[A Case of Unresectable Pancreatic Cancer with Massive Cancerous Ascites Responsive to KM-CART].

A 79-year-old woman visited our hospital complaining of bloating. An abdominal enhanced CT scan revealed pancreatic body cancer with cancerous ascites and multiple liver metastases. We started gemcitabine(GEM)plus nab-paclitaxel chemotherapy. Chemotherapy was not continued because she was unable to take oral medication owing to increased cancerous ascites. We conducted modified KM-cell-free and concentrated ascites reinfusion therapy(KM-CART). Her symptoms improved, and she began having oral intake after KM-CART. Chemotherapy was then re-initiated. Seven months have now passed since we started chemotherapy, and we can continue chemotherapy while conducting KM-CART repeatedly. KM- CART is useful for treating unresectable pancreatic cancer with massive cancerous ascites in terms of continuing chemotherapy.

A case of Turcot's syndrome type 1 with loss of immunoexpression of MSH6 in colon cancer and liver metastasis due to secondary somatic mutation in coding mononucleotide (C)8 tract: a case report.

BACKGROUND: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. CASE PRESENTATION: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. CONCLUSION: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.

Feasibility and efficacy of repeat laparoscopic liver resection for recurrent hepatocellular carcinoma.

BACKGROUND: Repeat hepatectomy is an acceptable treatment for recurrent hepatocellular carcinoma (HCC). However, repeat laparoscopic liver resection (LLR) has not been widely adopted due to its technical difficulty. This study aimed to assess the feasibility and efficacy of repeat LLR compared with repeat open liver resection (OLR) for recurrent HCC. METHODS: We performed 42 repeat OLR and 30 repeat LLR for cases of recurrent HCC between January 2007 and March 2018. This study retrospectively compared the patients' clinicopathological characteristics and operative and short-term outcomes including surgical time, intraoperative blood loss, duration of hospital stay, and postoperative complications between the two groups. RESULTS: There were no significant differences in patient characteristics between the two groups except in terms of Child-Pugh grade. The repeat LLR group had lower median intraoperative blood loss (100 mL vs. 435 mL; P = 0.001) and shorter median postoperative hospital stay (10 days vs. 14.5 days; P = 0.002). The other results including postoperative complications were comparable between the two groups. Further, comparison of two subpopulations of the repeat LLR group stratified by previous hepatectomy type (open or laparoscopic) or tumor location (segments 7 and 8 or other) revealed no significant differences in the postoperative clinical characteristics between them, although the morbidity rate tended to be higher in patients who underwent open hepatectomy for primary HCC than in patients who underwent laparoscopic hepatectomy. CONCLUSIONS: Repeat LLR for recurrent HCC is feasible and useful with good short-term outcomes although an appropriate patient selection seems to be necessary.

[MSI-H Small Bowel Cancer with Peritoneal Dissemination Successfully Treated with Pembrolizumab-A Case Report].

A 52-year-old man was diagnosed with small bowel adenocarcinoma(T4aN1M0, Stage ⅢA, according to the Japanese colorectal cancer classification)and treated with partial resection of the small bowel in June 2014. He also received adjuvant chemotherapy(XELOX: 8 courses)after surgery. Three and a half years after the operation, peritoneal dissemination recurred, and he received bevacizumab plus XELOX therapy. The regimen was adjusted to a total of 11 courses because of the disease progression. The primary lesion showed MSI-H. The patient was started on pembrolizumab therapy in April 2019. The tumor responded well to pembrolizumab(maximum therapeutic effect: PR, 31% reduction), but a new lesion appeared 6 months after the start of this regimen. He continued pembrolizumab therapy for 14 months without adverse events since it appeared to be clinically effective. Although MSI-H small bowel cancers are rare, accurate screening is essential to not miss the opportunity to administer pembrolizumab.

[A Case of Sigmoid Colon Cancer Recurrence at the Hand-Sewn Anastomosis Site Originated from Tumor Implantation].

