Clinicopathological analysis and survival outcome of duodenal adenocarcinoma

Duodenal adenocarcinoma is a rare cancer, contributing <10 % of periampullary carcinoma. This study reviews the single center experience of duodenal adenocarcinoma and analyzes the clinical and pathological factors to predict survival and recurrence. The records of 50 patients with duodenal adenocarcinoma who underwent surgical exploration or resection from 1995 to 2010 were reviewed retrospectively. Univariate and multivariate analyses were performed to identify the clinicopathological factors associated with survival and recurrence. There were 35 men and 15 women, with a mean age of 61 years. In multivariate analysis of 50 patients, R0 resection [p = 0.041, hazard ratio (HR) = 3.569, 95% confidence interval (CI) = 1.057–12.054] and symptom at initial admission (p = 0.025, HR = 11.210, 95% CI = 1.354–92.812) were independent prognostic factors for overall survival. Thirty-six patients underwent curative resection (resectability 72%). The 5-year survival rates for curative and noncurative resections were 46.4% and 0%, respectively. Univariate analysis of 36 patients who underwent R0 resection revealed that symptoms at initial admission (p = 0.023), presence of lymph node metastasis (p = 0.034), and perineural invasion (p = 0.025) were significant prognostic factors after curative resection. There was no significant factor for overall survival in the multivariate analysis. There was recurrence in 15 patients, mainly as liver metastasis. Multivariate analysis revealed that presence of symptom (p = 0.047, HR = 5.362, 95% CI = 1.021–28.149) and ulcerative tumor (p = 0.036, HR = 5.668, 95% CI = 1.123–28.619) were independent factors for disease free survival. An aggressive surgical approach to achieve R0 resection was important to enhance survival. Most of the recurrence occurred within 1 year after surgery. Close follow-up is necessary after surgical resection.     

Prognosis after resection for hepatitis B virus-associated intrahepatic cholangiocarcinoma

AIM:To investigate the prognostic factors after resection for hepatitis B virus(HBV)-associated intrahepatic cholangiocarcinoma(ICC) and to assess the impact of different extents of lymphadenectomy on patient survival.METHODS:A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed.The patients were classified into groups according to the extent of lymphadenectomy(no lymph node dissection,sampling lymph node dissection and regional lymph node dissection).Clinicopathological characteristics and survival were reviewed retrospectively.RESULTS:The cumulative 1-,3-,and 5-year survival rates were found to be 60 %,18 %,and 13 %,respectively.Multivariate analysis revealed that liver cirrhosis(HR = 1.875,95%CI:1.197-3.278,P = 0.008) and multiple tumors(HR = 2.653,95%CI:1.562-4.508,P 0.001) were independent prognostic factors for survival.Recurrence occurred in 70 patients.The 1-,3-,and 5-year disease-free survival rates were 36%,3% and 0%,respectively.Liver cirrhosis(HR = 1.919,P = 0.012),advanced TNM stage(stage Ⅲ/Ⅳ)(HR = 2.027,P 0.001),and vascular invasion(HR = 3.779,P = 0.02) were independent prognostic factors for disease-free survival.Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection.Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status.CONCLUSION:The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC,and routine lymph nodedissection is not recommended,particularly for those without lymph node metastasis.     

The role of lymph node ratio in recurrence after curative surgery for pancreatic endocrine tumours

BackgroundThe prognostic role of lymph nodes metastasis in pancreatic neuroendocrine tumours is unclear.MethodsRetrospective study of 53 patients who underwent a curative standard resection for pancreatic neuroendocrine tumours. The endpoint was to define the role of the lymph nodes ratio in recurrence after curative surgery. The following data were considered as possible factors for predicting the risk of recurrence: gender, age, presence of symptoms, hormonal status, site of tumours, type of resection, size of the tumours, radical resection, pathological T, N and M stage, the Ki67 index, the number of lymph nodes harvested, the number of metastatic lymph nodes and the lymph node ratio. Recurrence rate and time of recurrence were evaluated.ResultsTwelve (26.4%) patients developed a recurrence with a median time of 42.8 (1–305) months. At multivariate analysis, the only factors related to recurrence were: size of lesions (HR 1.1, C.I. 95% 1.0–1.1, P = 0.011), Ki67 ≥ 5% (HR 3.6, C.I. 95% 1.3–10, P = 0.014) and LNR > 0.07 (HR 5.2, C.I. 95% 1.1–25, P = 0.045).ConclusionsOur study confirmed that the lymph nodes ratio played an important role in the recurrence rate and suggested that a low number of metastatic lymph nodes reduced the disease free survival.     

