0.048 and p = 0.027, respectively).Frailty greatly impacts the prognosis of elderly patients with esophageal cancer, regardless of surgical or nonsurgical treatment. The CFS score could be a useful prognostic predictor.

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration., Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Evidence showing the functional significance of the choroid plexus is accumulating. Although it is clinically well-known that calcification is frequently seen in the choroid plexus of aged human brains, it is unclear why calcification occurs in the aged choroid plexus and what exert effects on the calcification has. In this study, immunohistochemical localizations of collagens and other molecules related to fibrosis or calcification were investigated on the choroid plexus of autopsied human brains. Densely fibrous or calcified materials were located in the stroma just below the epithelial cells of the choroid plexus of all human brains examined. Immunoreactivity for collagen type I was identified in the stroma just below the epithelial cells, consistent with the densely fibrous or calcified area, whereas that for collagen type III was observed in almost all stroma other than the densely fibrous or calcified areas. Linear or membranous immunoreactivity for collagen type IV was intermittently localized on the epithelium-facing side of the materials, suggesting an injured basement membrane. In addition, clear immunoreactivity for osteopontin was localized on the epithelium-facing side of the fibrous or calcified materials as well as in the cytoplasm of epithelial cells. These findings indicate that collagen type I exists in contact with osteopontin in and around the densely fibrous or calcified materials in the choroid plexus. They suggest that the densely fibrous or calcified materials are deposited in the subepithelial stroma just below an injured basement membrane of epithelial cells via the collagen type I and osteopontin.

The potential benefits of pancreatectomy with major arterial resection have been studied in the past, but findings remain controversial. Pancreatic neck/body cancer (PNBC) involving arteries frequently requires combined resection of the pancreas, artery and portal vein.Nine prospectively-registered consecutive patients with PNBC were enrolled, all underwent pancreatoduodenectomy with common hepatic artery en-bloc resection (PD-CHAR). We investigated the safety of PD-CHAR by blood flow evaluation with intraoperative indocyanine green fluorescence imaging in reconstructed vessels/organs.Among patients who underwent PD-CHAR, there was no severe morbidity. Artery/portal vein combined resection and reconstruction was performed in all patients. Four (44%) patients had pathological positivity for cancer cell invasion into the nerve plexus of artery at the site of radiographic artery involvement, although one (11%) was diagnosed with pathological artery involvement.PD-CHAR following neoadjuvant therapy might be feasible for PNBC without severe postoperative complications. Survival benefits in PNBC should be confirmed in further studies.

As the malignant potential of main duct (MD-) type intraductal papillary mucinous neoplasm (IPMN) has been discussed together with Mixed-type in most previous studies, the malignant potential of pure MD-type IPMN remains unclear. This study evaluated the specific characteristics and predictors of high-grade dysplasia (HGD) and invasive intraductal papillary mucinous carcinoma (IPMC) for pure MD-type IPMN.From 1,100 patients with IPMN, this study includes 387 patients that underwent surgery. We evaluated the specific characteristics of pure MD-type IPMN by comparing clinicopathological factors between MD-type (n = 79) and branch duct (BD-) type (n = 146) or Mixed-type IPMN (n = 162), and predictors of HGD/invasive IPMC in pure MD-type IPMN.The rate of HGD/invasive IPMC was significantly higher in MD-type than in BD-type (70.9 vs. 48.6%, P = 0.001), although there was no difference between MD-type and Mixed-type IPMNs (P = 0.343). Recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with MD-type were better than those of patients with Mixed-type (P = 0.008 and P = 0.009, respectively). There were no significant differences in RFS, overall survival, and DSS between patients with MD-type and patients with BD-type IPMNs. Multivariate analysis showed two independent predictors of HGD/invasive IPMC in MD-type IPMN; mural nodule height ≥5 mm (P = 0.025, odds ratio [OR]; 16.949) and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained by preoperative endoscopic retrograde pancreatography ≥50 ng/ml (P = 0.039, OR; 9.091).Measurement of mural nodule height and CEA in the pancreatic juice might be useful in determining surgical indication for pure MD-type IPMN, although further studies for confirmation are essential.

Background Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC. Methods JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients’ data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model. Results Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41–75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32–3.81] and many LVLs (HR 2.88, 95% CI 1.27–6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs. Conclusion The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning.

