Induction of Kallikrein-Related Peptidase 13 and TET2/3 by Anticancer Drugs and Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma After Preoperative Treatment.

BACKGROUND: Preoperative chemotherapy/chemoradiotherapy has been generally considered for the treatment of esophageal squamous cell carcinoma (ESCC) to improve prognosis. We examined the effects of anticancer drugs on the expression of kallikrein-related peptidase 13 (KLK13), a potential ESCC prognostic marker, and its clinical relevance in patients who received chemotherapy/chemoradiotherapy for ESCC. METHODS: Overall, 105 patients with ESCC who received chemotherapy or chemoradiotherapy before esophagectomy were enrolled. The expression of KLK13 in biopsy samples obtained before chemotherapy/chemoradiotherapy and resected ESCC tumors was assessed by immunohistochemical staining. The effects of 5-fluorouracil (5-FU) and/or cisplatin (CDDP) exposure on the expressions of KLK13 and ten-eleven translocation dioxygenases (TET) in ESCC cells were examined by reverse transcription-polymerase chain reaction. RESULTS: Immunohistochemical staining of paired ESCC specimens before (biopsy samples) and after (resected specimens) chemotherapy/chemoradiotherapy demonstrated a change in KLK13 expression. KLK13 and TET2/3 transcriptions were induced when human ESCC cell lines were treated with 5-FU and/or CDDP. Among patients with KLK13-negative status before chemotherapy/chemoradiotherapy, those with KLK13-positive resected tumors had a significantly poorer prognosis than those with KLK13-negative resected tumors (p = 0.0477). By using tumor cells isolated from ESCC biopsy tissues obtained before chemotherapy/chemoradiotherapy, we established a primary culture system and detected the induction of KLK13 expression by anticancer drugs. CONCLUSIONS: Preoperative treatments alter KLK13 expression in ESCC. The conversion of KLK13 expression from a negative status in biopsy samples to a positive status in resected tumor samples is a predictor of poor prognosis. KLK13 status is a potential marker for decision making to avoid harmful chemotherapy/chemoradiotherapy in patients with ESCC.

Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma.

Glutathione S-transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non-ciliated, columnar Clara cells, and type II alveolar cells, which have self-renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in LSCC cell lines inhibited cell growth and colony formation in vitro. In a subcutaneous xenograft model, GSTO2-transfected cells formed smaller tumors in nude mice than mock-transfected cells. Upon intravenous injection into nude mice, the incidence of liver metastasis was lower in mice injected with GSTO2-transfected cells than in those injected with mock-transfected cells. In addition, GSTO2 induction suppressed the expression of ß-catenin and the oxygen consumption rate, but it did not affect the extracellular acidification rate. Furthermore, GSTO2-transfected cells displayed lower mitochondrial membrane potential than mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, ß-catenin expression and mitochondrial membrane potential were recovered. Our study indicated that the loss of GSTO2 via DNA hypermethylation contributes to the growth and progression of LSCC, probably by modulating cancer metabolism via the p38/ß-catenin signaling pathway.

Expression Status of Serine Protease 27: A Prognostic Marker for Esophageal Squamous Cell Carcinoma Treated with Preoperative Chemotherapy/Chemoradiotherapy.

BACKGROUND: A previous study conducted a transcriptome analysis of paired normal and esophageal squamous cell carcinoma (ESCC) tissue samples. The results showed that the expression of serine protease 27 (PRSS27) was perturbed in tumor samples. Hence, this retrospective study aimed to validate the prognostic significance of PRSS27 in patients with preoperative treatment for ESCC. METHODS: We enrolled 86 patients who received preoperative treatment before esophagectomy for ESCC. The expression of PRSS27 in resected ESCC and biopsy tissue samples obtained before preoperative treatment was evaluated via immunostaining, and its relationship with clinicopathological features and prognosis was analyzed. RESULTS: In normal esophageal mucosa tissue samples, PRSS27 was expressed in the cytoplasm of spinous cells in the suprabasal layer and basal cells in the basal layer. Of 64 resected ESCC tissue samples, 35 (54.7%) expressed PRSS27 and 29 (45.3%) did not. Moreover, ectopic nuclear expression of PRSS27 was observed. Based on multivariate analysis, PRSS27 expression in resected tumor samples was a predictor of poor prognosis. In cases in which PRSS27 expression was observed in biopsy samples, patients with PRSS27-negative resected tumors had a better postoperative prognosis than those with PRSS27-positive resected tumors. CONCLUSIONS: PRSS27 expression in resected ESCC tissue samples is a poor prognostic factor in ESCC patients with preoperative treatment. Furthermore, conversion of PRSS27 expression from positive in biopsy samples to negative in resected tumor samples is a predictor of good prognosis in these patients. Hence, PRSS27 status is an effective tool for decision making regarding adjuvant treatment in ESCC patients.

