Surgical resection of double advanced pancreatic neuroendocrine tumors with multiple renal cell carcinoma associated with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder caused by a germline mutation, is associated with non-functional and slow-growing pancreatic neuroendocrine tumor (PNET) and kidney cancer. We describe the case of a 46 year-old man with a 35 mm mass in the pancreatic head causing stricture of the bile duct and main pancreatic duct, a 55 mm mass in the pancreatic tail causing obstruction of the splenic vein (SV), and multiple masses of > 36 mm on both kidneys. We performed a two-stage resection. First, a total pancreatectomy with superior mesenteric vein (SMV) resection and reconstruction and retroperitoneoscopic right partial nephrectomy (NP) for five lesions was performed, followed by retroperitoneoscopic left partial NP of the five lesions 6 months later. Postoperative histopathological examination revealed NET G2 in the pancreatic head with SMV invasion and somatostatin receptor type 2A (SSTR2A) positivity, NET G2 in the pancreatic tail showed SV invasion and negative SSTR2A, and multiple clear cell renal cell carcinomas (RCC) were also noted. Multiple liver recurrences occurred 22 months after primary surgery. The patient remains alive 41 months after primary surgery. Kidney cancer generally determines VHL prognosis; however, we experienced dual-advanced PNETs with a more defined prognosis than multiple RCC associated with VHL.

A rare case of synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report.

INTRODUCTION: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two primary liver cancers. Synchronous occurrence of both types is rare. Here, we present a case of synchronous, double primary liver cancer in a patient who underwent successful surgical resection. PRESENTATION OF A CASE: A 77-year-old woman presented with two suspected liver tumors. Dynamic computed tomography (CT) and ethoxybenzyl-magnetic resonance imaging revealed two lesions, one in hepatic segments S8/4 and another in S5. Positron emission tomography (PET)/CT scans revealed an elevated maximum standardized uptake value (SUVmax) of 5.7 in the S8/4 tumor, and no elevation in the S5 tumor. The S8/4 tumor was diagnosed as either ICC or mixed-type liver cancer, while the S5 tumor was confirmed HCC. Surgical resection confirmed the diagnosis, while pathology identified the S8/4 tumor as ICC and the S5 tumor as HCC. Two months post-operation, the patient received adjuvant chemotherapy and completed eight courses with no recurrence one year later. DISCUSSION: Synchronous double-primary HCC and ICC is uncommon and exhibits diagnostic and therapeutic challenges. Notably, PET-CT scans can differentiate between the two cancers, with HCC typically showing similar uptake to the background liver tissue, whereas ICC is often found with higher accumulation. This highlights the potential utility of PET/CT in preoperative diagnoses and the potential benefit of postoperative adjuvant chemotherapy in patients with double primary HCC and ICC. CONCLUSION: We report a successful case of synchronous double primary liver cancer, emphasizing the potential role of PET/CT in preoperative differentiation, and the efficacy of postoperative adjuvant chemotherapy.

Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy.

PURPOSE: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. METHODS: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. RESULTS: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. CONCLUSIONS: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.

Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis.

BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p <  0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.

A Multicenter, Open-Label, Single-Arm Phase I Trial of Dual-Wield Parenchymal Transection: A New Technique of Liver Resection Using the Cavitron Ultrasonic Surgical Aspirator and Water-Jet Scalpel Simultaneously (HiSCO-14 Trial).

