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Background/aims: Recent evidence indicates that reactive oxygen species (ROS) can induce a wide type of cellular responses from proliferation to senescence and cell death. ROS may not be an absolute carcinogenic factor or cancer suppressor. The aim of this study was to assess the biological paradox of ROS in colorectal cancer cells., Methodology: Blood specimens were obtained from the drainage vein of the tumor during operation in 135 patients with colorectal cancer. Serum ROS levels were measured using the derivatives of reactive oxygen metabolites (d-ROM) test., Results: Serum ROS levels increased significantly in tumor size larger than 40mm (p<0.01). On the other hand, serum ROS levels decreased significantly in patients with lymph node metastasis (p<0.01). Multiple linear regression models showed a significant association of serum ROS levels with serum carcinoembryonic antigen (CEA) levels (p<0.01) and lymph node metastasis (p=0.026)., Conclusions: In colorectal cancer cells, the increase of intracellular ROS is first associated with cell growth and invasion. However, a further increase inhibits cancer cell proliferation, whereas any decrease in ROS concentration needs to stimulate lymph node metastasis. Thus, a precise understanding how ROS are generated and involved in lymph node metastasis will help us to design better therapeutic strategies.

Purpose: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin in combination with levofolinate and infusion 5-fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with unresectable metastatic colorectal cancer., Methods: Sixty consecutive patients with histologically confirmed advanced or metastatic colorectal cancer were enrolled in the study. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred., Results: Two patients were ineligible. Toxicity was evaluated in 60 patients, who had received a part or all of the protocol therapy. A partial response was observed in 20 patients. The overall response rate was 34.5% (95% CI, 22.5%-48.1%) and the tumor control rate (partial response + stable disease) was 82.8%. The median progression-free survival was 6.9 months (95% CI, 5.1-9.8 months), and the median overall survival was 31.5 months (95% CI, 18.1-40.1 months). There were no toxicity-related deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a delay in the subsequent treatment course. Mild to moderate cumulative peripheral sensory neuropathy affected 71.7% of patients., Conclusion: The results showed good tolerability and efficacy for first-line FOLFOX4 in the treatment of patients with advanced colorectal cancer, indicating the promise of this regimen as first-line therapy for advanced colorectal cancer in the Japanese population.

Purpose: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin, levoforinate, and infusional 5-fluorouracil (FOLFOX4) as a second-line therapy for Japanese patients with unresectable advanced or metastatic colorectal cancer., Methods: A total of 53 patients with progressive disease after first-line chemotherapy were enrolled in the study. The treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred, or the patient chose to discontinue the treatment., Results: Four patients were ineligible and one did not receive the protocol therapy. Therefore, the response rate, overall survival (OS), and progression-free survival (PFS) were evaluated in 48 patients; toxicity was evaluated in 52 patients, excluding the patient who had not received the protocol therapy. A partial response was observed in 10 patients. The overall response rate was 20.8% (95% confidence interval [CI], 10.5%-35.0%). The median PFS was 5.6 months (95% CI, 4.1-7.0 months) and the median OS was 19.6 months (95% CI, 11.4-24.3 months). The most frequently encountered grade 3/4 hematological symptom was neutropenia (43.1%). The toxicity profile was generally predictable and manageable., Conclusion: The results showed good tolerability and efficacy for second-line FOLFOX4 in patients with advanced colorectal cancer, thus indicating the promise of this regimen as an effective second-line therapy for advanced colorectal cancer in the Japanese population.

Background/purpose: Laparoscopic cholecystectomy is difficult to perform in patients with a low-lying costal arch that entirely covers the liver. We conducted this study to clarify the factors related to a low-lying costal arch and establish countermeasures to circumvent this characteristic., Methods: The study included 103 consecutive patients who underwent a laparoscopic cholecystectomy. The possible clinical factors associated with a low-lying costal arch restricting the operative working space were analyzed. The position of the liver against the costal arch and the presumed surgical visual angle for laparoscopic cholecystectomy, comprising the hepatic porta, umbilicus, and costal arch, were estimated with abdominal multidetector computed tomography (MDCT)., Results: Seven (7%) patients had a low-lying costal arch presenting an inadequate exposure of Calot's triangle and restricted instrument mobility during laparoscopic cholecystectomy, and three patients required conversion to a laparotomy. A low-lying costal arch was significantly associated with advanced age, shorter stature, lighter body weight, coexisting kyphoscoliosis, gallbladder pathology, laparotomy conversion, and most of all, the liver edge lying above the costal arch and a narrow surgical visual angle upon MDCT. Of the seven patients with a critical low-lying costal arch, four underwent a successful laparoscopic cholecystectomy, this being done by lifting the right costal arch to create a workable surgical field; the rib-lifting procedure was planned as part of the scheduled procedure in the other three patients because the preoperative MDCT examination indicated a poor working space for a laparoscopic cholecystectomy., Conclusions: A low-lying costal arch is a substantial risk factor for conversion to a laparotomy when performing a laparoscopic cholecystectomy. However, the operative difficulty related to a low-lying costal arch can be predicted by using preoperative MDCT images and can be managed with proper planning and the appropriate use of the rib-lifting technique.