Glutathione S-transferase omega 2 regulates cell growth and the expression of E-cadherin via post-transcriptional down-regulation of ß-catenin in human esophageal squamous cells.

Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and ß-catenin at the cell-cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of ß-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

Impact of a modified peritoneal cancer index using FDG-PET/CT (PET-PCI) in predicting tumor grade and progression-free survival in patients with pseudomyxoma peritonei.

OBJECTIVES: The peritoneal cancer index (PCI) is widely used for assessing pseudomyxoma peritonei (PMP) in surgery. The aim of this study was to evaluate the utility of a modified PCI using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT (PET-PCI) for predicting pathologic grade and progression-free survival (PFS) in patients with PMP. METHODS: Thirty-five patients who underwent 18F-FDG-PET/CT before cytoreductive surgery and/or hyperthermic intraperitoneal chemotherapy were enrolled. PET-PCI was determined by summing up the visually scored 18F-FDG uptake of PMP lesions in 13 specific abdominal-pelvic regions. Uptake score was defined as 0, no lesion or lesion without uptake; 1, slight uptake less than or equivalent to mediastinal blood pool; 2, moderate uptake above mediastinal but below or equal to liver; and 3, intense uptake moderately to markedly higher than liver. SUVmax of the lesion was also evaluated. RESULTS: Pathologic diagnosis revealed 19 patients with low-grade PMP and 16 patients with high-grade PMP. Patients with high-grade PMP showed significantly higher PET-PCI and SUVmax than patients with low-grade PMP (PET-PCI 14.8 vs. 8.7, p = 0.007; SUVmax 3.6 vs. 2.6, p = 0.013). Using a cutoff PET-PCI of 12, Kaplan-Meier analyses showed a significant difference in PFS between patients with high and low PET-PCI (p < 0.001; hazard ratio (HR), 12.4). For SUVmax, the optimal cutoff was 2.7 and the correlation with PFS was also significant (p = 0.008; HR, 4.7). In multivariate Cox proportional-hazards regression, PET-PCI was independently and significantly correlated with PFS. CONCLUSIONS: PET-PCI can reflect histopathologic features and appears useful for predicting recurrence in patients with PMP. KEY POINTS: • Peritoneal cancer index using 18F-FDG-PET/CT (PET-PCI) has great potential for predicting progression-free survival in patients with pseudomyxoma peritonei. • PET-PCI provides higher prognostic performance than maximum standardized uptake value (SUVmax). • PET-PCI shows high correlation with histopathologic grade of pseudomyxoma peritonei.

Underestimated Amoebic Appendicitis among HIV-1-Infected Individuals in Japan.

Entamoeba histolytica is not a common causative agent of acute appendicitis. However, amoebic appendicitis can sometimes be severe and life threatening, mainly due to a lack of awareness. Also, its frequency, clinical features, and pathogenesis remain unclear. The study subjects were HIV-1-infected individuals who presented with acute appendicitis and later underwent appendectomy at our hospital between 1996 and 2014. Formalin-fixed paraffin-embedded preserved appendix specimens were reexamined by periodic acid-Schiff (PAS) staining and PCR to identify undiagnosed amoebic appendicitis. Appendectomies were performed in 57 patients with acute appendicitis. The seroprevalence of E. histolytica was 33% (14/43) from the available stored sera. Based on the medical records, only 3 cases were clinically diagnosed as amoebic appendicitis, including 2 diagnosed at the time of appendectomy and 1 case diagnosed by rereview of the appendix after the development of postoperative complications. Retrospective analyses using PAS staining and PCR identified 3 and 3 more cases, respectively. Thus, E. histolytica infection was confirmed in 9 cases (15.8%) in the present study. Apart from a significantly higher leukocyte count in E. histolytica-positive patients than in negative patients (median, 13,760 versus 10,385 cells/µl, respectively, P = 0.02), there were no other differences in the clinical features of the PCR-positive and -negative groups. In conclusion, E. histolytica infection was confirmed in 9 (15.8%) of the appendicitis cases. However, only 3, including one diagnosed after intestinal perforation, were diagnosed before the present analyses. These results strongly suggest there is frequently a failure to detect trophozoites in routine examination, resulting in an underestimation of the incidence of amoebic appendicitis.

Development of Pancreatic Cancer, Disease-specific Mortality, and All-Cause Mortality in Patients with Nonresected IPMNs: A Long-term Cohort Study.

PURPOSE: To determine the cumulative incidence, disease-specific mortality, and all-cause mortality of pancreatic cancer (PC) in patients with intraductal papillary mucinous neoplasms (IPMNs) and to identify imaging findings that are associated with these outcomes. MATERIALS AND METHODS: This retrospective study had institutional review board approval, and the need to obtain patient consent was waived. Data from an electronic database were analyzed and supplemented by chart reviews for 285 patients with nonresected IPMNs who were periodically followed up with imaging (1273 multidetector computed tomography and 750 magnetic resonance cholangiopancreatography examinations). The Kaplan-Meier method was used to estimate the cumulative development of PC, PC mortality, and all-cause mortality (factors were compared by using the log-rank test). RESULTS: Over a median imaging follow-up period of 39 months, 12 (4.2%) of 285 patients developed PC; the cumulative 5-year PC incidence was 3.9% for branch duct (BD)-IPMNs, 45.5% for main duct (MD)-IPMNs (P < .01), 7.7% for cysts 30 mm or larger, and 5.3% for cysts smaller than 30 mm (P = .82). Over a median survival follow-up period of 47.5 months, seven (2.5%) of 285 patients died of PC and 14 (4.9%) patients died of other causes. Cumulative 5-year PC mortality was 2.1% for BD-IPMNs, 18.5% for MD-IPMNs (P < .01), 2.6% for cysts 30 mm or larger, and 2.8% for cysts smaller than 30 mm (P = .90). Cumulative 5-year all-cause mortality was 5.5% for BD-IPMNs, 18.5% for MD-IPMNs (P < .01), 12.5% for cysts 30 mm or larger, and 5.9% for cysts smaller than 30 mm (P = .89). CONCLUSION: Five-year PC development, disease-specific mortality, and all-cause mortality were approximately 4%, 2%, and 6% for BD-IPMNs and 46%, 19%, and 19% for MD-IPMNs, respectively. The presence of an MD-IPMN, but not cyst size, was significantly associated with PC development and subsequent mortality.

Pseudomyxoma peritonei of a mature ovarian teratoma caused by mismatch repair deficiency in a patient with Lynch syndrome: a case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1-2 cases per million individuals per year. PMP is characterized by the accumulation of abundant mucinous or gelatinous fluid derived from disseminated tumorous cells. Most of the tumorous cells are originated from rupture of appendiceal neoplasms, but some are from the metastasis of cancer of the colon, ovary, fallopian tube, urachus, colorectum, gallbladder, stomach, pancreas, lung and breast. Although frequent mutations in KRAS and/or GNAS genes have been reported, precise molecular mechanism underlying PMP remains to be elucidated. It is of note that mucinous tumour is one of the frequent histological features of colorectal cancer (CRC) in Lynch syndrome (LS), an autosomal dominantly inherited disease caused by a germline mutation of the DNA mismatch repair (MMR) genes including human mutL homolog 1 (MLH1), human mutS homolog 2 (MSH2), human mutS homolog 6 (MSH6), and postmeiotic segregation increased 2 (PMS2). Therefore, typical LS-associated tumours show mismatch repair instability. Although LS patients are most strongly predisposed to CRC, PMPs from mucinous CRC have not been reported in LS patients. CASE PRESENTATION: In this report, we report a case of PMP originating from an ovarian teratoma in a LS patient. The patient had surgical treatment of PMP arising from an ovarian teratoma at the age of 38 years, and later developed a transverse colon cancer at the age of 40. The patient's family history fulfilled the Amsterdam criteria, and genetic analysis of the peripheral leukocytes identified a germ line mutation in the MLH1 gene (MLH1 c.1546dupC p.Q516PfsX3). Interestingly, immunohistochemical staining showed that the expression of MLH1 was lost in the colon cancer as well as the ovarian teratoma. Consistent with the loss of MLH1 expression, both tumours showed high microsatellite instability (MSI-H). CONCLUSION: This case suggested that LS patients may develop various types of tumours including ovarian PMP, and that mismatch repair deficiency may play a role in the development of PMP derived from, at least, a part of ovarian teratomas.

A case of ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size followed by surgical resection.

A 65-year-old woman presented to a nearby clinic with a painful mass in the right lower abdominal region. She was suspected of having an appendiceal tumor on abdominal computed tomography (CT) and was referred to our hospital for surgery. Blood testing revealed increased inflammatory markers. Contrast-enhanced abdominal CT revealed a mass with poorly defined margins in the ileocecal region, which was adjacent to the external iliac vessels. A barium enema revealed unilateral wall deformities in the cecum through to the terminal ileum, whereas lower gastrointestinal endoscopy showed no clear epithelial tumor component. The patient was clinically diagnosed with ileocecal actinomycosis and treated with high-dose penicillin G. On day 15 of treatment, contrast-enhanced abdominal CT showed a reduction in mass size. On day 26, right hemicolectomy (D3) with combined resection of the external iliac vein (which could not be separated from the mass) was performed. Pathological examination revealed granulation tissue with granules of actinomyces, with filamentous bacteria detected by Grocott staining. With no evidence of malignancy, the final diagnosis of ileocecal actinomycosis was made. This report presents a case of clinically suspected ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size, followed by surgical resection.

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BACKGROUND: Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. METHODS: A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985-2012 were retrospectively reviewed. Clinical data were collected from patient medical records. RESULTS: Mean CD4 counts of patients were 77.0 cells/µL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/µL in naïve patients (ART (-) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (-) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (-) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (-) patients (1.5%; P = 0.026). CONCLUSIONS: The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (-) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (-) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.

Different gastric mucosa and CagA status of patients in India and Japan infected with Helicobacter pylori.

BACKGROUND AND AIM: Despite similar incidence of Helicobacter pylori infection, the frequency of gastric cancer is sevenfold higher in Japan than in India. The objective of this work was to define differences in H. pylori-induced gastritis and to identify the bacterial virulence factors involved. MATERIALS AND METHODS: We prospectively enrolled 353 consecutive patients who underwent endoscopy and received three gastric biopsies in Tokyo, Japan, and Hyderabad, India. Immunohistochemistry against H. pylori and East Asian CagA and hematoxylin-eosin and Giemsa stain were used to examine gastric mucosal biopsy specimens. Histological scores were assessed in accordance with the updated Sydney System. Subjects with H. pylori infection were matched by age and sex to compare histopathology and bacterial virulence. RESULTS: Sixty patients infected with H. pylori were prospectively selected. Median histological scores for neutrophil and mononuclear cell infiltration and for atrophy were significantly higher in Japan than in India (neutrophils 4.0 vs 3.0, p < 0.01; mononuclear cells 5.0 vs 4.5, p = 0.03; atrophy 3.0 vs 2.0, p < 0.01, respectively). Scores for H. pylori density and intestinal metaplasia were also higher in Japan, albeit without statistical significance (H. pylori 5.0 vs 3.0, p = 0.08; intestinal metaplasia 0.0 vs 0.0, p = 0.08). Prevalence of East Asian CagA-positive H. pylori was significantly higher in Japan (73.3 vs 0.0 %, p < 0.01). CONCLUSION: The significantly higher prevalence of histologically severe gastritis and East Asian CagA in patients from Japan with H. pylori infection may be involved in the pathogenesis of gastric cancer.

