Jiro Shimazaki

Hepatoid adenocarcinoma of the stomach

Although gastric cancer occurs frequently in Japan, few cases of hepatoid adenocarcinoma, a cancer with an extremely poor prognosis, have been reported. Here, we describe a 67-year-old Japanese man referred to our hospital with suspected gastric cancer. Gastrointestinal fiberscopy revealed an elevated lesion with a central depression on the lesser curvature, extending from the antrum to the body of the stomach. On the preoperative examinations, abdominal computed tomography scan, magnetic resonance imaging, and abdominal ultrasonography revealed multiple metastases to the liver and no cirrhotic change. The serum level of alpha-fetoprotein (AFP) was markedly elevated (10,084 ng/ml). After a diagnosis of AFP-producing gastric cancer with multiple liver metastases was made, total gastrectomy, without liver resection, was performed. Microscopically, the tumor showed two main histological features. The main part of the tumor resembled moderately differentiated hepatocellular carcinoma, and the rest showed fetal-type adenocarcinoma. Some parts of the hepatoma-like lesion showed periodic acid-Schiff (PAS)-positive granules. Furthermore, the tumor showed diffuse immunohistochemical positivity for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. According to these histopathological findings, the tumor was diagnosed as hepatoid adenocarcinoma of the stomach. Although anastomotic leakage occurred postoperatively and the liver metastases have increased in size, the patient remains alive 11 months after the operation. Because of the poor prognosis for this histological type of tumor, accurate diagnosis of hepatoid adenocarcinoma is important, and long-term follow-up is required. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Overexpression of MDM2 oncoprotein correlates with possession of estrogen receptor alpha and lack of MDM2 mRNA splice variants in human breast cancer.

To evaluate the significance of murine double minute 2 (MDM2) oncoprotein in human breast cancer as a nuclear-cytoplasmic shuttling protein, an estrogen receptor (ER) alpha regulator, and a prognostic marker and to study how MDM2 is overexpressed, we investigated its status in tissue samples and examined the correlation between overexpression and MDM2 gene abnormalities, status, and clinicopathological parameters. We detected MDM2 oncoprotein in both nucleus and cytoplasm by frozen-section immunohistochemistry. There was a significant correlation between MDM2 overexpression and low-grade nuclear atypia, absence of lymph node involvement, and increased levels of ER alpha protein. Our molecular assays found no point mutations in Ser17, but there was a correlation between MDM2 overexpression and the lack of splice variant mRNAs. These results suggest that the distribution of MDM2 reflects its nuclear-cytoplasmic shuttling ability; that interaction between p53 and MDM2 for tumor progression is not enhanced by point mutations at codon 17; and that the expression of MDM2 splice variants is a reason for the lack of its overexpression. MDM2 overexpression correlates with favorable prognostic parameters. A decreased level of MDM2 will lead to a deviation from the ER alpha signaling pathway.

Solitary schwannoma of the colon: report of two cases.

Abstract Some patients with gastrointestinal schwannoma (GIS) have been previously reported in the literature. However, GIS of the colon is quite rare. In addition, it is sometimes difficult to differentiate neurogenic tumors from other soft tissue tumors. We herein describe two cases of schwannoma of the colon, while also reviewing the relevant Japanese literature. The first case, a 73-year-old woman underwent a sigmoidectomy with lymph node dissection following the diagnosis of submucosal tumor. In the second case, a submucosal tumor was located in the cecum of a 44-year-old man. An endoscopic tumor resection was performed in the second case. The resected tumors measured 3.6 and 1.0 cm in maximal diameter, respectively. Microscopically, the tumors consisted predominantly of spindle-shaped cells that proliferated in an interlaced fashion. Mitosis was rarely seen in these tumors. Immunohistochemically, the tumor cells were strongly positive for S-100 protein, weakly positive for glial fibrillary acidic protein, and negative for CD34, α-smooth-muscle actin, and cytokeratin (CAM 5.2) in both cases. The tumors in the two cases were both diagnosed to be benign schwannoma of the colon. In general, schwannoma of the gastrointestinal tract is considered to be benign and should therefore be distinguished from other spindle-cell tumors or malignancies. Once diagnosed as schwannoma, extensive surgery should be avoided. Actually, such patients tend to show a good postoperative course with no evidence of recurrence.

