[A Case of Rectal GIST Resected using the TAMIS Method].

We reported a case of rectal gastrointestinal stromal tumor(GIST)performed transanal surgery. A 46-year-old woman was pointed out uterinal cancer and lower rectal GIST. After operation for uterine cancer, GIST was treated. Because of the patent's opinion for anal preservation, chemotherapy with imatinib for 3 months was performed and local resection was done by transanal minimally invasive surgery(TAMIS). The histopathological diagnosis was low-grade GIST and immunostaining showed the tumor was positive for c-kit, CD34, DOG-1 and α-SMA. Because capsule of the GIST was damaged intraoperatively, imatinib therapy was started and she has no recurrence after 2 years.

The color pattern inducing gene wingless is expressed in specific cell types of campaniform sensilla of a polka-dotted fruit fly, Drosophila guttifera.

A polka-dotted fruit fly, Drosophila guttifera, has a unique pigmentation pattern on its wings and is used as a model for evo-devo studies exploring the mechanism of evolutionary gain of novel traits. In this species, a morphogen-encoding gene, wingless, is expressed in species-specific positions and induces a unique pigmentation pattern. To produce some of the pigmentation spots on wing veins, wingless is thought to be expressed in developing campaniform sensillum cells, but it was unknown which of the four cell types there express(es) wingless. Here we show that two of the cell types, dome cells and socket cells, express wingless, as indicated by in situ hybridization together with immunohistochemistry. This is a unique case in which non-neuronal SOP (sensory organ precursor) progeny cells produce Wingless as an inducer of pigmentation pattern formation. Our finding opens a path to clarifying the mechanism of evolutionary gain of a unique wingless expression pattern by analyzing gene regulation in dome cells and socket cells.

[A Case of Laparoscopic Surgery for Sigmoid Lymph Node Metastases after Surgery for Rectal Cancer].

Herein, we report a case of laparoscopic surgery for sigmoid lymph node metastases after surgery for rectal cancer. A 58- year-old man underwent laparoscopic surgery for rectal cancer. He underwent D2 lymph node dissection, and he was undergoing dialysis for renal disease as a complication of diabetes. CT imaging performed 15 months after surgery revealed recurrence of tumors in the sigmoid lymph nodes. Subsequently, laparoscopic removal of the sigmoid lymph nodes was planned, as the patient had no tumor recurrence at any other location, and because his condition was not suitable for chemotherapy. The postoperative course was uneventful, and the patient was discharged a few days after surgery.

[A Case of Superior Mesenteric Artery Syndrome Following Transverse Colon Cancer Surgery].

We reported a case of superior mesenteric artery(SMA)syndrome after decreased body weight and unstable oral intakes due to anastomotic leakage of postoperative transverse colon cancer. A 63-year-old man underwent laparoscopic left hemicolectomy and D3 lymph node dissection with a diagnosis of transverse colon cancer. He had postoperative anastomotic leakage and was discharged after conservative treatment on postoperative day 35. However, he had visited our hospital by the symptom of bowel obstruction caused by anastomotic stenosis and had been admitted twice. After second colonoscopic balloon dilation on postoperative day 129, he was diagnosed as anastomotic perforation and emergency reoperation was performed. In the postoperative course, he repeated vomiting and his body weight decreased and superior mesenteric artery syndrome was diagnosed. He improved after conservative treatment by fasting, a nasogastric intubation and total parenteral nutrition and was discharged 22 days after the diagnosis.

[A Case of Small Intestinal Cancer Resected by Laparoscopic Surgery].

We report a case of laparoscopic surgical resection of a small intestinal cancer. A woman in her 40s was referred to our department for prolonged abdominal problems(epigastralgia, nausea, diarrhea, and constipation). CT scan revealed a small intestinal tumor with dilatation of the oral side of the intestine. She was admitted to our hospital, and an ileus tube was introduced. One week after admission, she experienced laparoscopic partial resection of the small intestine. She was soon discharged without any problems and has had no recurrence of small intestinal cancer after 8 months of surgery without any adjuvant chemotherapy. Small intestinal cancer is frequently detected in an advanced stage, resulting in poor prognosis, but curative surgery can improve the prognosis. Optimal therapy for small intestinal cancer has not been established yet because it is rare. A multi-centered study of small intestinal cancer for the establishment of its diagnosis and therapy needs to be conducted.

Fever of unknown origin following parathyroidectomy prior to onset of typical polymyalgia rheumatica symptoms: a case report.

Polymyalgia rheumatica (PMR) is a disease commonly seen in elderly individuals, however, the etiology has not been reported. Typical clinical features include bilateral shoulder pain and morning stiffness, while serologic autoantibody test findings are negative. Approximately 40%-50% of affected patients present with low-grade fever, fatigue, and appetite loss, which we often experience in the field of general medicine, and thus, the condition should not be given low priority. However, knowledge regarding such constitutional manifestations is also limited. We encountered an elderly woman with a fever of unknown origin that developed following a parathyroidectomy for a single parathyroid adenoma, after which severe shoulder pain and morning stiffness emerged, leading to a diagnosis of PMR. The fever developed several days prior to appearance of severe pain, which is an uncommon presentation in PMR cases. Our patient had low-grade inflammation without pyrexia prior to the surgery, which might have been an important reason for the accelerated immoderate immune activation leading to PMR induced by surgery in this case. Furthermore, she was infected with the influenza A virus 3 weeks before coming to us. Some reports have suggested a relationship between the influenza virus or vaccine and PMR. It is difficult to conclude regarding the definite trigger in our patient, though the details of this case should be helpful for a better understanding of the disease.

The EPOS-CC Score: An Integration of Independent, Tumor- and Patient-Associated Risk Factors to Predict 5-years Overall Survival Following Colorectal Cancer Surgery.

BACKGROUND: Surgical audit is an essential task for the estimation of postoperative outcome and comparison of quality of care. Previous studies on surgical audits focused on short-term outcomes, such as postoperative mortality. We propose a surgical audit evaluating long-term outcome following colorectal cancer surgery. The predictive model for this audit is designated as 'Estimation of Postoperative Overall Survival for Colorectal Cancer (EPOS-CC)'. METHODS: Thirty-one tumor-related and physiological variables were prospectively collected in 889 patients undergoing elective resection for colorectal cancer between April 2005 and April 2007 in 16 Japanese hospitals. Postoperative overall survival was assessed over a 5-years period. The EPOS-CC score was established by selecting significant variables in a uni- and multivariate analysis and allocating a risk-adjusted multiplication factor to each variable using Cox regression analysis. For validation, the EPOS-CC score was compared to the predictive power of UICC stage. Inter-hospital variability of the observed-to-estimated 5-years survival was assessed to estimate quality of care. RESULTS: Among the 889 patients, 804 (90%) completed the 5-years follow-up. Univariate analysis displayed a significant correlation with 5-years survival for 14 physiological and nine tumor-related variables (p < 0.005). Highly significant p-values below 0.0001 were found for age, ASA score, severe pulmonary disease, respiratory history, performance status, hypoalbuminemia, alteration of hemoglobin, serum sodium level, and for all histological variables except tumor location. Age, TNM stage, lymphatic invasion, performance status, and serum sodium level were independent variables in the multivariate analysis and were entered the EPOS-CC model for the prediction of survival. Risk-adjusted multiplication factors between 1.5 (distant metastasis) and 0.16 (serum sodium level) were accorded to the different variables. The predictive power of EPOS-CC was superior to the one of UICC stage; area under the curve 0.87, 95% CI 0.85-0.90 for EPOS-CC, and 0.80, 0.76-0.83 for UICC stage, p < 0.001. Quality of care did not differ between hospitals. CONCLUSIONS: The EPOS-CC score including the independent variables age, performance status, serum sodium level, TNM stage, and lymphatic invasion is superior to the UICC stage in the prediction of 5-years overall survival. This higher accuracy might be explained by the inclusion of physiological factors, thus also taking non-tumor-associated deaths into account. Furthermore, EPOS-CC score may compare quality of care among different institutions. Future studies are necessary to further evaluate this score and help improving the prediction of long-term survival following colorectal cancer surgery.

