Successful treatment of postoperative nonobstructive recurrent cholangitis by tract conversion surgery after total pancreatectomy: a case report.

BACKGROUND: Postoperative cholangitis is a complication of biliary reconstruction during hepatobiliary pancreatic surgery. Most cases are associated with anastomotic stenosis, but there are also cases of cholangitis without stenosis, and treatment can be difficult, especially in patients with recurrent symptoms. In this report, we describe a case of repeated nonobstructive cholangitis in a patient after total pancreatectomy, in which a good outcome was obtained after performing tract conversion surgery. CASE PRESENTATION: The patient was a 75-year-old man. He underwent total pancreatectomy for stage IIA cancer of the pancreatic body, hepaticojejunostomy via the posterior colonic route, gastrojejunostomy and Braun anastomosis via the anterior colonic route using the Billroth II method. The patient had a good postoperative course and was receiving adjuvant chemotherapy on an outpatient basis, but he developed his first episode of cholangitis 4 months after surgery. Although conservative treatment with antimicrobial agents was successful, the patient continued to have recurrent biliary cholangitis and was repeatedly admitted and discharged from the hospital. Since stenosis at the anastomosis was suspected, endoscopic observation of the anastomosis was performed using small bowel endoscopy for close examination, but no apparent stenosis was observed. Small bowel imaging indicated a possible influx of contrast medium into the bile duct, and reflux due to food residue was suspected as the cause of cholangitis. Since conservative treatment alone did not suppress the flare-up of symptoms, the decision was made to perform tract conversion surgery for curative purposes. The afferent loop was cut midstream, and jejunojejunostomy was performed downstream. The postoperative course was good, and the patient was discharged on the 10th day after surgery. He is currently an outpatient and has been free of cholangitis symptoms for 4 years without cancer recurrence. CONCLUSIONS: Although the diagnosis of nonobstructive retrograde cholangitis can be difficult, surgical treatment should be considered in patients with recurrent symptoms and refractory treatment.

[A Case of Fournier's Gangrene during Second-Line IRIS plus Bevacizumab Chemotherapy for Rectal and Anal Canal Cancer].

A 52-year-old man diagnosed with Stage ⅢA rectal and anal canal cancer underwent abdominal perineal resection using Miles's method. Two years later, local recurrence and lung metastases were detected using contrasted CT imaging. First-line chemotherapy of XELOX was administered for 4 months until the disease progressed and lung metastases developed. After 4 courses of second-line IRIS plus bevacizumab chemotherapy, fever and swelling of the right buttock appeared; he visited and was admitted to our hospital. A CT scan revealed a pelvic abscess which resulted in septic shock. Swelling and pain extended to the right scrotum, and acute necrotizing fasciitis was suspected, and emergency surgery was performed. An incision was made from the right buttock to the right scrotum, bloody purulent drainage with a foul odor was observed, and a diagnosis of Fournier's gangrene was made. Although typical CT findings such as emphysema due to gas-producing bacteria were not observed in this case, early diagnosis and intervention of systemic management including early surgical drainage and operation were effective. For pelvic infections occurring during bevacizumab chemotherapy, Fournier's gangrene should considered for differential diagnosis, even if CT findings are atypical.

Focal neuroendocrine carcinoma mixed with adenocarcinoma of the gallbladder with aggressive lymph node metastasis in a patient who did not meet the mixed neuroendocrine-non-neuroendocrine neoplasm criteria.

A 70-year-old Japanese woman who was treated for interstitial pneumonia (IP) with steroid therapy developed cholecystitis. A serial computed-tomography (CT) imaging showed irregular thickness of the fundus wall of the gallbladder and two rapidly enlarged lymph nodes (LNs): number (no.) 12 and no. 8a. Positron-emission tomography-computed tomography (PET-CT) scan showed an abnormal uptake at the site of the gallbladder tumor and those LNs. We subsequently performed open radical cholecystectomy and LN dissection of the no. 12 and 8a LNs, following complete remission of IP. The histology showed gallbladder adenocarcinoma, with a single focus of neuroendocrine carcinoma (NEC) component of less than 30%; Ki-67 index > 80%, synaptophysin (Syn) (+), chromogranin A (CgA) (+), and clusters of differentiation (CD) 56 (+) (T2bN1M0, Stage IIIB). LN no. 8a was diffusely metastatic with NEC components. LN no. 12c, which was adjacent to the cystic duct, revealed necrosis without apparent tumor cells, but was highly suspicious for tumor necrosis. The final diagnosis was adenocarcinoma of the gallbladder with focal NEC (< 30%), which did not meet the criteria for mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN). Postoperatively, she completed 4 cycles of adjuvant chemotherapy for NEC (Cisplatin plus Etoposide), and no recurrence was observed after 12 months.

Machine Learning-based Model for Predicting Postoperative Complications among Patients with Colonic Perforation: A Retrospective study.

OBJECTIVES: Surgery for colonic perforation has high morbidity and mortality rates. Predicting complications preoperatively would help improve short-term outcomes; however, no predictive risk stratification model exists to date. Therefore, the current study aimed to determine risk factors for complications after colonic perforation surgery and use machine learning to construct a predictive model. METHODS: This retrospective study included 51 patients who underwent emergency surgery for colorectal perforation. We investigated the connection between overall complications and several preoperative indicators, such as lactate and the Glasgow Prognostic Score. Moreover, we used the classification and regression tree (CART), a machine-learning method, to establish an optimal prediction model for complications. RESULTS: Overall complications occurred in 32 patients (62.7%). Multivariate logistic regression analysis identified high lactate levels [odds ratio (OR), 1.86; 95% confidence interval (CI), 1.07-3.22; p = 0.027] and hypoalbuminemia (OR, 2.56; 95% CI, 1.06-6.25; p = 0.036) as predictors of overall complications. According to the CART analysis, the albumin level was the most important parameter, followed by the lactate level. This prediction model had an area under the curve (AUC) of 0.830. CONCLUSIONS: Our results determined that both preoperative albumin and lactate levels were valuable predictors of postoperative complications among patients who underwent colonic perforation surgery. The CART analysis determined optimal cutoff levels with high AUC values to predict complications, making both indicators clinically easier to use for decision making.

[A case of endocrine cell carcinoma of the ascending colon with liver metastasis treated with hepatectomy after excision of the primary lesion and systemic chemotherapy].

A 77-year-old man who complained of melena was admitted to our department. Colonoscopy revealed a type 2 tumor in the hepatic flexure of the ascending colon. Biopsy examination revealed a poorly differentiated adenocarcinoma. Abdominal computed tomography(CT)revealed 3 tumors within the posterior segment of the right hepatic lobe. Initially, a right hemicolectomy was performed. Immunohistochemically, the tumor was diagnosed as an endocrine cell carcinoma. After surgery, a capecitabine, oxaliplatin, and bevacizumab(CapeOX/BEV)regimen was administered. However, after 5 chemotherapy courses, abdominal CT revealed enlargement of the 3 tumors in the posterior segment of the right hepatic lobe. There was no metastasis besides the liver metastasis. The patient underwent a radical hepatectomy of the posterior segment. At 8 months post-surgery, the patient remains alive and well. Endocrine cell carcinoma of the colon and rectum is usually malignant and is associated with a very poor prognosis because of rapid hematogenous or lymphogenous metastasis. Effective multimodal treatment regimens, including surgery and new chemotherapies such as molecular targeted therapies, should be established to improve the prognosis of patients with endocrine cell carcinomas of the colon and rectum.

[Pathological complete response in advanced gastric carcinoma by S-1/CDDP combination chemotherapy].

