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Background: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA., Methods: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins., Results: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression., Conclusion: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA., (© 2021. The Author(s).)

Purpose: The aim of this study was to assess the safety of rectal surgery after 5-fluorouracil-leucovorin-oxaliplatin chemotherapy (FOLFOX6)., Methods: This was a prospective, multicenter study in 11 Japanese hospitals. We included patients with rectal cancer who received 4 courses of modified FOLFOX6 (mFOLFOX6) before rectal surgery and examined the postoperative complication rate, the clinicopathological response, and the rate of chemotherapy-related adverse events (UMIN 000012559)., Results: The study population included 36 men and 5 women. The average age of the patients was 60.8 years and the average body mass index was 23.1 kg/m 2 . After 4 courses of chemotherapy, grade 2 peripheral nerve disorder and other grade 3 adverse events were seen in 3 patients each (7.3%). Twenty-eight (73.7%) and 8 (21.1%) patients underwent low anterior resection and abdominoperineal resection, respectively. The pelvic nerves were preserved in 35 patients. Surgical morbidity (grade ≥ 3) occurred in 4 patients (10.5%). Anastomotic leakage occurred after surgery in 2 patients (7.1%). No patients achieved pathologically complete remission. However, downstaging of the clinical stage and N stage was seen in 17 (41.5%) and 22 (53.7%) patients, respectively., Conclusions: Surgery after four courses of mFOLFOX6 chemotherapy can be a safe and promising strategy for patients with locally advanced rectal cancer.

A 53-year-old man underwent an esophagogastroduodenoscopy that showed a 20-mm subepithelial lesion in the middle gastric body. Endoscopic ultrasound revealed a hypoechoic mass located in the submucosa. Biopsy specimens revealed a benign gastric mucosa with severe lymphocytic infiltration in the submucosa. Malignant lymphoma or gastric cancer with lymphoid stroma was suspected. We performed endoscopic submucosal dissection for definitive diagnosis. Histological examination showed undifferentiated adenocarcinoma, which showed positive Epstein-Barr virus-encoded RNA in situ hybridization results, invading the submucosa mixed with dense lymphocytic infiltration. Thus, Epstein-Barr virus-positive gastric cancer with lymphoid stroma was diagnosed. Gastric cancer with lymphoid stroma is a rare subtype of gastric cancer, which is associated with Epstein-Barr virus infection; it sometimes appears as a subepithelial lesion, which makes it difficult to diagnose using standard biopsy. Endoscopic submucosal dissection was useful in obtaining a sufficient tissue for full histological assessment, including immunostaining.

Background and Aim: Differentiation between gastric adenocarcinoma and low-grade adenoma/dysplasia (LGA) on endoscopic forceps biopsy is difficult. We aim to clarify the incidence of carcinoma in specimens, obtained by endoscopic resection (ER), from cases that had been diagnosed as LGA (Vienna category 3) on endoscopic biopsy., Methods: In this multicenter, prospective, observational study, patients with gastric adenoma (Vienna category 3 or 4.1) diagnosed on endoscopic forceps biopsy were enrolled. All the specimens were subjected to histopathological central review. Primary endpoint was the incidence of carcinoma (Vienna category 4.2 or over) among the biopsy-proven gastric LGA. Secondary endpoints were the histological findings of resected specimens, clinicopathological features of carcinoma, and short-term outcomes of all ER cases., Results: Ninety-five patients with 104 lesions diagnosed as gastric adenoma were enrolled. After central review of the biopsy specimens, 47 lesions were diagnosed as LGA and seven lesions (15%) as adenocarcinoma (95% confidence interval, 7.6-28%). Carcinoma was detected in lesions that had a minimum size of 6 mm; the incidence of carcinoma was higher in the larger lesions. There was a histological discrepancy between biopsy and ER material in more than 60% of the cases., Conclusions: A substantial proportion of biopsy-proven gastric LGA specimens were diagnosed as adenocarcinoma after ER. This indicated histological discrepancy between biopsy-proven gastric LGA and histology of the resected material., (© 2017 Japan Gastroenterological Endoscopy Society.)