Adjuvant therapy with imatinib mesylate after resection of primary high-risk gastrointestinal stromal tumors in Japanese patients.

BACKGROUND: Imatinib mesylate, a small-molecule tyrosine kinase inhibitor, is currently used for adjuvant therapy of patients who have undergone resection of high-risk gastrointestinal stromal tumors (GISTs). There are no data concerning the efficacy and safety of postoperative adjuvant therapy with imatinib for Japanese or East Asian patients with GIST. METHODS: A single-arm, open-label, multicenter trial was conducted in 17 hospitals in Japan. The eligibility criteria included histologically proven primary high-risk GISTs with macroscopic complete resection. Patients were treated with imatinib at a dose of 400 mg/day for 1 year after surgery. The primary endpoint was recurrence-free survival as assessed by Kaplan-Meier analysis. The secondary endpoints were overall survival and safety. This study was registered with ClinicalTrials.gov, number NCT00171977. RESULTS: A total of 64 patients were enrolled between September 2004 and July 2006. The median age of the patients was 59.5 years. Forty-nine (76.6%) patients completed the 1-year treatment, whereas 15 (23.4%) patients did not complete the treatment owing to recurrence, toxicities, and consent withdrawal. At the median follow-up period of 109 weeks, 20 patients had recurrence. The 3-year recurrence rate was 42.7% (95% confidence interval 29.2-56.3%), which exceeded the expected recurrence rate in this trial. The recurrence-free and overall survival rates at 2 years were 71.1 and 93.7%, respectively. The most frequent adverse drug reaction of any grade was eyelid edema (48.4%), followed by neutropenia (40.6%), leukopenia (39.1%), nausea (39.1%), rash (37.5%), and peripheral edema (37.5%), most of which were mild and manageable. CONCLUSIONS: Adjuvant therapy with imatinib at 400 mg/day for 1 year is well tolerated by Japanese patients and possibly reduces the risk of early recurrence of high-risk GISTs.

A multicenter prospective study of surgical audit systems.

OBJECTIVE: This study was undertaken to evaluate a modified form of Estimation of Physiologic Ability and Surgical Stress (E-PASS) for surgical audit comparing with other existing models. BACKGROUND: Although several scoring systems have been devised for surgical audit, no nation-wide survey has been performed yet. METHODS: We modified our previous E-PASS surgical audit system by computing the weights of 41 procedures, using data from 4925 patients who underwent elective digestive surgery, designated it as mE-PASS. Subsequently, a prospective cohort study was conducted in 43 national hospitals in Japan from April 1, 2005, to April 8, 2007. Variables for the E-PASS and American Society of Anesthesiologists (ASA) status-based model were collected for 5272 surgically treated patients. Of the 5272 patients, we also collected data for the Portsmouth modification of Physiologic and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) in 3128 patients. The area under the receiver operative characteristic curve (AUC) was used to evaluate discrimination performance to detect in-hospital mortality. The ratio of observed to estimated in-hospital mortality rates (OE ratio) was defined as a measure of quality. RESULTS: The numbers of variables required were 10 for E-PASS, 7 for mE-PASS, 20 for P-POSSUM, and 4 for the ASA status-based model. The AUC (95% confidence interval) values were 0.86 (0.79-0.93) for E-PASS, 0.86 (0.79-0.92) for mE-PASS, 0.81 (0.75-0.88) for P-POSSUM, and 0.73 (0.63-0.83) for the ASA status-based model. The OE ratios for mE-PASS among large-volume hospitals significantly correlated with those for E-PASS (R = 0.93, N = 9, P = 0.00026), P-POSSUM (R = 0.96, N = 6, P = 0.0021), and ASA status-based model (R = 0.83, N = 9, P = 0.0051). CONCLUSION: Because of its features of easy use, accuracy, and generalizability, mE-PASS is a candidate for a nation-wide survey.

Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate.

PURPOSE: Motesanib (AMG 706) is a multitargeted anticancer agent with an inhibitory action on the human vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and the cellular stem-cell factor receptor (KIT). The aim of this single-arm phase II clinical study was to assess the efficacy and safety of single-agent motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. METHODS: All patients had experienced progression or relapse while undergoing with imatinib as 400 mg/day or higher. The patients were administered 125 mg of motesanib once daily. The primary endpoint was overall response. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumor, and safety was assessed according to the Common Terminology Criteria for Adverse Events (version 3). RESULTS: Of 35 enrolled and treated patients, no patient showed a complete response, and one patient showed a partial response (PR). Seven had stable disease (SD) for at least 24 months, two of whom continued to have SD for more than 2 years. The median progression-free survival time was 16.1 weeks. Motesanib was well tolerated; commonly reported treatment-related adverse events were hypertension, diarrhea, and fatigue. Anemia was the only hematological toxicity that was reported. CONCLUSIONS: One patient showed PR, and seven patients showed SD more than 24 weeks. Motesanib was found to be safe and well tolerated. The observed toxicities were consistent with Phase I study findings.

Role of vascular endothelial growth factor-C and -D mRNA in breast cancer.

Vascular endothelial growth factor (VEGF)-C and VEGF-D belong to the VEGF family, and are thought to be involved in lymphangiogenesis and angiogenesis. At present, this is the only known system that can induce lymphatic vessel growth in the body. However, the roles of VEGF-C and VEGF-D in breast cancer tissue have not been clarified. In the present study, we measured the mRNA expression of VEGF-C and VEGF-D in the breast cancer tissue of 109 patients by real-time polymerase chain reaction (RT-PCR). Between non-infiltrating breast cancer (n=6) and infiltrating breast cancer (n=103), there were no significant differences in the mRNA expression of VEGF-C and VEGF-D. In infiltrating cancer, the expression of HER2 exhibited a positive correlation to VEGF-C and VEGF-D mRNA expression (p=0.027, p=0.048). However, mRNA expression ofVEGF-C and VEGF-D did not exhibit any significant correlation to lymphatic vessel invasion or lymph node metastasis. Among patients without lymph node metastasis, the mRNA expression of VEGF-C and VEGF-D for patients with lymphatic vessel invasion was significantly higher than that for patients without lymphatic vessel invasion (p=0.001, p=0.050). The results suggest that, in breast cancer, VEGF-C and VEGF-D are involved in lymphatic vessel invasion prior to lymph node metastasis, and their expression decreases after lymph node metastasis occurs.

Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202).

BACKGROUND: Imatinib mesylate, an inhibitor of KIT, ABL protein, and platelet-derived growth factor receptor alpha (PDGFRalpha) tyrosine kinase, has recently been found to have a dramatic antitumor effect on gastrointestinal stromal tumor (GIST). The aim of this study was to assess the efficacy and safety of imatinib mesylate in Japanese patients with advanced GIST. METHODS: Patients with measurable lesions were enrolled between April 1, 2002, and September 20, 2002, using a design based on previous phase II studies in the United States and the European Union. The diagnosis of GIST was proven histologically with positive immunostaining for KIT (CD117). Imatinib mesylate was administered at a dose of either 400 mg or 600 mg once a day. Pharmacokinetic parameters and mutation analysis of c-kit were also assessed in a subgroup of patients. RESULTS: A total of 74 patients (28 receiving imatinib mesylate at 400 mg/day; 46 receiving 600 mg/day); median age, 56.0 years, were enrolled. No patient had a complete response, 51 patients (69%) had a partial response, and 19 patients (26%) had stable disease. The median progression-free survival time was 96 weeks. The estimated 3-year overall survival (Kaplan-Meier) rate for all patients was 73.6%. The most frequent adverse effects related to the drug were nausea (78%), diarrhea (70%), dermatitis (62%), facial edema (61%), edema of the lower limbs (58%), vomiting (54%), and eyelid edema (51%). Most of the adverse effects were mild and manageable. CONCLUSION: Imatinib mesylate is generally safe and has significant activity in the treatment of advanced GIST in Japanese patients.

Tyrosine1248-phosphorylated HER2 expression and HER2 gene amplification in female invasive ductal carcinomas.

BACKGROUND: Phosphorylated HER2 (pHER2) may more accurately reflect the signaling and functional activity of the HER2 protein than detection of HER2 itself. The detection of HER2 gene amplification using fluorescence in situ hybridization (FISH) provides superior prognostic information for the diagnosis of breast cancer. However, the relationship between pHER2 expression in tissue samples and HER2 gene amplification remains unclear. METHODS: A total of 210 cases were recruited. The expression of HER2 and tyrosine (Tyr)1248-pHER2 was investigated by immunohistochemistry, and HER2 gene amplification was analyzed by FISH. Spearman's rank correlation test was employed to confirm correlation between HER2 and Tyr1248-pHER2. Chi-square and Student's t test were used to determine a significant difference between the baseline characteristics of tumors and the FISH, HER2 and Tyr1248-pHER2 results. The phosphorylation rate of HER2 was calculated using a digital-analysis system. RESULTS: HER2 expression was significantly (P < 0.001) associated with Tyr1248-pHER2 expression. HER2 gene amplification could be detected in 55 (26.2%) of the 210 tumors; 40 were HER2 positive and 32 were Tyr1248-pHER2 positive. The sensitivity and specificity of HER2 and Tyr1248-pHER2 for HER2 gene amplification were 72.7 and 58.2%, and 91.6 and 95.5%, respectively. In cases with an HER2 score of 2, and a phosphorylation score of 2 or 3, gene amplification was observed in 4 (80.0%) out of 5 tumors. CONCLUSIONS: Tyr1248-pHER2 expression is highly specific for HER2 gene amplification. The phosphorylation status might provide an adjunct to the assessment of gene amplification in patients with an HER2 score of 2.

Paraesophageal mediastinal desmoid tumor: case report.

A 45-year-old man presented with dysphagia. Computed tomography and magnetic resonance imaging showed an abnormal shadow in the paraesophageal mediastinum, which a thoracoscopic biopsy revealed to be a desmoid tumor that had infiltrated the surrounding tissues. We attempted esophageal stent placement; however, the esophageal stenosis could not be dilated, and bypass surgery was performed first, with tumor resection postponed, and radiation and hormonal therapy were added. Mediastinum desmoid tumors are rare, with only 22 other cases reported in the English language literature. Herein, we report the details of our patient and provide a review of other cases.

Combination analysis of a whole lymph node by one-step nucleic acid amplification and histology for intraoperative detection of micrometastasis.

OBJECTIVE: The aim was to develop a more efficient molecular detection system than histological examination (HE) for lymph node (LN) metastasis. METHODS: Cytokeratin (CK) 19 mRNA copy numbers of 5 colon carcinoma cell lines (Lovo, DLD1, WiDr, Colo201 and Colo320) were calculated and compared by one-step nucleic acid amplification (OSNA) and conventional real-time reverse-transcription polymerase chain reaction (RT-PCR). Then, 91 LN submitted for HE from 6 patients with advanced colorectal adenocarcinoma and 64 LN submitted for frozen diagnosis from 47 patients with different malignancies were examined by OSNA and HE. RESULTS: CK19 mRNA copy numbers of all but Colo320 cells detected by OSNA were within double of those detected by RT-PCR. The least cell count of Lovo cells detected at one reaction (2 microl) by OSNA was calculated as 0.8 cells. Carcinoma metastasis showing either HE+ or OSNA+ was detected in 7.9% of the LN from advanced colorectal adenocarcinomas and in 30.0% of the LN for frozen diagnosis from different malignancies; HE-/OSNA+ metastasis was detected in 4.8 and 4.0%, respectively. OSNA analysis of 1 LN could be completed within 40 min. CONCLUSION: A combined analysis of LN by HE and OSNA could increase the sensitivity for detecting micrometastasis during surgery.

Giant adrenal myelolipoma: report of a case.

Adrenal myelolipomas are rare benign tumors composed of mature adipose tissue and hematopoietic elements that resemble bone marrow. They are usually asymptomatic, and most cases are incidentally found at radiological examination or autopsy. Symptoms such as abdominal pain and increasing girth occur only when the tumor grows large. We report the case of a giant adrenal myelolipoma in a 51-year old man who presented with a huge abdominal mass and abdominal pain. The resected tumor weighed 6,000 g and could represent the largest such tumor ever documented in the literature. We discuss the diagnosis and treatment of this unusual tumor.