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Primary pancreatic lymphomas are extremely rare, accounting for 0.1-0.5% of malignant lymphomas and about 0.2% of primary pancreatic tumors. They occur most commonly in the pancreatic head of elderly males, with diffuse large B-cell lymphoma being the most common subtype. Primary pancreatic follicular lymphoma is the most commonly reported primary pancreatic indolent lymphoma, accounting for 9-14% of primary pancreatic lymphomas. We report two cases of primary pancreatic follicular lymphoma treated with obinutuzumab, a second-generation humanized anti-CD20 monoclonal antibody, and bendamustine. One was diagnosed by endoscopic ultrasound-guided fine-needle aspiration, while the other required laparoscopic lymph node sampling to reach a diagnosis. Both achieved complete response with induction therapy and opted for maintenance therapy with obinutuzumab. We also conducted a literature review of primary pancreatic follicular lymphoma cases reported over the last 30 years.

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Lauren's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P

Background Bochdalek hernia in an adult is very rare and often needs an immediate surgical repair for the herniation. Although its etiology and surgical techniques have frequently been reported, perioperative complications, especially cardiopulmonary problems, remain unknown. We reported two adults with Bochdalek hernia and reviewed the published literatures with a focus on these issues. Case presentation We experienced two adult cases of Bochdalek hernia with gastrointestinal strangulation. One case had massive herniation of the stomach, colon, spleen, and pancreas in the left chest, causing repeated vomiting. The other had a right-side hernia with strangulation of the colon. We successfully performed emergency repairs of these diaphragmatic hernias without any postoperative complications. Conclusions Our literature review revealed that life-threatening cardiopulmonary complications, such as empyema or cardiac arrest caused by the tamponade effect of the herniated viscera, sometimes occurred in patients with Bochdalek hernia. These complications were found in Bochdalek hernia with gastrointestinal strangulation.

Acquired isolated hypoganglionosis is a rare intestinal neurological disease, which presents in adulthood with the clinical symptoms of chronic constipation. A 39-year-old man underwent laparoscopic low anterior resection and covering ileostomy for locally advanced-rectal cancer. A 6-month course of postoperative adjuvant chemotherapy was completed, followed by closure of the ileostoma. After the closure, he developed severe colitis which required 1-month of hospitalization. Mucosal erosions and pseudo-membrane formation were evident on colonoscopy and severe mucosal damage characterized by infiltration of inflammatory cells and crypt degeneration were pathologically confirmed. Even after the remission of the colitis, he suffered from severe constipation and distention. At 4 years after the stoma closure, he decided to undergo laparoscopic total colectomy. Histopathologically, the nerve fibers and ganglion cells became gradually scarcer from the non-dilated to dilated regions. Immunohistochemical staining examination confirmed that the ganglion cells gradually decreased and became degenerated from the normal to dilated region, thereby arriving at the final diagnosis of isolated hypoganglionosis. The patient recovered without any complications and there has been no evidence of any relapse of the symptoms. We present a case of acquired isolated hypoganglionosis-related megacolon, which required laparoscopic total colectomy, due to severe enterocolitis following stoma closure.

Rectal multiple neuroendocrine tumors (M-NETs) are rare, with only few epidemiologic reports on the topic. Therefore, their clinicopathological features are not completely known, and the appropriate treatment strategy has not been established. This study aimed to compare the clinicopathological malignant potential (lymphatic or venous invasion-positive and lymph node metastasis rates) of M-NETs with that of solitary NETs (S-NETs). We retrospectively investigated 369 patients with NETs of the rectum. Patients who underwent colonoscopy at the Cancer Institute Hospital between January 1979 and 2016 and diagnosed with S-NETs were included, and S-NETs were found in 348 patients. Patients with M-NETs were classified into two groups as follows: patients with

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS.