Background Childhood rhabdomyosarcoma (RMS) of perineal or perianal origin (PRMS) is rare, accounting for only 2% of all RMSs. PRMS has been reported to show different characteristics depending on the patient’s age, and patients aged 10 years or older have a poor prognosis. Disseminated intravascular coagulation (DIC) is considered to be an uncommon complication of RMS. However, it could occur occasionally in patients with widespread RMS with bone marrow infiltration. Pulmonary lymphangitic sarcomatosis (PLS) has been reported to be rare, and to our knowledge, only 18 cases (including 4 patients with RMS) have been reported to date. Case report A 15-year-old female patient with suspected RMS was admitted to our hospital. The patient was diagnosed with PRMS following radiological evaluations and effusion cytology, and chemotherapy was initiated on the 6th day of admission. During the course, the patient suffered from severe dyspnea and DIC. Despite treatment, the bleeding tendency did not improve, and hepatic and renal failure progressed. The patient died of progressive respiratory failure on the 13th day of admission. An autopsy, performed 2 h after death, revealed a perianal tumor with pseudoalveolar growth pattern. In the lungs, a relatively large number of small metastatic foci, presumed to be lymphatic spread, were identified. It was diagnosed as PLS due to alveolar RMS. Conclusion Although PLS is reported to be an unexpected form of metastasis, it might cause severe dyspnea in patients with RMS, as 4 of 18 reported cases of PLS are associated with RMS.

Background Although patients with positive lavage cytology (CY1) are classified as having stage IV disease, long-term survival without other unresectable factors (P0CY1) has been reported. Conversion gastrectomy in patients with a change in cytology status after induction chemotherapy might improve survival, but appropriate treatment remains controversial. Here, we reviewed our experience in treating CY1 gastric cancer to evaluate the best treatment strategy. Methods Clinical and pathological findings of patients with a diagnosis of P0CY1 gastric cancer at Toranomon Hospital between February 2006 and April 2019 were retrospectively analyzed. Patients were classified into two groups according to initial treatment: a surgery-first group and a chemotherapy-first group. In addition, the patients were categorized into subgroups based on the subsequent treatment pattern. The surgery-first group was divided into two subgroups: adjuvant chemotherapy and palliative gastrectomy only. The chemotherapy-first group was divided into three subgroups with the subsequent treatment pattern depending on the response to chemotherapy: conversion gastrectomy, palliative gastrectomy after induction therapy, and palliative chemotherapy. Results In total, 38 patients were eligible for inclusion in this study. After initial assessment of cytology status, 21 patients underwent gastrectomy as initial treatment (surgery first) and 17 received induction chemotherapy (chemotherapy first). Ten patients underwent surgery first with adjuvant chemotherapy, 11 underwent palliative gastrectomy alone, 5 underwent conversion surgery, 5 with CY1 disease after induction chemotherapy underwent palliative gastrectomy, and 7 received palliative chemotherapy only. The 3-year survival rate was 23.4% (median survival, 17.7 months) in the surgery-first group and 27.3% (median survival, 19.7 months) in the chemotherapy-first group. The 3-year survival rate was 75% for conversion gastrectomy, 16.7% for palliative chemotherapy, and 0% for palliative gastrectomy after induction chemotherapy. Conclusions There was no significant difference in outcome according to whether surgery or chemotherapy was performed first. The prognosis of conversion surgery with curative resection was better than that of the other types of treatment. However, the outlook after induction chemotherapy was poor. Patients with advanced gastric cancer should be treated cautiously until more effective treatment options become available.

Background Adjuvant chemotherapy for resectable colorectal liver metastasis (CRLM) is widely used, but its efficacy lacks clear evidence. This retrospective cohort study investigated the effectiveness of neoadjuvant chemotherapy (NAC) compared to upfront surgery for CRLM. Methods Data from patients with resectable CRLM were analyzed. Short-term outcomes and long-term prognosis were analyzed using propensity score matching. CRLM was stratified according to the H-classification (H1 and H2), and the effectiveness of adjuvant chemotherapy was analyzed in each group. Results We analyzed 599 cases that were matched into an NAC group (n = 136) and an upfront surgery group (n = 136). The proportion of synchronous metastases, H2-classification, and postoperative chemotherapy rate did not differ between the groups. Overall survival (OS) after initial treatment was significantly worse in the NAC group than in the upfront surgery group (P = 0.029). The 5-, 7-, and 10-year OS rates for H1 patients were significantly better in the upfront surgery group than in the NAC group (64%, 51%, and 44% vs. 50%, 31%, and 18%, respectively) (P = 0.004). Conclusion Patients with resectable CRLM should undergo upfront surgery, because NAC did not improve OS after initial treatment in these patients.

