The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in glioma stem cells.

Glioblastomas (GBMs) maintain their cellular heterogeneity with glioma stem cells (GSCs) producing a variety of tumor cell types. Here we interrogated the oncogenic roles of Lim domain only 2 (LMO2) in GBM and GSCs in mice and human. High expression of LMO2 was found in human patient-derived GSCs compared with the differentiated progeny cells. LMO2 is required for GSC proliferation both in vitro and in vivo, as shRNA-mediated LMO2 silencing attenuated tumor growth derived from human GSCs. Further, LMO2 is sufficient to induce stem cell characteristics (stemness) in mouse premalignant astrocytes, as forced LMO2 expression facilitated in vitro and in vivo growth of astrocytes derived from Ink4a/Arf null mice and acquisition of GSC phenotypes. A subset of mouse and human GSCs converted into vascular endothelial-like tumor cells both in vitro and in vivo, which phenotype was attenuated by LMO2 silencing and promoted by LMO2 overexpression. Mechanistically, the action of LMO2 for induction of glioma stemness is mediated by transcriptional regulation of Jagged1 resulting in activation of the Notch pathway, whereas LMO2 directly occupies the promoter regions of the VE-cadherin gene for a gain of endothelial cellular phenotype. Subsequently, selective ablation of human GSC-derived VE-cadherin-expressing cells attenuated vascular formation in mouse intracranial tumors, thereby significantly prolonging mouse survival. Clinically, LMO2 expression was elevated in GBM tissues and inversely correlated with prognosis of GBM patients. Taken together, our findings describe novel dual roles of LMO2 to induce tumorigenesis and angiogenesis, and provide potential therapeutic targets in GBMs.

Relevance of hepatoduodenal ligament lymph nodes in resectional surgery for gastric cancer.

BACKGROUND: Hepatoduodenal lymph node (HDLN) positivity is considered distant metastasis in gastric cancer according to the seventh American Joint Committee on Cancer (AJCC) classification. In contrast, the International Union Against Cancer seventh edition and the Japanese Gastric Cancer Association both consider HDLN as a regional lymph node that can be included in the context of a curative resection. The purpose of this study was to determine whether there was justification for considering HDLN involvement as a distant metastasis for which resectional surgery could not have survival benefit. METHODS: This study enrolled consecutive patients with gastric cancer having D2 or greater resections, with removal and pathological assessment of the HDLN, between 1989 and 2009. The pathological stage of all patients was determined based on the seventh AJCC criteria, with HDLN included as a regional lymph node. RESULTS: A total of 1872 patients had their HDLN removed, of whom 68 had a metastatic lymph node in the hepatoduodenal ligament. The 5-year survival rate of these 68 patients was 30 per cent, compared with 47·7 per cent for those with stage III (P < 0·001) and 9·8 per cent for those with stage IV (P = 0·007) HDLN-negative tumours. The 5-year survival rate of 41 patients with HDLN metastasis and no evidence of distant metastasis at any other site was significantly higher than that among 120 patients with stage IV disease without HDLN metastasis (P < 0·001), whereas 5-year survival did not differ between the 41 patients with stage I-III disease with HDLN metastasis and 568 patients with stage III tumours without HDLN metastasis (P = 0·184). HDLN metastasis was not a significant factor for survival in multivariable analysis. CONCLUSION: It is inappropriate to include the HDLN in the distant metastatic lymph node group in gastric cancer. The seventh AJCC criteria for node grouping should be revised.