Background. A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion ( P = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Background Primary neuroendocrine tumor (NET) originating from the extrahepatic bile duct is rare, although liver metastasis from gastroenteropancreatic NET is frequently observed. We herein report a case who successfully underwent repeat hepatectomy for liver metastases from bile duct NET grade 2 (G2). Case presentation A 75-year-old man presented with jaundice and was suspected of perihilar cholangiocarcinoma by computed tomography (CT) and magnetic resonance imaging (MRI). He underwent extended left hepatectomy, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological findings showed a NET G2 of the biliary tract arising from the common bile duct. Two years and 11 months after surgery, a liver metastasis was detected and hepatectomy was performed. During the surgery, another liver metastasis was detected, and limited liver resection for the two lesions was performed. Pathological findings showed four liver metastases of NET G2. Five years and 4 months after the first surgery (2 years and 5 months after the second hepatectomy), four liver metastases were detected. Thereafter, he received somatostatin analogues for 1 year. Although the size of tumors increased slightly, the number did not change. He underwent limited liver resections and was diagnosed with 7 liver metastases of NET G2. Finally, another hepatectomy (fourth hepatectomy) was performed and long-term survival without recurrence was obtained for as long as 8 years after the first surgery. Conclusions Repeat hepatectomy is a good option to obtain long-term survival for liver metastases from bile duct NET G2 in select patients.

BACKGROUND There is limited evidence of parametric MR mapping to characterize carotid plaques associated with cerebral ischemic events. PURPOSE To explore the apparent diffusion coefficients (ADCs) and longitudinal relaxation rates (R1 ) of carotid plaques, including areas of hemorrhage, lipid-rich/necrotic core (LR/NC) without hemorrhage, and fibrous tissue (Fbr) STUDY TYPE: Prospective. SUBJECTS Twelve patients who underwent carotid endarterectomy. FIELD STRENGTH/SEQUENCE R1 was measured using double angle Look-Locker acquisition on 3T systems. Single-shot spin-echo echo-planar imaging with fat suppression and outer-volume suppression (OVS-DWEPI) with b values of 10 and 500 s/mm2 was used for diffusion-weighted imaging. ASSESSMENT A phantom study using diluted gadolinium solutions and polyvinyl alcohol solutions was used to validate the two protocols. Regions of interest (ROIs) were manually outlined on MR images for areas of LR/NC, hemorrhage, and Fbr based on histological cross-sections. Pixel-based R1 and ADC values in the ROIs were plotted for each component. The probability density function of the plots determined the optimum contours to separate the three components in the ADC-R1 plane. The LR/NC, hemorrhage, and Fbr regions were mapped on MR images based on the above results and compared to histological results. STATISTICAL TESTS The R1 values of the phantom measurements were tested using Bland-Altman analysis. The accuracies of the MRI classification were calculated. RESULTS R1 values

A 55-year-old man visited our hospital for a detailed examination of a gastric submucosal tumor that was first detected 10 years prior. The tumor continued to grow and had developed a depressed area in its center. A histopathological examination of biopsy specimens revealed gastric adenocarcinoma of the fundic gland type (GA-FG). It was diagnosed as T2 based on the invasion depth as determined by white-light endoscopy and endoscopic ultrasonography. A total gastrectomy with lymphadenectomy was performed and a GA-FG in the mucosa and submucosa was confirmed histopathologically. However, there was a gradual transition to an infiltrative tubular adenocarcinoma with poorly differentiated components in the muscular and subserosal layers. Metastasis was identified in a dissected lymph node (LN). This is the first report of a GA-FG progressing to an aggressive cancer with LN metastasis. These findings modify our understanding of the pathophysiology of GA-FG.

