Safe suprapancreatic lymph node dissection for gastric cancer with ectopic common hepatic artery.

Suprapancreatic lymph node dissection for patients with gastric cancer in whom the common hepatic artery is located neither at the suprapancreatic margin nor in front of the portal vein is a more difficult procedure than when the common hepatic artery is in a more typical position. There is an increased risk of injury to the vessels that need to be preserved and inadequate lymph node dissection. Measures that have been reported for use in this situation are preoperative diagnosis with three-dimensional computed tomography angiography, dissection using the portal vain as a guide, and safe exposure of the portal vein with dissection to preserve the nerves at the suprapancreatic margin and in front of the portal vein. We review the literature and report our experience with a patient whose common hepatic artery was not located in the suprapancreatic margin who safely underwent suprapancreatic lymph node dissection using these methods.

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 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.

Validating the Japanese version of the Gastrointestinal Quality of Life Index (GIQLI) questionnaire.

AIM: To validate a Japanese version of the Gastrointestinal Quality of Life Index (GIQLI) in patients with symptomatic gallstone disease. METHODS: We investigated responsiveness, reliability, and convergent validity of the translated GIQLI in patients who underwent elective laparoscopic cholecystectomy. Questionnaire scores were compared with the Gastrointestinal Symptom Rating Scale (GSRS) to verify convergent validity. RESULTS: There were 120 patients originally enrolled in the study; three were excluded after their surgery as they no longer met the inclusion criteria. Questionnaires were collected from the remaining 117 patients (100% response rate). At 2 weeks post-surgery, total GIQLI score increased significantly from pre-surgery levels, suggesting high responsiveness. Cronbach's alpha ranged from 0.901 to 0.934 for the total score, while a comparison of scores at 2 vs 6 weeks post-surgery yielded an intraclass correlation coefficient of 0.843; thus, the Japanese version of the questionnaire was reliable. Correlations with GSRS ranged between -0.459 and -0.679, indicating fair to good convergent validity. CONCLUSION: The Japanese GIQLI had high responsiveness and reliability to assess how surgery for symptomatic gallstone disease influenced patient quality of life.

A case of multiple metastatic gastric cancer with primary lesion vanished after administrating nivolumab, and the effect remains even after discontinuance of therapy.

Nivolumab is one of the immune checkpoint inhibitors available for chemotherapy-resistant gastric cancer. There have been few reports of confirmed prominent shrinkage of the primary tumor and some reports of prolonged antitumor effect after discontinuance of the drug, but it is not universal. A 67-year-old male was admitted to our hospital and diagnosed with metastatic gastric cancer that had spread to the bilateral lobe of the liver, distant lymph nodes, and peritoneum. He received five courses of S-1 plus oxaliplatin, followed by three courses of ramucirumab plus paclitaxel leading to disease progression. Then, the patient was administered nivolumab as third-line therapy. Tumor size was markedly reduced after three courses, esophagogastroduodenoscopy (EGD) revealed scar formation on the lower gastric corpus after seven courses, and biopsy specimen showed no malignancy. When a slight lower limb muscle weakness manifested, possibly an immune-related adverse event (irAE) after 15 courses, we stopped administration of nivolumab. The patient has survived for 26 months since his first visit, and elimination of the primary tumor and ascites with noted shrinkage of liver and lymph node metastases have followed for more than 10 months since discontinuance of nivolumab.

A long-term survival case of unresectable gastric cancer with multidisciplinary therapy including immunotherapy and abscopal effect.

