Pim-2 Modulates Aerobic Glycolysis and Energy Production during the Development of Colorectal Tumors.

Tumor cells have higher rates of glucose uptake and aerobic glycolysis to meet energy demands for proliferation and metastasis. The characteristics of increased glucose uptake, accompanied with aerobic glycolysis, has been exploited for the diagnosis of cancers. Although much progress has been made, the mechanisms regulating tumor aerobic glycolysis and energy production are still not fully understood. Here, we demonstrate that Pim-2 is required for glycolysis and energy production in colorectal tumor cells. Our results show that Pim-2 is highly expressed in colorectal tumor cells, and may be induced by nutrient stimulation. Activation of Pim-2 in colorectal cells led to increase glucose utilization and aerobic glycolysis, as well as energy production. While knockdown of Pim-2 decreased energy production in colorectal tumor cells and increased their susceptibility to apoptosis. Moreover, the effects of Pim-2 kinase on aerobic glycolysis seem to be partly dependent on mTORC1 signaling, because inhibition of mTORC1 activity reversed the aerobic glycolysis mediated by Pim-2. Our findings suggest that Pim-2-mediated aerobic glycolysis is critical for monitoring Warburg effect in colorectal tumor cells, highlighting Pim-2 as a potential metabolic target for colorectal tumor therapy.

[Surgical treatment and prognosis of cancer of hepatic flexure of colon invading the duodenum in 65 patients].

OBJECTIVE: To discuss surgical treatment of right colon carcinoma of hepatic flexure invading the duodenum. METHODS: Sixty-five patients with right colon carcinoma of hepatic flexure invading the duodenum, treated in our department from 1987 to 2007, were included in this study. Their clinicopathological data were retrospectively reviewed and analyzed. All the cases were divided into three types (local invasion, regional invasion, and cancer with internal fistula) according to duodenal defect, including local invasion (< 2.0 cm), wide invasion (> 2.0 cm) and the presence of internal fistula. RESULTS: 25 patients with local invasion underwent en bloc resection of the duodenal wall. Pedicled ileal flap was used to cover the large duodenal defect measuring 2.0 - 3.0 cm in 5 patients. Dudenojejunostomy was used to reconstruct the large defect measuring more than 5 cm in 3 patients. Conservative resection of right-sided colon was performed in 18 patients with wide invasion. 4 patients underwent pancreaticoduodenectomy combined with right hemicolectomy for colon cancer involving the pancreatic head. 10 underwent duodenal diverticularization. One patient with anastomotic leakage healed within 3 weeks. Other patients were cured without postoperative complications. The total 3-year and 5-year survival rates after surgery were 53.8% and 9.2%, respectively. CONCLUSION: The surgical procedure to be performed is usually decided according to the cancer location, extent, and duodenal defect and invasion, which are important for prolonging life time, improving of quality of life and prognosis in these patients.

Assessment of duodenal circular drainage in treatment of superior mesenteric artery syndrome.

AIM: To assess the clinical value of duodenal circular drainage for superior mesenteric artery syndrome (SMAS). METHODS: Forty-seven cases of SMAS were treated with duodenal circular drainage from 1959 to 2001. Clinical data were analyzed retrospectively. RESULTS: In this group, good effects were achieved in 39 cases treated with duodenal circular drainage after 2-15 years of follow-up. The other eight cases were first treated with anterior repositioning of the duodenum (two cases), duodenojejunostomy (five cases), subtotal gastrectomy and billroth II gastrojejunostomy (one case), but vomiting was not relieved until duodenal circular drainage was performed again. A follow-up study of 8-10 years revealed satisfactory results in these eight patients. CONCLUSION: In SMAS, if the reversed peristalsis is strong and continuous, and vomiting occurs frequently, the symptom can not be relieved even if the obstruction of duodenum is removed surgically. The key treatment is the relief of reversed peristalsis. The duodenal circular drainage can resolve the drainage direction of duodenal content, thus relieving the symptom of vomiting.

[Diagnosis and surgical treatment of carcinoid tumors of the appendix in 64 patients].

OBJECTIVE: To summarize the experience in the diagnosis and surgical treatment of carcinoid tumors of the appendix. METHODS: From 1972 to 2006, 64 patients with carcinoid tumors of the appendix received surgical treatment in our hospitals. The clinical data of those patients were retrospectively analyzed. RESULTS: Of the 64 cases, only 6 cases (9.4%) were correctly diagnosed preoperatively, while 58 (90.6%) not confirmed, with a misdiagnosis rate of 90.6%. All patients underwent surgical treatment, including appendectomy in 54, ileocecectomy in 4, right hemicolectomy in 2 and right hemicolectomy with regional lymph node dissection in 4 cases. The operation modes were determined according to the doctor's judgments based on the age of the patients, the nature, size, location, infiltration depth and lymph node metastasis of the tumors. Of the 64 patients, 58 were followed up with a longest follow-up period of 13 years, while 6 lost follow-up. Fifty-seven of those were still surviving, only one died of liver metastasis at 13 years after operation. CONCLUSION: Carcinoid tumor of the appendix is rare with a high rate of misdiagnosis before operation. Surgical resection is the only effective treatment for this disease and proper operation mode is the key to achieve good survival.