Alternatively spliced MDM2 transcripts in human breast cancer in relation to tumor necrosis and lymph node involvement

Several short forms of alternatively spliced Murine double minute 2 (MDM2) transcripts have recently been shown to correlate with high‐grade malignancy in a number of human tumors. We examined the frequency of splice variants and their correlation with clinicopathological features in 60 cases of human breast cancer. Seven short forms coexpressed with wild‐type mRNA were detected by nested RT‐PCR. Sequencing of all the MDM2 variants demonstrated mRNA splicing which disrupted not only the conserved p53‐binding domain but also, further towards the carboxy‐terminus, the conserved nuclear localization sequence and/or the acidic and zinc finger domains. There was no significant correlation between the coexpression of splice variants and tumor size, histologic type or hormone (estrogen and progesterone) receptor status. However, cases with spliced MDM2 transcripts tended to be of a more aggressive type with axillary lymph node involvement and extensive necrosis in the tumors. Although the functional significance of MDM2 variants remains obscure, we anticipate that these variants will be confirmed as a novel prognostic marker in human breast cancer.

The perioperative granulocyte/lymphocyte ratio is a clinically relevant marker of surgical stress in patients with colorectal cancer.

PURPOSE This study was to assess the clinical relevance of the blood granulocytes to lymphocytes (G/L) ratio as an early marker of surgical stress in patients with colorectal cancer. METHODS Thirty-three patients with colorectal cancer were prospectively to undergo laparoscopic-assisted (n=12) or open (n=21) surgical resection. Granulocyte and lymphocyte counts were used to calculate the G/L ratios in blood samples from all patients before the operation and post-operatively on days 1, 3 and 7. Additionally, serum inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF were assayed as markers of surgical stress. RESULTS Seven of 33 patients developed unexpected complications. Serum IL-6 (P<0.0001), G-CSF (P=0.0257), and M-CSF (P<0.0001) were higher on day 1 vs before the operation. Similarly, the G/L ratios were higher on days 1-3 vs before the operation (P<0.0001) and then gradually decreased together with the surgical stress levels. The G/L ratios and the numbers of granulocytes and lymphocytes in the blood showed no correlation with serum IL-1β or TNF-α. In contrast, the G/L ratios and the numbers of granulocytes in the blood showed significant correlation with IL-6 (Rs=0.710, P<0.0001, Rs=0.653, P<0.0001, respectively), with G-CSF (Rs=0.626, P<0.0001, Rs=0.578, P<0.0001), with M-CSF (Rs=0.470, P<0.0001, Rs=0.372, P<0.0001). However, the number of lymphocytes showed inverse correlation with IL-6 (Rs=-0.493, P<0.0001), G-CSF (Rs=-0.440, P<0.0001) and M-SCF (Rs=-0.443, P<0.0001). CONCLUSION The G/L ratio appears to be a simple and clinically relevant parameter for the assessment of perioperative stress in patients undergoing colorectal surgery.

Gastric tube perforation after esophagectomy for esophageal cancer.

We searched for cases of perforation of the gastric tube after esophagectomy for esophageal cancer by reviewing the literature. Only 13 cases were found in the English literature, and serious complications were seen in all cases, especially in cases of posterior mediastinal reconstruction. However, in the Japanese literature serious complications were also frequently seen in retrosternal reconstruction. Gastric tubes are at a higher risk of developing an ulcer than the normal stomach, including an ulcer due to Helicobacter pylori infection, insufficient blood supply, gastric stasis, and bile juice regurgitation. H. pylori eradication and acid-suppressive medications are important preventive therapies for ordinary gastric ulcers, but for gastric tube ulcers the effects of such treatments are still controversial. We tried to determine the most appropriate treatment to avoid serious complications in the gastric tubes, but we could not confirm an optimal route because each had advantages and disadvantages. However, at least in cases with severe atrophic gastritis due to H. pylori infection or a history of frequent peptic ulcer treatment, the antesternal route is clearly the best. Many cases of gastric tube ulcers involve no pain, and vagotomy may be one of the reasons for this absence of pain. Therefore, periodic endoscopic examination may be necessary to rule out the presence of an ulcer.

The Clinical Outcomes after Total Pancreatectomy

Background: Total pancreatectomy (TP) is not more beneficial than less aggressive resection techniques for the treatment of pancreatic neoplasms and is associated with high morbidity and mortality. However, with advances in surgical techniques and glycemic monitoring, and the development of synthetic insulin and pancreatic enzymes for postoperative treatment, TP has been increasingly indicated. This is a review of the recent literature reporting the clinical outcomes after TP. Methods: We reviewed the publications reporting the use of TP starting 2007. The clinicophysiological and survival data were analyzed. Results: Few studies evaluated the differences in clinical outcomes between TP and pancreaticoduodenectomy (PD) with inconsistent results. It was reported that while the perioperative morbidity did not decrease, the mortality decreased compared to previous literature. All patients who underwent TP required insulin and high dose of pancreatic enzyme supplements. The 5-year survival rates after TP and PD for pancreatic cancer were similar. Conclusion: The perioperative mortality decreased in patients who underwent TP with advances in the operative procedures and perioperative care. The long-term survival rates were similar for TP and PD. Therefore, treating pancreatic neoplasms using TP is feasible. Patients undergoing TP should receive adequate treatment with synthetic insulin and pancreatic enzyme supplements.