A woman in her 60s was referred to our hospital with a superficial depressed lesion measuring 8mm in diameter on the lesser curvature of the lower gastric body. Initial biopsy of the lesion indicated a moderately differentiated adenocarcinoma. Endoscopic submucosal dissection was performed, and pathological examination revealed a tumor comprised of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration, with the final pathological diagnosis being gastric mixed adenoneuroendocrine carcinoma (MANEC). Laparoscopic gastrectomy was subsequently performed. No recurrence was observed after 18 months. Most neuroendocrine carcinomas including MANEC are diagnosed at an advanced stage and require surgical resection. Here we report a case of gastric MANEC mimicking early gastric cancer that was removed en bloc via endoscopic submucosal dissection.

Background: Although conventional endoscopy (CE) and EUS are considered useful for predicting the invasion depth (T-staging) in early gastric cancer (EGC), no effective diagnostic strategy has been established., Objective: To produce simple CE criteria and to elucidate an efficient diagnostic method by combining CE and EUS for accurate T-staging., Design: Single-center retrospective analysis., Setting: Academic university hospital., Patients: Consecutive patients with EGC from April 2007 to March 2012 who underwent CE and EUS before treatment., Interventions: Recorded endoscopic images were independently reviewed by 3 observers. The CE criteria for massive invasion were defined, and their utility and the additional value of EUS were assessed., Main Outcome Measurements: The accuracy of CE based on the criteria and the accuracy of EUS., Results: Two hundred thirty patients were enrolled: 195 with mucosal cancer or cancer in the submucosa less than 500 μm from the muscularis mucosae and 35 with invasive cancers. Multivariate analysis of the CE findings by 1 observer revealed that an irregular surface and a submucosal tumor-like marginal elevation were significantly associated with massive invasion. The simple CE criteria, consisting of those 2 features, had an overall accuracy of 73% to 82% and no significant differences in the diagnostic yield compared with EUS in all observers. CE accurately revealed mucosal cancer, and EUS efficiently salvaged the lesions that were over-diagnosed by CE. With our strategy, which involved the CE criteria and the optimal use of EUS, the comprehensive accuracy exceeded 85% in each observer., Limitations: Retrospective, single-center study., Conclusions: We demonstrated a practical strategy for T-staging in EGC using simple CE criteria and EUS., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Study Aims: The safety and efficacy of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms (SENs) have not been evaluated in a multicenter survey. The aim of this study was to investigate the clinical outcomes in a multicenter study that included municipal hospitals., Patients and Methods: Of 312 consecutive patients with 373 esophageal lesions treated by ESD at 11 hospitals from May 2005 to December 2012, a total of 368 SENs in 307 patients were retrospectively analyzed., Results: The median tumor size was 18 mm (range 2 - 85 mm). The median procedure time was 90 minutes (range 12 - 450 minutes). The en bloc resection and complete resection rates were 96.7 % (95 % confidence interval [CI] 94.4 % - 98.1 %) and 84.5 % (95 %CI 80.5 % - 87.8 %), respectively. Perforation (including mediastinal emphysema), postoperative pneumonia, bleeding, and esophageal stricture, occurred in 5.2 % (95 %CI 3.3 % - 7.9 %), 1.6 % (95 %CI 0.7 % - 3.5 %), 0 %, and 7.1 % (95 %CI 4.9 % - 10.2 %) of patients, respectively. All of these complications were cured conservatively. No procedure-related mortality occurred. Early treatment periods (odds ratio [OR] = 4.04; P < 0.01) and low volume institutions (OR = 3.03; P  = 0.045) were significantly independent risk factors for perforation. The circumference of the lesion was significantly associated with postoperative stricture (OR = 32.3; P < 0.01). The procedure times significantly decreased in the later period of the study (P < 0.01). Follow-up data (median 35 months; range 4 - 98 months) showed significant differences in overall survival (P = 0.03) and recurrence-free survival (P < 0.01) rates between patients with curative and noncurative resections., Conclusions: Esophageal ESD has become feasible with acceptable complication risks and favorable long term outcomes., (© Georg Thieme Verlag KG Stuttgart · New York.)