PURPOSE: This study evaluated the safety and feasibility of a technique of liver resection named dual-wield parenchymal transection technique (DWT), using cavitron ultrasonic surgical aspirator (CUSA) and water-jet scalpel simultaneously. METHODS: This multicenter, prospective, open-label, and single-arm phase I trial included patients aged 20 years or older with hepatic tumors indicated for surgical resection and scheduled for open radical resection. This study was conducted at two institutions affiliated with the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO). The primary endpoint was the proportion of massive intraoperative blood loss (≥ 1000 mL). The secondary endpoints were the amount of blood loss, operative time, parenchymal transection speed, postoperative complications, and mortality. The safety endpoints were device failure and adverse events associated with devices. RESULTS: From June 2022 to May 2023, 20 patients were enrolled; one was excluded and 19 were included in the full analysis set (FAS). In the FAS, segmentectomy was performed in nine cases, sectionectomy in four cases, and hemihepatectomy in six cases. Radical resection was achieved in all patients. Intraoperative blood loss greater than 1000 mL was observed in five patients (26.3%). The median amount of blood loss was 545 mL (range, 180-4413), and blood transfusions were performed on two patients (10.5%). The median operative time was 346 minutes (range, 238-543) and the median parenchymal transection speed was 1.2 cm2/minute (range, 0.5-5.1). Postoperative complications of Clavien-Dindo classification ≥ Grade 3 occurred in four patients (21.1%). No mortalities occurred in this study. In the safety analysis, there were no device failures or adverse events associated with devices. CONCLUSIONS: This study demonstrated the safety and feasibility of DWT for liver resection. The efficacy of the DWT will be evaluated in future clinical trials.

Circulating tumor necrosis factor-related biomarkers predict kidney function decline in Japanese patients with diabetes: An observational cohort study.

AIMS: Tumor necrosis factor (TNF) receptors (TNFRs: TNFR1 and, TNFR2) are reportedly associated with chronic kidney disease (CKD) progression chiefly in Caucasian patients with diabetes. We assessed the prognostic value of TNF-related biomarkers for CKD progression in Japanese patients with diabetes. METHODS: We estimated TNF-related biomarkers using an enzyme-linked immunosorbent assay in 640 patients with diabetes. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) per one standard deviation (SD) increase in a log-transformed biomarker. The kidney and the composite outcome were defined as a 30% reduction in estimated glomerular filtration rate (eGFR) from baseline, and kidney outcome plus death before kidney outcome, respectively. RESULTS: During the median follow-up of 5.4 years, 75 (11.7%) patients reached the kidney outcome and 37 (5.8%) died before reaching the kidney outcome. Each SD increase in baseline circulating TNFR1, TNFR2, and ephrin type-A receptor 2 (EphA2) was associated with a higher risk of the kidney outcome independently from baseline eGFR and urine albumin-to-creatinine ratio. However, circulating osteoprotegerin was associated with the composite outcome only. CONCLUSIONS: Elevated TNFR1, TNFR2, and EphA2 were associated with both kidney and composite outcomes in Japanese patients with diabetes.

Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients.

BACKGROUND: This study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients. METHODS: We measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status. RESULTS: The proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer. CONCLUSION: This study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.

Micro-lymph node metastasis in intrahepatic cholangiocarcinoma showing pathological complete response to primary tumor and intrahepatic metastasis treated by gemcitabine plus cisplatin chemotherapy and radical surgery.

Surgical resection is the only curative treatment option for achieving long-term survival in biliary tract cancer patients. However, regional lymph node dissection in intrahepatic cholangiocarcinoma (ICC) is controversial. Herein, we document our experience with a 76-year-old man who had a 70 mm mass in liver segments 6 and 7 and a 10 mm mass in liver segment 3, which were diagnosed as poorly differentiated adenocarcinomas by needle biopsy. Lymphadenopathy was not evident on multidetector computed tomography scanning. Twenty courses of gemcitabine plus cisplatin chemotherapy were administered to the patient. The tumor masses shrunk and exhibited a partial response to chemotherapy as per the Response Evaluation Criteria in Solid Tumors version 1.1. Although tumor markers were all within normal limits, renal function parameters showed deterioration due to systemic chemotherapy. Therefore, continuing systemic chemotherapy was deemed unfeasible and we decided to perform a radical resection using extended posterior segmentectomy and partial liver resection with regional lymph node dissection. Postoperative histopathological examination revealed complete response of primary tumor and intrahepatic metastases; however, a micro-lymph node metastasis was found. The patient is still alive, without recurrence, more than 30 months after treatment initiation and 15 months after surgery. Even if remarkably effective pathological findings may be observed in the primary tumor, there are cases in which a micro-lymph node metastasis remains that are not identified on imaging examinations. Thus, regional lymphadenectomy may be useful in obtaining the exact state of disease progression and evaluation of chemotherapeutic effect in radical surgery.