The role of small intestinal bacterial overgrowth in postgastrectomy patients.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is expected in postgastrectomy patients; however, its role has not been clarified. This study was to estimate the prevalence of SIBO and investigate the clinical role of SIBO in postgastrectomy patients. METHODS: This prospective study involved 76 patients who underwent gastrectomy for early gastric cancer with no evidence of recurrence. An H(2)-CH(4) breath test with oral glucose challenge test was performed to diagnose SIBO and dumping syndrome. Sigstad dumping questionnaires, serum glucose, hematocrit and pulse rate were simultaneously monitored for every 30 min for 3 hours. KEY RESULTS: There were significant differences in SIBO between the postgastrectomy patients and controls (77.6%vs 6.7%, P < 0.01). Abdominal fullness or borborygmus during oral glucose load were more common in SIBO-positive than in negative patients (50.8%vs 17.6%, P = 0.03), and were the independent factors for predicting SIBO in postgastrectomy patients (P = 0.02). The prevalences of dumping syndrome and hypoglycemia after oral glucose were 35 (46.1%) and 19 (25.0%), and were not different between both groups. However, the plasma glucose was significantly lower in SIBO-positive than in SIBO-negative patients at 120 and 150 min after oral glucose load (P < 0.05). No significant differences were observed in pulse rate and hematocrit in both groups. CONCLUSIONS & INFERENCES: SIBO is common among postgastrectomy patients. It appears to be associated with postprandial intestinal symptoms and might aggravate late hypoglycemia. SIBO could be a new therapeutic target for managing intestinal symptoms in postgastrectomy patients.

Impact of tumor infiltration pattern into the surrounding tissue on prognosis of the subserosal gastric cancer (pT2b).

BACKGROUND: The aim of this study was to clarify the impact of infiltration pattern on prognosis in patients with gastric carcinoma invading subserosa. METHODS: Clinicopathologic findings in patients with ssgamma pattern (n = 144) were compared with those in patients with ssalpha/ssbeta cancers (n = 222). Prognostic factors of pT2b patients were analyzed by univariate and multivariate analysis. RESULTS: Compared with the ssalpha/beta group, ssgamma gastric cancer exhibited more frequent undifferentiated histology, disseminated lymph node metastasis and perineural invasion. Frequency of postoperative peritoneal recurrence was significantly higher in ssgamma gastric cancer (P < 0.05). The 5-year survival rate for patients with ssgamma gastric cancer was significantly lower compared with ssalpha/beta group (63.2% vs. 74.8%, respectively; P < 0.05). Lymph node metastasis, vein invasion and infiltrative pattern (ssgamma) were significant independent prognostic factors affecting survival in pT2b patients. CONCLUSION: In patients with gastric cancer invading the subserosa, infiltrative type growth pattern is closely related to carcinomatosis and poorer prognosis.

Morphology and metabolism of hepatocytes microencapsulated with acrylic terpolymer-alginate using gelatin and poly(vinyl alcohol) as extracellular matrices.

Microcapsules with good mechanical stability were prepared using an appropriate mixture of alginate and acrylic terpolymer. It was found from the microscopic observation that the microcapsules had a porous structure with interconnected pores, with a size of 50-150 nm. The results of the permeability experiment of microcapsules using FITC-dextrans showed that the capsule had a molecular mass cut-off of 120 kDa. The hepatocytes encapsulated in both alginate and acrylic terpolymer with gelatin and PVA rapidly aggregated in the core. The aggregated cells showed high albumin synthesis and ammonia removal, suggesting good metabolic function.

Pharyngo-enteral anastomosis for esophageal reconstruction in diffuse corrosive esophageal stricture.

BACKGROUND: Diseases involving the entire esophagus usually require extensive surgical procedures to accomplish functional reconstruction. These procedures are extremely stressful for undernourished patients. We have utilized a simpler procedure for total esophageal reconstruction. METHODS: This retrospective report reviews the experience in 8 patients who underwent esophageal reconstruction by pharyngo-colo-gastrostomy or jejunostomy without any resection of bony structures. RESULTS: There was no operative or hospital death. Complications included anastomotic stenosis, transient leak from the ileal stump, and late enterocutaneous fistula, each in 1 patient. Laryngeal function was maintained without special treatments. After swallowing training for approximately 1 week, oral feeding was resumed. All patients have gained 7 to 21 kg at 35 to 67 months after surgery. CONCLUSIONS: Our surgical procedure is shown to be safe and effective in undernourished patients with diffuse esophageal stricture.