The prognosis of unresectable gastric cancer remains poor. Multidisciplinary treatment of unresectable gastric cancer is, therefore, thought to be essential for improving patients' outcomes. Here, we report a successful case of multidisciplinary therapy for unresectable gastric cancer. The patient was a 69-year-old woman who was diagnosed with type 2 gastric cancer with remote lymph node metastases and peritoneal dissemination. Although shrinkage of the primary lesion and remote lymph nodes were observed following chemotherapy, we performed distal gastrectomy to deal with continuous bleeding from the primary lesion. Combination therapy with radiation and chemotherapy was effective for multiple metastases in both subclavian lymph nodes and metachronous multiple axillary lymph nodes. Nivolumab combined with radiation therapy also induced regression of remote lymph node metastases, peritoneal dissemination, and adrenal metastasis. Abscopal effects, i.e., shrinkage of the non-irradiated lesions, were also observed. Thus far, the patient has been able to maintain a good quality of life while receiving continued nivolumab therapy. Multidisciplinary therapy including immunotherapy and abscopal effect may improve the quality of life and contribute to long-term survival of patients with unresectable gastric cancer.

Neoplastic meningitis due to colorectal cancer.

Herein, we describe a rare case of neoplastic meningitis in a 54-year-old male with a history of colorectal cancer. He first noticed a loss of sensation in his left thigh along with back pain. Magnetic resonance imaging showed a tumor lesion in the cauda equina. The tumor was surgically resected and pathologically diagnosed as a metastatic tumor of the descending colon cancer for which he had undergone resection a year earlier. The patient was treated with chemotherapy using capecitabine, oxaliplatin, and cetuximab. During chemotherapy, his tumor markers decreased and magnetic resonance imaging showed tumor shrinkage, but he became aware of neurological symptoms such as hearing loss, tinnitus, and headache. The patient's condition suddenly worsened during the 5th course of chemotherapy and he died 5 months after the diagnosis. Neoplastic meningitis occurs in 4-15% of patients with solid tumors, but it is rarely seen in colorectal cancer. It should be considered when a patient with a history of cancer has back pain or neurological symptoms. The progression of neoplastic meningitis is fast and it has a poor prognosis. Diagnosis in the early stages is important to prevent progression of neurological symptoms and to provide the most effective treatment.

Reactive oxygen species upregulate expression of muscle atrophy-associated ubiquitin ligase Cbl-b in rat L6 skeletal muscle cells.

Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798-4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at -110 to -60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway.

[Impacts of physical exercise on remodeling and hypertrophy of skeletal muscle.]

The skeletal muscle has high sensitivity for the mechanical stress. Because it is enlarged by training, whereas it is easily withered by lack of exercise. When we exercise, skeletal muscle cells per se sense mechanical loading, and muscular remodeling and the muscular hypertrophy occur. It has been revealed that the intracellular signaling through PGC-1α participates in the remodeling of the skeletal muscle, while PGC-1α4, an isoform of PGC-1α, and the dystrophin-glycoprotein complex play important roles in muscular hypertrophy. This review describes the impact of physical exercise gives on the remodeling and hypertrophy of muscle through the signaling.

The Selective Arterial Calcium Injection Test is a Valid Diagnostic Method for Invisible Gastrinoma with Duodenal Ulcer Stenosis: A Case Report.

The localization and diagnosis of microgastrinomas in a patient with multiple endocrine neoplasia type 1 is difficult preoperatively. The selective arterial calcium injection (SACI) test is a valid diagnostic method for the preoperative diagnosis of these invisible microgastrinomas. We report a rare case of multiple invisible duodenal microgastrinomas with severe duodenal stenosis diagnosed preoperatively by using the SACI test. A 50-year-old man was admitted to our hospital with recurrent duodenal ulcers. His serum gastrin level was elevated to 730 pg/ml. It was impossible for gastrointestinal endoscopy to pass through to visualize the inferior part of the duodenum, because recurrent duodenal ulcers had resulted in severe duodenal stenosis. The duodenal stenosis also prevented additional endoscopic examinations such as endoscopic ultrasonography. Computed tomography did not show any tumors in the duodenum and pancreas. The SACI test provided the evidence for a gastrinoma in the vascular territory of the inferior pancreatic-duodenal artery. We diagnosed a gastrinoma in the peri- ampullary lesion, so we performed Subtotal Stomach-Preserving Pancreatico- duodenectomy with regional lymphadenectomy. Histopathological findings showed multiple duodenal gastrinomas with lymph node metastasis and nonfunctioning pancreatic neuroendocrine tumors. Twenty months after surgery, the patient is alive with no evidence of recurrence and a normal gastrin level. In conclusion, the SACI test can enhance the accuracy of preoperative localization and diagnosis of invisible microgastrinomas, especially in the setting of severe duodenal stenosis.