Among the various diagnostic modalities for small bowel hemangioma, video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) can be recommended as part of the work-up in patients with obscure gastrointestinal bleeding (OGIB). DBE is superior to VCE in the accuracy of diagnosis and therapeutic potential, while in most cases total enteroscopy cannot be achieved through only the antegrade or retrograde DBE procedures. As treatment for small bowel bleeding, especially spout bleeding, localization of the lesion for the decision of DBE insertion facilitates early treatment, such as endoscopic hemostatic clipping, allowing patients to avoid useless transfusion and the worsening of their disease into life-threatening status. Applying endoscopic India ink marking prior to laparoscopic surgical resection is a particularly useful technique for more minimally invasive treatment. We report two cases of small bowel hemangioma found in examinations for OGIB that were treated with combination of laparoscopic and endoscopic modalities.

Objectives Serrated lesions of the colorectum often have complex histological morphology, and some groups include subtypes with different molecular biology. This study aimed to characterize serrated lesions with heterogeneous histology that was dominated by a traditional serrated adenoma (TSA) component. Methods Representative lesions were selected based on both endoscopic and histological features. If a lesion had more than one component, each of the different structural parts was considered as a separate sample. DNA was extracted from 177 samples of 60 lesions and amplified to screen for BRAF and K/NRAS mutations. Results Heterogeneous TSA samples were classified into four categories: sessile serrated lesion with TSA (SA-1); TSAs with microvesicular hyperplastic polyp (SA-2); TSAs with unclassified adenoma, characterized by tubulo-serrated histology (SA-3); and TSAs with conventional adenomas (SA-4). On endoscopy, SA-1 lesions had sessile-elevated morphology with the small reddish elevations; SA-2 lesions had a pedunculated appearance with a whitish mucosal component at the stalk; SA-3 lesions had a sessile-elevated component surrounded by flat spreading margins; and SA-4 lesions had mixed adenomatous morphology. Eighteen of the 19 category SA-1 and -2 lesions (95%) had BRAF mutations, and all of the SA-3 and -4 lesions had K/NRAS mutations. Conclusions Traditional serrated adenomas were classified into two phenotypes according to their molecular characteristics: microvesicular serrated subtypes with BRAF mutations (SA-1 and -2 lesions) and subtypes containing tubulo-serrated/conventional adenoma with K/NRAS mutations (SA-3 and -4 lesions). Each subtype had characteristic macroscopic and microscopic morphologies and was distinct on endoscopy.

An 85-year-old woman was transported to our emergency room by ambulance with a complaint of slurred speech. Neurological examination revealed dysarthria only. We considered that lingual edema identified on physical examination might have influenced dysarthria. However, we were unable to perform sufficient evaluation, since she could not open her mouth widely or push the tongue out beyond the lips. We considered the incidence of acute cerebrovascular disease because of the acute onset, and performed emergency brain MRI. Imaging revealed that although no abnormality was present in the brain parenchyma, edema of the tongue and soft palate was evident on T2-weighted sagittal imaging. We confirmed the dysarthria was caused by tongue edema due to angioedema. In addition, we diagnosed angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, because ACEI had been started 2 months earlier as pharmacotherapy for hypertension. Tongue swelling due to angioedema should be considered when examining patients with dysarthria.

The risk of malignancy in inflammatory myopathy patients is well recognized. However, the incidence of germ cell tumor (GCT) with inflammatory myopathy is low, and most reported cases of GCT also exhibit testicular tumors. Therefore, a case of extragonadal GCT with dermatomyositis (DM) is reported in the current study to better understand this paraneoplastic syndrome. A 53-year-old man presented with bilateral cervical lymph node enlargement. A lymph node biopsy showed embryonal carcinoma, and computed tomography showed multiple lymph node and lung metastases. A period of one month after bleomycin, etoposide and cisplatin (BEP) chemotherapy, this patient developed an erythematous eruption over the extensor surfaces of bilateral fingers, or Gottron's sign and facial erythema. The patient was diagnosed with DM with a positive anti-TIF-1γ-antibody result. High-dose prednisolone was effective, and there has been no evidence of cancer recurrence for over one year. The literature review identified 17 cases of GCT with inflammatory myopathy that have been reported so far, and it was indicated that this is the first case of extragonadal GCT with DM following chemotherapy. This case highlights the importance of monitoring after the completion of cancer treatment, as distinctive dermal and muscular symptoms should cause us to consider the possibility of paraneoplastic inflammatory myopathy.