Summary Background The long-term outcomes after esophagectomy for esophageal cancer remain uncertain and the optimal surveillance strategy after curative surgery remains controversial. Methods In this study, the clinicopathological characteristics of patients who underwent curative thoracic esophagectomy between 1991 and 2015 at Toranomon Hospital were retrospectively analyzed and reviewed until December 2020. We evaluated the accumulated data regarding the pattern and rates of recurrence and second malignancy. Results A total of 1054 patients were eligible for inclusion in the study. Of these, 97% were followed up for 5 years, and the outcomes after 25 years could be determined in 65.5%. Recurrence was diagnosed in 318 patients (30.2%), and the most common pattern was lymph node metastasis (n = 168, 52.8%). Recurrence was diagnosed within 1 year in 174 patients (54.7%) and within 3 years in 289 (90.9%). Second malignancy possibly occurred through the entire study period after esophagectomy even in early-stage cancer, keeping 2%–5% of the incidental risk. There was no significant difference in the prognosis between 3-year survivors with and without a second malignancy. Conclusions Most recurrences after resection of esophageal cancer occurred within 3 years regardless of disease stage. However, these patients have an ongoing risk of developing a second malignancy after esophagectomy. Further consideration is required regarding the efficacy of long-term surveillance.

Purpose Short bowel syndrome is associated with intestinal mucosal inflammation and microbial dysbiosis, leading to intractable complications. Partially hydrolyzed guar gum (PHGG) has trophic and anti-inflammatory effects on the intestine. We investigated whether PHGG ameliorates small intestinal mucosal damage and alters the intestinal microbiota using a rat small bowel resection (SBR) model. Methods Sprague Dawley rats were divided into sham operation (Sham), Sham/PHGG, SBR, and SBR/PHGG groups. On day 21, all rats were euthanized. To assess small intestinal mucosal damage, the degeneration rate was morphometrically evaluated and immunohistochemically examined using anti-CD45 antibodies. Analyses of fecal microbiota using 16S rRNA and short-chain fatty acid production were also performed. Results The mucosal degeneration rate was significantly higher in the SBR group than in the Sham or SBR/PHGG groups. The number of CD45-positive cells was significantly higher in the SBR group than in the Sham, Sham/PHGG, or SBR/PHGG groups. The relative abundance of family Lachnospiraceae was significantly higher in the SBR/PHGG group than in the SBR group. Conclusions PHGG administration alleviated small intestinal mucosal damage which could be associated with modulation of the intestinal microbiota.

Diaphragmatic herniation (DH) is a rare but potentially fatal event after total gastrectomy (TG). Despite being life-threatening, risk factors for postoperative DH have yet to be elucidated. We conducted a retrospective analysis to identify clinical characteristics of patients developing DH after TG, along with a comprehensive review of the published literature. Among 1361 consecutive patients undergoing TG for esophagogastric cancer between 1985 and 2013 in Toranomon Hospital, those requiring surgical intervention for postoperative DH were included. We also conducted a PubMed literature search on DH following TG. Five patients (four males, one female), with a median age of 68 at DH surgery, were identified. Intervals between TG and DH repair ranged from 2.9 to 189.0 (median, 78.1) months. Four patients had needed emergency surgery. Three patients had undergone open TG and two others laparoscopic TG, suggesting a significantly higher incidence of DH after laparoscopic TG (3/1302 vs. 2/59, p = 0.017). The diaphragmatic crus incision, creating the space for esophagojejunostomy, had been performed in all cases. The literature yielded seven relevant publications (16 patients). Intervals between TG and DH reduction ranged from 2 days to 36 months. All operations for DH had been carried out emergently. The risk of DH persisted after TG. DH is potentially a very late complication of TG, presenting as a surgical emergency. Laparoscopic TG was suggested to be a risk factor for postgastrectomy DH. Incising the crus might also be a predictor of DH. Measures to prevent DH, e.g., appropriate closure of the crus, would be recommended in minimally invasive TG.

Introduction We conducted a retrospective study to investigate the progress of the operative outcome after laparoscopic splenectomy (LS), with a special reference to the administration of prophylactic antibiotics (PA). Methods The study included 123 patients who underwent elective LS. Operative outcomes before and after the operative procedure was standardized and the impact of treatment with PA on surgical-site infection were investigated. Results With regard to complications, wound infection developed in one (0.8%), portal trunk thrombosis in one (0.8%), pancreatic fistula in one (0.8%), postoperative bleeding in two (1.6%), pleural effusion in one (0.8%), and reoperation because of bowel injury in one (0.8%). Although morbidity did not differ between patients in the early (until the end of 2010) and late (after the beginning of 2011) periods, intraoperative blood loss was lower in patients in the late period. During the late period, no patients required conversion to open surgery. The proportion of patients with surgical-site infection did not differ between those who received PA 1 h before the start of surgery and every 3 h during surgery and those who received PA 1 h before the start of surgery, every 3 h during surgery, and twice a day for 24-72 h after surgery. Conclusion Operative outcomes after LS improved after the standardization of the operative procedure. The administration of PA 1 h before surgery and every 3 h during surgery seems to be sufficient to prevent surgical-site infection during LS.