We report a case of anastomotic recurrence following laparoscopic sigmoidectomy with hand-sewn anastomosis, which was attributable to the implantation of exfoliated cancer cells. A 78-year-old man diagnosed with early colon cancer underwent endoscopic submucosal dissection(ESD); however, ESD was suspended due to infiltrated muscle fibers. Subsequently, he underwent laparoscopic sigmoidectomy with hand-sewn anastomosis, accompanied by D3 lymph node dissection. Histopathological findings revealed a well-differentiated tubular adenocarcinoma, pT2(MP), tub1>tub2>por2, ly0, v1, PM0, DM0, RM0, N0M0, pStage Ⅰ. The follow-up CT 6 months after surgery, showed enhanced wall thickening and irregular surface of the sigmoid colon. Colonoscopy revealed a type 2 tumor located on the anastomotic line. Based on the diagnosis of anastomotic recurrence, the patient underwent partial colectomy. Histopathological findings were similar to those of the primary tumor and suggested implantation of exfoliated cancer cells as the origin of anastomotic recurrence. Cancer cells had infiltrated all layers. In conclusion, we recommend the performance of appropriate operative procedures to prevent anastomotic recurrence, such as the cleaning of the anastomosed intestinal tract. Careful follow-up in colon cancer patients is of the utmost importance and the risk of anastomotic recurrence should always be considered.

[Two Cases of Colorectal Liver Metastasis with Localized Biliary Dilatation].

We encountered 2 cases of colorectal liver metastasis with biliarydilatation mimicking cholangiocarcinoma. Case 1: A 70- year-old male patient, who was diagnosed with colorectal cancer and underwent transverse colectomy3 years prior, was preoperativelydiagnosed with cholangiocarcinoma with biliarydilatation of the medial and lateral segments. He underwent left hemi-hepatectomy. The pathological diagnosis was colorectal liver metastasis with intra-biliarytumor thrombosis. Case 2: A 67-year-old male patient was diagnosed with descending colon cancer and cholangiocarcinoma with biliarydilatation of the medial segment. He underwent left hemi-colectomyand left hemi-hepatectomy. The pathological diagnosis was descending colon cancer and colorectal liver metastasis with biliaryinfiltration. The immunopathological findings showed double positivityfor CK20 and CDX2 antibodies and negativityfor CK7 antibodyin these cancer lesions.

[A Case of Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

A 71-year-old man was diagnosed as having Type 2 gastric cancer(tub2, HER2-negative). Abdominal computed tomography( CT)revealed bulky metastatic lymph nodes around the stomach and para-aorta(No. 16a2, b1). Our clinical diagnosis was cT4a(SE)N+M1(PAN), cStage Ⅳb, and SOX therapy was immediately administered. After 3 courses of chemotherapy, the treatment effect was PR, and after 6 courses, the patient was diagnosed with ycT2(MP)N0M0, ycStageⅠB. No Grade 2 or higher adverse events were observed during chemotherapy. At this stage, we determined that radical resection was feasible; thus, distal gastrectomy and D3 dissection(para-aortic lymph node dissection)were performed. No cancer cells were found in the primary lesion on histopathology. The histological response of the primary lesion was Grade 3, and the lymph node was Grade 2b. On follow-up observation, the patient is alive without tumor recurrence at 1 year postoperatively.

[Surgical Resection of Hepatic Portal Lymph Node Metastasis after Repeated Treatment for Hepatocellular Carcinoma Recurrence].

We encountered a case of hepatic portal lymph node metastasis after repeated treatment for hepatocellular carcinoma (HCC)recurrence. A 73-year-old male patient underwent partial gastrectomy following rupture of a gastrointestinal stromal tumor 8 years ago. A 70mm tumor was simultaneously revealed in the posterior segment of the liver, and imatinib treatment was initiated based on the diagnosis of a metastatic liver tumor. Due to the absence of an increasing tendency in the tumor, extended posterior segmentectomy was performed, and the pathological diagnosis was moderately differentiated HCC. During observation, transcatheter arterial chemoembolization(TACE)plus radiofrequency ablation(RFA)therapy was performed twice, and partial resection of the liver was performed once again for HCC recurrence. Recently, PIVKA-Ⅱ showed a high value of 1,720mAU/mL, and follow-up computed tomography showed HCC recurrence in S4/8 and hepatic portal lymph node metastasis. TACE was administered for recurrent lesions in S4/8, and surgical resection of the hepatic portal lymph node was performed together. The pathological diagnosis revealed extensive liver tissue necrosis and moderately-topoorly differentiated HCC in the excised lymph nodes. Lymph node metastasis of HCC is rare, and in this case, a change in lymph flow caused by repeated treatment for HCC recurrence was considered a factor influencing the course.

