A glypican-1-targeted antibody-drug conjugate exhibits potent tumor growth inhibition in glypican-1-positive pancreatic cancer and esophageal squamous cell carcinoma.

An antibody-drug conjugate (ADC) is a promising therapeutic modality because selective and effective delivery of an anti-cancer drug is achieved by drug-conjugated antibody-targeting cancer antigen. Glypican 1 (GPC1) is highly expressed in malignant tumors, including pancreatic ductal adenocarcinoma (PDAC) and esophageal squamous cell carcinoma (ESCC). Herein, we describe the usefulness of GPC1-targeting ADC. Humanized anti-GPC1 antibody (clone T2) was developed and conjugated with monomethyl auristatin E (MMAE) via maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PABC) linkers (humanized GPC1-ADC[MMAE]). Humanized GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC and ESCC cell lines via inducing cycle arrest in the G2/M phase and apoptosis in vitro. The binding activity of humanized GPC1-ADC(MMAE) with GPC1 was comparable with that of the unconjugated anti-GPC1 antibody. The humanized GPC1-ADC(MMAE) was effective in GPC1-positive BxPC-3 subcutaneously xenografted mice but not in GPC1-negative BxPC-3-GPC1-KO xenografted mice. To assess the bystander killing activity of the humanized GPC1-ADC(MMAE), a mixture of GPC1-positive BxPC-3 and GPC1-negative BxPC-3-GPC1-KO-Luc cells were subcutaneously inoculated, and a heterogenous GPC1-expressing tumor model was developed. The humanized GPC1-ADC(MMAE) inhibited the tumor growth and decreased the luciferase signal, measured with an in vivo imaging system (IVIS), which suggests that the suppression of the BxPC-3-GPC1-KO-Luc population. The humanized GPC1-ADC(MMAE) also inhibited the established liver metastases of BxPC-3 cells and significantly improved the overall survival of the mice. It exhibited a potent antitumor effect on the GPC1-positive PDAC and ESCC patient-derived xenograft (PDX) models. Our preclinical data demonstrate that GPC1 is a promising therapeutic target for ADC.

Intrahepatic bile duct adenoma in a patient with gastric cancer.

We report a case of intrahepatic bile duct adenoma (BDA) detected during laparoscopic distal gastrectomy for gastric cancer. A 70-year-old man was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed an irregular, nodular, and elevated lesion on the greater curvature side of the middle third of the stomach. Abdominal contrast-enhanced computed tomography showed wall thickening with homogeneous enhancement in the middle part of the stomach, and no lesions in the liver. The patient underwent laparoscopic distal gastrectomy with regional lymphadenectomy, and during the operation a small whitish nodule was observed on the lateral segment of the liver surface. The lesion was excised by partial resection of the liver for the purpose of both histological diagnosis and treatment. Pathological examination of the liver lesion revealed no structural or cellular atypia, no stromal invasion, and immunohistochemical positivity for CK7 and CK19, but negativity for p53. The final diagnosis was well-differentiated adenocarcinoma invading the gastric serosal layer without lymph node metastasis, and intrahepatic BDA measuring 0.4 × 0.3 cm. Following surgery, the patient remained symptom-free without evidence of recurrence for 5 months. To the best of our knowledge, this is the first case of BDA with gastric cancer. Because it is difficult to distinguish BDA from other liver tumors including metastatic cancer due to its characteristically small size and lack of specific morphological features on standard imaging, surgical resection should be considered as the most suitable approach for both accurate diagnosis and treatment.

Early gastric cancer with multiple submucosal heterotopic gastric gland: A case report.