Ruptured left colic arterial aneurysm treated by transcatheter arterial embolization alone and without a subsequent laparotomy: report of a case.

We herein report the case of a 49-year-old male patient with a ruptured aneurysm originating in the left colic artery, which was successfully treated by transcatheter arterial embolization (TAE) Abdominal computed tomography revealed a large hematoma with a central small aneurysm in the left upper abdomen. Celiac and superior mesenteric arteriography showed no dye extravasation. Subsequent aortography showed an aneurysm arising from the branch of the left colic artery that was successfully treated by selective TAE. Further surgery for subsequent ischemia was not performed. In cases presenting with an unclear source of intraabdominal bleeding, an aneurysm of the inferior mesenteric arterial branch should be considered. Transcatheter arterial embolization is a plausible initial treatment option as an effective therapeutic approach because it provides a curative and less invasive alternative to other therapies. Based on our experience and a review of the literature, surgery may not necessarily be imperative, even in cases of a ruptured aneurysm of a colic arterial branch after TAE.

Diffuse large B-cell lymphoma in the ampulla of vater causing obstructive jaundice: report of a case.

We report a case of diffuse large B-cell lymphoma (DLBCL) in the ampulla of Vater, causing painless obstructive jaundice in a 78-year-old woman. Duodenal endoscopy revealed a mass in the ampulla of Vater and narrowing of the second portion of the duodenum, although diagnosing DLBCL from an endoscopic biopsy was impossible because there were several kinds of leukocytes in the infiltrate. We performed pylorus-preserving pancreatoduodenectomy to establish a histological diagnosis, relieve the obstructive jaundice, and remove the narrowed second portion of the duodenum. Histological and immunohistochemical examination of the surgically resected specimen confirmed a diagnosis of DLBCL. Chemotherapy is the mainstay of treatment for DLBCL; however, surgery still plays an important role when the histological diagnosis cannot be established preoperatively and when complications are not amenable to nonsurgical therapy.

Changes in intestinal flora after administration of panipenem/betamipron or sulbactam/cefoperazone for treatment of postoperative infections in gastrectomy patients.

To determine the effect of antibiotics used for the treatment of postoperative infections on the normal intestinal flora in patients who have undergone gastroenterological surgery, we performed a prospective randomized study in patients who had undergone distal gastrectomy. Cefazoline was administered up to postoperative day 3 for prophylaxis. For the treatment of postoperative infections, either panipenem/betamipron (PAPM/BP; n = 5) or sulbactam/cefoperazone (SBT/CPZ; n = 5) was adminstered to ten patients with signs of postoperative infections. Feces were examined for bacteria before and 4 and 7 days after the commencement of administration of these therapeutic antibiotics. The anaerobic bacterial count decreased significantly in four of five patients treated with SBT/CPZ, from 1010.2+/-0.36/g before treatment to 105.22+/-3.51/g. In the PAPM/BP-treated group, the anaerobic bacterial count did not change after antibiotic therapy. We also investigated the major genera of colonic anaerobes, and found that the numbers of bifidobacteria were maintained during PAPM/BP administration. However, in the SBT/CPZ group, the number of bifidobacteria decreased to below the detection limit in four of five patients. Little change was observed in the aerobic bacterial count in either group. However, Enterobacteriaceae were replaced by enterococcus or candida in all patients from the SBT/CPZ group and in one of five patients from the PAPM/BP group. Physicians should be alert for the possible clinical consequences of changes in intestinal microflora after antibiotic treatment of postoperative infections.