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INTRODUCTION: Pembrolizumab was approved for the treatment of microsatellite instability (MSI)–high pancreatic cancer that is unresponsive to systemic chemotherapy. However, pancreatic cancer has a low prevalence of MSI-high status (<1%). We report a rare case of MSI-high pancreatic tail cancer successfully treated with pembrolizumab, which enabled conversion surgery to be performed.CASE PRESENTATION: A 78-year-old male patient received the diagnosis of unresectable metastatic (UR-M) pancreatic tail cancer with para-aortic and anterior mediastinal lymph node metastases. Tests found high MSI due to the loss of MSH2 and MSH6 expression. Following 6 courses of pembrolizumab, he achieved a partial response. Pembrolizumab was discontinued after immune-related renal dysfunction developed during the 7th course. Fluorodeoxyglucose positron emission tomography/computed tomography demonstrated decreased uptake in the anterior mediastinal and para-aortic lymph nodes, allowing a radical resection to be performed. The patient underwent a radical antegrade modular pancreatosplenectomy with a left adrenalectomy and para-aortic lymph node sampling. Currently, at postoperative month 6, he is alive and recurrence-free. The present case is an extremely rare instance of MSI-high, unresectable pancreatic cancer that was removed by curative resection after pembrolizumab therapy.CONCLUSIONS: The present rare case of conversion surgery for MSI-high UR-M pancreatic tail cancer, achieving a pathological partial response after pembrolizumab treatment, highlights the potential of pembrolizumab against this specific molecular subtype of pancreatic cancer and underscores the clinical significance of proactively testing for MSI to identify candidates for immunotherapy and curative conversion surgery.

Background Oxaliplatin-based regimens are commonly used as adjuvant chemotherapy following surgery for colorectal cancer. Adverse events associated with oxaliplatin include blue liver, which is caused by sinusoidal dilation and diffuse peliosis hepatis. We report herein a case of localized peliosis hepatis closely resembling a metastatic liver tumor. Case presentation The patient, a 50-year-old male, underwent a robotically assisted colectomy for rectosigmoid colon cancer, which was discovered when hematochezia occurred. The patient received a diagnosis of pStage IIIb and was treated with four courses of CAPOX as adjuvant chemotherapy starting at postoperative month 1. At postoperative month 4, contrast-enhanced computed tomography (CT) of the abdomen revealed a 20-mm, low-density area with heterogeneous internal structure in S6/7 of the liver. Abdominal ultrasound and gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) findings led to a diagnosis of metastatic liver tumor, for which a laparoscopic partial hepatectomy was performed. The resected lesion was a dark reddish-brown nodule with indistinct margins that appeared to be continuous with the surrounding area. Histopathological analysis revealed severe, localized dilatation of the sinusoids and congestion consistent with the gross nodule. Based on these findings, localized peliosis hepatis associated with oxaliplatin-induced sinusoidal damage was diagnosed. Conclusions Localized peliosis hepatis associated with oxaliplatin use can be difficult to distinguish from a metastatic liver tumor on imaging studies.

Aim This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1‐NACRT) for resectable pancreatic ductal adenocarcinoma. Methods The medical records of 132 patients who received S1‐NACRT for resectable pancreatic ductal adenocarcinoma from 2010 to 2019 were reviewed. The S1‐NACRT regimen consisted of S1 at a dose of 80‐120 mg/body/day together with 1.8 Gy of radiation in 28 fractions. The patients were re‐evaluated 4 weeks after S1‐NACRT completion, and a pancreatectomy was then considered. Results Adverse events of S1‐NACRT ≥grade 3 occurred in 22.7% of the patients, and 1.5% discontinued therapy. Of the 112 patients who underwent a pancreatectomy, 109 underwent R0 resection. Adjuvant chemotherapy with relative dose intensity ≥50% was administered to 74.1% of the patients who underwent resection. The median overall survival of all patients was 47 months, and the median overall survival and recurrence‐free survival of patients who underwent resection was 71 and 32 months, respectively. According to the multivariate analyses of prognostic factors for overall survival in patients who underwent resection, negative margin status (hazard ratio: 0.182; P = 0.006) and relative dose intensity of adjuvant chemotherapy ≥50% (hazard ratio 0.294; P < 0.001) were independent prognostic factors of overall survival. Conclusions A multidisciplinary approach incorporating S1‐NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits. This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1‐NACRT) for resectable pancreatic ductal adenocarcinoma. The median overall survival of all patients was 47 months, and the median overall survival and recurrence‐free survival of patients who underwent resection were 71 months and 32 months, respectively. A multidisciplinary approach incorporating S1‐NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits.

