Laparoscopic repair and total gastrectomy for delayed traumatic diaphragmatic hernia complicated by intrathoracic gastric perforation with tension empyema: a case report.

BACKGROUND: Blunt traumatic diaphragmatic hernia (TDH) is a complication of blunt diaphragmatic injury. If missed, it could lead to critical presentations, such as incarceration or strangulation of the herniated intra-abdominal organs, and thus, early surgical repair is required. Methods of the operative approach against delayed TDH remain unclear. Even with the spread of the minimally invasive approach, laparotomy has been predominantly selected for cases with hemodynamic or gastrointestinal complaints. Literature on the use of laparoscopy for repair of such cases is limited, and no study has been conducted for those with intrathoracic gastric perforation. CASE PRESENTATION: A 55-year-old male patient with a history of multiple traumas presented with shock, followed by left hypochondrium pain and vomiting. The patient was admitted to the emergency department of our institution and diagnosed with delayed TDH complicated by intrathoracic gastric perforation, and tension empyema. Emergency surgery using laparoscopic approach was performed, despite unstable hemodynamics, considering orientation, exposure, and operativity compared with laparotomy. Repair of the diaphragm plus total gastrectomy was successfully performed by minimally invasive management. The patient made an uneventful recovery without recurrence after 8 months. CONCLUSION: Unstable hemodynamic conditions and intrathoracic gastric perforation could not be contraindications to laparoscopic repair in treating delayed TDH.

The necessity of routine screening for deep vein thrombosis before surgery.

Background: Pulmonary embolism (PE) from deep venous thrombosis (DVT) can be a fatal postoperative complication. Preventive measures for venous thromboembolism (VTE) was evaluated in this hospital. Materials and methods: Preoperative DVT screening following surgery under general anesthesia in 2009-2016 was examined, and then, 217 patients diagnosed with DVT by preoperative leg-ultrasound (US) between 2014 and 2016 were retrospectively analyzed. Results: There were 24,826 operations under general anesthesia in the study period. Preoperative leg-US was performed in 5345 (21.5%) patients, and 648 (12.1% of patients, 2.6% of total operations) were diagnosed with DVT. In 2014-2016, 217 patients, which is 11.7% of patients undergoing leg-US, were diagnosed with DVT. DVT was found in the proximal veins (upper popliteal vein) in 86 (39.6%) patients. A total of 143 (62%) patients were considered to have organized thrombi, no patient developed pulmonary embolism, and 133 (58%) patients were discharged without follow-up examination for DVT. Ninety-six patients were evaluated for changes on leg-US, with no difference in the results with and without anticoagulant use. On multivariate logistic regression analysis, anticoagulants appeared effective for non-organized thrombi, higher D-dimer levels (≥10 µg/mL), or orthopedic surgery. Conclusion: Preoperative screening for DVT did not appear useful, and treatment of asymptomatic DVT was not always necessary.

A case of large cell neuroendocrine carcinoma exhibiting rhabdoid features in the esophagogastric junction.

We report a case of large cell neuroendocrine carcinoma with rhabdoid features in the esophagogastric junction. An 81-year-old man presented to Saku Central Hospital Advanced Care Center with a tumor in the esophagogastric junction. During upper gastrointestinal endoscopy, an ulcerative tumor, measuring 4 × 3 cm in diameter, was observed. Computed tomography revealed lymph node metastasis, but no metastasis to other organs was observed. A thoracoscopic subtotal esophagectomy was performed. Histopathologically, anaplastic large cells exhibited a solid growth pattern with focal and geographic necrosis. Approximately half of the tumor cells exhibited large nuclei with conspicuous nucleoli; an eosinophilic "rhabdoid" cytoplasmic inclusion; and a nucleus displaced eccentrically by the cytoplasmic inclusion body. Immunohistochemically, tumor cells, including rhabdoid cells, were focally positive for pan-cytokeratin and diffusely positive for vimentin and synaptophysin. Additionally, electron microscopy identified dense-core granules in the tumor cells. Therefore, a diagnosis of large cell neuroendocrine carcinoma with rhabdoid features was made. A few cases of esophageal neuroendocrine tumors with rhabdoid features have been reported in the lung and pancreas; however, this is the first report of large cell neuroendocrine carcinoma with rhabdoid features in the esophagogastric junction.

[Gastric Neuroendocrine Carcinoma(NEC)Treated with CDDP plus CPT-11 Chemotherapy].