[Unresectable Esophageal Cancer on the Elderly Woman Which Was Treated Effectively with Ipilimumab plus Nivolumab-A Case Report].

Until now, the standard treatment regimen was cisplatin plus 5-FU as the chemotherapy for unresectable advanced esophageal cancer. Immune checkpoint inhibitors have brought about changes to the cancer treatment. Ipilimumab plus nivolumab was approved in June 2022 for unresectable advanced esophageal cancer. An 86-year-old woman who was normal ADL and cognitive function was diagnosed with unresectable esophageal cancer with multiple lymph node metastasis. We thought surgery or chemotherapy is impossible because of her age and health status, so we treated with ipilimumab plus nivolumab. After 2 cycles, tumor became reduced in size on endoscopic examination and accumulation in primary lesion and lymph node metastases was decreased considerably on positron emission tomography/computed tomography(PET-CT). Though the cycle after initiation of chemotherapy was uneventful, tumor regrowth on the examinations at 5 months. The patient's condition of the disease was improved temporarily after change chemotherapy to paclitaxel as the second-line therapy, but she died due to disease progression at 11.4 months from initiation of treatment. Ipilimumab plus nivolumab can become one of the effective treatments for patients who are impossible to treat with conventional chemotherapy.

[Surgical Resection and Adjuvant Chemotherapy for Early Multiple Peritoneal Recurrence after Rejection of Hepatocellular Carcinoma-A Case Report].

Thus far, no consensus has been reached regarding the treatment of peritoneal dissemination of hepatocellular carcinoma (HCC). Here, we report a case of surgical resection and postoperative adjuvant chemotherapy for early multiple peritoneal recurrences of HCC. A 74-year-old man was found to have hepatic mass of 80 mm in size in S7 and 57 mm in S8, and was diagnosed with HCC. The patient underwent an open anterior segmentectomy and S7 subsegmentectomy of the liver. Peritoneal washing cytology revealed the presence of malignant cells. The tumor strongly adhered to the diaphragm, necessitating partial resection of the diaphragm. Six months after surgery, multiple disseminated recurrences were found on the CT scan. Atezolizumab plus bevacizumab combination therapy was initiated, but tumor size enlargement and elevation of tumor markers were observed after 3 courses. Resection of the dissemination(2 on the surface of the lung right lower lobe, 1 on the right renal superior retroperitoneum, 1 on the omentum, and 1 invading the jejunum)was performed. Considering the high risk of recurrence, postoperative adjuvant chemotherapy with lenvatinib was administered for 1 year. No recurrence has been found for 16 months after the resection. Although more cases are needed to conclude, this case report suggests that surgical resection and postoperative administration of lenvatinib may be effective in the treatment of disseminated HCC lesions at a high risk of recurrence.

Downregulation of thrombomodulin contributes to ischemia-reperfusion injury in mice with steatotic liver.

AIM: Ischemia-reperfusion (IR) injury is one of the most critical complications commonly associated with liver surgery, including liver transplantation. Steatotic livers are particularly vulnerable to IR injury. However, the underlying mechanisms of this increased susceptibility have not fully been understood. In the present study, we used heterogeneous thrombomodulin (TM)-knockout (KO) (TM+/- ) mice, which express about 50% functional activity of TM as compared with wild type, to investigate whether dysregulation of TM enhances IR injury in steatotic livers. METHODS: Steatotic livers were induced using choline-deficient diets (CDD) in mice. The biological activity of TM was assessed using the productivity of protein C. Susceptibility to IR injury was compared between steatotic livers and non-steatotic livers and also assessed in TM-KO mice. We investigated whether recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1) ameliorated IR injury in steatotic livers. RESULTS: Protein C activity was significantly decreased to less than 20% in CDD-fed mice compared with mice with non-steatotic livers. Steatotic livers showed exaggerated IR injury compared with non-steatotic livers. Recombinant TM (rTM) and the lectin-like domain of TM (rTM-D1), which has anti-inflammatory effects, ameliorated IR injury in steatotic livers. TM+/- mice showed increased susceptibility to IR injury, and rTM ameliorated the increased IR injury in TM+/- mice. CONCLUSION: We conclude that downregulation of TM increases susceptibility to hepatic IR injury in steatotic livers and that rTM ameliorates hepatic IR injury through anti-inflammatory action.