White opaque substance (WOS) is observed in the gastric neoplasia of 0-IIa type using magnifying endoscopy with narrow band imaging (NBI-ME). Colonic and duodenal neoplasms with WOS have also been reported. Immunohistochemical examination with adipophilin reveals WOS in gastric neoplasms as lipid droplets, and WOS is specific for neoplasm with intestinal or gastrointestinal phenotype. We herein report a case of adenocarcinoma of the esophagogastric junction with WOS. A male patient in his sixties was found by esophagogastroduodenoscopy to have an esophageal elevated lesion. NBI-ME showed whitish deposits that looked similar to WOS in gastric neoplasms. The patient underwent endoscopic submucosal dissection and the lesion was resected in a single piece. This tumor had diffuse positivity for adipophilin and gastrointestinal phenotype., (© 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.)

A 62-year-old man was referred to our hospital with dysphagia. Blood examination revealed significantly elevated serum CA19-9 levels but normal CEA and SCC levels. Imaging uncovered thoracic esophageal cancer with lung and bone metastasis, and subsequent endoscopic biopsy specimens of the primary esophageal tumor showed poorly differentiated squamous cell carcinoma. The patient underwent palliative chemoradiotherapy, but died due to progression of multiple metastases and increasing serum CA19-9 levels. Autopsy revealed adenocarcinoma in multiple metastatic foci, although the squamous component had disappeared in the primary and metastatic lesions. Therefore, we concluded that the adenocarcinoma component of adenosquamous cell carcinoma was refractory to chemoradiotherapy.

Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions.

We report a 69-year-old female patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone(SIADH)following systemic chemotherapy with cisplatin(CDDP)and vinorelbine(VNR). She was admitted to our hospital for chemo-radiotherapy for advanced lung cancer, and became restless 4 hours after the administration of CDDP and VNR. Symptoms such as restlessness and incontinence were worsening despite the massive infusion that was completed. Laboratory examinations on day 6 after chemotherapy showed severe hyponatremia(107mEq/L)with decreased serum osmolarity(227mOsm/L)and increased urine osmolarity(452mOsm/L). The serum anti-diuretic hormone(ADH)level was elevated to 16. 7 pg/mL despite severe hyponatremia. She was diagnosed with SIADH and was treated with hypertonic saline infusion and fluid restriction. Her restlessness and other psychiatric symptoms were improved. The use of carboplatin and VNR in the subsequent course did not develop SIADH, indicating that the SIADH was induced by CDDP. Although SIADH following CDDP administration is rare, the electrolyte balance should be carefully monitored throughout the clinical course of chemo-radiation therapy, when psychiatric symptoms are found in patients with lung cancer.

Background: Treatment with endoscopic submucosal dissection (ESD) for gastric noninvasive neoplasia (NIN) diagnosed by endoscopic forceps biopsy specimen, whether as a follow-up or "total incisional biopsy", is controversial. To validate the use of ESD for total incisional biopsy in NIN, we examined the underdiagnosis rate of NIN and the rates of complication associated with ESD., Methods: This is a cross-sectional multicenter retrospective study from 10 hospitals. Subjects diagnosed with NIN (equivalent to category 3 or 4.1 of the Vienna classification) by endoscopic forceps biopsy and treated with ESD were included. From March 2003 to December 2009, a total of 468 subjects were included and analyzed. The underdiagnosis rate was defined as the proportion of lesions diagnosed with adenocarcinoma after ESD. We assessed the complete en-bloc resection rate and the complication rate of ESD., Results: Among the 468 subjects with NIN, 205 were diagnosed with adenocarcinoma after ESD, with an underdiagnosis rate of 44% (95% confidence interval: 39-49%). Two submucosal cancer lesions had invaded beyond 500 μm and one had lymphatic involvement. The complete en-bloc resection rate was 97%. The incidences of post-ESD bleeding, perforation, and serious complications were 5.5, 4.7, and 0.43%, respectively. There were no procedure-related deaths., Conclusions: In this large-scale, multicenter cross-sectional study, over 40% of the noninvasive gastric neoplasia specimens were determined to have adenocarcinoma, and the ESD-related complication rate was relatively low. Therefore, ESD was useful and may be a therapeutic option for gastric NIN.