A clinical analysis of gasless endoscopic thyroidectomy.

Gasless endoscopic surgery was applied to a thyroidectomy. Compared with the previous method of endoscopic thyroidectomy, this method is superior in obtaining hemostasis and minimizing the possible complications of gas-insufflating surgery, such as a hypercapnia or massive subcutaneous emphysema. We successfully removed 37 thyroid tumors in 35 patients by gasless endoscopic surgery without any significant complications. No scars remained in the neck, and all patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy is a safe and technically feasible alternative to conventional thyroidectomy for cases of benign thyroid tumors and has good cosmetic results.

Clinical Analysis of PTEN, p53 and Her-2/neu Expressions in Thyroid Cancers.

PURPOSE: The dual-specificity phosphatase PTEN/ MMAC1/TEP1 has recently been identified as the tumor suppressor gene most frequently mutated and/or deleted in human tumors. However, PTEN mutations have rarely been detected in sporadic thyroid cancers. Therefore, this study investigated the PTEN expression of thyroid cancer and the relationship between PTEN, clinical status and other biologic factors such as HER-2/neu and p53. MATERIALS AND METHODS: The study samples consisted of 62 thyroid cancer specimens and 24 benign thyroid tumor specimens from patients who were operated on the Department of Surgery, Uijongbu St. Mary's hospital during the 5 years from January 1995 until January 2000. All tumors were studied by immunohistochemical staining using monoclonal antibodies against PTEN, HER-2/neu and p53. The results were analyzed statistically. RESULTS: PTEN protein was found to be under-expressed more frequently in thyroid cancers (29%) than in benign thyroid tumors (4.2%). The reduction in PTEN expression in thyroid cancers was not significantly related with the recorded clinical factors such as size, age, lymph node metastasis and p53, except for HER-2 which was found to be significantly related (p=0.001). HER-2 over- expression was noted in thyroid cancer (83.8%) more frequently than in benign tumors (16.7%). CONCLUSION: This study has demonstrated that the under-expression of PTEN protein and the over-expression of HER-2 protein may play a role in the carcinogenesis and development of thyroid cancer.

Laparoscopic procedures during the third trimester of pregnancy.

Pregnancy no longer is considered to be an absolute contraindication for laparoscopic procedures. Furthermore, clinically helpful guidelines are in place for laparoscopic procedures during pregnancy. However, laparoscopic operations in women in the third trimester have not yet been reported fully. We successfully operated on torsion of an ovarian cyst in a woman during her third trimester using laparascopic procedure. The patient experienced an uneventful recovery.

Toxic amebic colitis coexisting with intestinal tuberculosis.

A patient with a fulminant amebic colitis coexisting with intestinal tuberculosis had a sudden onset of crampy abdominal pain, mucoid diarrhea, anorexia, fever and vomiting with signs of positive peritoneal irritation. Fulminant amebic colitis occurring together with intestinal tuberculosis is an uncommon event and may present an interesting patho-etiological relationship. The diagnosis was proven by histopathologic examination of resected specimen. Subtotal colectomy including segmental resection of ileum, about 80 cm in length, followed by exteriorization of both ends, was performed in an emergency basis. Despite all measures, the patient died on the sixth postoperative day. The exact relationship of fulminant amebic colitis and intestinal tuberculosis is speculative but the possibility of a cause and effect relationship exists. Fulminant amebic colitis may readily be confused with other types of inflammatory bowel disease, such as idiopathic ulcerative colitis, Crohn's disease, perforated diverticulitis and appendicitis with perforation. This report draws attention to the resurgence of tuberculosis and amebiasis in Korea, and the need for the high degree of caution required to detect it.

Enhanced adenoviral transduction efficiency in HER-2/neu-overexpressing human breast cancer cells not induced by an integrin pathway.

Adenoviruses are currently widely used as vectors in gene therapy. The steps involved in adenoviral infection have been investigated, but the factors regulating viral entry to the cell have not been clearly identified. We observed a high adenoviral infection rate in HER-2/neu-overexpressing breast cancer cells in vitro (435.eb1 and MCF-7/H18) and in vivo (435.eb1). We used emodin, a tyrosine kinase inhibitor that suppresses autophosphorylation and transphosphorylation activities of the HER-2/neu tyrosine kinase, to test the role of HER-2/neu in adenoviral transduction. Emodin treatment resulted in a marked decrease in the transduction efficiency of HER-2/neu-overexpressing cells but not in the parental cells. Because previous studies have shown that epidermal growth factor and tumor growth factor-alpha increase the expression level of integrin. Because integrin alphav is known as a promotor of viral internalization, penetration, or both, we investigated whether the observed increased transduction rate in HER-2/neu transfectants was mediated through the increased expression of integrin alphav. To test this hypothesis, we examined the level of integrin alphav of in HER-2/neu overexpressing cells. We found that the level of integrin alphav expression detected in HER-2/neu overexpressing cells by immunoblot analysis was similar to the level of integrin alphav found in its parental cells. These results suggest that HER-2/neu expression may have a significant role in the viral transduction efficiency through an integrin alphav independent pathway.

Ileo-rectal fistula complicating advanced ovarian carcinoma.

Fistula between the bowels and an ovarian carcinoma is recognized but rare complication. Internal malignant fistula of the gastrointestinal tract involving two or more loops of different segments of the bowel and genitourinary structure are rare. The colon is frequently one of the participating loops. In reviewing the literature, however, we were unable to find a previous report of ileo-rectal fistula as a complication of an ovarian carcinoma. A case report and review of the English medical literature are presented with emphasis on the cause, clinical presentation, and management of advanced ovarian cancer with ileo-rectal involvement.

Late development of umbilical metastasis after laparoscopic cholecystectomy for a gallbladder carcinoma.

A periumbilical mass developed 47 months after laparoscopic cholecystectomy. Pathologic examination of this mass showed features of moderately differentiated papillary adenocarcinoma, similar to that identified within the previously removed early stage (pT1b) gallbladder carcinoma. The cause of this at the laparoscope port is unclear. after laparoscopic cholecystectomy for gallbladder carcinoma has not been reported previously. We reported a case with late periumbilical tumor seeding at the navel trocar insertion site in a 65-year-old female. A review of the preventative information of tumor recurrence and management is discussed. The use of gasless laparoscopy, slow desufflation, trocar site washout, wound protector and specimen bags are recommended.

Mutation of the hMSH2 gene in two families with hereditary nonpolyposis colorectal cancer.

We examined 18 unrelated individuals who have colorectal cancer or cancers associated with the HNPCC syndrome and have a family history of cancer for mutations in exon 13 of the hMSH2 gene. Two of the 18 individuals had the same previously unreported single-base deletion in codon 705 of hMSH2, resulting in a frame-shift mutation. Two other individuals had a T-to-C base change in the intron sequence at -6 position of the splice acceptor site at the 5' end of exon 13 which has previously been reported to be a polymorphism found in normal individuals (Leach et al., 1993). Nucleotide sequence changes were not detected in the remaining 14 individuals. We examined DNA from additional family members of the two subjects with codon 705 mutations. Of these, two individuals were identified with the mutation who were older than 50 years and who are apparently cancer free. The occurrence of breast cancer in both families (including one individual with a confirmed codon 705 mutation) suggests that breast cancer may be a part of the HNPCC syndrome. This is the first study to describe mutations in the hMSH2 gene in families that do not fit the definition of HNPCC. Because both families with the mutations at codon 705 failed to meet the Amsterdam criteria for HNPCC (Vasen et al., Dis Colon Rectum 34:424-425, 1991), our findings suggest that these criteria should now be reconsidered for purposes of diagnosis of HNPCC.