A case of early gastric cancer involving multiple submucosal gastric glands that was treated by distal gastrectomy was described in the present case report. An 85-year-old man was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed an irregular, nodular, elevated lesion on the posterior wall of the middle third of the stomach, and biopsy specimens indicated well-differentiated tubular adenocarcinoma. Submucosal tumor (SMT)-like lesions were detected in the area adjacent to the nodular lesion, in the anterior wall side of the middle third of the stomach. Abdominal contrast-enhanced computed tomography showed cystic lesions in the middle part of the stomach, and no mass lesions in the liver. The patient underwent distal gastrectomy with regional lymphadenectomy. Macroscopic examination of the resected specimen showed an SMT-like lesion measuring 2.8×2.6 cm in contact with a superficial, depressed lesion measuring 1.7×0.9 mm in the middle third of the stomach, and another SMT-like lesion measuring 1.5×1.4 cm in diameter, which was also in the middle third of the stomach. The pathological diagnosis was well-differentiated tubular adenocarcinoma invading the gastric submucosal layer without lymph node metastasis, but with nearby submucosal heterotopic gastric gland (SHGG) detected. Following surgery, the patient remained symptom-free without evidence of recurrence for 3 months. The finding of SHGG remains a rare entity, and further studies are warranted to clarify the association between these submucosal lesions and the development of cancer.

Prognostic significance of serum alkaline phosphatase and lactate dehydrogenase levels in patients with unresectable advanced gastric cancer.

BACKGROUND: This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. METHODS: The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3-4 compared to T1-2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015-3.220; P = 0.044), T2-3 (HR 2.622; 95% CI 1.224-5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341-4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. CONCLUSIONS: High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Pathological Complete Response by S-1 Chemotherapy in Advanced Gastric Cancer.

A pathological complete response (pCR) to treatment for gastric cancer is a rare event, even when powerful treatment regimens are used. Herein, a case of 61-year-old male referred to our hospital with advanced gastric cancer who achieved a pCR following chemotherapy using S-1, and subsequently underwent total gastrectomy is reported. His initial esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the upper third of the stomach that was analyzed by biopsy to be a moderately differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed gastric wall thickening and lymph node swelling in the perigastric area. The patient was clinically diagnosed with cT3N1M0, stage IIB advanced gastric cancer. The patient decided against curative surgery due to his work circumstances and was started on S-1 (80 mg/m2) chemotherapy administered orally twice a day for 4 weeks, followed by 2 weeks of no chemotherapy. After four such courses of systemic S-1 chemotherapy, EGD showed a small, reddened lesion with aggregated, whitish lines. The gastric wall thickening and lymphadenopathy in the perigastric area were also reduced remarkably. The patient subsequently agreed to surgery, undergoing total gastrectomy with D2 lymphadenectomy. Gross examination of the surgically resected specimen showed a slightly erythrogenic, flat lesion measuring 1.5×1.0 cm. Pathological examination of the resected specimen and harvested lymph nodes detected no malignant cells. The postoperative course was uneventful. The patient has continued to receive S-1 chemotherapy, with no evidence of recurrence at 4 months post-surgery. To the best of our knowledge, this is only the second case of a gastric cancer patient achieving a pCR by S-1 monotherapy reported in the English literature and indicates the potential adoption of curative resection after S-1 chemotherapy as a treatment strategy for advanced gastric cancer.

Successful treatment of liver metastases arising from early gastric cancer achieved clinical complete response by nivolumab.

BACKGROUND: Although a recent randomized clinical trial has demonstrated that the objective response rate to nivolumab for metastatic gastric cancer was 11.2%, there was no patients confirmed complete response. Herein, we report on a case of liver metastasis arising from early gastric cancer in which a complete clinical response was achieved to nivolumab as third-line therapy. CASE PRESENTATION: A 77-year-old man was referred to Kochi Medical School Hospital for the treatment of liver metastases from gastric cancer. The patient had undergone laparoscopic total gastrectomy with regional lymph node dissection 30 months prior for early gastric cancer, with a final diagnosis of T1N0M0, stage IA. The patient developed solitary splenic metastasis measuring 42 mm 28 months later and underwent splenectomy because there was no evidence of further metastatic lesions in any other organ. The patient was treated with S-1 plus oxaliplatin based on negative immunohistochemical staining of the resected specimens for human epidermal growth factor receptor 2 (HER2). Four months after the splenectomy, the patient developed multiple liver metastases and was treated with ramucirumab plus paclitaxel. Because of disease progression, the patient was administered 3 mg/kg, i.v., nivolumab every 2 weeks. After 4 cycles of systemic treatment using nivolumab, abdominal computed tomography revealed marked shrinkage of the liver metastases. After 12 cycles of nivolumab, the liver metastases had disappeared completely. The patient did not develop any adverse reactions, including immune-reactive adverse events, during treatment. The patient continues to receive nivolumab, and there is no evidence of disease recurrence in the 8-month period since starting nivolumab. CONCLUSIONS: To the best of our knowledge, this is the first case report in the English literature of a gastric cancer patient achieving a complete clinical response to nivolumab, and highlights the potential for successful treatment of metastatic gastric cancer using nivolumab.