Purpose: To establish whether the serum levels of carcinoembryonic antigen (CEA) in drainage venous blood (d-CEA) is a better predictor of prognosis or survival than the preoperative CEA level in peripheral venous blood (p-CEA), and how these two CEA levels compare as predictive factors for metachronous hepatic metastasis., Methods: We examined specimens of peripheral and drainage venous blood from 119 patients with colorectal cancer., Results: There was a strong positive correlation between p-CEA and d-CEA levels. The 5-year survival rates were 81.5% and 80.2% for patients with normal p-CEA and d-CEA levels (< or =5 ng/ml), respectively, and 68.4% and 71.1% for those with abnormal p-CEA and d-CEA levels (>5 ng/ml). The p-CEA and d-CEA levels were both normal in seven of ten patients with metachronous hepatic metastasis. The CEA gradient between the d-CEA and p-CEA levels (d-p CEA gradient) was not a significant predictive factor for hepatic metastases., Conclusions: There was virtually no change between preoperative p-CEA and d-CEA levels. These findings suggest that the d-CEA level is not a predictor for metachronous hepatic metastasis and that measuring p-CEA levels is sufficient in the surveillance of colorectal cancer.

A 57-year-old man was transferred to our hospital because of gluteal pain. His right buttock had flare and swelling. Complete blood count showed leukocytosis, and renal failure was evident. Pelvic computed tomography (CT) revealed that the abscess, including gas, was widespread into the hypodermal tissue of the right buttock. Fournier's gangrene had been suspected, and immediate drainage was performed on the right buttock. The symptom and the condition improved rapidly, but on the day after the operation, the patient became drowsy and fell into endotoxic shock. Magnetic resonance imaging (MRI) revealed strong inflammation along the entire fascia of the right femur and necrotizing fasciitis. MRI was very useful for identification of the necrotic range. Immediately, an emergency operation was performed; 3 wide incisions were made on the right thigh and crus for drainage. The patient was cared for intensively under a sedated condition, and irrigation and debridement were repeated every day. Culture of the pus revealed mixed infection of Escherichia coli and anaerobic bacteria, and a large quantity of antimicrobial drug was used. The inflammatory reaction decreased, and the patient's general condition tentatively improved. With Fournier's gangrene, initiating adequate surgical and medical treatment is essential. Therefore, MRI should be used in the early exact diagnosis of this disease to obtain knowledge of the extent of necrosis and to determine the adequate area for debridement.

Background: Adenoma of the major papilla carries a relatively high risk of malignant transformation to carcinoma, the leading cause of death in patients with familiar adenomatous polyposis (FAP) after colectomy., Case Report: A 35-year-old man had undergone prophylactic colectomy for FAP 3 years earlier. On the forward-viewing and side-viewing endoscopy done for surveillance, the overlying mucosa of the major papilla showed even granularity. On magnifying duodenoscopy using a narrow-band system (NBI), which uses modified optical filters and yields clear images of fine surface structures on the mucosal layer, a compact formation of round pits was seen in the affected ampulla. The microvascular architecture on NBI magnification showed no abnormalities, such as dilated, tortuous or network-like vessels, suggestive of malignancy. On endoscopic retrograde pancreaticocholangiography there was no intraductal growth, and endoscopic ultrasonography showed confinement to the mucosal layer. The ampullary lesion was completely resected using endoscopic snare papillectomy. Histopathological examination of the removed specimen showed tubular adenoma without malignant foci. The patient's post-treatment course was uneventful and without complications, and no local recurrence was noted on repeat endoscopy., Conclusions: Thus, endoscopic surveillance and removal of ampullary adenomas appear to be justified.

Background/aims: Elevated oxidative status has been found in many types of cancer cells. Recent studies have shown that the enzymatic product of thymidine phosphorylase (TP) generated reactive oxygen species (ROS) within cancer cells. The aim of this study was thus to evaluate the signal transduction pathway and the role of ROS in colorectal cancer., Methodology: Blood specimens were obtained from the drainage vein of the tumor during operation in 76 patients with colorectal cancer. Serum ROS levels were measured using the derivative-Reactive Oxygen Metabolites (d-ROM) test and serum TP levels were examined by a highly sensitive ELISA method., Results: There was no significant correlation between serum levels of ROS and TP. Serum ROS levels were elevated in proportion to tumor invasion and had a significant positive correlation with tumor size (p < 0.05). However, they did not increase in patients with liver metastasis., Conclusions: These findings suggest that ROS are independent of TP-triggered signaling transduction and are associated with increased tumor invasion, but not liver metastasis in patients with colorectal cancer. From this point of view, new strategies related to ROS may provide improved therapeutic results as well as a preventative effect on carcinogenesis of the colorectum.

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.

We herein report the case of an idiopathic liver cystic mass which aggressively infiltrated the thoraco-abdominal wall. A 74-year-old woman who had a huge cystic lesion in her right hepatic lobe was transferred to our hospital for further examinations. Imaging studies revealed a simple liver cyst, and the cytological findings of intracystic fluid were negative. She was followed up periodically by computed tomography (CT) scans. Seven years later, she complained of a prominence and dull pain in her right thoraco-abdominal region. CT revealed an enlargement of the cystic lesion and infiltration into the intercostal subcutaneous tissue. We suspected the development of a malignancy inside the liver cyst such as cystadenocarcinoma, and she therefore underwent surgery. A tumor extirpation was performed, including the chest wall, from the 7th to the 10th rib, as well as a right hepatic lobectomy. Pathologically, the lesion consisted of severe inflammatory change with epithelioid cell granuloma and bone destruction without any malignant neoplasm. No specific pathogens were evident based on further histological and molecular examinations. Therefore the lesion was diagnosed to be a destructive granuloma associated with a long-standing hepatic cyst. Since undergoing surgery, the patient has been doing well without any signs of recurrence.

A 58-year-old woman was scheduled for resection of anterior mediastinal tumor. Prolonged mechanical ventilation was required following surgery because of bilateral diaphragmatic injury. Pleural effusion, atelectasis, and syndrome of vena cava superior were observed during the treatment. BiPAP was useful for respiratory support. The patient was discharged from our hospital nine months after surgery. Oxygen therapy was not necessary in the day time. But the patient required respiratory support with BiPAP at night.