A man in his seventies visited our hospital due to positive a fecal occult blood test. Colonoscopy showed a submucosal tumor in the rectum covered with reddish and irregular mucosa. Pathological examination of the biopsy specimen revealed well differentiated adenocarcinoma. The tumor was resected, and pathological examination showed carcinoid and adenocarcinoma components coexisting and mixed with each other. Because a previous colonoscopy had shown a submucosal tumor with a smooth surface, this case was diagnosed as a collision tumor of adenocarcinoma which developed on a carcinoid.

Background: We have reported previously that docetaxel (TXT) induces apoptosis and nuclear factor-kappaB (NF-kappaB) activation, and that blockade of NF-kappaB activation augments TXT-induced apoptosis in human gastric cancer cells. In addition, we have also shown that a protein-bound polysaccharide PSK enhances TXT-induced apoptosis through NF-kappaB inhibition in human pancreatic cancer cells. Based on these observations, in the present study the possibility that PSK could enhance TXT-mediated tumor suppression was examined in vivo and in vitro., Materials and Methods: A gastric cancer xenograft model was used to examine the enhanced TXT-mediated tumor suppression by PSK in vivo. The effects of PSK on proliferation and apoptosis induced by TXT in gastric cancer cells were evaluated in vitro using a human gastric cancer cell line, MK-1. The effect of PSK on increased TXT-induced invasion was also measured., Results: PSK enhanced TXT-mediated tumor suppression in vivo. Immunohistochemical analyses of the tumors revealed that TXT increased NF-kappaB activation in the tumors and this was suppressed by PSK. In the ex vivo experimental system, PSK enhanced the growth inhibition and apoptosis induced by TXT in the MK-1 cells and reduced the increased invasive ability induced by TXT., Conclusion: PSK enhanced TXT-induced tumor suppression in a gastric cancer xenograft model.

A 47-year-old man who was diagnosed as Crohn's disease at the age of 27 became aware of a mass on the forehead. CT and PET scan revealed many scattered tumors in his body. The CEA level was 4424 ng/ml. Primary lesion was not detected by the surveillance of whole gastro-intestinal tract. Liver tumor biopsy samples were histologicaly analyzed and were diagnosed as adenocarcinoma. Further immunohistochemical analysis revealed that the biopsy material had colonic character determined by positive CK20 and negative CK7 staining. Therefore, we performed 12 cycles of mFOLFOX6 chemotherapy. It was effective with the reduced size of tumors and the decreased level of CEA.

The patient was a 39-year-old woman admitted with complaints of fever, clubbed fingers and arthralgia. A chest roentgenogram and chest computed tomographic scan revealed a mass in the left lower lobe. Transbronchial lung biopsy was performed, and a diagnosis of moderately differentiated adenocarcinoma was made. Physical examination confirmed finger clubbing in both hands. Bone scintigram showed marked accumulation of 99mTc-MDP in the long bones, bones of the elbows, and patellae. These findings yielded a diagnosis of pulmonary hypertrophic osteoarthropathy associated with primary lung cancer in young adult. The patient had fever and disturbance of gait of arthralgia on admission, and was treated with an oral non-steroidal anti-inflammation drug (NSAID). Advanced non small cell lung cancer (clinical stage T2 N3 M1, Stage IV) was then diagnosed. Gefitinib was administered after EGFR mutation was found in the tumor specimen. NSAID therapy alleviated the fever and arthralgia. After starting gefitinib and discontinuing the NSAID, She had kept a remission of rational symptom with cytoreductive effect. The abnormal findings of bone scintigrams subsequently disappeared and the patient's serum ICTP dropped.