Clinical application of photodynamic medicine technology using light-emitting fluorescence imaging based on a specialized luminous source.

The natural amino acid 5-aminolevulinic acid (ALA) is a protoporphyrin IX (PpIX) precursor and a new-generation photosensitive substance that accumulates specifically in cancer cells. When indocyanine green (ICG) is irradiated with near-infrared (NIR) light, it shifts to a higher energy state and emits infrared light with a longer wavelength than the irradiated NIR light. Photodynamic diagnosis (PDD) using ALA and ICG-based NIR fluorescence imaging has emerged as a new diagnostic technique. Specifically, in laparoscopic examinations for serosa-invading advanced gastric cancer, peritoneal metastases could be detected by ALA-PDD, but not by conventional visible-light imaging. The HyperEye Medical System (HEMS) can visualize ICG fluorescence as color images simultaneously projected with visible light in real time. This ICG fluorescence method is widely applicable, including for intraoperative identification of sentinel lymph nodes, visualization of blood vessels in organ resection, and blood flow evaluation during surgery. Fluorescence navigation by ALA-PDD and NIR using ICG imaging provides good visualization and detection of the target lesions that is not possible with the naked eye. We propose that this technique should be used in fundamental research on the relationship among cellular dynamics, metabolic enzymes, and tumor tissues, and to evaluate clinical efficacy and safety in multicenter cooperative clinical trials.

Epstein-Barr virus-associated early gastric carcinoma with lymphoid stroma, accompanied with lymph node metastasis.

The present case report presents a rare case of Epstein-Barr virus (EBV)-associated early gastric carcinoma with lymphoid stroma, accompanied by lymph node metastasis. A 61-year-old woman was referred to our hospital following observation of a gastric mass lesion that was initially diagnosed at a medical check-up. Esophagogastroduodenoscopy revealed a slightly elevated lesion with a central irregular depression in the middle third of the stomach. Endoscopic ultrasonography revealed a well-circumscribed hypoechoic mass located predominantly within the submucosa and the mucosa. Biopsy specimens of the lesion indicated the possibility of carcinoma with lymphoid stroma with a lymphoepithelial lesion. Abdominal contrast-enhanced computed tomography (CT) revealed a well-defined mass with homogeneous enhancement approximately 1.2 cm in diameter in the middle part of the stomach, demonstrating lymphadenopathy in the perigastric area at a maximum size of 1.4 cm in diameter. The patient underwent laparoscopic distal gastrectomy with regional lymphadenectomy due to suspicion of a gastric carcinoma with lymphoid stroma. Histopathological and immunohistochemical findings verified the diagnosis of carcinoma with lymphoid stroma, which were positive for EBV-encoded RNA (EBER-ISH) by in situ hybridization. There was one lymph node metastasis, which was in line with the CT imaging. Marked infiltration of lymphoid cells was observed in the tumor stroma, which were negative for EBER-ISH. The present case is informative of the pathological characteristics of this condition, and clinicians should recognize the features of this disease to make an accurate diagnosis and select the appropriate treatment.

[A Case of Long-Term Survival in a Patient with Lung Metastasis of Gastric Cancer Treated Using Curative Surgery].

