Traian Dumitrascu

Posterior versus standard approach in pancreatoduodenectomy: a case-match study

Background and aimsPosterior approach pancreatoduodenectomy (paPD) technique is one of the many modifications of the standard Whipple procedure (sPD). The most important modification of the technique is first approach of the superior mesenteric artery, thus enabling a complete dissection of the right side of this artery and of the portal vein, as well as a complete excision of the retroportal pancreatic lamina. The present study is a case-match one, comparing the paPD to sPD.Materials and methodsThe present study includes two groups of patients. A first group of 21 patients with PD by posterior approach (group 1, reference group, paPD) and a second group including 21 matched patients with PD by standard approach (group 2, control group, sPD). Demographic characteristics (sex, age), intraoperative data (approach type, operative time, blood loss, intraoperative complications, need for vascular resections and type of reconstruction, type of resection upon remnant tissue), histological diagnosis and pathology data (tumor location, TNM staging, tumor grading, tumor vascular invasion), patient outcomes (postoperative length of stay, in-hospital postoperative mortality and morbidity, survival time) were analyzed in both groups of patients and compared.ResultsThere were no significant differences in the two groups regarding early morbidity and mortality rates, length of hospitalization, overall survival, and survival according to tumor type. However, it was noticed that there was a significant lesser mean blood loss in the pa PD group vs SPD group (P = 0.0314) and a shorter operative time in the paPD group vs sPD group (P = 0.0002).ConclusionThe paPD offers an early selection of patients during the operation (in terms of local resectability, by assessing the SMA infiltration), allows an optimal exposure of arterial abnormalities (a replaced right hepatic artery from the SMA), and better detection of venous invasion. In cases with PV/SMV invasion, paPD is particularly useful allowing a “no-touch” resection with no intraportal tumor dissemination and facilitates the vascular reconstruction. In addition, the operative bleeding and time are lower in the paPD group, probably due to early ligation of the inferior pancreaticoduodenal artery and reduced congestion of the pancreatic head.

An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

Objectives We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Results Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor &agr; (TNF-&agr;) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-&agr;, IL-1&bgr;, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1&bgr;, and TNF-&agr; correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-&agr; correlated with CEA levels. Circulating IL-8, TNF-&agr;, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. Conclusions The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

Curative-intent surgery for hilar cholangiocarcinoma: prognostic factors for clinical decision making

BackgroundThe surgical approach for hilar cholangiocarcinoma (HC) has largely evolved, and increased resectability rates are reported. Large series of patients with resections for HC were published in the last years, and potential predictors for survival were explored. However, the usefulness of these predictors in clinical decision making is controversial.PurposeThe aim of the present review is to explore the main prognostic factors after curative-intent surgery for HC, as emerged from the current literature. Furthermore, the impact of these predictors on clinical decision making is assessed.ConclusionAn aggressive surgical approach has improved the survival rates in patients with HC and implies bile duct resection associated with liver resection and loco-regional lymph node dissection. The AJCC staging system remains the main tool to assess the prognosis after resection of HC. Margin-negative resections and absence of lymph node metastases are the main prognostic factor after curative-intent surgery for HC. Response to chemotherapy is also a prognostic factor. Markers of systemic inflammatory response might predict prognosis of patients with HC, but their usefulness in clinical decision making remains unclear.

Central Pancreatectomy versus Spleen-Preserving Distal Pancreatectomy: A Comparative Analysis of Early and Late Postoperative Outcomes

Background/Aim: The aim of the present study is to compare the postoperative and long-term outcomes of central pancreatectomy (CP) and spleen-preserving distal pancreatectomy (SPDP). Methods: Clinical, pathological and long-term data were compared between 22 patients who underwent CP and 25 patients who underwent SPDP (2002–2012). Results: The median length of resected pancreas was 8.5 cm in the SPDP group and 5 cm in the CP group (p < 0.001). The median estimated blood loss was significantly lower in the CP group (p = 0.019). Morbidity was 50% for CPs and 40% for SPDPs (p = 0.564). The rate of pancreatic fistulae was 36% for CPs and 40% for SPDPs (p = 0.530). The rate of new-onset diabetes was nil in the successful CP group and 16% in the SPDP group (p = 0.111). Conclusion: Morbidity and pancreatic fistula rates are not higher after CP when compared to SPDP. The loss of normal pancreatic tissue is significantly lower for CP, and thus there is potentially better preservation of the pancreatic endocrine functions. CP should be considered only in selected cases when preservation of the pancreas is of utmost importance, especially for lesions situated at the level of the pancreatic neck.