Predisposing Factors of Hepatocellular Carcinoma Recurrence Following Complete Remission in Response to Transarterial Chemoembolization

Background and Aim

The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE).

Methods

A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time.

Results

Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥60 years; HR 1.531, P = 0.043), advanced Child–Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR.

Conclusions

Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.     

Prognostic factors before and after recurrence of resected non-small cell lung cancer

BackgroundThe post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited.MethodsFrom a group of 775 NSCLC patients who consecutively underwent curative surgery, 133 patients showing recurrence were retrospectively analyzed.ResultsRecurrence was most often seen in smokers and patients with advanced stage disease. In patients experiencing relapse, the 1- and 2-year recurrence rates were 58% and 84%, respectively. A multivariate analysis showed that patients who underwent limited surgery, had non-adenocarcinoma disease, or had metastatic lymph node involvement showed early recurrence (p-values: <0.01, 0.04, and 0.04, respectively). Among all relapsed patients, the 2-year overall survival rate after recurrence was 37%. A multivariate analysis demonstrated that patients with lymph node metastasis at the time of surgery and patients who experienced early recurrence were significantly more likely to have a shorter survival time after recurrence (hazard ratio, 1.73; p=0.03; hazard ratio, 2.56; p<0.001, respectively).ConclusionsPatients who are node-positive, show non-adenocarcinoma disease, and/or undergo limited surgery should receive careful follow-up during the first year after surgery for NSCLC. The present data provide additional information about postoperative recurrence in NSCLC patients.     

Midkine promotes perineural invasion in human pancreatic cancer

AIM:To investigate midkine(MK)and syndecan-3protein expression in pancreatic cancer by immunohistochemistry,and to analyze their correlation with clinicopathological features,perineural invasion,and prognosis.METHODS:Pancreatic cancer tissues(including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor)were taken from 42 patients who were undergoing a partial duodenopancreatectomy.MK and syndecan-3proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method,and analyzed for their correlation with clinicopathological features,perineural invasion,and prognosis.Associations of neural invasion with aggressive characteristics of pancreatic cancer and the presence of perineural invasion were assessed by two independent observers blinded to the patient status.RESULTS:MK and syndecan-3 were found in 26(61.9%)and 24(57.1%)specimens,respectively.MK and syndecan-3 expression was associated with perineural invasion(P=0.018 and 0.031,respectively).High MK expression was closely associated with advanced tumor,node and metastasis stage(P=0.008),lymph node metastasis(P=0.042),and decreased postoperative survival at 3years(51.0%vs 21.8%,P=0.001).Syndecan-3 levels were correlated with tumor size(P=0.028).Patients who were syndecan-3 negative had a higher cumulative survival rate than those who were positive,but the difference was not significant(44.0%vs 23.0%,P>0.05).CONCLUSION:MK and syndecan-3 are frequently expressed in pancreatic cancer and associated with perineural invasion.High expression of MK and syndecan-3may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer.     

Macroscopic serosal invasion and small tumor size as independent prognostic factors in stage IIA colon cancer

Background

This study aimed to investigate the prognostic factors of patients with stage IIA (T3N0M0) colon cancer in terms of macroscopic serosal invasion and small tumor size.

Methods

We enrolled 375 stage IIA colon cancer patients who underwent curative resection between January 2004 and December 2011. Macroscopic serosal invasion was defined as tumor nodules or colloid changes protruding the surface of the serosa. The clinicopathologic characteristics were analyzed to identify independent prognostic factors.