Background: The incidence trend of esophagogastric junction (EGJ) adenocarcinoma in Japan has not been sufficiently investigated. Little is known about the microsatellite instability (MSI) status of this tumor. Summary: Previously published studies analyzing the trend of EGJ adenocarcinoma in Japan were reviewed. And a trend of surgically resected cases (Siewert type I-III) utilizing a retrospective multicenter cohort of 379 patients from 4 academic institutions in Japan investigated. Although an increasing trend in the last 2 reports was considered controversial, our cohort demonstrated a growing number of EGJ adenocarcinoma cases between 2006 and 2013. This trend was evident, especially in Siewert type I cases. In the previous 16 studies that performed MSI testing, MSI-high tumors ranged 0–8.3%, though there were no fixed microsatellite markers on EGJ adenocarcinoma. In a recent comprehensive genetic analysis by The Cancer Genome Atlas, MSI testing using the following 7 markers, BAT25, BAT26, BAT40, D2S123, D5S346, D17S250 and TGFR-II showed a favorable correlation with hypermutated tumors. We performed MSI testing using 6 of those markers, except TGFR-II, on 206 cases from one institution, and detected 15 cases (7.3%) with MSI-high. The prevalence of MSI-high was 0% in Siewert type I, 7.6% in type II, and 16.7% in type III. Key message: The number of surgically resected EGJ adenocarcinoma cases gradually increased, and MSI-high was infrequent in Siewert type I-II tumors in our Japanese cohort. Considering MSI-high as a predictive biomarker for emerging immune checkpoint inhibitors, MSI status is becoming more beneficial in EGJ adenocarcinoma.

Determining the depth of invasion of early stage colorectal cancer has been emphasized as a means of improving endoscopic diagnostic accuracy. Recent studies have focused on other pathological risk factors for lymph node metastasis (LNM). We investigated the significance of depth of invasion and predictive properties of other endoscopic findings. We retrospectively investigated 846 patients with submucosal invasive (T1) colorectal cancer who received an accurate pathological diagnosis and were treated between January 2005 and December 2016. Pathological risk factors associated with LNM were reviewed. We divided patients into groups: low-risk T1 colorectal cancer (LRC; no risk factors) and high-risk T1 colorectal cancer (HRC; exhibiting lymphovascular invasion, tumor budding grade of 2/3, and/or poor differentiation) and studied predictive endoscopic factors for HRC. Significant risk factors for LNM in multivariate analysis were lymphovascular invasion [odds ratio (OR) 8.09; 95% confidence interval (CI) 3.84–17.1], tumor budding (OR 1.89; 95% CI 1.09–3.29), and histological differentiation (OR 2.09; 95% CI 1.12–3.89). The LNM-positive rate with only deep submucosal invasion was 1.6%. Significant predictive factors for HRC in multivariate analysis identified rectal tumor location (OR 1.92; 95% CI 1.35 –2.72, depression (OR 2.73; 95% CI 1.96 –3.80), protuberance within the depression (OR 2.58; 95% CI 1.39– 4.78), expansiveness (OR 2.39; 95% CI 1.27– 4.50), and loss of mucosal patterns (OR 1.90; 95% CI 1.20 –3.01) as significant factors. Rectal tumor location, depression, protuberance within the depression, expansiveness, and loss of mucosal patterns could be predictive factors for HRC.