Mutation spectrum of hepatocellular carcinoma from eastern-European patients betrays the impact of a complex exposome.

Genomic analysis of hepatocellular carcinoma (HCC) has been shown to provide clues about local risk factors. In the last decades, the mortality from malignant liver tumors increased sharply in Romania, where both hepatitis viruses and environmental pollutants are known to be highly prevalent. To date, HCC from this country has not been subject to molecular characterization. We analyzed a series of 48 consecutive HCC cases. Point mutations were searched in 9 nuclear genes and the mitochondrial D-loop. Oxidative stress response was monitored through measurement of gene expression (NRF2, KEAP1, SRXN1, and CES1) by qRT-PCR. An atypical mutation spectrum was observed, as more than 40% of DNA changes were oxidative stress-associated T>C or T>G lesions (T>S). These mutations affected primarily genes encoding for β-catenin and NRF2 (P<0.0001). Besides, tumors from patients born in Greater Bucharest carried TP53 mutations more frequently than others (45 vs 10%, P=0.02). Finally, a R249S mutation of TP53, well-known hallmark of aflatoxin B1 exposure, was found. Our findings indicate, therefore, that distinct mutagenic processes affect Romanian patients with HCC. Further analyses are now warranted in order to identify causal lifestyle or environmental factors.

Influence of hepatitis viruses on clinico-pathological profiles and long-term outcome in patients undergoing surgery for hepatocellular carcinoma

BACKGROUND The global risk of hepatocellular carcinoma (HCC) is largely due to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In recent years, however, an increased prevalence of non-viral HCC has been noted. The clinical impact of the presence/absence of viral infections in HCC remains controversial. The present study aimed to assess the effect of hepatitis viruses on demographics, clinical and pathological features and long-term outcome in a large cohort of Romanian patients who underwent surgery for HCC. METHODS The study included 404 patients with HCC who had undergone resection, transplantation or radiofrequency ablation at a single institution between 2001 and 2010. The patients were divided into four groups: 85 patients with hepatitis B virus infection (HBV group), 164 patients with hepatitis C virus infection (HCV group), 39 patients with hepatitis B and C virus co-infection (HBCV group), and 116 patients without viral infection (non-BC group). RESULTS The patients of both HBV (56.0+/-11.3 years) and HBCV groups (56.0+/-9.9 years) were significantly younger than those of the HCV (61.0+/-8.5 years, P=0.001) and non-BC groups (61.0+/-13.0 years, P=0.002). Interestingly, the prevalence of liver cirrhosis was significantly lower in the non-BC group (47%) than in any other subsets (72%-90%, P<0.002). Furthermore, the non-BC patients were more advanced according to the Barcelona Clinic Liver Cancer stages than the patients of the HCV or HBCV groups (P<0.020); accordingly, they were more frequently assessed beyond the Milan criteria than any other groups (P=0.001). No significant differences in the disease-free or overall survival rates were observed among these groups. CONCLUSIONS Patients with non-viral HCC are diagnosed at advanced ages and stages, a situation plausibly due to the poor effectiveness of cancer surveillance in community practice. The presence of viral infections does not appear to impair the long-term prognosis after surgical treatment in patients with HCC; however, there is a trend for worse disease-free survival rates in HBCV patients, though statistical significance was not reached.

Central pancreatectomy for pancreatoblastoma in a 16-year-old girl

Long-term functional results after standard pancreatic resections are a major concern, especially in children. An alternative pancreas-sparing procedure (such as central pancreatectomy) should be taken into consideration whenever it is feasible, and a prolonged survival is expected. Pancreatoblastoma is an unusual malignant tumor in childhood. However, in initially resectable tumors, the 15-year survival is more than 80%. Thus, there is a potential role of a conservative pancreatic resection in successful treatment of pancreatoblastoma. The management in a case of a 16-year-old girl with a pancreatoblastoma in the body of pancreas is presented. Complete surgical resection by central pancreatectomy followed by chemotherapy led to a prolonged disease-free survival, with good functional results. Central pancreatectomy could be an alternative surgical technique in some selected cases of pancreatoblastoma, having the lowest incidence of postoperative exocrine and endocrine insufficiency rate and offering the best nutritional status.