Results

The median follow-up was 47 months (range, 1–90 months). On multivariate survival analysis, macroscopic serosal invasion (adjusted hazard ratio [HR]?=?4.750; p?=?0.013), tumor size <?5 cm (adjusted HR?=?3.112, p?=?0.009), perineural invasion (adjusted HR?=?3.528; p?=?0.002), <?12 retrieved lymph nodes (adjusted HR?=?4.257; p?=?0.002), and localized perforation (adjusted HR?=?7.666; p?=?0.008) were independent risk factors for recurrence.

Conclusion

We found novel prognostic factors of stage IIA colon cancer, including macroscopic serosal invasion and small tumor size (<?5 cm). Further studies are needed to evaluate the benefit of adjuvant chemotherapy in patients with these prognostic factors.

     

Factors associated with survival in older patients affected by COVID-19: A retrospective cohort study

AimMortality is high in Coronavirus disease 2019 patients with pre-existing comorbidities and advanced age. Associated complications have added to the negative prognosis. Nevertheless, many have fully recovered, even among the most fragile. Factors associated with their survival was investigated.MethodsRetrospective study of patients aged ≥90 years admitted for COVID-19 to the Internal Medicine wards of two hospitals in Lombardy, Italy.ResultsAmong 34 patients with SARS-CoV-2 pneumonia, 33 (97.1%) had respiratory failure. Eighteen patients (52.9%) survived and 16 (47.1%) died during hospital stay. Survivors compared to deceased had a significantly longer hospitalization (19 vs. 10 days respectively; p = 0.02), a better PaO2:FiO2 ratio (241 vs. 171 respectively; p = 0.003), higher lymphocyte counts (p = 0.01) and lower serum LDH levels (p < 0.001) at admission. At multivariate analysis only higher PaO2:FiO2 was associated with survival (OR 1.06 [95%CI 1.0–1.03]; p = 0.02). Kaplan-Meier analysis showed a significant difference in event-free survival between patients treated or not with LMWH (p < 0.0001) and between those treated or not with beta-blockers (p = 0.008). Cox regression, performed in the subgroup of patients who received LMWH, did not show significant difference for sex (HR 2.7 [95% CI 0.53–14.3], p = 0.23), CCI (HR 0.7 [95% CI 0.37–1.45], p = 0.38), PaO2:FiO2 ratio (HR 0.98 [95% CI 0.97–1.0], p = 0.07), corticosteroid therapy (HR 0.99 [95% CI 0.22–4.5], p = 0.99) and beta-blocker therapy (HR 2.8 [95% CI 0.56–14,7], p = 0.21).ConclusionsDespite higher mortality in elderly, treatment with LMWH and betablockers might be associated with better survival. Dedicated studies are required to confirm our result.     

Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer

Purpose

DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis.

Methods

Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan–Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model.

Results

Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 % at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 % (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041).

Conclusions

DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.     

Prediction of the Postoperative Prognosis of Intrahepatic Cholangiocarcinoma (ICC): Importance of Preoperatively-Determined Anatomic Invasion Level and Number of Tumors

Background

Preoperative prediction of the prognosis of patients with intrahepatic cholangiocarcinoma (ICC) following surgical treatment remains quite difficult and controversial. We attempted to identify the preoperative and postoperative predictors of the overall survival rates in patients with ICC in order to clarify the appropriate indications for surgical resection of ICC.

Patients and Methods

We retrospectively investigated the clinicopathological features of ICC and outcome of surgical resection in 111 consecutive patients who underwent surgical treatment at our hospital between 1980 and March 2012. Both preoperative factors and operatively confirmed factors were evaluated as potential risk factors for determination of the post-surgical prognosis.

Results

Curative resection (R0) was performed in 72 patients (64.9 %). The 1- and 3-year overall survival rates were 85.0 and 59.7 % in the R0 group. Two preoperative factors [hilar invasion as recognized by computed tomography (HR 3.16, P = 0.020) and multiple intrahepatic tumors (HR 7.09, P = 0.0002)] and two operatively confirmed factors [multiple intrahepatic tumors (HR 9.17, P = 0.0009) and lymph node metastasis as confirmed by final histology (HR 6.41, P = 0.003)] were identified as significant risk factors adversely influencing the overall survival rate after surgery. Furthermore, solitary, small (<5 cm) and peripheral ICCs were associated with a very low probability of lymph node metastasis.