High-grade tumor budding is an adverse prognostic factor for submucosal invasive (T1) colorectal cancer used to predict the risk for lymph node metastasis in endoscopically resected specimens. Cytokeratin immunohistochemistry is a potential option for evaluating tumor budding. The optimal cut-off value between low- and high-grade budding has not yet been determined, however, and the high inter-observer variability in selecting budding foci remains problematic. We explored the optimal cut-off value for predicting lymph node metastasis using cytokeratin immunohistochemistry, and developed a novel computer-assisted semiautomatic quantification method to reduce inter-observer variability. A retrospective single-institution study of 463 T1 colorectal cancer cases was conducted. Cases were split into derivation and validation datasets. Tumor budding foci were counted manually and semiautomatically using Image J software on cytokeratin immunohistochemistry-stained specimens. We determined the cut-off values and compared inter-observer variability among pathologists between the two methods. Univariate and multivariate analyses of the derivation dataset were performed to select the risk factors for lymph node metastasis. Predictive simulation for the validation dataset was conducted. The optimal cut-off values for the manual and semiautomatic methods were ≥10 and ≥12, respectively. For both methods, multivariate analyses revealed that venous invasion, lymphatic invasion, and high-grade tumor budding were independent risk factors for lymph node metastasis. The semiautomatic method provided significantly better inter-observer agreement. The predictive and observed lymph node metastasis frequencies were highly correlated in the validation dataset.

Hyalinizing clear cell carcinoma of the bronchial glands is a very rare tumor. Since only five reports describing six tumors have been published to date, only a little is known about specific histologic findings and clinical features. Because of its rarity, hyalinizing clear cell carcinoma has not been described in the latest WHO classification of pulmonary tumors yet. Here we present three cases of bronchial hyalinizing clear cell carcinomas, confirmed by both fluorescence in situ hybridization (FISH) and RT-PCR, focusing on histologic and immunohistochemical characteristics in a comparison with three cases of salivary gland origin. In addition, we compared immunohistochemical features with bronchial mucoepidermoid carcinoma, a lesion that needs to be taken into account in differential diagnosis of hyalinizing clear cell carcinoma. All our bronchial hyalinizing clear cell carcinoma cases were surgically resected. Histologically, tumor cells showed clear to eosinophilic cytoplasm with hyalinizing stroma in various proportions, resembling those of salivary gland origin. Immunohistochemically, tumor cells were positive for CK7, CK5/6, p40, p63, and ATF1, while they were negative for TTF1, Napsin A, HMB45, and SOX10. The CK5/6 staining pattern varied in mucoepidermoid carcinomas, while that of hyalinizing clear cell carcinoma was uniformly positive. FISH revealed EWSR1-ATF1 fusion, and RT-PCR with sequencing confirmed specificity of the chimeric gene for hyalinizing clear cell carcinoma. Clinically, bronchial hyalinizing clear cell carcinoma was characterized by occurrence in the fourth to sixth decades, no link with smoking history, and a predilection for the right lung, in line with previous reports. In summary, our study confirmed that the bronchial hyalinizing clear cell carcinoma is a histologically and genetically identical tumor to that of salivary gland origin, and that gene rearrangement analysis can play a critical role in distinction from mucoepidermoid carcinoma.

Aims The aim of this study was to determine the localization of the rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) and its metabolite in mice kidneys after adriamycin (ADR)-induced renal failure. We also examined the effect of l -tryptophan (Trp) administration on this model. Main methods BALB/c mice were treated with 15 mg/kg ADR to induce renal failure. The change of IDO and l -kynurenine (Kyn) following ADR-induced renal failure was examined by immunostaining combined with hematoxylin and eosin (HE) and Periodic acid-Schiff (PAS) staining for morphological analysis, and the concentration of l -Kyn was measured by HPLC. The effect of l -Trp administration on ADR-induced renal failure was also investigated. Key findings Time-dependent increase of IDO immunostaining was observed in tubular cells from Day 4 after ADR injection. It was found that mice fed with l -Trp had less chance of renal failure at four days after ADR injection than mice untreated with l -Trp, but not at seven days. Further, l -Trp treatment significantly suppressed an increased level of TNF-alpha mRNA, but not of TGF-beta and IL1-beta after renal injury. Significance Local IDO expression in tubules was induced markedly after ADR- induced renal failure. l -Trp administration can be effective in suppressing ADR-induced renal failure at an early stage.