A 50-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy(EGD)revealed an irregular nodular lesion with an ulcer in the esophagogastric junction, the biopsy specimens of which showed moderately differentiated adenocarcinoma. Abdominal computed tomography(CT)showed a lymph node measuring 1.2 cm in the perigastric area. A clinical diagnosis of advanced gastric cancer was made, and the patient underwent total gastrectomy with D2 lymphadenectomy followed by Roux-en-Y reconstruction. Microscopic examination confirmed that the moderately differentiated adenocarcinoma invaded the muscularis propria with 1 lymph node metastasis and lymphovascular invasion. The final diagnosis according to the Japanese classification of gastric carcinoma was UE, Less, Type 2, 3.8×1.7 cm, T2(MP), M0, H0, P0, N1(1/15), tub2, ly1, v2, StageⅡ. The postoperative course was uneventful, and he received postoperative adjuvant chemotherapy with S-1. The patient underwent periodic follow-up physical examinations, and 1 year after the surgery, CT showed a well-defined mass measuring 1.0 cm in diameter located in the middle lobe of the right lung. Because there was no evidence of further metastatic lesions in any other organs, he underwent surgical resection of the solitary pulmonary lesion by video-assisted thoracic surgery. Pathological examination confirmed the presence of moderately differentiated adenocarcinoma, and the proliferating tumor cells were positive for cytokeratin(CK)7 and CK20, and negative for thyroid transcription factor 1, which confirmed metastasis from gastric cancer. After the surgery, the patient received combination chemotherapy with S-1 plus cisplatin, followed by S-1 monotherapy. Five years after pulmonary metastasectomy, we discontinued chemotherapy because of no evidence of recurrence and the patient's wishes. The patient has remained in good health without evidence of recurrence for 7 years following the second surgery. Resection of the metastatic lesion might be a promising treatment for solitary pulmonary metastasis of gastric cancer; however, further investigations involving the accumulation of a large number of cases and prospective cohort studies are required to verify the above issue, and future development of multidisciplinary therapy is expected.

Serum carbohydrate antigen 125 is a significant prognostic marker in patients with unresectable advanced or recurrent gastric cancer.

PURPOSE: We evaluated the diagnostic and prognostic value of three tumor markers: carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), in the pretreatment serum of patients with unresectable advanced or recurrent gastric cancer. METHODS: The subjects of this retrospective analysis were 245 patients with unresectable advanced or recurrent gastric cancer diagnosed at Kochi Medical School between 2007 and 2015. We ascertained the sensitivity of CEA, CA19-9, and CA125 to identify a certain survival time and then evaluated the relative prognosis of the patients. RESULTS: The overall positive rates for each tumor marker in the study group were as follows: 57.6% (141/245) for CEA, 38.4% (94/245) for CA19-9, and 34.3% (84/245) for CA125; the sensitivity of these three biomarkers in combination was 73.1% (179/245). The median survival time of the CA125-positive patients was 4.5 months, which was significantly shorter than that of a normal range group (18.3 months, P < 0.001). Multivariate survival analysis identified that high CA125 was independently associated with a worse prognosis (HR 3.941; 95% CI 2.544-6.106; P < 0.001). CONCLUSIONS: Pretreatment serum CA125 is a useful prognostic biomarker in patients with unresectable advanced or recurrent gastric cancer. Evaluating a panel of serum tumor biomarkers is a useful diagnostic tool as elevated values might be associated with poor survival.

Metachronous solitary splenic metastasis arising from early gastric cancer: a case report and literature review.

BACKGROUND: The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. CASE PRESENTATION: A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. CONCLUSION: To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.

Gastric adenocarcinoma at the anastomotic site 50 years after gastrojejunostomy: A case report.

We herein report a rare case of superficially spreading early gastric cancer occurring 50 years after gastrojejunostomy. An 83-year-old woman was diagnosed with gastric cancer after complaining of epigastric discomfort. The patient had undergone gastrojejunostomy with Braun jejunojejunostomy for benign chronic peptic ulcer 50 years prior. Esophagogastroduodenoscopy revealed an irregular nodular lesion on the gastric side of the anastomosis of the gastrojejunostomy. No abnormal lesions were identified by abdominal contrast-enhanced computed tomography. The patient underwent distal gastrectomy with regional lymphadenectomy. The final diagnosis was signet ring cell carcinoma invading the gastric submucosal layer, without lymph node metastasis, located in the area surrounding the original gastrojejunostomy and measuring 9.5×4.5 cm. In addition, dilated cystic glands were found in the submucosal layer, indicating gastritis cystica profunda. Following surgery, the patient remained symptom-free without evidence of recurrence for 46 months. Although it is not clear whether the adenocarcinoma at the stomal site was associated with the superficial spreading-type tumor in the present case, the observations may provide clues as to the pathogenic process of this entity.