Diagnosis and surgical treatment of hepatic hilar cholangiocarcinoma.

BACKGROUND: Hepatic hilar cholangiocarcinoma can be diagnosed early with the progress in diagnostic imaging, and thus the rate of resection of the tumor has increased markedly. To assess the effectiveness of resection, we reviewed 185 cases of hepatic hilar cholangiocarcinoma diagnosed and treated at our hospital. METHODS: The clinical data of 185 patients with hepatic hilar cholangiocarcinoma who had been treated surgically from 1972 to 2006 were retrospectively analyzed. RESULTS: The records of the 185 patients were divided into first stage (1972-1986) or second stage (1987-2006) according to the incidence of the tumor and its resection rate. Primary symptoms included upper abdominal discomfort or pain, anorexia, tiredness, weight loss and progressive jaundice. Ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) were first line methods for atraumatic diagnosis. If the patients displayed intrahepatic bile duct dilatation or were diagnosed as suffering from extrahepatic obstructive jaundice, percutaneous transhepatic cholangiography (PTC), MRCP or endoscopic retrograde cholangiopancreatography (ERCP) should be used. In this series, 87 patients underwent resection of the tumor (47.0%). Of the 87 patients, 43 received radical resection and 44 palliative resection. Fifteen patients underwent resection in the first stage and 72 in the second stage. A total of 74 patients were followed up after the resection. The median survival time of the radical resection group was 37 months and that of the palliative resection group was 17 months (P<0.001). The other 62 patients receiving no resection died within 1.5 years. CONCLUSIONS: Once patients are diagnosed with hepatic hilar cholangiocarcinoma, they should undergo exploratory laparotomy. Resection is the most effective method for the treatment of hepatic hilar cholangiocarcinoma.

[Clinical analysis of primary small intestinal neoplasms in 305 cases].

OBJECTIVE: To summarive the experience in diagnosis and treatment of primary small intestinal neoplasm. METHODS: The data of 305 patients with pathologically confirmed primary small intestinal tumor collected from 6 hospitals around the Songhua River during the past 33 years were analyzed retrospectively. RESULTS: There were 42 benign and 263 malignant tumors in this series with a ratio of 1: 6.26. The 263 malignant tumors in this series consisted of 135 adenocarcinomas, 57 malignant stromal tumors, 37 malignant lymphomas, 20 carcinoids, and etc. Chronic occult bleeding, gradual of body weight loss and mild abdominal pain (three obscurities) were the common clinical features and alerting massage of intestinal tumor. Correct preoperative diagnostic rate was only 57.0% (174/305) due to difficulty in early diagnosis, which was 67.2% (92/137) in the duodenal tumors, and 51.9% (82/168) in the jejunoileal tumors. All of the 42 benign tumors were resected completely. For the 263 patients with malignant tumors, radical dissection was performed in 153, palliative resection in 34, and gut by-pass or biopsy in 76. The median survival of the patients who underwent radical resection of their malignant tumors was 92 months, which was significantly higher than that of the other groups. CONCLUSION: Early diagnosis of primary small intestinal tumors is difficult and with a preoperative misdiagnosis rate of 43.0%. Total intestinal barium swallowing, endoscopy and superior mesenteric arteriography are three critical examinations for diagnosis and location. Early surgical resection is crucial in improving the prognosis. The primary small intestinal tumor should be resected as early as possible if no distant metastasis is detected.

Clinical analysis of patients with iatrogenic bile duct injury.

BACKGROUND: The main cause of iatrogenic bile duct injury is misidentification of the common bile duct as the cystic duct. In this article, we summarize the experience in the treatment of 112 patients with iatrogenic bile duct injury. METHOD: Clinical data of these patients treated at 10 hospitals of Songhua river area, Heilongjiang province, China from January 1978 to January 2005 were analyzed retrospectively. RESULTS: In 55.4% patients (62/112), iatrogenic bile duct injury was due to misidentification of the anatomy of Calot's triangle before cholecystectomy. Their diagnosis was based on clinical features, celiac puncture and imaging examination in which ultrasonography was most sensitive, giving a diagnostic rate of 97.5%. Six types of injury were identified according to their locations, and type III damage was commonly seen (92/112). The curative rate in this group was 95.5% (107/112). Eighty-seven patients (77.7%) underwent Roux-en-Y choledochojejunostomy with a cure rate of 94.3% (82/87). CONCLUSION: The prevention of iatrogenic bile duct injury lies in identifying the topography of extrahepatic bile ducts. Roux-en-Y choledochojejunostomy is usually the treatment of choice.