44 Background: High level of microsatellite instability (MSI-high) is an actionable molecular status in oncology, informing tumor response to immune checkpoint inhibitor. However, little is known about MSI-low. The aim of this study is to unveil the characteristics of MSI-low tumor in esophagogastric junction (EGJ) adenocarcinoma. Methods: Using 372 cases with chemo-naive EGJ adenocarcinoma tissue, MSI testing and Epstein Barr Virus (EBV)-DNA detection were performed by DNA fragment analysis (BAT25, BAT26, BAT40, D2S123, D5S346, and D17S250) and real-time PCR, respectively. MSI-high was defined as having two or more unstable markers, MSI-low as one, and microsatellite stable (MSS) as none. MSI status was compared with clinicopathological and molecular status including epigenetic alteration in MLH-1, LINE-1, and CpG methylator phenotype (CIMP), TP53 status (sequencing and immunohistological expression), Ki-67 index, intra-/peri-tumoral lymphocyte counts (CD8+ or FOXP3+), combined positive score (CPS) of PD-L1 expression. Results: MSI-low was detected in 29, MSI-high in 28, and EBV (+) in 9 cases. Three cases with MSI-low showed EBV (+), but MSI-high and EBV (+) were mutually exclusive. In 363 EBV (-) cases, MSI-low was associated with younger age (MSI-high 71.7 ± 11.3, MSI-low 61.3 ± 12.5, and MSS, 65.0 ± 12.3 years old, P = 0.003). Notably, MSI-low exhibited an intermediate type between MSI-high and MSS, in terms of no. of lymph node metastasis, and tumor immune microenvironment [no. of intra-/peri-tumoral CD8+ cells, no. of intra-/peri-tumoral FOXP3+ cells, and CPS of PD-L1 (all P among the 3 groups < 0.05)]. In contrast to MSI-high tumors, MSI-low tumor was not associated with epigenetic alteration in any of MLH-1, LINE-1, or CIMP status. In survival analysis, 3-year disease-specific survival rate of MSI-low was better than that of MSS tumors, and similar to MSI-high (92.2% for MSI-low, 92.2% for MSI-high, and 69.6% for MSI-low). This trend was also observed in time to recurrence (P = 0.01). Conclusions: MSI-low cases exhibited an intermediate immune microenvironment between MSI-high and MSS, and favorable outcome. Our results may implicate MSI-low as a predictive biomarker for immune checkpoint inhibitor.

症例は22歳，女性．小児期より間歇的腹痛発作を繰り返していた．平成21年12月これまでと同様の腹痛が出現し，嘔吐，血便も認め，当科紹介受診．腹部単純CTにて腸重積症と診断し，同日緊急手術を施行した．開腹したところ，Treitz靱帯近傍から左側の骨盤内に至るまで，著明に拡張した空腸を認め，空腸空腸型の腸重積であった．Hutchinson手技で重積を整復したところ，Treitz靱帯から15cm肛門側の空腸に直径6cmの軟らかな腫瘤を認め，これが先進部となっていた．腫瘤を含めて空腸を15cm切除した．病理診断の結果は，異所性胃粘膜であり悪性所見はなかった．腸重積症は小児に好発し，成人に発症することは稀であるが，成人発症例では器質的原因のあることが多い．本症例は手術時は成人であったが，小児期から異所性胃粘膜が存在して同部を起点に腸重積状態を繰り返していたものと考えられた．繰り返す腹痛発作の一因として腸重積も考慮すべきと考えられた．