Clinical presentation and treatment of gastric metastasis from other malignancies of solid organs.

The aim of the present study was to analyze the clinicopathologic features and treatment outcomes of gastric metastasis from other malignancies of solid organs. A review was conducted of patients with metastatic tumors in the stomach from other malignancies of solid organs detected endoscopically at the Department of Surgery, Kochi Medical School, from January 1991 to December 2015. Seven patients (four men and three women), with a median age of 64 years (range, 42-71 years), had metastatic gastric tumors. Median tumor size was 7.3 cm (range, 2.5-12.0 cm). The primary malignancy leading to metastatic tumors in the stomach was esophageal cancer in three patients, breast cancer in two patients, renal cell carcinoma in one patient, and ovarian cancer in one patient. Gastric metastasis presented as solitary lesions in six patients and as multiple lesions in one patient. Four patients had solitary gastric metastasis, whereas three had multiple metastases in other organs. The median tumor size was significantly smaller in patients with solitary rather than multiple metastases (4.6 vs. 12.0 cm, respectively; P=0.038). Three patients received systemic therapy and four underwent surgical resection of the metastatic tumor, and of these, only one was alive 58 months after surgery. Clinicians should be aware of the possible existence of metastatic gastric cancer, especially in breast carcinoma and esophageal cancer. Surgical resection may considerably improve patients' quality of life, and could be of benefit when there is a risk of bleeding and/or a solitary metastasis.

Subcutaneous metastasis arising from gastric cancer: A case report.

A 59-year-old man was referred to the Kochi Medical School Hospital due to left shoulder pain. Physical examination revealed a nodular, painful mass lesion in the subcutaneous tissue of the right chest wall, with a diameter of ~2 cm. Esophagogastroduodenoscopy revealed a large ulcerated tumor in the lower gastric body near the lesser curvature, and biopsy specimens of the gastric and humeral lesions revealed poorly differentiated adenocarcinoma. Abdominal computed tomography revealed multiple low-density lesions in the liver and a well-defined, 2.2-cm mass in the subcutaneous tissue of the right chest wall. The diagnosis was advanced gastric cancer with metastases to the liver, bone and skin, and systemic chemotherapy with radiotherapy for the bone metastasis was recommended. The patient also underwent distal gastrectomy to control bleeding from the primary gastric cancer lesion due to unresolved anemia, not improving by blood transfusion, and a low hemoglobin level. The subcutaneous tumor in the right chest wall was resected at the same time, to alleviate the pain caused by the mass. Macroscopic examination of the resected specimen revealed a well-circumscribed, solid tumor, measuring 2.2×2.1 cm, with a firm consistency. Microscopic examination showed infiltration of poorly differentiated adenocarcinoma cells into the subcutaneous tissue. Subcutaneous metastasis from gastric cancer is a rare manifestation, with a reported incidence of 0.8-1.0%. Cutaneous metastasis of cancer generally appears late in the course of the disease. Surgical resection of metastatic skin tumors is occasionally undertaken as palliative treatment to improve the patient's quality of life by controlling severe symptoms, including pain and hemorrhage.

Juxtapapillary Duodenal Diverticulum Impacted with Enterolith.