Intrahepatic cholangiocarcinoma with extensive intraductal extension of high-grade biliary intraepithelial neoplasia: a case report.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is frequently associated with precursor lesions, and biliary intraepithelial neoplasia (BilIN) may play a significant role in the development of ICC. However, the exact sequence and progression of these lesions remain to be elucidated. We report a rare case of ICC that exhibited extensive longitudinal intraductal extension of high-grade BilIN in the posterior bile ducts and involved the hepatic hilum and the peripheral hepatic parenchyma. CASE PRESENTATION: A 70-year-old female presented with anorexia. Computed tomography (CT) revealed a 15 mm enhancing intrahepatic tumor extending to the right intrahepatic secondary confluence. This was associated with a 7 mm diameter cystic dilatation of the segment 6 bile duct (B6). Endoscopic retrograde cholangiopancreatography (ERCP) revealed stenosis at the bifurcation of the posterior bile duct branch. Bile cytology confirmed the diagnosis of adenocarcinoma cells. Therefore, the patient was diagnosed with an ICC involving the right glissonean pedicle and underwent a right hepatectomy and lymph node dissection. Histologic examination revealed the tumor consisted of moderately differentiated adenocarcinoma. In connection with this lesion, diffuse intraductal atypical epithelial cells, which were diagnosed as high-grade BilIN, was observed not only in the dilated B6 but in the entire posterior bile ducts, which measured approximately 120 mm in diameter. Furthermore, two distinct foci of adenocarcinomas were identified in the peripheral hepatic parenchyma. A lymph node metastasis was also present. The pathological diagnosis was ICC pT4N1M0 stage IVA. The patient underwent adjuvant chemotherapy and has shown no recurrence 5 years after surgery. Imaging modalities were unable to accurately assess the extent of the intraductal neoplastic lesions due to their low papillary or sessile intraductal tubular growth. No risk factors for BilIN development, which has the potential to predispose to cholangiocarcinoma, were identified in the present case. CONCLUSIONS: We present a case of ICC involving the right hepatic hilum, accompanied by extensive longitudinal extensions of high-grade BilIN and multifocal microscopic invasions in peripheral hepatic parenchyma. Notably, the intraductal lesions involved the entire posterior intrahepatic bile ducts. The presence of biliary neoplasia with extensive intraductal extension, in conjunction with ICC, should be considered as a variant of BilIN.

Nutritional Status Indicators Affecting the Tolerability of Postoperative Chemotherapy After Total Gastrectomy in Patients With Gastric Cancer.

Purpose: Nutritional problems after gastrectomy affect continuation of postoperative chemotherapy. There have been no studies limited to total gastrectomy, which is particularly prone to nutritional problems. In this study, we aimed to investigate the factors that predict the continuation of postoperative chemotherapy. Materials and Methods: We included 101 patients who underwent curative total gastrectomy and postoperative chemotherapy at Hiroshima Memorial Hospital. The effects of 37 factors, including perioperative inflammatory, nutritional, and tumor status, on the persistence of postoperative chemotherapy were analyzed. Results: In univariate analysis of preoperative factors, age, carbohydrate antigen 19-9, platelet-to-neutrophil ratio, Onodera's prognostic nutritional index (PNI), controlling nutritional status score, and nutritional risk screening (NRS-2002) score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of preoperative factors, age (≥74 years) was an independent factor for a shorter duration of postoperative chemotherapy (hazard ratio [HR], 5.24; 95% confidence interval [CI], 2.19-12.96; P<0.01). In univariate analysis of factors before postoperative chemotherapy, intraoperative blood loss, perioperative weight loss rate, postoperative performance status, PNI, albumin-to-bilirubin index, and NRS-2002 score were significantly associated with the duration of postoperative chemotherapy. In multivariate analysis of factors before postoperative therapy, age (≥74 years) (HR, 5.75; 95% CI, 1.90-19.49; P<0.01) and PNI (<39) (HR, 3.29; 95% CI, 1.26-8.56; P=0.02) were independent factors for a shorter duration of postoperative chemotherapy. Conclusions: Age and PNI are useful predictors of postoperative chemotherapy intolerance after total gastrectomy and may determine the treatment strategy and timing of chemotherapy initiation.

Triple metachronous primary pancreatic and gallbladder cancer associated with pancreaticobiliary maljunction: a case report.