Effects of zinc transporter on differentiation of bone marrow mesenchymal stem cells to osteoblasts.

The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step during bone formation. However, the exact mechanisms regulating the early stages of osteogenic differentiation remain unknown. In the present study, we found that ZnT7, a member of the zinc transporter family SLC30A(ZnTs), was downregulated during dexamethasone-induced differentiation of rat MSCs into osteoblasts. Dexamethasone treatment resulted in significantly lower levels of ZnT7 compared with cocultured cells without dexamethasone. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and staining for ALP, von Kossa, collagen type I, and osteocalcin. Overexpression of ZnT7 decreased the expression of the osteoblast alkaline phosphatase, type I collagen, as well as calcium deposition in mesenchymal cells. In contrast, knockdown of ZnT7 using siRNA promoted gene expression associated with osteoblast differentiation and matrix mineralization in vitro. Moreover, according to the ZnT7 inhibition or activation experiments, Wnt and ERK signaling pathways were found to be important signal transduction pathways in mediating the osteogenic effect of MSCs, and this effect is intensified by a decrease in the level of ZnT7 induced by dexamethasone. These findings suggest that ZnT7 is involved in the switch from the undifferentiated state of MSC to an osteogenic program, and marking the expression level of ZnT7 may be useful in the detection of early osteogenic differentiation.

Glutathione S-transferase polymorphisms and bone tumor risk in China.

AIM: We aimed to study the potential role of GSTM1 and GSTT1 in the risk of osteosarcoma in Chinese population. METHODS: We collected 110 osteosarcomas by pathologic examination and 226 controls from the First Affiliated Hospital of Harbin Medical University during December 2008 to December 2010. Genotyping was based upon duplex polymerase-chain-reaction with the PCR-CTPP method. RESULTS: Individuals carrying null GSTM1 and GSTT1 had 1.50 and 2.07 fold risks of osteosarcoma when compared with non-null genotypes, respectively. The increased risk associated with the GSTT1 polymorphism seemed more evident among males (Null GSTT1 genotype vs. non-null genotype, adjusted OR= 2.43, 95% CI: 1.29-3.30) than females (adjusted OR =1.66, 95% CI: 1.02-2.78). The increased risk was also more evident among individuals aged 15 years or less (adjusted OR for null GSTT1 genotype vs. non-null genotype = 2.24, 95% CI: 1.20-3.24) than those aged more than 15 years (adjusted OR = 1.82, 95% CI: 1.07-2.95). CONCLUSION: Our study of the association between polymorphisms in GSTM1 and GSTTI and the risk of osteosarcoma in a Chinese population provided evidence that null GSTTI might be a useful marker of susceptibility to osteosarcoma development, especially for male sand young age individuals.

[Clinical analysis of gastrointestinal stromal tumor: a report of 29 patients].

OBJECTIVE: To investigate the clinical manifestations, diagnosis and treatment of gastrointestinal stromal tumor (GIST). METHODS: Clinicopathological data of 29 cases with GIST from 2003 to 2005 were retrospectively analyzed. RESULTS: The most common clinical manifestations were abdominal pain, distention or discomfort in 16 cases (55.2%), abdominal mass in 9 (31.0%), melena and hematemesis in 5 cases (17.2%). The tumor was located in the stomach in 16 cases, the small intestine in 9, the colorectum in 2, the esophagus in one, and the duodenum in one case. All the cases underwent operation, included total gastrectomy in one case, subtotal gastrectomy in 8, partial gastrectomy in 4, local excision of the tumor in 5 cases, partial small intestine resection in 9 and right colectomy in 2 cases. The resection rate was 100% and no complication and death occurred. The positive rates of CD117(+) and CD34(+) were 93.1% and 51.7% respectively. After follow up from one to 2 years after operation, 2 cases died of tumor recurrence and metastasis, the others survived. CONCLUSIONS: Immunohistochemical examinations of CD117 and CD34 are important diagnostic markers. Surgery is the main method of final diagnosis and treatment.

[Expressions and clinical implications of kruppel-like factor 6 and APC in human colorectal carcinoma].