A 69-year-old man with chronic gastritis, reflux esophagitis, esophageal hiatal hernia, and history of appendicitis surgery complained of difficulty swallowing. Upper gastrointestinal endoscopy revealed a 10 cm sized Type 3 gastric cancer. Immunostaining was positive for chromogranin A(2+), synaptophysin(3+), CD56(-), and Ki-67>70%. Contrast computed tomography(CT)showed upper gastric wall thickening, and #1, #3, #7, #8a, and #11p enlarged lymph nodes but no distant metastasis. We diagnosed gastric cancer, UM, Less, Type 3, gastric neuroendocrine carcinoma, cT4aN3M0P0CY0, Stage ⅢC. We administered 2 courses of CDDP plus CPT-11 chemotherapy, and a partial response was obtained for the primary gastric lesion and lymph node metastases. We subsequently performed open distal gastrectomy, D2 lymph node dissection, and splenectomy. Pathological examination confirmed that the lesion was gastric cancer, U, Less, Type 3, gastric neuroendocrine carcinoma, MP, Ul-Ⅱ(+), int, INF b, ly2, v0, PM0, DM0, R0, ypT2N2, Stage ⅡB, with a therapeutic value of Grade 2. The patient was discharged on day 15 after the surgery and received 2 courses of adjuvant chemotherapy with CDDP plus CPT-11. Nine months after the surgery, metastasis of the left adrenal grand was found. We performed open left adrenal gland resection and administered adjuvant S-1 chemotherapy.

[A case of rupture of post-gastrectomy afferent loop obstruction due to invasion by pancreatic cancer].

A 77-year-old man with history of distal gastrectomy with Billroth II reconstruction for peptic ulcer disease performed 55 years ago was admitted to our hospital for diarrhea and abdominal pain. Abdominal computed tomography revealed a dilatation of the afferent loop and the duodenum, and a low density mass located in the body of the pancreas, which invaded the gastro-jejunal anastomosis site as well as the celiac axis and the superior mesenteric artery. Judging from these findings, we diagnosed this case as acute afferent loop obstruction due to an unresectable pancreatic cancer. Endoscopic decompression of the afferent loop was unsuccessful. After a while, the patient complained a severe abdominal pain, and an emergency surgery was performed under the diagnosis of rupture of the afferent loop. At laparotomy, a perforation of the jejunum located at a 15 cm anal side from Ligament of Treitz was found, and Braun's anastomosis was performed using the perforated site. The patient was treated with chemotherapy and survived for 15 months after the operation. Prompt decompression of afferent loop should be performed for preventing a rupture in case of acute obstruction of the afferent loop.

Protein overexpression and gene amplification of HER-2 and EGFR in colorectal cancers: an immunohistochemical and fluorescent in situ hybridization study.

Overexpression of HER-2 and the epidermal growth factor receptor (EGFR) has been observed in many cancers, sometimes accompanied by gene amplification. To assess whether novel chemotherapies targeting these overexpressed proteins may be effective for the treatment of colorectal cancers, we examined the exact frequency of HER-2 and EGFR overexpression, the relationship between gene amplification and protein expression, and the heterogeneity of gene amplification within and between primary and metastatic tumors. We evaluated 244 colorectal cancers immunohistochemically. All tumors found to overexpress HER-2 or EGFR were further analyzed for gene amplification by fluorescent in situ DNA hybridization. Overexpression of HER-2 and EGFR was found in 8 (3%) and 19 (8%) of the 244 colorectal carcinomas, respectively. Gene amplification was observed in 100 and 58% of the tumors exhibiting HER-2 and EGFR overexpression, respectively. HER-2 amplification in cancer cells was characterized by clusters of hybridization signals, suggesting amplicons in homogeneously staining regions that were predominant in most primary and metastatic tumors. EGFR amplification, observed as scattered signals reminiscent of amplicons in double minute chromosomes, or coamplification of EGFR with the centromeric regions was observed as a minor population within primary tumors, and found in variety of populations in metastatic tumors. Overexpression of HER-2 and EGFR were observed in only a small fraction of colorectal carcinomas, but were frequently accompanied by gene amplification.

Perspectives on cancer therapy: cell cycle blockers and perturbators.

Over the past few decades, remarkable advances have been achieved in cancer therapy, including chemotherapeutic agents, their mode of application and more broader therapeutic strategies. Promising new therapeutic targets have emerged in the past ten years as a result of recent advances in our understanding of the pathobiology of malignant cells, in particular, regarding functions of suppressor oncogene products. Among them, the agents that alter the cell cycle have recently been of particular interest, since cell cycle regulation is basic mechanism underlying cell fate, i.e., proliferation, differentiation or death. Furthermore, the human genome project has made possible the future development of so-called "tailor-made medicine", i.e. the design of appropriate drugs for specific genetic profiles and application of drugs that are tailored to each tumor and patient. In this article, we will introduce and discuss recent progress in the development of agents that influence the cell cycle and their future potential in cancer therapy from three standpoints with our own experimental works; i) the inhibition of cell proliferation and/or induction of differentiation by cyclin-dependent kinase (cdk)-inhibitor, e.g. olomoucin, butyrolactone-I, ii) induction of apoptosis by directing "abortive cell cycle", or the transient upregulation of cdk activity, e.g. flavopiridol, and iii) countering the development of drug resistance by adjunctive administration of cdk-inhibitors with conventional anti-cancer drug, e.g., p21-gene transfer with cisplatin. Conclusively none of these three approaches by itself is satisfactory, and that the effective cancer therapies will require the administration of several agents and/or methods under the design of their synergistic effects.

Expression of epidermal growth factor receptor in gastric carcinomas.

BACKGROUND & AIMS: Epidermal growth factor receptor belongs to the family of type I receptor tyrosine kinases. Overexpression of epidermal growth factor receptor has been observed in a variety of cancers with or without amplification of the gene. Novel chemotherapies targeting receptor tyrosine kinases might be effective for the treatment of cancers in which overexpression of this protein is a feature. The aim of this study was to assess the potential efficacy of epidermal growth factor receptor-targeted therapy in gastric cancer. This was achieved by determining the frequency of increased epidermal growth factor receptor expression in gastric cancers and investigating the relationship between protein overexpression and gene amplification. METHODS: Immunohistochemical evaluation of 413 gastric cancers was carried out by using a monoclonal antibody to the epidermal growth factor receptor. The intensity of reactivity was scored by using a 4-tier system (negative, 1+, 2+, and 3+). All positive staining (>1+) tumors overexpressing the protein were then analyzed for gene amplification by fluorescence in situ hybridization by using a gene-specific probe. RESULTS: High levels of overexpression (2+ or 3+ staining) were found in 9 of 413 (2.2%) patients, whereas low levels of overexpression (1+) were found in 34 (8.2%) of the study cohort. Fluorescence in situ hybridization analysis showed that more than 10 copies of the gene were recognized in all 5 cancers with 3+ staining and in 2 of the 4 tumors with 2+ staining. CONCLUSIONS: Although a high level of overexpression of epidermal growth factor receptor is uncommon in gastric carcinomas, it almost exclusively occurs by gene amplification.

Detection of c-erbB-2 (HER-2/neu) amplification in breast carcinoma by fluorescence in situ hybridization on tissue sections and imprinted cells.

Abnormalities in c-erbB-2 have attracted a great deal of attention. Treatment using an antibody against the c-erbB-2 gene product is effective against breast cancers with amplification and/or overexpression of c-erbB-2. There is an urgent need to establish methodology for selecting patients who would benefit from this therapy. A total of 235 breast carcinomas were examined for c-erbB-2 protein overexpression by immunohistochemistry. Tissue sections with discernible immunostaining from 52 tumors, 70 negative tumors and smear imprints from 35 patients were examined by dual-color fluorescence in situ hybridization (FISH) using probes specific for c-erbB-2 and the centromeric region of chromosome 17. The concordance between gene amplification and protein overexpression was 95.7%. When the findings of the two FISH preparation techniques were compared, no discrepancies were found in 24 of the tumors. However, differences were seen in eight cases. In six of these cases the differences did not affect the presence or absence of amplification, but in the other two cases, considered to show low-level amplification on paraffin sections, polysomy 17 was detected instead. It was concluded that FISH is an excellent tool to detect gene amplification in particular, and FISH on touch imprints is a useful adjunct to differentiate between low-level amplification and polysomy 17.

Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay.

c-erb-2 amplification and overexpression are currently attracting a great deal of attention because a new adjuvant therapy using an antibody against the c-erbB-2 gene product, trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), has proved effective in treating breast cancer with amplification and/or overexpression of c-erbB-2. Aberrations of c-erbB-2 have also been detected in ovarian, endometrial and gastric carcinomas at varied frequencies. Amplification of the c-erbB-2 locus (17q12-q21.32), overexpression of c-erbB-2 protein (p185) and serum levels of soluble c-erbB-2 protein fragments (p105) were examined in gastric cancer patients using fluorescence in situ hybridization (FISH), immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Overexpression of c-erbB-2 protein was found in 29 (8.2%) of the 352 gastric carcinomas analyzed. In FISH analysis, all tumors with 3+ immunostaining and 1 of 5 tumors with 2+ staining showed high-level amplification of c-erbB-2. Pre-operative serum p105 was quantified in serum specimens from 129 patients with gastric cancer and 28 patients with benign diseases. There were no significant differences in the serum p105 levels among 11 patients with c-erbB-2-overexpressing carcinomas, 118 patients with c-erbB-2 non-overexpressing carcinomas and 28 controls, although a single case of gastric carcinoma overexpressing c-erbB-2 with extensive liver metastasis had a higher level than the cut-off value. The mechanisms of overexpression of p185 and high-level amplification of c-erbB-2 in gastric adenocarcinomas seem similar to those well-established in breast cancers. Patients having gastric adenocarcinoma with c-erbB-2 amplification are potential candidates for a new adjuvant therapy using humanized monoclonal antibody.