[A Case of Lynch Syndrome with Repeated Asynchronous Colorectal Cancer in a Short Period].

This case was a 73-year-old woman who previously underwent a partial colectomy for ascending colon cancer at the age of 70. She had a history of cancer of the uterus, descending colon, bladder, and left ureter. She had a family history of colorectal cancer and met the Amsterdam Ⅱ criteria for Lynch syndrome. She was diagnosed as Lynch syndrome with a MSH2 germline mutation by genetic analysis. One year later, a partial colectomy was performed for sigmoid colon cancer. Six months later, colonofiberscopy revealed early-stage cancer in the rectum, and EMR was performed. Despite adequate surveillance, she had frequent recurrences of advanced colorectal cancer within a short period of time. We report here risk factors of colorectal cancer in Lynch syndrome and indications for prophylactic total colectomy.

[A Case of Sclerosing Angiomatoid Nodular Transformation Resected for Suspected Relapse of Diffuse Large B-cell Lymphoma].

We report a case of sclerosing angiomatoid nodular transformation(SANT)5 years after remission of diffuse large B-cell lymphoma(DLBCL). A 64-year-old woman was diagnosed a nodular mass at the spleen by a contrast-enhanced CT scan 5 years after the relief for DLBCL. The mass showed accumulation of FDG. Because the possibility of the recurrence of malignant lymphoma could not be ruled out, laparoscopic splenectomy was performed for diagnosis and treatment. Immunohistologically, the resected mass revealed 3 different vascular components pattern(CD31, CD34 and CD8), so we diagnosed SANT. It is difficult to distinguish from malignant lymphoma or cancer even with various examination, so laparoscopic splenectomy is useful for diagnosis and treatment.

Transcriptomic Analysis of Annexin A10 and Chemosensitivity in Gastric Adenocarcinoma Cells.

BACKGROUND/AIM: Gastric cancer (GC) is the third-leading cause of cancer-related deaths worldwide; thus, novel diagnostic and therapeutic biomarkers are needed. Annexin A10 (ANXA10) is a calcium- and phospholipid-binding protein. As far as we are aware, there are no reports describing the detailed functions of ANXA10 in GC. Therefore, we investigated the downstream mRNA variation and the effects of ANXA10 on chemoresistance in GC cell lines. MATERIALS AND METHODS: ANXA10 knockout GC cell lines were generated, and we performed functional analyses, chemosensitivity drug testing, and microarray analyses. Additionally, immunohistochemistry for ANXA10 was performed on 40 patients with GC who had received 5-fluorouracil (5-FU)-based chemotherapy to compare their prognosis and clinicopathological factors. RESULTS: ANXA10 knockout GC cells showed significantly increased proliferation, invasion, and sensitivity to 5-FU. The overall survival of ANXA10-positive cases was considerably lower than that of ANXA10-negative cases in GC patients who received 5-FU-based chemotherapy. Microarray analysis revealed candidate pathways regulated by ANXA10 and claudin 1 (CLDN1), keratin 80 (KRT80), RANBP2-type and C3HC4-type zinc finger containing 1 (RBCK1), and solute carrier family 7 member 5 (SLC7A5) genes. CONCLUSION: ANXA10 knockout increased the susceptibility of GC cell lines to 5-FU; ANXA10 may be a predictive indicator for response to 5-FU treatment in GC cases. ANXA10 may be involved in the pathogenesis of GC, in collaboration with CLDN1, KRT80, RBCK1, and SLC7A5.

