Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer

Schematic diagrams of the signal cascade of EGF-induced DPD expression of EGFR-mutated type cells. TF, transcription factor; Mit A, mithramycin A. (JPG 130 kb

Clinicopathological Parameters Associated with Surgical Site Infections in Patients who Underwent Pancreatic Resection

Background/Aims: To clarify parameters associated with postoperative surgical site infection (SSI) after pancreatectomy, we examined clinicopathological and surgical records in 186 patients who underwent pancreatectomy at a single academic institute. Methodology: Patient demographics, liver functional parameters, histological findings, surgical records and post-hepatectomy outcomes during hospitalization were compared between the non-SSI and SSI group, in which SSIs included superficial and deep SSIs. Results: The prevalence of SSI (29-35%) has not changed over an 18-year period. With respect to patient demographics and laboratory data, no parameters were associated with postoperative SSI. In surgical records, the operating time in the SSI group tended to be longer in comparison with that in the non-SSI group (618 vs. 553 minutes, respectively) but not significantly different (p=0.070). With respect to postoperative outcomes, time to oral intake in the SSI group was significantly longer than that in the non-SSI group (21.2 vs. 13.7 days, respectively) (p<0.01). Incidences of pancreatic fistula, postoperative bleeding, long-term ascites and re-operation were significantly more frequent in the SSI group in comparison with the non-SSI group (p<0.05). Decrease of body weight after surgery in the SSI group was significantly greater than that in the non-SSI group (-4.1 vs. -2.7kg, respectively) (p<0.05). Period of hospital stay in the SSI group was significantly longer than that in the non-SSI group (37 vs. 25 days) (p<0.05). Multivariate analysis showed that only postoperative pancreatic fistula was significantly associated with SSI (p<0.01). Conclusions: SSI is an important risk factor of longer hospital stay after pancreatectomy and prevention of pancreatic fistula through the future improvement of surgical procedures is necessary to decrease SSI rates

Prediction of portal pressure from intraoperative ultrasonography

BackgroundPortal hypertension is a major risk factor for hepatic failure or bleeding in patients who have undergone hepatectomy, but it cannot be measured indirectly. We attempted to evaluate the intraoperative ultrasonography parameters that correlate with portal pressure (PP) in patients undergoing hepatectomy.MethodsWe examined 30 patients in whom PP was directly measured during surgery. The background liver conditions included chronic viral liver disease in seven patients, chemotherapy-associated steatohepatitis in four patients, fatty liver in one patient, hepatolithiasis in one patient, obstructive jaundice in one patient, and a normal liver in 16 patients. A multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for PP.ResultsThe mean PP was 10.4 ± 4.1 mm Hg. The PP tended to be increased in patients with chronic viral hepatitis. A univariate analysis identified the association of the six following parameters with PP: the platelet count and the maximum (max), minimum (min), endo-diastolic, peak-systolic, and mean velocity in the portal vein (PV) flow. Using multiple linear regression analysis, the predictive formula using the PV max and min was as follows: Y (estimated PP) = 18.235?0.120 × (PV max.[m/s])?0.364 × (PV min). The calculated PP (10.44 ± 2.61 mm Hg) was nearly the same as the actual PP (10.43 ± 4.07 mm Hg). However, there was no significant relationship between the calculated PP and the intraoperative blood loss and post hepatectomy morbidity.ConclusionsThis formula, which uses ultrasonographic Doppler flow parameters, appears to be useful for predicting PP

Clinical and molecular analysis of synchronous double lung cancers

Background: Since multiple lung cancer treatment strategies differ, it is essential for clinicians to be able to distinguish between separate primary lesions and metastasis. In the present study, we used array comparative genomic hybridization (aCGH) and somatic mutation (epidermal growth factor receptor: EGFR) to analyze genomic alteration profiles in lung cancer patients. To validate the consistency among the pathological assessments and clarify the clinical differences between double primary lesions and metastasis, we also examined synchronous double lung cancer clinical data. Methods: Between January 1970 and March 2010, 2215 patients with lung cancer underwent surgical resection at Nagasaki University Hospital. We performed molecular analysis of 12 synchronous double lung cancer patients without lymph node metastasis (intrapulmonary metastasis in the same lobe (pm1): n = 6, primary: n = 6). We then evaluated the clinical outcomes of patients with pathologically diagnosed synchronous double lung cancers (intrapulmonary metastasis (pm): n = 80, primary: n = 39) and other T3 tumors (n = 230). Results: Examination of the concordance rate (CR) of the copy number changes (CNCs) for paired tumors showed that the metastasis group was larger than the primary group (55.5% vs. 19.6%, p = 0.04). Pathological diagnosis and molecular classification were the same in 10 out of 12 cases (83%). As compared to the primary group, there tended to be an inferior 5-year survival curve for the pm group. However, in N0 patients, the survival curve for the pm group overlapped the primary group, while the survival rate of the pm1 group was much higher than that of other T3 group (p < 0.01). Conclusions: Both pathological and molecular assessment using aCGH adapted in the current study appeared to have a consistency. Pathological pm1(T3)N0 patients may have a better prognosis than other T3N0 patients

High Expression of Dihydropyrimidine Dehydrogenase in Lung Adenocarcinoma is Associated With Mutations in Epidermal Growth Factor Receptor: Implications for the Treatment of Non?Small-Cell Lung Cancer Using 5-Fluorouracil

BackgroundIt has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non?small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status.Patients and MethodsEGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines.ResultsAdenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression.ConclusionHigh DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC