Hiroki Ohge

Number of Metastatic Lymph Nodes, but Not Lymph Node Ratio, Is an Independent Prognostic Factor after Resection of Pancreatic Carcinoma

BACKGROUND This study evaluated the prognostic significance of the number of metastatic lymph nodes and the ratio of metastatic nodes to total number of examined lymph nodes (lymph node ratio, LNR) after resection of pancreatic carcinoma. STUDY DESIGN Records of 119 consecutive patients with pancreatic ductal carcinoma, who underwent R0 or R1 pancreatectomy with regional node dissection, were reviewed retrospectively. Clinical factors, pathologic factors including number of metastatic nodes and LNR, and survival were analyzed by univariate and multivariate analyses. RESULTS Overall survival rates were 78%, 28%, and 20% at 1, 3, and 5 years, respectively. The median numbers of evaluated lymph nodes and involved nodes were 28 and 3, respectively. Univariate analysis revealed that tumor location, postoperative adjuvant chemotherapy, tumor differentiation, choledochal invasion, portal or splenic vein invasion, extrapancreatic nerve plexus invasion, resection margin status, node status, number of involved nodes, LNR, International Union against Cancer (UICC) pT factor, and UICC stage correlated significantly (p < 0.05) with increased survival. By multivariate analysis, negative node metastasis (p = 0.008) and 0 or 1 involved node (p = 0.004), but not LNR, correlated independently with longer survival. The 1-, 3-, and 5-year survival rates of patients with 0 or 1 metastatic node and patients with 2 or more metastatic nodes were 91%, 48%, and 40% and 66%, 10%, and 0%, respectively. CONCLUSIONS The number of metastatic nodes, but not LNR, is one of the most powerful prognostic factors after resection of pancreatic carcinoma.

Pancreatoduodenectomy for Distal Cholangiocarcinoma: Prognostic Impact of Lymph Node Metastasis

BackgroundThe aim of this study was to identify useful prognostic factors in patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma.MethodsThe records of 36 patients with distal cholangiocarcinoma undergoing pancreatoduodenectomy were retrospectively reviewed. Potential clinicopathological prognostic factors that may affect survival were examined by univariate and multivariate analysis.ResultsThere was no mortality. Overall survival rates were 75%, 54%, and 50% for 1, 3 and 5 years, respectively (median survival time, 26 months). Univariate analysis found that age (≧ 65 years), pancreatic invasion, duodenal invasion, lymph node metastasis, perineural invasion and a positive surgical margin were significant predictors of poor prognosis (P < 0.05). Furthermore, lymph node metastasis was found to be a significant independent predictor of poor prognosis by multivariate analysis (P = 0.043). Moreover, there were significant differences in the 5-year survival between patients with 2 or less involved lymph nodes and those with 3 or more positive nodes (P < 0.001). There were no 2-year survivors of the group of patients with 3 or more positive nodes.ConclusionsThese results suggest that the presence and number of lymph nodes exhibiting metastatic disease might be useful in predicting the postsurgical outcome in patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma.

Combined Assessment of β- d -Glucan and Degree of Candida Colonization before Starting Empiric Therapy for Candidiasis in Surgical Patients

The purpose of the study was to investigate whether examination for plasma β-d-glucan, a cell wall constituent of fungi, is useful for selecting surgical patients with Candida colonization who would benefit from empiric antifungal therapy. We administered fluconazole to postoperative patients with Candida colonization who have risk factors for candidemia and complained of persistent fever despite prolonged antibacterial therapy. We then analyzed the clinical outcomes regarding the number of sites colonized with Candida spp. and plasma β-d-glucan. Of the 32 patients positive for β-d-glucan, 15 (46.9%) responded to the empiric therapy; only 9% of those who were negative responded (p < 0.01). In the multiple logistic regression analysis, being positive for β-d-glucan was a significant factor predicting response, with an adjusted odds ratio of 12.9 in patients with Candida colonization [95% confidence interval (CI) 2.07–80.73) (p < 0.01). In addition, the number of sites colonized with Candida spp. was a significant factor predicting response, with an estimated exposure odds ratio of 7.57 for those who were colonized at three or more sites compared with those colonized at one site (95% CI 1.20–47.70) (p = 0.031). In patients with Candida colonization, assessment of β-d-glucan was useful for deciding whether to start empiric therapy for suspected candidiasis in surgical patients.