A 64-year-old man underwent abdominal computed tomography (CT) as periodic follow-up following a distal gastrectomy with lymphadenectomy for gastric cancer and mucosal-associated lymphoid tissue (MALT) lymphoma conducted 31 months earlier. Contrast-enhanced CT demonstrated a well-circumscribed mass lesion with heterogeneous density measuring 2.2 cm in diameter located between the second segment of the duodenum and uncinate process of the pancreas. Esophagogastroduodenoscopy revealed no remarkable findings in the remnant stomach; however, the scope could not reach the duodenum due to altered anatomy by Roux-en-Y reconstruction after the distal gastrectomy. The patient underwent surgical resection of the mass lesion under the clinical diagnosis of MALT lymphoma relapse. An orange calculus was apparent in the thinly extended duodenal wall on stretching, and the hall was closed by meticulous primary suture after the duodenal resection. Macroscopically, the extracted calculus was solid and quite hard, measured 2.2 × 2.1 × 2.1 cm, and the cut surface revealed a layered structure in the outer areas with granulated contents in the center. Although duodenal diverticula are relatively common, an enterolith developing within a juxtapapillary duodenal diverticulum is rare, and to the best of our knowledge, this is the first such case due to altered anatomy after gastrectomy reported in the English literature.

[A Case of Advanced Gastric Cancer with Liver Metastasis Treated by Curative Surgery after Chemotherapy Using S-1 plus Oxaliplatin].

A 76-year-old man was referred to our hospital with gastric cancer.Esophagogastroduodenoscopy (EGD)revealed an irregular, nodulated lesion with ulcers in the lower part of the stomach, for which biopsy specimens indicated poorly differentiated adenocarcinoma.Abdominal computed tomography(CT)showed a well-defined mass lesion measuring 5.3 cm in the posterior segment of the liver.Under the clinical diagnosis of advanced gastric cancer with liver metastasis, the patient received chemotherapy using S-1 and oxaliplatin.After 8 courses of chemotherapy, abdominal CT and EGD revealed that the size of liver metastasis was reduced to 2.3 cm. He underwent distal gastrectomy with D2 lymphadenectomy and resection of the liver metastases because there was no evidence of further metastatic lesions in any other organs after 10 courses of chemotherapy.The gross appearance of the surgically resected specimen showed a shrunk gastric tumor measuring 3.5×3.0 cm and a well-circumscribed, solid liver mass.Pathological examination confirmed the diagnosis of solid-type, poorly differentiated adenocarcinoma in the stomach that had invaded the submucosal layer with no lymph node metastasis, and necrotic change of the liver mass.The postoperative course was uneventful, and the patient has been well, receiving maintenance chemotherapy using S-1, without evidence of recurrence for 9 months following the operation.Conversion surgery following chemotherapy might be a proposed treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to establish this treatment strategy.

Neurofibroma of the Gallbladder Not Associated with Neurofibromatosis.

An 82-year-old woman had visited her local clinic with a history of abdominal discomfort and dyspepsia related to meals over a period of several months. Esophagogastroduodenoscopy revealed a superficial spreading tumor that, on biopsy, was proven to be an adenocarcinoma, and colonoscopy revealed an ascending mass that was found to be an adenocarcinoma on biopsy, so the patient was referred to our hospital. Abdominal computed tomography revealed a mass in the ascending colon with regional lymph node swelling and a gallbladder stone measuring 1.5 cm in diameter. The patient underwent laparoscopy-assisted distal gastrectomy with cholecystectomy and right colectomy with regional lymph node dissection, resulting in a diagnosis of poorly differentiated adenocarcinoma invading the gastric submucosal layer and moderately differentiated tubular adenocarcinoma invading the colonic serosa with lymph node metastasis. Macroscopic examination of the gallbladder revealed a well-circumscribed, solid tumor measuring 0.3 x 0.3 cm with a firm consistency in the neck portion associated with lithiasis. Microscopic examination of the gallbladder tumor revealed infiltration of spindle-shaped neoplastic cells that were arranged in a fasciculated and woven pattern in abundant intersecting bundles. Immunohistochemical analyses were positive for S-100 protein and neurofilament. Although neurofibromas commonly occur in the superficial skin or subcutaneous region, isolated neurofibroma of the gallbladder is quite rare. To the best of our knowledge, this is only the 11th case of a neurofibroma of the gallbladder to be reported in English literature. In the present case, as in most previously reported cases, the tumor was found incidentally in the resected gallbladder following cholecystectomy for cholecystolithiasis.