抗利尿ホルモン分泌異常症候群（syndrome of inappropriate antidiuretic hormone secretion:以下SIADH）は，ADHの異常分泌のために水分貯留が起こり，その結果，低Na血症に至る症候群である．今回，われわれは進行食道癌に対する術前化学療法としてCDDP+5FU療法（以下FP療法とする）施行中にSIADHを発症した1例を経験した．食道癌化学療法中にSIADHをきたした報告例は少なく，そのうち切除可能症例で外科的切除を行ったのは自験例を含めて4例だけであった．今後，進行食道癌に対して術前化学療法を行う機会が増加することが予想され，その際にはSIADHの発症を念頭におく必要があると考えられた．本例では根治手術後に施行した術後補助化学療法でも同様のSIADHを発症しており，発症幾序の観点からも示唆に富んでいると考えられた．

A patient with amyopathic dermatomyositis associated with fatal rapidly progressive interstitial pneumonitis resistant to therapy is described. Pathologic examination of a transbronchial lung biopsy specimen showed diffuse alveolar damage and nonspecific interstitial pneumonia-organizing pneumonia-like findings. Bronchoalveolar lavage fluid contained many CD8+ lymphocytes, considered to be cytotoxic T cells. Analysis of bronchoalveolar lavage fluid in this case may provide prognostically and pathogenetically important information.

Background: Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI·CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI·CHP for cisplatin (CDDP) during HAI chemotherapy. Methods: CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI·CHP in 14 mongrel dogs. HVI·CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined by flameless atomic absorption spectrophotometry. Results:During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER) by CHP filter were always higher in the STS group than in the control group, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05). Conclusions: These results indicated that concomitant STS infusion could further increase the effect of HVI·CHP on CDDP removal after HAI.

はじめに:大腸多発癌の臨床的特徴より多発癌のリスクファクターを把握し, 術後のfollow upの方法を考察した.方法:最近16年間の大腸癌切除828例を単発癌と多発癌に分類し, 臨床的に比較検討した.結果:多発癌は64例(7.7%)で, 同時性47(5.7%), 異時性17例(2.1%)であった. 同時性計102病巣の分布は単発癌と差は無かった. 異時性第1 癌は右側結腸2(12.5%), 左側結腸12(75.0%), 直腸2(12.5%), 不明1で, 単発より左側が有意に高率であった. 第1～第2癌までは最長18年で, 平均7年3か月であった. 5年以内に第2癌が進行癌で発見された4例中2例は術前に口側の検索が不十分, 2例は腺腫併存例で, 術後定期的全大腸内視鏡がされていなかった. 多発癌で単発癌より高率であった因子は腺腫の併存(多発93.3%, 単発73.1%), 胃癌の合併(多発12.8%, 単発4.8%)であった.考察:多発癌のリスクファクターとして腺腫の併存, 胃癌の合併, および大腸癌家族歴の存在が考えられ, 異時性第2癌の早期発見にはこれらの因子を念頭に置き, 術後全大腸内視鏡による定期的follow upが重要である.

IDO, an enzyme that degrades the essential amino acid l-tryptophan to N-formylkynurenine, is known to exert immunomodulatory effects in a number of diseases and disorders. IDO expression is increased in tumors, where it is thought to be involved in tumor evasion by suppressing the immune response. A competitive inhibitor of IDO is currently being tested in clinical trials for relapsed or refractory solid tumors; however, there remains a concern that attenuation of the immunosuppressive function of IDO might exacerbate inflammatory responses. In this study, we investigated the role of IDO in 2,4,6-trinitrobenzene sulfate (TNBS)–induced colitis in mice by gene deletion and pharmacological inhibition. TNBS treatment induced significantly more severe colitis in Ido1 gene–deficient (Ido1−/−) mice than in Ido1 wild-type (Ido1+/+) mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with this, the expression of Ido1 was increased in the colonic interstitial tissues of TNBS-treated Ido1+/+ mice. Furthermore, transplantation of Ido1+/+ bone marrow cells into Ido1−/− mice reduced the pathological damage associated with colitis, altered the expression of cytokines, including IFN-γ, TNF-α, and IL-10, and increased the number of CD4+ Foxp3+ regulatory T cells in the colon. Pharmacological inhibition of IDO enzymatic activity by oral administration of 1-methyltryptophan (1-methyl-l-tryptophan or 1-methyl-d-tryptophan) significantly increased the severity of TNBS-induced colitis in mice, demonstrating that both stereoisomers can promote colitis. Collectively, our data indicate that IDO1 plays an important immunoregulatory role in the colon.