Background Pancreatic exocrine insufficiency (PEI) is known to occur after total gastrectomy. We experienced a case of PEI occurring 18 years after surgery, leading to a potentially fatal condition of capillary leak syndrome (CLS). Case presentation The case is a 58-year-old man on a healthy diet who underwent total gastrectomy 18 years before. He was admitted for a 3-month history of anasarca, steatorrhea, and hypoalbuminemia. An episode of fever occurred during workup, followed by pulmonary edema and shock. The patient was transferred to the intensive care unit and was started on fluid management with albumin infusion. A multidisciplinary team meeting was held, and a clinical diagnosis of PEI resulted in CLS was made and we started administration of oral pancrelipase to show clinical improvement. The patient was discharged, and he remained asymptomatic for 13 months. Conclusion In a post-gastrectomy patient with malnutrition, PEI should be suspected regardless of the period since surgery. When recognized, immediate replenishment of albumin and pancreatic enzymes should be initiated to prevent clinical deterioration.

We investigate the feasibility of using indocyanine green (ICG) fluorescence imaging with interventional radiology (IVR) techniques for indication of liver segments during laparoscopic anatomical liver resection (LapAR). Ten patients with planned LapAR (segmentectomy V, VI, VII, or VIII) were enrolled. Both IVR and LapAR were performed in a hybrid operating room. Two dyes (indigo carmine and ICG) and embolic solutions were injected into the target liver segment. We compared imaging results during LapAR. ICG fluorescence imaging (ICGFI) provided clear visual contrast. Median contrast index value of ICGFI was 1.12, superior to that of indigo carmine (0.21; P=0.005). ICGFI was still visible during liver resection. Estimated liver resection volume and actual resected liver weight correlated significantly (R=0.906; P

BackgroundPrimary malignant melanoma of the esophagus is a rare tumor with a poor prognosis; the optimal treatment strategy has yet to be established. This study aimed to clarify clinical features, courses, and outcomes of patients undergoing surgical resection of primary malignant melanoma of the esophagus.MethodsSix patients with primary malignant melanoma of the esophagus, in whom the absence of other primary melanomas had been confirmed, were selected from the medical database maintained in Toranomon Hospital. Their clinicopathological characteristics and long-term outcomes were retrospectively reviewed and analyzed.ResultsAll 6 patients (five males and one female) underwent radical esophagectomy with three-field regional lymphadenectomy, and none received neoadjuvant therapy. Tumor invasion was classified into T1 in 5 (83%) cases and T3 in one (17%). Four (67%) patients had nodal metastases (one N1, one N2 and two N3). No distant metastatic lesions were detected preoperatively in any of our cases. Postoperative surveillance revealed recurrence in all 6 patients, and 5 (83%) died of the disease. The median overall survival was 24 months. One patient with a T3N3M0 tumor was treated after surgery with a dacarbazine-nimustine-vincristine regimen followed by irradiation for bone recurrence and survived for 87 months postoperatively. Another patient with a T1N3M0 tumor who survived for 27 months after liver and bone recurrence was treated with nivolumab, ipilimumab, and dacarbazine.ConclusionAlthough the courses of patients with primary malignant melanoma of the esophagus were consistently unfavorable, surgical resection with multidisciplinary therapeutic modalities may prolong survival in some cases.

This study used a randomized controlled trial (RCT) to evaluate whether mattress suture of pancreatic parenchyma and the seromuscular layer of jejunum (modified Blumgart method) during pancreaticojejunostomy (PJ) decreases the incidence of clinically relevant postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD).Several studies reported that mattress suture of Blumgart anastomosis in PJ could reduce POPF rate. This, however, is the first RCT.Between June, 2013 and May, 2017, 224 patients scheduled for PD were enrolled in this study in Wakayama Medical University Hospital. Enrolled patients were randomized to either interrupted suture or modified Blumgart mattress suture. The primary endpoint was the incidence of grade B/C POPF based on the International Study Group on Pancreatic Fistula criteria. This RCT was registered with ClinicalTrials.gov (NCT01898780).Patients were randomized to either interrupted suture (103 patients) or modified Blumgart mattress suture (107 patients) and were analyzed by intention-to-treat. Grade B/C POPF occurred in 7 patients (6.8%) in the interrupted suture group and 11 (10.3%) in the mattress suture group (P = 0.367). Mortality within 90 days was 0 in both groups. There were no significant differences in all postoperative complications between the interrupted suture group and the modified Blumgart mattress suture group.Mattress suture of pancreatic parenchyma and the jejunal seromuscular layer during PJ (modified Blumgart technique) did not reduce clinically relevant POPF compared with interrupted suture.