Analysis of Factors Associated with Weight Loss After Esophagectomy for Esophageal Cancer.

AIM: To investigate the factors associated with weight loss (WL) after esophagectomy for esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 136 patients who underwent esophagectomy for esophageal cancer. Preoperative characteristics, surgical methods, postoperative outcomes and weight changes at 6 months after surgery were analyzed. RESULTS: Seventy-eight patients had more than 10% WL compared to their weight at surgery. On univariate analysis, higher body mass index [(BMI): ≥20.8; p=0.012] and shorter length of hospitalization [(LOH); p=0.041] demonstrated an association with more than 10% WL. On multivariate analysis, higher BMI [odds ratio (OR)=2.821; 95% confidence interval (CI)=1.238-6.426; p=0.014] and shorter LOH (OR=2.953; 95% CI=1.009-8.646; p=0.048) were independently associated with more than 10% WL. CONCLUSION: Higher BMI and shorter LOH were unfavorable risk factors for WL after esophagectomy for esophageal cancer.

Antitumor Effects of Eribulin Mesylate in Gemcitabine-resistant Pancreatic Cancer Cell Lines.

BACKGROUND/AIM: One reason of poor survival rate of patients with pancreatic cancer is the development of chemoresistance. The aim of the present study was to investigate the effects of eribulin mesylate in gemcitabine-refractory advanced pancreatic cancer cell lines. MATERIALS AND METHODS: Three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate. Cell viability after treatment of cells with different concentrations of gemcitabine and eribulin mesylate was evaluated using water-soluble tetrazolium salts (WST) assays; cytotoxic effects were evaluated on the basis of morphological changes to cells. RESULTS: Gemcitabine had no effect on cell viability of AsPC-1 nor Panc-1 cells, whereas gemcitabine reduced cell viability of SUIT-2 cells in a dose-dependent manner. Eribulin mesylate significantly reduced cell viability of both AsPC-1 and Panc-1 cells (p<0.001 and p=0.002, respectively), but had no effect on hPE cells. Microscopic examination of AsPC-1 and Panc-1 cells after treatment with eribulin mesylate revealed morphological changes that included cell shrinkage, membrane blebbing, and fragmentation of the cells after drug exposure, and these were concentration-dependent effects. CONCLUSION: The findings of the present study suggest that eribulin mesylate may be a promising potential anticancer drug for gemcitabine-refractory advanced pancreatic cancer.

Evaluation of a trastuzumab-containing treatment regimen for patients with unresectable advanced or recurrent gastric cancer.

The present study aimed to evaluate the efficacy and safety of trastuzumab plus chemotherapy for patients with unresectable advanced or recurrent gastric cancer. A retrospective analysis of 213 patients with unresectable advanced or recurrent gastric cancer who received systemic chemotherapy, including 15 patients who were also administered trastuzumab, at Kochi Medical School between 2007 and 2013 was performed. The overall survival was compared between patients who received trastuzumab plus chemotherapy and patients who received chemotherapy alone, and the safety and efficacy of the trastuzumab-containing regimen was evaluated. Human epidermal growth factor receptor (HER)2 status was examined in 86 patients, of whom 15 (17.4%) exhibited strong positive HER2 expression. The rate of strong positive HER2 expression was significantly higher for intestinal type tumors compared with diffuse type tumors [23.6 (13/55) vs. 6.5% (2/31); P=0.044]. The median overall survival of the patients treated with trastuzumab was significantly longer compared with that for patients who were not treated with trastuzumab (22.9 vs. 11.6 months; P=0.014). The objective response rate and disease control rate for trastuzumab plus chemotherapy were 46.7 and 86.7%, respectively. Frequently encountered grade 3-4 toxicities included neutropenia (26.7%; 4/15), anemia (13.3%; 2/15) and fatigue (13.3%; 2/15). Trastuzumab plus chemotherapy is effective for patients with HER2-positive advanced or recurrent gastric cancer, and the frequencies of hematological and non-hematological toxicities experienced by patients in the present study indicated that it can be safely administered clinically.