A Simple Index to Predict Liver Functional Reserve after Hepatectomy.

BACKGROUND/AIMS: It is difficult to estimate the functional reserve of the liver required for safe hepatectomy in patients with severe chronic liver disease The aim of this study was to retrospectively construct simple model based on routine laboratory data to predict both early liver failure (ELF) and mortality from recurrence-free liver failure (MLF) as an index for late liver failure after hepatectomy. METHODOLOGY: Between 2000 and 2004, 196 consecutive patients underwent curative hepatectomy, and data from 127 minor hepatectomies were included in this study. RESULTS: Mean survival time was [mean (SD)] 1252 (670) days after hepatectomy. ELF and MLF were observed in 29 and 13 patients, respectively. PT%, TB, and direct bilirubin (DB) were the best predictors in patients with both ELF and MLF. PT% alone was the best predictor of ELF and MLF with area under ROC curves of 0.70 and 0.81, respectively. By using a preoperative PT% of ≤ 70, we could accurately predict ELF and MLF in 77% and 87% of patients, respectively. ICG-R15 could not accurately predict both ELF and MLF for any cut-off values. CONCLUSIONS: Unlike ICG-R15, PT% is a simple noninvasive index for estimating liver functional reserve to predict both ELF and MLF.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

A case of gastric adenocarcinoma with pyloric gland-type infiltrating submucosa.

BACKGROUND: The development of immunohistochemical staining has revealed that gastric adenocarcinoma with the gastric phenotype can be divided into the foveolar, fundic gland, and pyloric gland phenotypes. Gastric adenocarcinoma of the pyloric gland type is difficult to diagnose using biopsy because of its low atypia and rarity. Herein, we describe a case of gastric adenocarcinoma of the pyloric gland type that was diagnosed immunohistochemically after endoscopic resection. CASE PRESENTATION: A 67-year-old man was referred to our hospital for the diagnosis and treatment of a 30-mm elevated lesion on the lesser curvature side of the middle of the gastric body. Although four biopsies were performed, it was difficult to determine whether the lesion was benign or malignant. Therefore, endoscopic submucosal dissection was performed, and the presence of tumor cells infiltrating the submucosa with venous invasions was identified. Immunohistochemical staining revealed that the tumor cells were positive for MUC5AC and MUC6 and negative for Pepsinogen I and H + /K + -ATPase. From the above findings, he was diagnosed as having gastric adenocarcinoma with pyloric gland type. The patient underwent a laparoscopic distal gastrectomy and was discharged without any adverse events. CONCLUSIONS: Gastric adenocarcinoma of the pyloric gland type is a rare disease, and endoscopic resection can serve as a viable diagnostic option for this condition when it is difficult to diagnose using biopsy. Immunohistochemical pathology images can aid in the diagnosis of gastric adenocarcinoma of the pyloric gland type.

Combined endoscopy, aspiration, and biopsy analysis for identifying infectious colitis in patients with ileocecal ulcers.

BACKGROUND & AIMS: The ileocecal area is commonly involved in infection and inflammatory colonic diseases, but differential diagnosis can be difficult. We identified definitive endoscopic findings and a sample collection method for diagnosing infectious colitis. METHODS: In a retrospective study, we analyzed data on 128 patients with ileocecal ulcer who underwent colonoscopy from 2007-2011 at the National Center for Global Health and Medicine in Tokyo, Japan. We collected information on location, size, number, and distinctive endoscopic findings and estimated diagnostic odds ratios (ORs). The sensitivities of microscopy, culture, polymerase chain reaction, and histologic methods in identifying patients with infection were compared with those of standard stool, endoscopic aspirated intestinal fluid, or biopsy analyses. RESULTS: Of the 128 patients, 100 had infections, and 28 had Crohn's disease, Behçet's disease, or other inflammatory diseases. Predictive endoscopic findings were as follows: for amebiasis of the cecum (OR, 17.8), with exudates (OR, 13.9) and round-shaped ulcer (OR, 5.77); for tuberculosis (TB) with transverse-shaped ulcer (OR, 175), scar (OR, 34.6), linear-shaped ulcer (OR, 23.9), or ≥10 mm (OR, 14.0); for cytomegalovirus with round-shaped ulcer (OR, 4.09); and for Campylobacter with cecal valve lesion (OR, 58.3) or ≥10 mm (OR, 10.4). The sensitivity of endoscopic sample collection was significantly higher than that of standard stool sample collection for the diagnosis of amebiasis, TB, non-TB mycobacteria, and other bacteria (P < .05). The methods that detected infection with the highest levels of sensitivity were biopsy with histology for amebiasis, biopsy with culture for TB, biopsy with polymerase chain reaction for cytomegalovirus, and aspiration of intestinal fluid with culture for Campylobacter. CONCLUSIONS: Combining results from endoscopic analysis with appropriate sample collection and pathogen detection methods enables infectious colitis to be differentiated from other noninfectious colonic diseases.

A case of malignant insulinoma: successful control of glycemic fluctuation by replacing octreotide injections with octreotide LAR injections.

A 73-year-old woman with malignant insulinoma was treated with 100 µg/day octreotide for unresected insulinoma and liver metastases. The daily administration of the drug induced hyperglycemia after dinner in addition to existing fasting hypoglycemia possibly because this drug suppressed both insulin and glucagon secretion and its blood concentration was unstable. After replacing a daily injection of octreotide with a monthly injection of octreotide long-acting repeatable (LAR), blood glucose levels stabilized within the normal range. The findings of the present study showed that octreotide LAR could be useful for the long-term treatment of unresectable insulinomas.

Kallikrein-related peptidase 13 expression and clinicopathological features in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LSCC) is associated with poor prognosis. Molecular targeting drugs have been demonstrated to be effective for lung adenocarcinoma; however, they are often not effective for LSCC. Kallikrein-related peptidase 13 (KLK13) expression enhances the malignancy of lung adenocarcinoma; however, its expression and crucial role in LSCC remain largely unknown. The present study examined the relationship between the KLK13 expression and clinicopathological features of LSCC. A total of 94 patients diagnosed with LSCC who underwent lobectomy, segmentectomy or wedge resection were selected. KLK13 expression was evaluated through immunostaining of formalin-fixed paraffin-embedded sections of surgical specimens. Of the 94 LSCC samples, 70 exhibited no KLK13 expression, while the remaining 24 exhibited ectopic expression. KLK13 expression in tumors was focal and restricted to the cytoplasm of keratinized cells. LSCC cases were classified into KLK13-negative and KLK13-positive groups, and KLK13 expression was positively associated with E-cadherin expression (P=0.0143). Associations between KLK13 expression and keratinization (P=0.0052) or absence of lymphatic vessel invasion (P=0.0603) were observed; however, these trends did not reach statistical significance. The present findings indicated that KLK13 expression in keratinized LSCC may have a protective role in lymphatic vessel invasion of LSCC, which suggests its significance for therapeutic applications against LSCC.

Gastric cancer with a giant lymph node metastasis: a case report and review of the literature.

A 78-year-old man presented with a large abdominal mass detected by ultrasonography during a regular checkup. Even if the mass was > 10 cm in diameter, he was asymptomatic. Computed tomography detected an oval-shaped mass, with a maximum diameter of 12 cm, adjacent to the greater curvature of the stomach. Esophagogastroduodenoscopy revealed a 20 mm slightly depressed (type 0-IIc) lesion on the posterior wall of the gastric antrum, which was confirmed to be adenocarcinoma. Three cycles of combination chemotherapy with S-1 and oxaliplatin were administered as neoadjuvant chemotherapy. After neoadjuvant chemotherapy, the patient underwent distal gastrectomy, and a histopathological study identified the 12 cm giant mass as a lymph node metastasis. The postoperative course was uneventful, and thus far, the patient has completed adjuvant chemotherapy without relapse. Cases of gastric cancer with a giant lymph node metastasis are extremely rare. In this study, we report the present case and review the previous literature.