Background Bile duct tumor thrombus (BDTT) is one of the features of advanced hepatocellular carcinoma (HCC). In the resection of HCC with BDTT, it is important to detect the BDTT tip to decide the appropriate point of bile duct division. In this regard, the efficacy of indocyanine green (ICG) fluorescence navigation has been confirmed for the detection of HCC, whereas its utility for BDTT has not yet been reported. Herein, we describe our experience with right hepatectomy for HCC with BDTT using ICG fluorescence navigation. Case presentation A 72-year-old woman had experienced local recurrences of HCC after radiofrequency ablation, with BDTT reaching the confluence of the right anterior branch and posterior branch. Right hepatectomy was planned, and 2.5 mg of ICG was injected one day before surgery. After transection of the liver parenchyma, the right liver was connected with only the right hepatic duct. ICG fluorescence imaging visualized the tip of BDTT in the bile duct with clear contrast; the proximal side (hepatic side) of the right hepatic duct showed stronger fluorescence than the distal side (duodenal side). The bile duct was divided at the distal side of the BDTT border, and the tip of BDTT was recognized into the resected right hepatic duct without laceration. The patient had an uneventful postoperative course and currently lives without recurrences for 6 months. Conclusions ICG fluorescence navigation assisted in the precise resection of the bile duct in HCC with BDTT.

Background Renal cell carcinoma (RCC) is a primary tumor with the highest frequency of pancreatic metastasis. Although surgical resection can improve the prognosis of some patients with pancreatic metastasis of RCC (PM-RCC), the role of palliative surgery remains unclear. Herein, we described a case of jejunal limb occlusion caused by a tumor thrombus arising from a PM-RCC which was treated by surgical resection. Case presentation A 75-year-old, male patient with metastatic RCC was admitted to our hospital with new-onset dysphagia and weight loss. Twenty years earlier he underwent a right nephrectomy with an adrenalectomy for the first surgical resection of RCC, and 12 years ago he underwent a left partial nephrectomy for metachronous primary RCC. Nine years later, multiple pancreatic metastases were detected. After discontinuing interferon therapy, he was followed up at his request without anticancer treatment. Multiple, pulmonary metastases developed 3 years ago, and resection of a brain metastasis was performed 6 months ago. He had also undergone a total gastrectomy with Roux-en Y reconstruction and splenectomy for gastric cancer 23 years ago. Computed tomography revealed a metastatic lesion in the pancreatic tail extending into the jejunal limb, which was obstructed by a tumor thrombus. Jejunal limb resection was performed concomitantly with a distal pancreatectomy as palliative surgery. The jejunal limb remnant was approximately 30 cm long and was re-anastomosed to the esophagus using a circular stapler. Blood perfusion at the anastomotic site was confirmed by indocyanine green fluorescence imaging. He was discharged on postoperative day 24 and was followed in the outpatient clinic. He achieved sufficient oral intake at 8 months postoperatively. Conclusions PM-RCC can invade the gastrointestinal tract and cause tumor thrombus formation resulting in bowel occlusion requiring surgical intervention.

Background Pancreatic cancer (PC) has serious malignant potential, thus requiring complete resection and adequate regional lymphadenectomy with tumor-free margins. 1 , 2 A standard laparoscopic distal pancreatectomy (LDP) procedure for PC is not yet established due to lack of supportive evidence. 3 – 6 Methods In our hospital, we first administered neoadjuvant chemoradiotherapy for resectable PC. Considering the benefits offered by a laparoscopic magnified caudo-dorsal view, we devised and standardized an LDP procedure for PC, which we employed in five patients with left-sided resectable tumors. First, the retroperitoneum was incised between the proximal jejunum and the inferior mesenteric vein with the transverse colon pushed up ventrally and cranially and with the proximal jejunum moved to the right. Then, the left renal vein (LRV) could be easily identified at this site. The retroperitoneal tissue was dissected along the LRV, and the origin of the superior mesenteric artery (SMA) also was identified just above the LRV easily. The left adrenal gland was removed to secure the dorsal margin, if needed. The retroperitoneal dissection was continued along the major anatomical landmarks, including the LRV, the left renal artery, the left kidney, and the crus of the diaphragm beside the origin of the SMA. Using the same operative field, lymphadenectomy around the SMA was performed before dividing the pancreas. We could safely and easily expose the left aspect of the SMA after dissecting the ligament of Treitz. The dissection around the SMA was performed toward the side of the arterial root that had already been exposed above the LRV. Thus, the most important difficult steps of LDP for PC, such as retroperitoneal dissection and lymphadenectomy around the SMA, were safely performed early in the operation with a good laparoscopic view. Results The median operative time was 341 (range 288–354) minutes, and median blood loss was 150 (range 50–150) ml. An intraoperative transfusion was not required for any patient. Severe postoperative complications or mortality were absent. An R0 resection was achieved in all patients. Conclusions LDP using the “caudo-dorsal artery first approach” is safe and useful for performing a minimally invasive, curative resection for left-sided PC.