BACKGROUND: Metachronous pancreatic and gallbladder cancer is a rare condition and has a dismal prognosis. Herein, we present a patient with triple metachronous primary pancreatic and gallbladder cancer associated with pancreaticobiliary maljunction who achieved long-term survival after undergoing repeat curative surgery. CASE PRESENTATION: A 65-year-old female patient with advanced gallbladder cancer associated with pancreaticobiliary maljunction underwent extended cholecystectomy with extrahepatic bile duct resection. The pathological diagnosis was T3N0M0 stage III A papillary adenocarcinoma with hepatic invasion. During a monthly follow-up, a diffuse hypovascular 2.0 × 1.5-cm mass was detected in the pancreatic head 6.2 years after the initial surgery. Hence, the patient underwent pancreaticoduodenectomy. Histological examination revealed T3N0M0 stage IIA well-differentiated adenocarcinoma without lymph node metastases. Marked inflammatory reaction was observed in the non-cancerous lesions of the proximal pancreatic head parenchyma containing bile pigment within ductular lumens. After 12.5 years from the initial surgery, total pancreatectomy for a 4.0 × 3.0-cm mass in the remnant pancreas was performed. Histological examination revealed T3N1M0 stage IIB moderately differentiated adenocarcinoma with lymph node metastases. Hence, surgical curative resection was achieved. Based on the pathological findings, a definitive diagnosis of triple metachronous pancreatic and gallbladder cancer was made. The pathology suggests no precursor lesions such as pancreatic intraepithelial neoplasia (PanIN) and atypical flat lesions, but marked inflammations in the non-cancerous lesions, strengthening our hypothesis that chronic inflammation induced by the pancreaticobiliary maljunction is related to carcinogenesis of the pancreas. Despite further adjuvant chemotherapy, the patient's general condition worsened; however, she remained alive 15.2 years after the initial surgery while receiving the best supportive care. CONCLUSIONS: Repeat curative surgery for triple metachronous cancer was associated with a favorable prognosis. Both the biliary tract and the pancreas should be closely monitored during follow-up among patients with pancreaticobiliary maljunction, which can be managed with curative surgery.

A Case of Advanced Gastric Cancer with Peritoneal Metastasis Treated Successfully with Nivolumab.

Peritoneal metastasis (PM) is detected in 14% of gastric cancers at the time of initial diagnosis, with a median survival time of 4 months. A 66-year-old woman diagnosed with cT4a(SE) N2M1(LYN) cStage IV was treated with three lines of chemotherapy for a year. During the third line of chemotherapy, computed tomography (CT) scan revealed a large amount of ascites, periportal collar sign, and bilateral ureteral stenosis owing to PM. The tumor biomarkers (CEA and CA 19-9) remained elevated similar to the initial levels. The patient was administered 3 mg/kg nivolumab intravenously biweekly as the fourth line of chemotherapy. Three months after the nivolumab treatment, gastroscopy revealed an extreme reduction of the tumor size, while CT scan revealed the absence of ascites and a well-controlled tumor. There was no immune-related adverse event with nivolumab during and after the treatment, and performance status improved to 0. The patient has been alive for about 2.5 years since her first visit with her sixth line of chemotherapy (docetaxel). We report a case of advanced gastric cancer with PM that was treated successfully with nivolumab.

Laproscopic treatment for small bowel bleeding after detection by double-balloon endoscopy: A case report.

INTRODUCTION: The frequency of small bowel bleeding is relatively low and the process for the diagnosis and treaVtment remains difficult. Here, we report a case of massive small bowel bleeding due to arteriovenous malformation (AVM), treated by a combination of double-balloon endoscopy and laparoscopic resection. PRESENTATION OF CASE: A 59-year-old man was admitted to our hospital due to a hemorrhagic stool. The patient presented transient hemorrhagic shock and contrast-enhanced CT revealed a hyper-vascularized tumor in the small bowel. India ink tattooing for the responsible lesion with double-balloon endoscopy was performed. The tattooed lesion was easily confirmed during the subsequent laparoscopic observation and segmental resection was done. Pathological examination showed arteriovenous malformation of the small bowel. DISCUSSION: Prior to laparoscopic resection, the localization of the responsible area might be a significant consideration when the lesion is invisible. Endoscopic marking with DBE enables intraluminal detection and laparoscopic observation from the serosal side. CONCLUSION: Preoperative marking with the use of double-balloon endoscopy followed by laparoscopic resection might be an optimal option for the treatment of massive small intestinal bleeding.