Takashi Shono

Primary hepatic gastrinoma as an unusual manifestation of zollinger-ellison syndrome

We report a rare case of primary hepatic gastrinoma. A 77-year-old woman exhibited continuous watery diarrhea for 8 months and weight loss. Bacterial cultures of the stools were negative and colonoscopy revealed no abnormalities. Esophagogastroduodenoscopy showed severe reflux esophagitis and multiple duodenal erosions. Computed tomography and magnetic resonance imaging detected two solid masses measuring <2 cm in diameter in the right lobe of the non-cirrhotic liver. Microscopically, the tumor was consistent with neuroendocrine tumor (grade 2) with abundant gastrin-immunoreactive cells. Endoscopic ultrasound detected no other alternative primary source of an endocrine tumor. The serum gastrin levels exceeded 40,000 pg/ml in the absence of H2 receptor antagonist and proton pump inhibitor administrations. Based on an arterial stimulation and venous sampling test, the patient was diagnosed as primary gastrinoma of the liver. Our findings demonstrated the presence of Zollinger-Ellison syndrome in a patient who was subsequently cured by surgical resection of the liver tumors.

Pancreatic metastasis from mixed adenoneuroendocrine carcinoma of the uterine cervix: a case report.

Metastatic cancers of the pancreas are rare, accounting for approximately 2-4% of all pancreatic malignancies. Renal cell carcinoma is the most common solid tumor that metastasizes to the pancreas. Here, we present a case of uterine cervical carcinoma metastasizing to the pancreas and review the literature regarding this rare event. A 44-year-old woman with a uterine cervical tumor had undergone radical hysterectomy and had been diagnosed pathologically with stage Ib mixed adenoneuroendocrine carcinoma in 2004. She underwent concurrent radiotherapy and chemotherapy postoperatively. Pulmonary metastases subsequently appeared in 2008 and 2011, and she underwent complete resection of the lung tumors by video-assisted thoracic surgery. Although she was followed up without any treatment and with no other recurrences, positron emission tomography revealed an area of abnormal uptake within the pancreatic body in 2012. Enhanced computed tomography demonstrated a 20-mm lesion in the pancreatic body and upstream pancreatic duct dilatation. Endoscopic ultrasonography-guided fine needle aspiration was performed and pathological examination suggested neuroendocrine carcinoma (NEC). On the basis of these results and the patients oncological background, lesions in the pancreatic body were diagnosed as secondary metastasis from the cervical carcinoma that had been treated 8 years earlier. No other distant metastases were visualized, and the patient subsequently underwent middle pancreatectomy. Pathological examination showed NEC consistent with pancreatic metastasis from the uterine cervical carcinoma. The patient has survived 7 months since the middle pancreatectomy without any signs of local recurrence or other metastatic lesions.

Carbohydrate antigen 19-9 is a useful prognostic marker in esophagogastric junction adenocarcinoma

The incidence rate of esophagogastric junction (EGJ) adenocarcinoma has been rapidly increasing worldwide. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA19‐9) are major serum tumor markers in gastrointestinal cancers. However, the role of these markers in EGJ adenocarcinoma has not been thoroughly investigated. A total of 211 patients with EGJ adenocarcinoma who underwent surgery or endoscopic submucosal dissection at two academic institutions, Kumamoto University Hospital or Kyushu University Hospital between January 1996 and March 2014, were eligible for this study. Serum CEA and CA19‐9 were examined within 1 month before resection. The cut‐off values for CEA and CA19‐9 were set at 5.0 ng/mL and 37 U/mL, respectively. The clinicopathological features and prognostic roles of the markers were examined using univariate and multivariate analyses. The positive ratios for preoperative CEA (>5.0 ng/mL) and CA19‐9 (>37 U/mL) were 20.3% and 12.9%, respectively. The positive ratio of CEA and CA19‐9 was significantly higher in patients with tumors invading muscular or deeper layers (P = 0.002 and <0.001, respectively). Cox proportional hazards model revealed that CA19‐9 positivity, but not CEA positivity, was an independent prognostic factor in patients with EGJ adenocarcinoma for cancer‐specific survival (multivariate hazard ratio [HR] = 3.89, 95% confidence interval [CI] 1.41–10.33; P = 0.010) and overall survival (multivariate HR = 2.43, 95% CI 1.03–5.35; P = 0.043). Preoperative serum CA19‐9 is a useful prognostic marker in patients with EGJ adenocarcinoma.

Diagnosis of boundary in early gastric cancer.

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique, which allowsresection of larger superficial tumors in the esophagus, stomach, and colon. Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD, because too much resection can potentially take more time and can induce a higher complication rate, while too little resection can result in a non-curative resection. The boundary diagnosis is often difficult for early gastric cancer, mainly because of the underlying condition of chronic gastritis. Due to recent developments in endoscopy, including magnified endoscopy and narrow band endoscopy, the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.

Spleen Dose–Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer

Aim: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. Materials and Methods: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. Results: Multivariate linear regression analysis revealed that docetaxel use and spleen dose–volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose–volume parameters significantly predicted lymphopenia. Conclusion: Higher spleen dose–volume parameters were associated with severe lymphopenia during chemoradiotherapy.

Increased EZH2 expression during the adenoma‑carcinoma sequence in colorectal cancer

The adenoma-carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well-established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma-carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma-carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non-cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki-67 (Ki-67), cyclin-dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin-fixed paraffin-embedded blocks and reverse transcription-quantitative polymerase chain reaction analysis of these genes was performed. Ki-67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki-67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21.

Impact of retroflexion in the right colon after repeated forward-view examinations: Impact of retroflexion in right colon

Right colon polyps can especially be overlooked when they are located on the backs of haustral folds. Previous studies have reported that repeated forward‐view examinations in the right colon were effective in reducing adenoma miss rates. The aim of this study was to clarify the impact of retroflexion in the right colon after repeated forward‐view examinations.

Esophageal adenocarcinoma with enteroblastic differentiation arising in ectopic gastric mucosa in the cervical esophagus: A case report and literature review

BACKGROUND Adenocarcinoma with enteroblastic differentiation is a subtype of alpha-fetoprotein (AFP) producing adenocarcinoma. This type of tumor is associated with a poor prognosis and is prone to metastasize. Esophageal adenocarcinoma with enteroblastic differentiation is extremely rare. CASE PRESENTATION The patient was a 65-year-old woman who was referred to our hospital with dysphagia. Endoscopic examination revealed an elevated lesion 20mm in diameter at 17cm from the upper incisors. Endoscopic submucosa dissection (ESD) was performed and histopathological examination revealed tubular adenocarcinoma composed of cuboidal cells with clear cell cytoplasm. Immunohistochemical stain was diffusely positive for Sall-like protein 4 (SALL4) and weakly positive for AFP and glypican 3. From this result, we diagnosed esophageal adenocarcinoma with enteroblastic differentiation. The patient is still alive without recurrence of cancer 40 months after ESD. CONCLUSION To our knowledge, this is the first report to undergo ESD for esophageal adenocarcinoma with enteroblastic differentiation arising from ectopic gastric mucosa in the esophagus.

Preoperative Diagnosis of Intestinal Endometriosis by Magnifying Colonoscopy and Target Biopsy

Endometriosis can affect any portion of the gastrointestinal tract. A preoperative definitive diagnosis of intestinal endometriosis is difficult, because there is no characteristic endoscopic finding and the endoscopic biopsies usually sample insufficient endometrial tissue for pathologic diagnosis. To our knowledge, the magnifying endoscopic features of intestinal mucosal endometriosis have not been well documented. In this study, we report a case of intestinal endometriosis diagnosed preoperatively by magnifying image-enhanced colonoscopy and target biopsy. A 45-year-old woman was referred to our hospital with abdominal pain in the left lower quadrant. Colonoscopy showed a submucosal tumor-like lesion of approximately 30 mm in diameter exhibiting surface reddening and granular changes in the sigmoid colon. Magnifying endoscopy revealed sparsely distributed round pits in the granules. The mucosal biopsy specimen from the granule provided the diagnosis of intestinal endometriosis. Segmental sigmoidectomy was performed, and pathological examination revealed that the surface colonic mucosa was partially replaced by endometrial tissue, which accounted for the granular change detected in the colonoscopy. It can be speculated that the round pit might reflect the endometrial glands surrounded by endometrial stroma. This case illustrated the characteristic finding and utility of magnifying endoscopy for mucosal intestinal endometriosis.

Clinical Outcome of Endoscopic Submucosal Dissection for 352 Lesions of Superficial Gastric Neoplasms in 284 Patients

One of the most significant topics for therapeutic endoscopy in recent years is the develop‐ ment of new therapeutic strategies for gastric neoplasms, called endoscopic submucosal dis‐ section (ESD)[1]-[7]. This technique was developed to allow resection of difficult lesions with characteristics such as large size, irregular shape, coexisting ulcer findings or difficult location that could not be resected en bloc using conventional endoscopic mucosal resection (EMR). One of the most important benefits of this procedure is to obtain accurate histologi‐ cal diagnosis. Additional benefits of ESD include that it is minimally invasive in nature and allows preservation of the entire stomach, resulting in the improved postoperative quality of life[8], [9]. Therefore, ESD is widely accepted as a standard treatment strategy for gastric ne‐ oplasm.