Background Intermittent clamping (IC) and ischemic preconditioning (PC) reportedly protect the liver against the ischemia/reperfusion (I/R) injury induced by inflow occlusion during hepatectomy. While IC cycles consisting of 15 min of clamping with 5 min of reperfusion are used empirically, the optimal IC cycle has not been established. We compared the effects of various cycles of IC and PC in the rat liver. Methods Rats subjected to 60 min of inflow occlusion were assigned to the following five groups ( n  = 8 each): 60 min of continuous ischemia; 4 cycles comprising 15 min of ischemia/5 min of reperfusion; 6 cycles comprising 10 min of ischemia/3.3 min of reperfusion; 12 cycles comprising 5 min of ischemia/1.7 min of reperfusion (the time ratio of ischemia to reperfusion in the IC groups was 3:1); and PC (10/10 min of ischemia/reperfusion) prior to 60 min of ischemia. The severity of liver injury was assessed by determining the serum alanine aminotransferase (ALT) level, bile flow, tissue glutathione content, and induction of apoptosis (terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling [TUNEL] staining and DNA laddering), and by histological examination of areas of severe necrosis. Results All the parameters indicated that liver injury was attenuated in the three IC groups compared with the continuous group; furthermore, this effect became increasingly marked with shorter cycles of IC. PC did not exert a protective effect under the present experimental conditions. Conclusion Various cycles of IC consistently conferred protection against I/R injury, and IC with shorter cycles of ischemia and reperfusion was more effective. No protective effect of PC was evident. IC is a more robust strategy than the PC protocol for liver protection.

Abstract Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

Background The incisional surgical site infection (SSI) is an extremely common complication following open abdominal surgery and imposes a considerable treatment and cost burden. Method We conducted a multicenter open-label randomized controlled trial at three Tokyo Metropolitan medical institutions. We enrolled adult patients who underwent either an elective or an emergency open laparotomy. Eligible patients were allocated preoperatively to undergo wound closure with either subcuticular sutures or staples. A central Web-based randomization tool was used to assign participants randomly by a permuted block sequence with a 1:1 allocation ratio and a block size of 4 before mass closure to each group. The primary endpoint was the occurrence of a superficial SSI within 30 days after surgery in accordance with the Centers for Disease Control and Prevention criteria. This trial was registered with UMIN-CTR as UMIN 000004836 ( http://www.umin.ac.jp/ctr ). Results Between September 1, 2010 and August 31, 2015, 401 patients were enrolled and randomly assigned to either group. One hundred and ninety-nine patients were allocated to the subcuticular suture and 202 patients to the staple groups (hereafter the “suture” and “staple” group, respectively). Three hundred and ninety-nine were eligible for the primary endpoint. Superficial SSIs occurred in 25 of 198 suture patients and in 27 of 201 staple patients. Overall, the rate of superficial SSIs did not differ significantly between the suture and staple groups. Conclusion Subcuticular sutures did not increase the occurrence of superficial SSIs following open laparotomies mainly consisting of clean-contaminated surgical procedures. The applicability of the wound closure material and method is likely to depend on individual circumstances of the patient and surgical procedure.

Background Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by thrombocytosis and a propensity for both thrombotic and hemorrhagic events. ET rarely occurs simultaneously with colorectal cancer. Here, we report a case of colorectal cancer in an ET patient treated using laparoscopic ileocecal resection. Case presentation A 40-year-old woman was admitted to our hospital after presenting with liver dysfunction. She had been previously diagnosed with ET; aspirin and anagrelide had been prescribed. Subsequent examination at our hospital revealed cecal cancer. Distant metastasis was absent; laparoscopic ileocecal resection was performed. Anagrelide was discontinued only on the surgery day. She was discharged on the seventh postoperative day without thrombosis or hemorrhage. However, when capecitabine and oxaliplatin were administered as adjuvant chemotherapy with continued anagrelide administration, she experienced hepatic dysfunction and thrombocytopenia; thus, anagrelide was discontinued. Five days later, her platelet count recovered. Subsequently, anagrelide and aspirin administration was resumed, without any adjuvant chemotherapy. Her liver function normalized gradually in 4 months. One-year post operation, she is well without tumor recurrence or new metastasis. Conclusions To our knowledge, this is the first report of laparoscopic colectomy performed on an ET patient receiving anagrelide. Our report shows that complications such as bleeding or thrombosis can be avoided by anagrelide administration. Contrastingly, thrombocytopenia due to anagrelide intake should be considered when chemotherapy that could cause bone marrow suppression is administered.