A59 -year-old woman was referred to our hospital for a close examination and treatment of an advanced gastric carcinoma. A physical examination and CT scan showed that the right cervical and axillar lymph nodes were swelling, and a histopathological examination of the axillar lymph node revealed metastatic growth of the gastric carcinoma (Stage IV). Then, we started S-1/CDDP combination chemotherapy. S-1 (80 mg/m2/day)was orally administered for 3 weeks followed by 2 weeks of rest, and CDDP (60 mg/m2) was administered by drip on day 8. Since the distant metastases were greatly reduced after 6 courses of combination therapy, a distal gastrectomy with lymph nodes dissection (D2) was performed. Histopathological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. The clinical course after the operation went well without any complications, and the patient is alive with no evidence of recurrence 1 year after surgery. S-1/CDDP combination chemotherapy appears to be one of the effective treatments for advanced gastric carcinoma.

[A patient with pulmonary metastasis from breast cancer after surgery who responded to S-1].

We report a 60-year-old female with pulmonary metastasis from breast cancer who responded to S-1. In November 2001, she underwent surgery. In October 2005, relapse was detected. As there was no hormone sensitivity, chemotherapy was selected, and oral administration of S-1 at 120 mg/day (2 divided doses) was initiated. After the fourth course, the tumor marker level returned to the reference value. Thoracic CT at the end of the sixth course revealed the disappearance of the metastatic focus. Adverse reactions during the administration period were mild. S-1 showed potent antitumor effects and good tolerance, and it may be useful for treating metastatic/recurrent breast cancer.

[Examination of the safety of docetaxel/cyclophosphamide combination therapy for advanced recurrent breast cancer].

In the treatment of recurrent breast cancer in patients previously treated with anthracycline drugs, taxane drugs are generally used. This time, we retrospectively studied the safety of docetaxel/cyclophosphamide combination therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8 years old) were included in the study. Metastatic/recurrent sites included 3 skin, 2 each of contralateral breast, lung and bone, and 1 each of liver, carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a history of anthracycline treatment. The patients received TC at doses of 60 mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse events, non-hematotoxic events included alopecia in all the patients, generalized malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3 decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia associated with oral candida. The patient was admitted and treated with fluid replacement and granulocyte colony-stimulating factor (G-CSF). There were no other patients in whom the treatment was prolonged or dosage was reduced due to adverse reactions. TC therapy is considered to be a beneficial treatment method in terms of safety since it can be instituted on an outpatient basis.

[A case of postoperative pulmonary metastasis of breast cancer treated with docetaxel and cyclophosphamide therapy].

A 55-year-old woman underwent a partial breast resection in our hospital for breast cancer in May 2002. For adjuvant therapy, she received cyclophosphamide, pirarubicin and 5-FU infusion a total of 6 times, and anastrozole. Then, in May of 2004, an abnormal shadow was detected on her of chest X-ray. After CT scan we diagnosed multiple pulmonary metastasis of breast cancer. We used combination therapy of docetaxel 60 mg/m(2) and cyclophosphamide 500 mg/m(2). After 9 months, pulmonary metastasis disappeared on her CT scan. During chemotherapy, she showed no major side effect.

Cyclooxygenase-2 gene induction causes CDDP resistance in colon cancer cell line, HCT-15.

