Naru Kondo

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.

Benefit of Portal or Superior Mesenteric Vein Resection With Adjuvant Chemotherapy for Patients With Pancreatic Head Carcinoma

The aim of this study was to evaluate the efficacy of portal or superior mesenteric vein (PV/SMV) resection for patients with pancreatic carcinoma who underwent pancreatoduodenectomy.

Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection

BACKGROUND Although postoperative adjuvant chemotherapy for pancreatic carcinoma improves survival in some patients, its efficacy varies among individuals. The aim of this study was to determine the usefulness of intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) as predictive markers of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. METHODS The expression of intratumoral hENT1 and RRM1 was examined immunohistochemically in 109 patients with pancreatic carcinoma who received adjuvant gemcitabine-based chemotherapy after operative resection. Relationships between clinicopathologic factors, including hENT1 and RRM1 expression, and disease-free and overall survival (DFS and OS) were evaluated by univariate and multivariate analyses. RESULTS The 5-year DFS and OS rates for the 109 patients were 26% and 31%, respectively. In univariate analysis, both hENT1 and RRM1 expression were significantly associated with DFS (hENT1, P = .004; RRM1, P = .011) and OS (hENT1, P = .001; RRM1, P = .040). In multivariate analysis, both were independent factors for DFS (hENT1, P = .001; RRM1, P = .009) and OS (hENT1, P = .001, RRM1, P = .019). Evaluation of the combination analysis of both was also identified as a powerful independent predictor of DFS (P < .001) and OS (P < .001). CONCLUSION Expression of hENT1 and RRM1 is predictive of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. In addition, their combined analysis has greater predictive value than either factor alone.

Human equilibrative nucleoside transporter 1 expression predicts survival of advanced cholangiocarcinoma patients treated with gemcitabine-based adjuvant chemotherapy after surgical resection.

Objective:The aim of this study was to evaluate whether intratumoral human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Background:There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. Methods:Intratumoral hENT1 expression was investigated immunohistochemically in 105 patients with resected advanced cholangiocarcinoma. Relationships between intratumoral hENT1 expression and clinicopathological factors were evaluated by univariate and multivariate analyses. This study was a retrospective analysis on retrospectively collected tissue and data. Results:Fifty-one patients received AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74 (70%) and 31 patients (30%), respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival patients with high hENT1 expression were significantly better than those with low hENT1 expression among patients who received AGC (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received AGC and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with AGC by multivariate analysis (P = 0.027). Conclusions:Intratumoral hENT1 expression may be a potent predictive marker for advanced cholangiocarcinoma patients treated with AGC.

Long-term results of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for pancreatic carcinoma.

This study evaluated long‐term outcomes for patients who received adjuvant gemcitabine plus S‐1 chemotherapy after resection for pancreatic carcinoma.

Elevated perioperative serum CA 19-9 levels are independent predictors of poor survival in patients with resectable cholangiocarcinoma.

Identification of prognostic markers is important to establish a perioperative therapeutic strategy for resectable cholangiocarcinoma (CC). The aim of this study was to investigate whether perioperative serum carbohydrate antigen 19‐9 (CA19‐9) levels can predict survival of patients who underwent surgical resection for CC.

Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer.

Background:Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC.Methods:We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA.Results:Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001).Conclusions:Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment.

Prognostic impact of dihydropyrimidine dehydrogenase expression on pancreatic adenocarcinoma patients treated with S-1-based adjuvant chemotherapy after surgical resection.

The aim of this study is to investigate the prognostic value of intratumoral expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients treated with S‐1‐based chemotherapy after surgical resection for pancreatic adenocarcinoma.

Remnant pancreatic parenchymal volume predicts postoperative pancreatic exocrine insufficiency after pancreatectomy

BACKGROUND Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI. METHODS A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h) < 5% on the (13)C-labeled mixed triglyceride breath test was considered diagnostic of postoperative PEI. Relationships between postoperative PEI and clinicopathologic factors including remnant pancreatic volume were analyzed. RESULTS Pancreatoduodenectomy and distal pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P < .001). The cut-off value of remnant pancreatic volume for predicting postoperative PEI was 24.1 mL by receiver operating characteristic curve analysis. Multivariate analysis revealed that remnant pancreatic volume < 24.1 mL was the only independent predictive factor for the development of postoperative PEI in patients who underwent pancreatectomy (P < .001, hazard ratio; 5.94, 95% confidence interval; 2.96-12.3). CONCLUSION Remnant pancreatic volume is associated closely with postoperative PEI after pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy.

Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy

Background:The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC).Methods:Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated.Results:High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced.Conclusions:Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.