Major hepatectomies for perihilar cholangiocarcinoma: Predictors for clinically relevant postoperative complications using the International Study Group of Liver Surgery definitions

BACKGROUND/AIM Major hepatectomies are widely used in curative-intent surgery for perihilar cholangiocarcinoma, but morbidity rates are high. The aim of the study is to explore potential predictors for clinically relevant complications after major hepatectomies for perihilar cholangiocarcinoma. METHODS Seventy patients were included. Univariate and multivariate analyses were performed for risk factors of morbidities using the International Study Group of Liver Surgery definitions. RESULTS Severe morbidity rate was 36.5%. Clinically relevant posthepatectomy liver failure, bile leak, and hemorrhage rates were 24%, 22%, and 8.5%, respectively. A neutrophil-to-lymphocyte ratio > 3.3 is an independent prognostic factor for severe complications (hazard ratio = 1.258; 95% confidence interval 1.008-1.570; p = 0.042) while the number of blood units > 3 is an independent prognostic factor for clinically relevant liver failure (hazard ratio = 1.254; 95% confidence interval 1.082-1.452; p = 0.003). Biliary drainage and portal vein resection were not statistically correlated with any postoperative complication (p ≥ 0.101). Significantly higher bilirubinemia levels were observed in patients with postoperative hemorrhage (p = 0.023). CONCLUSION Clinically relevant morbidity rates after major hepatectomies for perihilar cholangiocarcinoma are high. Liver failure represents the main complication and is correlated with the number of transfused blood units. A patient with increased bilirubinemia appears to have a high risk for postoperative hemorrhage. Biliary drainage and portal vein resection does not appear to have a detrimental effect on morbidities. Neutrophil-to-lymphocyte ratio is a novel independent predictor for severe morbidity after major hepatectomies for perihilar cholangiocarcinoma and may contribute to better and informed decision-making.

Clinical value of spleen‐preserving distal pancreatectomy: a case‐matched analysis with a special emphasis on the postoperative systemic inflammatory response

The impact of splenectomy on outcomes after distal pancreatectomy was assessed in the present study, with a special emphasis on the postoperative systemic inflammatory response.

Curative-intent Surgery for Perihilar Cholangiocarcinoma with and without Portal Vein Resection - A Comparative Analysis of Early and Late Outcomes

Introduction: The safety of portal vein resection (PVR) during surgery for perihilar cholangiocarcinoma (PHC) has been demonstrated in Asia, America, and Western Europe. However, no data about this topic are reported from Eastern Europe. The aim of the present study is to comparatively assess the early and long-term outcomes after resection for PHC with and without PVR. PATIENTS AND METHODS The data of 21 patients with PVR were compared with those of 102 patients with a curative-intent surgery for PHC without PVR. The appropriate statistical tests were used to compare different variables between the groups. Results: A PVR was performed in 17% of the patients. In the PVR group, significantly more right trisectionectomies (p=0.031) and caudate lobectomies (0.049) were performed and, as expected, both the operative time (p=0.015) and blood loss (p=0.002) were significantly higher. No differences between the groups were observed regarding the severe postoperative morbidity and mortality rates, and completion of adjuvant therapy. However, in the PVR group the postoperative clinicallyrelevant liver failure rate was significantly higher (p=0.001). No differences between the groups were observed for the median overall survival times (34 vs. 26 months, p = 0.566). A histological proof of the venous tumor invasion was observed in 52% of the patients with a PVR and was associated with significantly worse survival (p=0.027). CONCLUSION A PVR can be safely performed during resection for PHC, without significant added severe morbidity or mortality rates. However, clinically-relevant liver failure rates are significantly higher when a PVR is performed. Furthermore, increased operative times and blood loss should be expected when a PVR is performed. Histological tumor invasion of the portal vein is associated with significantly worse survival.