Conclusions

Preoperatively diagnosed hilar invasion, multiple intrahepatic tumors and histologically confirmed lymph node metastasis were the main determinants of an adverse postoperative prognosis in patients with ICC. Lymph node dissection could be omitted for patients with solitary, small and peripheral ICCs.     

Serosal Invasion Strongly Associated With Recurrence After Curative Hepatic Resection of Hepatocellular Carcinoma: A Retrospective Study of 214 Consecutive Cases

The purpose of this study was to clarify the individual prognostic factors after curative and primary resection of hepatocellular carcinoma (HCC).Reliable prognostic factors and tumor staging for HCC have been required to predict an appropriate prognosis. However, in HCC, no staging system has received universal acceptance, and several tumor factors seem to relate to HCC prognosis, but they are not definitive. At present, few studies have mentioned the importance of serosal invasion as a prognostic factor.A retrospective search of our database identified 214 consecutive patients who underwent primary and curative hepatectomy for HCC at our department between January 1998 and December 2011. Risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed with Cox proportional hazard model, Kaplan-Meier method, and log-rank tests.Multivariate analyses showed that serosal invasion (hazard ratio [HR], 2.75; P = 0.0005) and vascular invasion (HR, 1.71; P = 0.0331) were independently correlated with RFS. Serosal invasion was significantly correlated with HCC recurrence (P = 0.0230). The Kaplan–Meier method and log-rank tests revealed that the patients with serosal invasion showed significantly worse prognosis both in RFS (P < 0.0001) and OS (P = 0.0016).Serosal invasion should be regarded as a strong independent predictor for recurrence in curatively resected HCC cases.     

Hepatitis C viral load predicts tumor recurrence after curative resection of hepatocellular carcinoma regardless of the genotype of hepatitis C virus

Purpose

To clarify the prognostic impact of the hepatitis C virus (HCV) genotype after curative resection for hepatocellular carcinoma (HCC).

Methods

A total of 199 patients who underwent a curative hepatic resection for HCV-related HCC were reviewed. The clinical outcomes were compared between patients infected with HCV genotype 1b (n = 160) and those infected with other genotypes (n = 39).

Results

With a comparable median HCV viral load (6.0 vs. 5.8 log₁₀ IU/mL, p = 0.17), the 3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5-year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log₁₀ IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL (HR, 1.64) were independent predictors of tumor recurrence, while the HCV genotype was not a significant risk factor. When the population was stratified according to the HCV viral load, a significant difference was observed in the RFS rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV viral load of 5.3 log₁₀ IU/mL.

Conclusions

The HCV genotype does not affect the surgical outcomes of patients with HCC. A lower HCV viral load is advantageous regardless of the HCV genotype.     

Multivariate statistical analysis of clinicopathologic factors influencing survival of patients with bile duct carcinoma

AIM：To evaluate the influence of various clinicopathologic factors on survival of patients with bile duct carcinoma after cuative resection.METHODS:A retrospective analysis was made for 86cases of bile duct carcinoma treated from January 1981to September1995,Fifteen clinicopathologic factors possibly influencing survival were selected.Independent variables were first analyzed by univariate methods.Survival for variable was estimated by the method of Kaplan and Meier.The variables that were statistically significant by univariate analysis were included in a multivariate analysis,which were confirmed using the Cox stepwise proportion hazard model with the help of SPSS10.0for Windows software.RESULTS:The overall cumulative survival rate was72.6%at 1year,32.4%at3years,and18.7%at5years,The results of univariate analysis showed that the major significant prognostic factors influencing survival of these patients were histological type of lesion.lymap node metastasis,pancreatic invasion.duodenal invasion,perineural invasion,macroscopic vessel involvement,resected surgical margin and depth of cancer invasion(P=0.02,0.02,0.004,0.005,0.01,0.43,0.03and0.04).Age,sex,location of tumor,size of tumor,macroscopic type of lesions,hepatic metastasis,and hepatic invasion were n ot significantly associated with prognosis(P&gt;0.05).Pancreatic invasion.perineural invasion and lymph node metastases were the three most imprtant prognostic factors by multivariate analysis using the Cox proortional hazards model.CONCLUSION;Pancreatic invasion.perineural invasion and lymph node metastases are the most important prognostic factors for bile duct carcinoma after curative resection.     

Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer

To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123–1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053–1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288–1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420–1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425–2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248–2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249–1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.     

Clinical outcomes of two-field lymphadenectomy for patients with clinical stage IA carcinoma of the thoracic esophagus

Background

The optimal treatment for early stage carcinoma of the thoracic esophagus is undecided and remains debatable. This report documents the results of a series of patients with clinical stage IA carcinoma of the thoracic esophagus treated at our institute with esophagectomy and two-field lymphadenectomy (2FL).

Methods

We analyzed 70 patients with clinical stage IA carcinoma who underwent radical esophagectomy with 2FL.

Results

The overall 5-year survival rate of the 70 patients was 81 %. Seventeen of the 70 patients (24 %) had lymph node metastasis. The overall 5-year survival rate of the 53 patients with no metastatic nodes (87 %) was significantly better than that of the 17 patients with positive nodes (65 %; p = 0.022). The operative morbidity was 44 %. Recurrence was recognized in 17 patients (24 %). The median disease-free interval (DFI) until recurrence was 20.5 months. With respect to the initial tumor recurrence, among the 16 patients with a recurrence, there were 9 with a cervical lymph node recurrence, 3 with a hematogenous recurrence, 2 with a combined recurrence, 1 with an abdominal lymph node recurrence in the paraaortic site, and 1 in the anastomotic site. The median DFI and survival times of the patients with a cervical lymph node recurrence were 26 and 55 months, respectively. Of the 9 patients with a cervical lymph node recurrence, 3 disease-free patients survived: 2 received surgery and 1 received radiotherapy.

Conclusions

Two-field lymphadenectomy might be enough for patients with clinical stage IA carcinoma of the middle and lower thoracic esophagus in regard to prognosis, but close follow-up for lymph node recurrence, especially at the cervical site, should be conducted.     

Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma

Background

Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC.

Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer

ObjectiveDNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC.Patients and MethodsPatients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed.Results130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48–9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04–3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13–5.48, p = 0.023) and high post-operative CA 19–9 level (>100 IU/ml) (HR:2.61 95% CI 1.40–4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53.ConclusionContrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.     

Local and systemic recurrence patterns of urothelial cancer after radical cystectomy

The aim of this study was to evaluate the local recurrence and distant metastasis rates for urothelial carcinoma of the bladder after radical cystectomy and to identify the predictive factors for local recurrence and distant metastasis. The study population was 347 consecutive patients treated with radical cystectomy for urothelial carcinoma of the bladder at our institution. Local recurrence, distant metastasis, and both local and distant recurrence rates were 49 (14.1%) months, 96 (27.7%) months, and 17 (4.9%) months, respectively. The mean follow-up times to recurrence were 14.37 ± 13.25 months (range, 2–60 months) and 14.43 ± 15.72 months (range, 2–109 months) for local recurrence and distant metastasis, respectively (p = 0.808). The mean post-recurrence disease-specific survival (PRDSS) times for local, distant, and both local and distant recurrences were 17.82 ± 3.18 months, 4.16 ± 0.39 months, and 11.41 ± 2.73 months, respectively (p < 0.001). The predictive factors for local recurrence and distant metastasis were stage and nodal involvement (p < 0.001). Sex, grade, lymphovascular invasion (LVI), carcinoma in situ (CIS), and lymph node density (LND; 10% cut-off value) were not predictors for recurrence in the results of the multivariate analysis. The current study demonstrated that stage and pathological nodal involvement were independent predictors of local recurrence and distant metastasis. The results of this study suggest that the early diagnosis and intervention of invasive bladder cancer cases may decrease the number of high stage and lymph node positive cases that have a high risk of local and distant recurrences. The adjuvant treatment options in the presence of risk factors for recurrence may improve survival outcomes.     

Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence

BackgroundMicroscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear.MethodsThirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival.ResultsVenous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion (P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival (P = 0.021).ConclusionsMicroscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.     

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma

Background/Objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).MethodsNinety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.ResultsThe low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19–9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.ConclusionsLow mitochondrial OGG1 expression might aggravate the PDAC prognosis.