Long-term results of seton drainage on complex anal fistulae in patients with Crohn's disease

Background: The aim of this study was to assess the long-term (greater than 2 years) results of seton drainage on anal fistulae in patients with Crohns disease. Methods: Between September 1990 and September 1999, 32 patients with Crohns disease underwent seton drainage for complex anal fistulae. The median follow-up time in these patients was 62 months (range, 25–133 months). In 10 patients (31.3%), recurrent perineal abscesses occurred with inlying seton drainage, and these were drained by re-insertion of the seton. A Malecot catheter was also inserted in 8 patients with recurrence. Results: The overall success rate of long-term seton usage was 87.5%. The subsequent associated procedure was simple seton removal (n = 9), secondary core-out fistulectomy (n = 7), or lay-open fistulotomy (n = 4). Eleven patients still had the seton in place. Recurrence developed in 3 patients (33%) who underwent simple seton removal and in 2 patients (18.2%) who underwent the secondary core-out procedure or fistulotomy. At the last follow-up examination, continence had not changed in 28 (87.5%) of the 32 patients. No change in continence was experienced by 10 of the 11 patients who underwent secondary fistulotomy or the secondary core-out procedure. Conclusions: Long-term seton drainage for complex anal fistula in Crohns disease is efficacious in both treating sepsis and preserving anal sphincter function. A relatively good result was achieved by the secondary core-out procedure or fistulotomy at the time of seton removal.

An Antecolic Roux-en Y type Reconstruction Decreased Delayed Gastric Emptying after Pylorus-Preserving Pancreatoduodenectomy

The aim of this study was to identify a preferable procedure reducing the incidence of delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PPPD). Data on 132 consecutive patients with pancreatobiliary disease, who underwent PPPD, were collected retrospectively. A retrocolic Billroth I type reconstruction (B-I group) and an antecolic Roux-en Y type reconstruction (R-Y group) were performed for 54 and 78 patients after PPPD, respectively. Clinical measures of DGE were compared between the two groups. The incidence of DGE was 81% in B-I group and 10% in R-Y group (P < 0.001). The type of reconstruction (P < 0.001), operative time (P = 0.016), and postoperative complications (P = 0.001) were significantly associated with DGE by univariate analysis. Only the type of reconstruction (P < 0.001) was identified as an independent factor, which was associated with DGE by multivariate analysis. An antecolic Roux-en Y type duodenojejunostomy could be a useful reconstruction method after PPPD to prevent the occurrence of DGE.

Adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic adenocarcinoma

BACKGROUND The aim of this study was to determine the effectiveness of adjuvant gemcitabine plus S-1 chemotherapy for patients with pancreatic carcinoma. METHODS Patients admitted for curative surgery for pancreatic adenocarcinoma received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each chemotherapy cycle consisted of intravenous gemcitabine, 700 mg/m(2), on day 1 and orally administered S-1, 50 mg/m(2), for 7 consecutive days, after which there was a 1-week pause of chemotherapy. RESULTS Twenty-seven patients were entered into this study. According to the TNM system, 4 (15%), 2 (7%), 6 (22%), and 15 (56%) patients were diagnosed with stage IA, IB, IIA, and IIB disease, respectively. Overall and disease-free survival rates were 86% and 60% at 1 year, 66% and 45% at 2 years, and 33% and 45% at 3 years, respectively. Toxicity during chemotherapy was mild. CONCLUSIONS Adjuvant gemcitabine plus S-1 chemotherapy appears to be a promising treatment for patients after surgical resection of pancreatic adenocarcinoma.

Intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms of the pancreas differentiated by ovarian-type stroma

BACKGROUND Intraductal papillary-mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) of the pancreas have similar clinicopathologic findings. This study was intended to clarify clinicopathologic characteristics in IPMNs and MCNs differentiated by ovarian-type stroma. METHODS Medical records for 77 patients with pancreatic cystic neoplasms with mucin secretion were reviewed. Patients were divided into IPMN (n = 70) or MCN (n = 7) according to the presence of ovarian-type stroma, and clinicopathologic parameters were compared between groups. RESULTS IPMNs consisted of 32 adenomas, 12 borderline neoplasms, 13 adenocarcinomas in situ, and 13 invasive adenocarcinomas; MCNs included 6 adenomas and 1 invasive adenocarcinoma. The mean age of IPMN patients (66 years) was significantly older than that of MCN patients (55 years). The male:female ratio in IPMN (53/17) was significantly greater (P < .001) than in MCN (0/7). The location of the pancreatic mass differed, with 76% 0f IPMNs occurring in the head, while 86% of MCNs occurred in the body or tail. Mass mean size was significantly smaller (28 mm vs 78 mm, P < .001), and mean diameter of the main pancreatic duct was larger (6.8 mm vs 3.1 mm, P < .001) in IPMN than in MCN. Patulous papilla was present in 44% (31/70) of IPMNs, but none was present in MCNs. Communication between the cyst and main pancreatic duct was more frequent in IPMNs (67/70) than in MCNs (1/7). Overall 5-year survival rates were 84% (IPMN) and 100% (MCN). CONCLUSIONS Clinicopathologic differences between IPMN and MCN are much clearer when differentiated by presence of ovarian-type stroma. Favorable prognosis for both neoplasms is offered by complete resection.