Genes generate various transcripts by alternative splicing, and these transcripts can have diverse functions. However, in most transcriptome studies, short-reads sequencing technologies (next-generation sequencers) have been used and full-length transcripts have not been observed directly. Although long-reads sequencing technologies would enable us to sequence full-length transcripts, analysis of the data is a difficult task. In the present study, we developed an analysis pipeline named SPLICE to analyze full-length cDNA sequences. Using this method, we analyzed cDNA sequences from 42 pairs of hepatocellular carcinoma (HCC) and matched non-cancerous liver with Oxford Nanopore technology. Our analysis detected 46,663 transcripts from the protein-coding genes in the HCCs and the matched non-cancerous livers, of which 5,366 (11.5 %) were novel. Comparison of expression levels identified 9,933 differentially expressed transcripts (DETs) in 4,744 genes. Importantly, 746 genes with DET were not found by the gene-level analysis. We also identified novel exons derived from transposable elements (TEs). In the analysis of transcripts from hepatitis B virus (HBV), HBx-human TE fusions were found to be overexpressed in the HCCs. Furthermore, fusion gene detection showed novel recurrent fusion events. These results suggest that long-reads sequencing technologies allow us to analyze full-length transcripts, and show the importance of splicing variants in carcinogenesis.

Simple Summary Less morbidity is considered among the advantages of laparoscopic liver resection for HCC patients. However, our previous international, multi-institutional study of laparoscopic repeat liver resection (LRLR) failed to prove it. We hypothesize that these results may be since the study included complex cases performed during the procedure’s developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the complexity. A propensity score matching earned 115 each patient of LRLR and open repeat liver resection (ORLR) without the proximity to major vessels, and the outcomes were compared. With comparable operation time and long-term outcome, less blood loss and less morbidity were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery. Abstract Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure’s developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first–second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, p = 0.001) and less morbidity (8.7 vs. 18.3 %, p = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.

Background Laparoscopic central bisectionectomy (Couinaud's segment IV, V, and VIII) needs exposure of the RHV and MHV on the surface of the remnant and the resecting side, respectively. Avoiding venous injury is mandatory and laparoscopy-specific cranio-caudal approach to hepatic veins might be helpful (Ueno et al., 2020) [1]. We present this procedure in performing laparoscopic central bisectionectomy. Patient A 45-year-old female was admitted to our hospital with a 6 cm HCC in the segment VIII and IV. Her comorbid disease was non-cirrhotic HBV hepatitis (Child-Pugh grade A) and diabetes (untreated). Method After cholecystectomy, G4 branches were dissected and cut by extra- or intra-hepatic approach. Hilar plate was dissected and the Gant was encircled and occluded by a vascular clip. Afterwards, exposure of the MHV was started at its root on IVC (Monden et al., 2020; Kim, 2019) [2,3] and extended in cranio-caudal direction (Ueno et al., 2020) [1]. After sufficient space was obtained around the Gant, the Gant and the MHV were cut. Parenchymal transection between right anterior and right posterior sections was also started form the root of the RHV to its cranio-caudal direction. Liver resection was finished with full exposure of the RHV. Results The operating time was 380 minutes, and the blood loss volume was 30 ml. Postoperative CT image showed exposure of the RHV and umbilical portion of Glissonean branch, and no fluid retention. Conclusion Laparoscopy-specific cranio-caudal approach to hepatic veins may be useful to avoid split injury of venous branches (Honda et al., 2020) [4], especially if the hepatectomy requires complete exposure of hepatic vein, such as central bisectionectomy.

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.

Background:We aimed to investigate whether a novel biomarker incorporating albumin, lymphocytes, and CRP can predict the prognosis for hepatocellular carcinoma (HCC) after hepatectomy., Methods:Between January 2011 and December 2013, 384 patients who underwent hepatectomy in four university hospitals in Japan were investigated as a discovery cohort. The CRP-Albumin-Lymphocyte (CALLY index) was defined as (Albumin × Lymphocyte)/(CRP × 104). Patients with a CALLY index ≥5 (n = 200) were compared to those with an index, Results:The number of TNM Stage III and IV patients was significantly higher in the CALLY, Conclusion:The CALLY index derived from CRP, albumin, and lymphocyte values is a promising predictive biomarker for postoperative prognosis of patients with HCC.