A 72-year-old man was admitted to our hospital, complaining of exertional breathlessness. Chest radiograph revealed a right pleural effusion. Cytology for pleural effusion revealed adenocarcinoma; thus, he was diagnosed with advanced lung cancer (clinical stage T 4 N 0 M 0, Stage IIIB). Since tumor recurrence occurred despite CBDCA+gemcitabine, docetaxel, gefitinib and vinorelbine administrations, he received fifth-line oral chemotherapy using TS-1 at 120 mg/day (80 mg/m(2)/day) for 28 days, followed by withdrawal for 14 days. Chest computed tomography showed a partial response. Hematologic and non-hematologic toxicities were mild with the TS-1 administration. TS-1 could be an effective agent for treatment of multidrug-resistant non-small cell lung cancer.

Purpose: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC)., Experimental Design: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples., Results: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022)., Conclusions: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

We performed allelotyping analysis at nine regions on chromosome 3p using 56 microdissected samples from 23 primary lung adenocarcinomas to examine the process of progression within individual lung adenocarcinoma with various grades of differentiation. Identical allelic patterns among various grades of differentiation were found in eight cases. Accumulation of allelic losses from high to lower differentiated portions was found in seven cases and accumulation of allelic losses from low to higher differentiated portions was found in five cases. Various allelic patterns among various grades of differentiation were found in three cases. These results suggested that allelic losses on 3p play an important role in morphological changes of lung adenocarcinomas. We also investigated the relationship between allelic losses on 3p and histological subtypes of lung adenocarcinoma. The frequencies of allelic losses at 3p14.2 and telomeric region of 3p21.3 were higher in papillary type tumour (nine out of 14, 64% and 11 out of 15, 73%) than in bronchioloalveolar carcinoma-type tumour (one out of 8, 13%; P=0.031 and four out of 12, 33%; P = 0.057). These results indicated that allelic losses at 3p14.2 and telomeric region of 3p21.3 are related to pattern of the proliferation of lung adenocarcinoma.

We have investigated the results of neonatal inoculation with a protein-bound polysaccharide, PSK, as it affects the defense mechanism of animals against cancer. Male BALB/c mice received a single i.p. injection of 10 mg/kg PSK within 48 h of birth. When the mice were 8 weeks of age, colon adenocarcinoma 26 (C26 tumor) cells were transplanted s.c. Injection of PSK increased the number of tumor-rejecting mice from 10 to 50% compared with the control mice transplanted with 5 x 10(3) tumor cells and prolonged the median survival period to 174% of control mice with tumors. When the number of transplanted tumor cells was increased to 1 x 10(6), PSK injection significantly prolonged the survival period, although tumors grew in all mice. The survival period was also significantly prolonged in male C57BL/6 mice that received an injection neonatally with PSK and were given a s.c. transplant of Lewis lung carcinoma or B16 melanoma at 8 weeks of age. The effect on survival was dependent on the PSK dose and the number of transplanted tumor cells. PSK was as effective for male mice 30 weeks of age as for mice 8 weeks of age treated with PSK during the neonatal period. However, prolongation of the survival period of tumor-bearing mice was not observed in the offspring (F1). Neonatal injection of PSK also significantly reduced the number of metastatic foci in the liver of mice inoculated with 1 x 10(5) C26 tumor cells in the splenic vein after 8 weeks of age. In addition, neonatal injection of PSK significantly reduced the number of aberrant crypts and aberrant crypt foci, the precancerous lesions in the colon of F344 rats that received injections s.c. with azoxymethane after 7 weeks of age, to 47% of that of rats that received an injection with saline at the same age. The effect on precancerous lesions was dependent on the timing of PSK injection and the dose. Regarding the mechanism, when animals thymectomized during the neonatal period or when congenitally athymic animals were used instead of healthy animals, the effect on survival or precancerous lesions did not appear. Neonatal injection of PSK significantly reduced the number of CD4+ CD8+ T cells and significantly increased the number of CD4+ CD8- and CD4- CD8+ T cells in the thymus of healthy mice 10 weeks of age and C26 tumor-bearing mice. Furthermore, neonatal injection of PSK significantly elevated the T-cell differentiation induced by a mouse thymus extract 10 weeks of age. These findings suggest that neonatal injection of PSK induces resistance in adult mice to challenge by syngeneic tumor cells and reduces the azoxymethane-induced precancerous lesions in the colon of adult rats via the thymus functions.