Prognostic Factors Associated with Preoperative Clinicophysiological Outcomes of Distal Cholangiocarcinoma

Background/Aims: Although biliary tract cancer is generally associated with a high mortality rate, patients with distal cholangiocarcinoma have better prognoses, compared to those with periampullary cancer. This study aimed to determine the preoperative clinicophysiological factors predictive of survival and recurrence in patients with distal cholangiocarcinoma. Methods: Forty-five patients (34 men) with distal cholangiocarcinoma who underwent pancreaticoduodenectomy between 2005 and 2013 were examined retrospectively at our center and associated hospitals. Clinicophysiological parameters included predictors of overall survival (OS). Kaplan-Meier survival curves were generated and compared using log-rank tests, and Cox proportional hazard multivariate analyses were performed. Results: The mean patient age was 68.8 years (range 54-81 years). Patients had a median OS duration of 43 months, and 1-, 3-, and 5-year OS rates of 91.1, 61.1, and 40.4%, respectively. Univariate analyses indicated that the body mass index, C-reactive protein (CRP) level, and carcinoembryonic antigen level were independent prognostic factors for OS; however, only the CRP level remained an independent prognostic factor in a multivariate analysis. Conclusions: A CRP level <0.3 mg/dL was predictive of a better outcome among patients with distal cholangiocarcinoma.

Pre-operative granulocyte/lymphocyte ratio as a predictive marker of post-operative complications in patients with colorectal cancer.

The aim of the present study was to assess the clinical relevance of the pre-operative granulocyte/lymphocyte (G/L) ratio as a predictive marker of post-operative complications in patients with colorectal cancer. In total, 85 patients (59 males and 26 females; mean age, 68.9 years) underwent surgery for colorectal cancer at the Department of Surgery, Ibraki Medical Center, Tokyo Medical University (Ami, Japan), and were divided into post-operative complication and non-complication groups. Clinical data, including age, gender, body mass index, tumor localization, tumor pathological type, cancer staging, surgery time, volume of surgical bleeding, pre-operative G/L ratio and further pre-operative laboratory data, including levels of albumin and C-reactive protein, Glasgow Prognostic Score, white blood cell count and levels of hemoglobin, creatine kinase, lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9 were analyzed between these groups. The total post-operative complication rate was 18.8%. On univariate analysis, the amount of surgical bleeding and the pre-operative G/L ratio were significantly higher in the complication group than in the non-complication group (299.8±361.7 vs. 155.6±268.6 ml, P<0.05; and 6.73±10.38 vs. 3.49±2.78, P<0.05, respectively). Multivariate logistic regression analysis for the risk factors of post-operative complications, determined using univariate analysis, demonstrated that the amount of surgical bleeding and the pre-operative G/L ratio were independent risk factors of post-operative complications in patients with colorectal cancer. In conclusion, the G/L ratio may be a clinically relevant pre-operative predictive marker for post-operative complications.

Removal of an intra‑abdominal desmoplastic small round cell tumor by repetitive debulking surgery: A case report and literature review

In the current study, a case of recurrent desmoplastic small round cell tumor (DSRCT) is presented, which was successfully treated by repetitive debulking surgery. In May 2010, a 39-year-old male, with a history of surgical resection of intra-abdominal DSRCT, visited the Ibaraki Medical Center, Tokyo Medical University Hospital (Ami, Japan) with severe lower abdominal discomfort. Abdominal computed tomography revealed a large tumor in the pouch of Douglas with a small number of nodules in the abdominal cavity. The recurrent DSRCT was diagnosed and removed via lower anterior resection; however, complete resection was impossible due to multiple peritoneal metastases. One year later, the patient developed pain in the right groin due to the growth of metastasized tumor cells in the groin lymph nodes. The affected lymph nodes were removed utilizing an extra-peritoneal approach. At the time of writing, the patient continues to survive without any symptoms 60 months since the initial surgery. In conclusion, surgical debulking is a significant procedure for relieving patient symptoms as well as improving the survival time of patients with metastatic and recurrent DSRCT.