A solid pseudopapillary neoplasm (SPN) of the pancreas has distinct histopathological features. A solid pattern of growth with pseudopapillary structures that result from degeneration is observed. On rare occasions, the tumor may vary from being entirely solid to completely cystic. The present study describes two unique cases of SPN. A 25-year-old male presented with a pancreatic tumor showing a predominantly solid pattern with no degenerative change, although the pre-operative cytological specimens that were obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) revealed pseudopapillary structures. The second case was of an 11-year-old female who presented with a pancreatic tumor with prominent degeneration. Nests and cords of the remaining neoplastic cells were located only at the periphery, with perineural invasion. An immunohistochemical analysis revealed that the tumor cells in the two cases were positive for CD10 and β-catenin and negative for trypsin. An awareness of the broad morphological variability of SPN and an immunohistochemical panel that includes CD10, β-catenin and trypsin are useful for establishing an accurate diagnosis.

Background and Purpose— A major disadvantage of carotid artery stenting (CAS) compared to carotid endarterectomy is the increased risk of cerebral embolism. Thus, establishing a simple method to discriminate fragile plaques on preoperative routine examination is important. The present study examined whether high-intensity signal (HIS) in the plaque on time-of-flight (TOF) MRA, performed for screening, can discriminate plaque at high risk for cerebral embolism during CAS. Methods— In the 30 patients treated using carotid endarterectomy, relationships between pathological findings of the plaques and TOF-MRA findings were analyzed. In the 112 patients treated using CAS, postoperative ipsilateral ischemic lesions on diffusion-weighted imaging and periprocedural ischemic symptoms were analyzed. Results— The percentage area of intraplaque hemorrhage stained by glycophorin A was significantly larger in HIS-positive plaques (51.8%±9.8%) than in HIS-negative plaques (8.6%±9.4%; P P =0.002). Periprocedural ischemic symptoms were more frequently observed in HIS-positive plaques (7/38; 18.4%) than in HIS-negative plaques (1/74; 1.4%; P =0.003). Multivariate logistic regression analysis identified HIS on TOF-MRA as an independent predictor of periprocedural ischemic symptoms (odds ratio, 15.08; 95% confidence interval, 1.76–129.0). Conclusions— HIS in the plaque on TOF-MRA performed for screening could discriminate plaques at high risk for cerebral embolism during CAS.

AIM: To describe a new surgical technique and evaluate the early results of segmental gastrectomy (SG) with modified D2 lymph node (LN) dissection for early gastric cancer (EGC). METHODS: Fourteen patients with EGC underwent SG with modified D2 dissection from 2006 to 2008. Their operative results and postoperative courses were compared with those of 17 patients who had distal gastrectomy (DG) for EGC during the same period. RESULTS: Operating time, blood loss, and hospital stay were similar between the 2 groups. Postoperative complications developed significantly more frequently in the DG group than in the SG group. Mean number of dissected LNs per each station in the SG group was comparable with that in the DG group. Postoperative recovery of body weight was significantly better in the SG group than in the DG group. The incidence of reflux esophagitis and gastritis after surgery was less frequent in the SG group than in the DG group. CONCLUSION: SG with modified D2 LN dissection may be a new function-preserving gastrectomy that is feasible for treatment of EGC with possible LN involvement.