Bacterial translocation in patients with Crohn's disease undergoing surgery.

AbstractPURPOSE: Much evidence, derived from experimental studies, suggests that bacterial translocation indeed occurs, yet its clinical significance is still a matter of controversy in humans. The aims of this study were to determine the prevalence of bacterial translocation in patients with Crohn’s disease undergoing laparotomy and to identify any association with postoperative septic complications or systemic inflammatory response syndrome. METHODS: Mesenteric lymph node and peripheral blood samples from 42 patients with Crohn’s disease undergoing laparotomy were collected for bacteriologic assessments. RESULTS: Bacterial translocation to mesenteric lymph node was identified in 20 patients (48 percent). The most common organism was Escherichia coli (27 percent). Blood cultures were positive in 2 of 20 patients in whom translocation to lymph node was identified. Bacterial translocation was associated with a greater than two-fold increase in the incidence of postoperative septic complications (35 vs.14 percent), but this difference was not significant. In the analysis of the occurrence of systemic inflammatory response syndrome, a significantly higher incidence continued until the third postoperative day in patients with vs. those without bacterial translocation. In a logistic regression analysis, bacterial translocation had a significant effect on the occurrence of systemic inflammatory response syndrome, even though septic complications were taken into account. CONCLUSIONS: Bacterial translocation to mesenteric lymph node predisposed patients with Crohn’s disease undergoing laparotomy to systemic inflammatory response syndrome.

Telomere Shortening and Telomerase Expression during Multistage Carcinogenesis of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has been increasingly identified as a precursor to infiltrating ductal adenocarcinoma. Telomerase activation in response to telomere crisis followed by telomere shortening is thought to be a crucial event in the development of most human cancers. The aim of this study was to determine when this event occurs in the context of histologically defined IPMN progression. We analyzed telomerase expression in 68 IPMN samples and assessed telomere length by quantitative fluorescence in situ hybridization in samples taken from 17 sequential IPMN patients that included 37 individual loci. Samples from pancreatic ductal adenocarcinomas (PDACs, n = 15) and chronic pancreatitis patients (n = 10) were also examined. Telomeres were significantly shortened in 36 (97.3%) of 37 IPMN loci, with average telomere length decreasing with IPMN progression. Notably, even adenoma IPMNs demonstrated a 50% reduction of telomere length in 7 of 14 foci examined. Marked telomere shortening was observed from the in situ IPMN carcinoma stage (P < 0.001; vs borderline IPMNs) through the invasive stage, although telomerase had been activated, indicating that telomeres had shortened to a critical length by this histological grade. Up-regulated human telomerase reverse transcriptase expression was detectable and increased gradually with cancer development and was primarily observed at the borderline IPMN stage and then in more advanced histopathologies. Progressive telomere shortening predominantly occurs during early IPMNs carcinogenesis before telomerase activation and progression from borderline to carcinoma in situ IPMNs is the critical stage of IPMNs carcinogenesis at which telomere dysfunction occurs.

Quantification of doripenem in human plasma and peritoneal fluid by high-performance liquid chromatography with ultraviolet detection

A simple and rapid HPLC method that includes ultrafiltration to remove plasma and peritoneal fluid protein was developed to determine doripenem concentrations in human plasma and peritoneal fluid. Doripenem was stabilized by immediate mixing of the plasma or peritoneal fluid with 1M 3-morpholinopropanesulfonic acid buffer (pH 7.0) (1:1). Doripenem and an internal standard were detected by measuring their ultraviolet absorbance at 300 nm. The calibration curves for doripenem in human plasma and peritoneal fluid were linear from 0.05 to 100 microg/mL. For plasma, both the intra- and the interday precision were less than 3.41% (CV), and the accuracy was between 97.4 and 101.7% above 0.05 microg/mL. For peritoneal fluid, the intra- and the interday precision were less than 2.98% (CV), and the accuracy was between 94.4 and 103.9% above 0.05 microg/mL. The limit of detection was 0.02 microg/mL in both plasma and peritoneal fluid. The assay has been applied to the therapeutic drug monitoring of doripenem in both plasma and peritoneal fluid.