Drug resistance to cisplatin (CDDP) would represent a major obstacle for cancer therapy. The adenosine triphosphate (ATP) binding cassette (ABC) family of transport proteins, such as the 170 kDa P-glycoprotein (multidrug resistance gene-1; MDR-1) and the 190 kDa multidrug resistance-associated proteins (MRPs), are associated with multidrug resistance, including resistance to CDDP. The purpose of the present study was to investigate the relationship between cyclooxygenase-2 (COX-2) expression and the level of chemosensitivity to CDDP. We established the COX-2-overexpressed colon cancer cell line TR-5 from HCT-15 cells. We quantified the expression of m-RNA for MRP-1 and MDR-1 by a real-time PCR method, determining that the values of each gene/standardized GAPDH in HCT-15 and TR-5 were 23+/-0.4 and 6.1+/-0.5 in MRP-1 (p<0.02) and 9.0+/-4.8 and 3.6+/-0.5 in MDR-1, respectively. With respect to chemosensitivity, survival rates for 3 microg/ml and 10 microg/ml of CDDP were 81.5+/-12.2% and 26.1+/-11.7% (IC50=6.5 microg/ml) for HCT-15 and 96.6+/-1.7% and 77.4+/-4.9% (IC50=18.5 microg/ml) for TR-5, respectively, thus TR-5 showed higher resistance to CDDP than HCT-15 did with statistical differences. We also demonstrated a successful re-sensitization to CDDP toxicity in TR-5 by means of the COX-2 selective inhibitor JTE-522, 4-(4-cyclohexyl-2-methyl-1, 3-oxazol-5-yl)-2-fluorobenzene sulfonamide, which markedly decreased the IC50 of CDDP for TR-5 (from 17.3+/-2.6 microg/ml to 8.6+/-2.5 microg/ml). In conclusion, COX-2 overexpression induced increased MRP-1 expression in a colon cancer cell line, TR-5, resulting in chemoresistance to CDDP that was approximately triple the level of chemoresistance observed in the original HCT-15 cells line, as measured by calculation of the IC50. We also confirmed the efficacy of pretreatment of TR-5 cells with the COX-2 selective inhibitor JTE-522 in restoring chemosensitivity of these cells to CDDP, suggesting a strategy for overcoming drug resistance to CDDP.

Thymidylate synthetase (TS) genotype and TS/dihydropyrimidine dehydrogenase mRNA level as an indicator in determining chemosensitivity to 5-fluorouracil in advanced gastric carcinoma.

BACKGROUND: One of the target enzymes of 5-fluorouracil (5-FU) is thymidylate synthetase (TS). The DNA sequence of the TS gene includes either double or triple tandem 28-bp repeats within the promoter region, such that TS genotypes can be classified as homozygous 3R/3R heterozygous 2R/3R or homozygous 2R/2R Several recent studies have shown that TS genotype affects mRNA expression, with 3R/3R homozygotes showing higher TS mRNA expression compared to the other genotypes. PURPOSE: We analyzed the TS genotype and TS and dihydropyrimidine dehydrogenase (DPD) mRNA expression levels in 22 advanced gastric carcinoma patients, and analyzed results with respect to patient 5-FU chemosensitivity, as detected by the tetrazolium-based colorimetric (MTT) assay and survival outcome. PATIENTS AND METHODS: Between September 2001 and April 2002, 22 Japanese patients with advanced gastric carcinoma were evaluated. Informed written consent was obtained from all patients and the study was approved by the ethical committee at our University Hospital Fresh surgical specimens from carcinoma lesions were enzymatically dissociated and incubated with 5-FU at a concentration of 50 microg/ml for 48 hours to determine the inhibition rate as detected by MTT assay. Normal and tumor tissue and peripheral blood samples were collected and stored at -80 degrees C until assay for TS genotype and TS and DPD mRNA level The TS genotype was assessed by PCR assay using peripheral monocytes, since monocyte genotypes represent the genotype of normal and tumor tissues. Quantification of TS and DPD mRNA levels was performed using real-time PCRP Survival outcome was assessed according to the disease-free survival period in cases with similar clinical backgrounds. RESULTS: TS genotyping revealed 19 3R/3R homozygotes and 3 2R/3R heterozygotes. After analysis of normal and tumor tissues, samples from homozygote 3R/3R cases showed higher TS mRNA expression than heterozygote 2R/3R cases, which was statistically significant at p<0.05. We also observed a statistically significant correlation in TS mRNA levels between normal and tumor tissues, while no significant correlation was observed for DPD mRNA levels between normal and tumor tissues. While no relationship between 5-FU chemosensitivity and TS genotype or mRNA expression was observed, cases with high DPD mRNA expression were resistant to 5-FU and exhibited poor survival outcomes. CONCLUSION: While TS genotype affected TS mRNA expression in both normal and tumor tissues in advanced gastric cancer, there is no relationship between TS genotype or mRNA expression level and 5-FU chemosensitivity. CONCLUSION: Our finding, that DPD mRNA expression appears to be a factor in determining 5-FU chemosensitivity and the survival outcome of advanced gastric cancer patients, is comparable with previous reports.