[A Case of Pancreatoduodenectomy for Multiple Nonfunctioning Neuroendocrine Tumors of the Duodenum].

A 42-year-old woman was referred to our hospital because of incidentally discovered multiple neoplastic lesions of the duodenum. Upper gastrointestinal endoscopy showed there were more than 10 submucosal tumors and less than 10 mm in diameter. Histological examination of the biopsy specimen revealed nonfunctioning neuroendocrine tumor(NET). Enhanced computed tomography(CT)showed neither regional lymph node nor distant metastasis, so we performed pancreatoduodenectomy with regional lymph node dissection. Pathological examination showed multiple NET G2 less than 5 mm in size with invasion to muscularis propria and 3 lymph node metastases, so diagnosed as pT2(m)N1M0, Stage Ⅲ. She is alive without tumor recurrence for 14 months after surgery. In general, sporadic nonfunctioning NET of the duodenum less than 10 mm in diameter has low possibility of lymph node metastasis. However, our case suggested the possibility of lymph node metastasis in patients with multiple NETs of the duodenum, in spite of small size. Therefore, pancreatoduodenectomy with regional lymph node dissection should be considered for multiple nonfunctioning NETs of the duodenum.

Utility of TMPRSS4 as a Prognostic Biomarker and Potential Therapeutic Target in Patients with Gastric Cancer.

BACKGROUND: Transmembrane serine protease 4 (TMPRSS4) belongs to the family of type II transmembrane serine proteases that are known to be upregulated in many malignant tumors. However, there is a paucity of studies documenting the clinical impact and biological effects of TMPRSS4 on gastric cancer (GC) patients who underwent surgery. METHODS: Tissues samples were obtained from 105 patients with GC who underwent gastrectomy followed by adjuvant chemotherapy, excluding those at stage I. The expression of TMPRSS4 was examined through immunohistochemical analysis. The association between TMPRSS4 expression and clinico-pathological features as well as prognosis was assessed. Moreover, the effects of TMPRSS4 expression on cell migration and sensitivity to 5-FU were investigated. RESULTS: The expression rate of TMPRSS4 was 56.3% (59/105) in GC cases. The expression of TMPRSS4 was positively correlated with the depth of tumor (T) and venous (V) invasion. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (p=0.0001 and p=0.005, respectively). Especially, there was significant differences in OS and RFS of patients with stage III cancer between the two groups (p=0.0064 and 0.012, respectively). Multivariate analysis demonstrated that TMPRSS4 expression and the stage of cancer were crucial prognostic factors for RFS. TMPRSS4-silenced GC cells exhibited increased sensitivity to 5-FU when compared with the non-specific control siRNA-transfected cells. CONCLUSION: TMPRSS4 can be considered as a potential prognostic biomarker, especially for stage III, and a promising therapeutic target for GC.

High Annexin A10 expression is correlated with poor prognosis in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death. Owing to its poor prognosis, new molecular biomarkers for PDAC are needed. Annexin A10 (ANXA10) is a calcium-/phospholipid-binding protein belonging to the annexin family of proteins. ANXA10 is not only associated with gastric phenotypes, but also acts an independent prognostic factor in several cancers. However, the role of ANXA10 in PDAC remains unknown. Therefore, we examined the relationship between ANXA10 and the prognosis of PDAC. We analyzed the expression of ANXA10 using data from public databases, and performed immunohistochemistry analysis for 81 PDAC cases. We then investigated the relationship between ANXA10 expression and clinicopathological features. ANXA10 was detected in 47 of 81 PDAC cases (58%). High expression of ANXA10 was significantly related to poor overall survival (OS; p=0.011). Univariate analysis of OS revealed three prognostic parameters: tumor grade (p=0.046), perineural invasion (p=0.017), and ANXA10 expression (p=0.012). Multivariate analysis indicated that ANXA10 expression (p<0.01) alone was a prognostic factor in PDAC cases. Our findings suggest that ANXA10 expression is an independent prognostic factor in PDAC cases and shows promise as a new biomarker in PDAC.