OBJECTIVE: To investigate the expressions and clinical implications of kruppel-like factor 6(KLF-6) and APC in human colorectal carcinoma. METHODS: The expressions of KLF-6 and APC in tumor and normal tissues from 32 patients with colorectal carcinoma were investigated by RT-PCR and immunohistochemical technique. RESULTS: The expression rates of KLF-6 and APC mRNA were 37.5% and 34.3% in tumor tissue, 96.9% and 93.8% respectively in normal tissues (both P< 0.05). The expression rates of KLF-6 and APC protein were 28.1% and 25.0% in colorectal carcinomas, 81.3% and 84.43% respectively in normal tissues (both P< 0.05). There was a significant correlation between the expressions of KLF-6 and APC in colorectal carcinomas (P < 0.05). The expressions of KLF-6 and APC were significantly correlated with tumor differentiation, depth of infiltration, lymph node metastasis and clinical stage (P< 0.05). CONCLUSION: Down-regulations of KLF-6 and APC might play an important role in the carcinogenesis, development, metastasis of human colorectal carcinoma.

[Clinical analysis of gastroparesis syndrome after nongastrectomy abdominal operation: a report of 22 cases].

OBJECTIVE: To investigate the causes, diagnosis and treatment of gastroparesis syndrome after nongastrectomy abdominal operation. METHODS: The clinical data of 22 cases with gastroparesis syndrome after nongastrectomy abdominal operation from 1972 to 2004 were retrospectively analyzed. RESULTS: Gastroparesis syndrome after nongastrectomy abdominal operation often occurred during 4-6 days postoperatively when the patients began to take in food, characterized by upper abdominal distension, nausea, vomiting, strong splashing bowel sound, weak bowel sound and large quantity of gastric drainage ranging from 1000 to 3000 ml every day. Barium meal was valuable not only in the diagnosis but also effective for promoting gas motility. It revealed a non-peristaltic, flabby and static stomach, and retention of contrast medium in the stomach even 5-6 hours later. All the patients recovered through non-operative therapy for 5-25 days including continuous gastrointestinal decompression, TPN and gastro-intestinal dynamic medicine. CONCLUSIONS: The causes of gastroparesis syndrome after nongastrectomy abdominal operation are multifactorial, most of such patients can be cured by non-operative therapy.

[Diagnosis and treatment of paraduodenal hernia: a report of 16 cases].

OBJECTIVE: To summarize the experience of diagnosis and treatment for paraduodenal hernia (PDH). METHODS: The clinical data of 16 cases with PDH surgically treated from 1962 to 2003 were analyzed retrospectively. RESULTS: The average age of the patients was 36 years old. There were 13 cases with left PDH (Landzerts hernia) and 3 cases with right PDH (Waldeyer's hernia). Ten patients usually had no symptoms, while acute abdominal pain occurred after full food in 3 case and after vigorous movement in 13 cases respectively. X-ray revealed complete or incomplete intestinal obstruction in 12 cases, while ultrasonography and CT revealed dilated cystic jejunal loop between the pancreas and the stomach in 6 cases. Fourteen cases (87.5%) were misdiagnosed before operation. The hospital stay ranged from 10 to 13 days. All patients were followed up from 2 to 4 years without recurrence. CONCLUSION: With high misdiagnostic rate, it is the key to perform exploratory operation for suspicious PDH.

[Analysis of clinical manifestations and surgical treatment of Crohn disease: a report of 82 cases].

OBJECTIVE: To elucidate the clinical types of Crohn disease and evaluate its surgical treatment. METHODS: Clinical data of 82 cases with Crohn disease were retrospectively analyzed from June 1972 to June 2003. RESULTS: Among 82 cases with Crohn disease,38 cases were diagnosed before operation,and 44 cases(53.7% ) were misdiagnosed. Main clinical manifestations included abdominal pain(96.3% ),diarrhea(89.0% ) and abdominal mass(28.0% ),other clinical manifestations included fistulation,intestinal hemorrhage and extra- intestinal manifestations such as ulcerative stomatitis,mycotic stomatitis. Patients received different surgical procedures as following: partial enterectomy in 57 cases,hemicolectomy and colostomy in 4 patients,partial ileectomy and ileostomy in 2,ileocolic bypass procedure in 3 patients,partial enterectomy and colectomy and anastomosis in 3 patients because of internal fistula,repair of ileal perforation in 2,lysis of adhesion in 6,drainage of intraperitoneal abscess and ostomy in 3,radical operation in 2 due to colon cancerization. Seventy- three cases(89.0% ) were cured by operation,postoperative complications occurred in 9 patients and 2 cases died. CONCLUSION: It is the key point to achieve successful operation that the corresponding operative modes respectively for varied types of Crohn disease should be adopted.