[A Case of Anal Canal Cancer with Pagetoid Spread and a Significant Response to Preoperative Chemoradiotherapy].

Perianal Pagetoid spread is a rare condition for which there is no proven therapy. We experienced a case of anal canal cancer with Pagetoid spread which exhibited a significant response to preoperative chemoradiotherapy(CRT). A 76-year-old man with anal stenosis was referred to our hospital. He was diagnosed with anal canal cancer with Pagetoid spread. No infiltration into the surrounding tissue was observed, but metastasis to the left inguinal lymph node was noted. The patient received preoperative CRT(oral S-1, 1.8 Gy×25 Fr, a total dose of 45 Gy)including the bilateral inguinal region. After CRT, the main tumor size was reduced and PET-CT showed disappearance of the abnormal accumulation in the left inguinal lymph nodes. Laparoscopic abdominoperineal resection and left inguinal trans lymphadenectomy were performed. The macroscopic findings of the surgical specimen confirmed no residual carcinoma or lymph node metastasis. Although more proof is needed, this case suggested that CRT may be effective for anal canal cancer with pagetoid spread.

[A Case of Laparoscopic Surgery for Colon Metastasis of Renal Cancer].

A 67-year-old man underwent laparoscopic partial left nephrectomy for renal cell carcinoma 2.5 years ago. CT showed a well-defined 3 cm mass with contrast effect bordering on the descending colon, and PET-CT showed an accumulation of SUVmax 6.01 in the same area. Colonoscopy revealed a submucosal tumor-like mass in the descending colon. The patient was diagnosed with a local recurrence of renal cell carcinoma and invasion of the descending colon, and laparoscopic colectomy was performed. The excised specimen was a pale yellowish submucosal tumor measuring 4.5×3.8 cm, which was histologically diagnosed as metastasis of clear cell renal cell carcinoma. Surgical resections for metastases of renal carcinoma have been reported and expected prolong survival. We report a case of laparoscopic colon resection for recurrence of descending colon metastasis of renal cell carcinoma.

Clinical complete response after nivolumab administered as a third-line treatment for unresectable advanced gastric cancer with peritoneal dissemination: A case report.

INTRODUCTION AND IMPORTANCE: Nivolumab, which is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has been recommended as a third-line treatment based on the results of the ATTRACTION-2 study involving patients with unresectable advanced gastric cancer. CASE PRESENTATION: A 69 year-old woman was referred to our department with a diagnosis of gastric cancer based on an upper gastrointestinal endoscopy during a medical examination. The endoscopy, along with various tests, helped establish a diagnosis of unresectable advanced gastric cancer (cT4aN3aM1P1c, cStage IV) with peritoneal dissemination. The first and second-line chemotherapy administered was S-1 plus oxaliplatin followed by ramucirumab and nab-paclitaxel, respectively. In this case, the disease was evaluated as progressive disease due to increased peritoneal dissemination. Nivolumab was administered as the third-line treatment. The patient developed interstitial pneumonia after nine courses of nivolumab, for which chemotherapy was discontinued and prednisolone treatment was initiated. The patient had a complete response to treatment endoscopically, 9 months after the last administration of nivolumab. After that, there was no recurrence of the cancer, despite there being no treatment for 5 months. CLINICAL DISCUSSION: It was suggested that the therapeutic effect of nivolumab could be maintained for a long period after discontinuation of its administration. In addition, a correlation has been reported between the treatment efficacy and immune-related adverse events associated with nivolumab. CONCLUSIONS: The synergistic effect of the sustained effect of nivolumab and later-line treatment may contribute to the prolongation of survival after discontinuation of nivolumab in patients who are refractory or intolerant to treatment.