Paweł Lampe

Hepaticojejunostomy vs. End-to-end Biliary Reconstructions in the Treatment of Iatrogenic Bile Duct Injuries

BackgroundRetrospective comparison of short- and long-term results and quality of life in patients treated for iatrogenic bile duct injuries (IBDI) with Roux-Y hepaticojejunostomy (HJ) or end-to-end ductal anastomosis (EE).MethodsBetween January 1990 and March 2005, 94 patients underwent reconstructive surgery for IBDI: 49, Roux-Y HJ, and 45, EE.ResultsEarly postoperative complications were observed in 12 (24.5%) patients undergoing HJ and three (6.7%) undergoing EE (p = 0.0239). Reoperations in the early postoperative period were performed in four (8%) patients after HJ and in zero patients after EE. Following HJ, one (2%) hospital death occurred due to acute circulatory insufficiency. Long-term results were evaluated in 69 (72%) patients. Postoperative mean weight gain was significantly higher after EE than HJ (p = 0.0191). Recurrent stricture was observed in two (5.3%) patients after HJ and three (9.6%) after EE (p = 0.6509). Terblanche long-term results were comparable in both groups (p = 0.3173). Good Karnofsky quality of life was comparable in both groups (p = 0.8377).ConclusionsMore early complications occurred after HJ than after EE. Long-term results were comparable after both reconstructive methods. After EE, patients achieved a higher weight gain than after HJ. Quality of life in both groups was comparable.

NBL1 and anillin (ANLN) genes over-expression in pancreatic carcinoma

The aim of the study was to analyze the gene expression profile of pancreatic cancer to derive novel molecular markers of this malignancy. The snap-frozen or RNA-later preserved samples of 18 pancreatic adenocarcinomas, 5 chronic pancreatitis cases and 6 specimens of grossly normal pancreas were used for microarray analysis by HG-U133 Plus 2.0 oligonucleotide Affymetrix arrays. Validation was carried out by real-time quantitative PCR (Q-PCR) in the set of 66 samples: 31 of pancreatic cancer, 14 of chronic pancreatitis and 21 of macroscopically unchanged pancreas. By Principal Component Analysis of the microarray data we found a very consistent expression pattern of normal samples and a less homogenous one in chronic pancreatitis. By supervised comparison (corrected p-value 0.001) we observed 11094 probesets differentiating between cancer and normal samples, while only seventy six probesets were significant for difference between cancer and chronic pancreatitis. The only gene occurring within the best 10 genes in both comparisons was S100 calcium binding protein P (S100P), already indicated for its utility as pancreatic cancer marker by earlier microarray-based studies. For validation we selected two genes which appeared as valuable candidates for molecular markers of pancreatic cancer: neuroblastoma, suppression of tumorigenicity 1 (NBL1) and anillin (ANLN). By Q-PCR, we confirmed statistically significant differences in these genes with a 9.5 fold-change difference between NBL1 expression in cancer/normal comparison and a relatively modest difference between cancer and pancreatitis. For ANLN even more distinct differences were observed (cancer/normal 19.8-fold, cancer/pancreatitis 4.0-fold). NBL1 and anillin are promising markers for pancreatic carcinoma molecular diagnostics.

Intraductal oncocytic papillary neoplasms of the pancreas and bile ducts: a description of five new cases and review based on a systematic survey of the literature

BackgroundIntraductal oncocytic papillary neoplasms (IOPN) are rare tumors of the pancreatic and biliary ductal system. It is not absolutely clear if the molecular and clinicopathologic characteristics of IOPN differ significantly from other related lesions, namely intraductal papillary mucinous neoplasms (IPMN). Therefore it is not clear if it is reasonable to consider IOPN as a separate diagnostic and clinical entity.MethodsIn order to describe the clinicopathologic characteristics of IOPN and to compare them with the IPMN profile, we performed a systematic review of the literature and additionally studied five previously unreported IOPN cases.ResultsIOPN differ from IPMN by lack of K-ras gene mutations in all studied cases. Several differences in the clinical and biological profile between IOPN and IPMN exist, but they are of quantitative rather than of qualitative nature. Additionally, pancreaticobiliary or gastric-foveolar IPMN components may coexist with IOPN component within a single lesion, which suggests at least a partial relation of the pathogenetic pathways of IPMN and IOPN. Importantly, the pathogenesis of accumulation of mitochondria and oxyphilic appearance of IOPN remains unknown.ConclusionsAt present, there are no reliable criteria other than histopathological picture and K-ras gene status to differentiate IOPN from IPMN. In particular, no clear differences in optimal treatment options and prognosis between these tumors are known. Further studies are needed to clarify the biology of IOPN and to establish their position in clinicopathologic classifications of pancreatic tumors.

Neuroendocrine neoplasms of the small intestine and the appendix — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.

Discrepancies between two alternative staging systems (European Neuroendocrine Tumor Society 2006 and American Joint Committee on Cancer/Union for International Cancer Control 2010) of neuroendocrine neoplasms of the pancreas. A study of 50 cases

The aim of our study was to identify and describe potential inconsistencies between two alternative staging systems of pancreatic neuroendocrine neoplasms (pNENs)--the European Neuroendocrine Tumor Society (ENETS) system (2006) and the American Joint Committee on Cancer/Union for International Cancer Control (AJCC-UICC) system (2010). To address this issue, we performed a retrospective clinico-pathological study of 50 cases of pNENs. We found 9 (18%) cases of ENETS/AJCC-UICC discrepancies regarding the primary tumor stage. They included 7 cases of T2/T3 disagreement and 2 cases of T3/T4 disagreement. In addition, we discussed the issue of potential T1/T2 discrepancy (however, we did not observe any such a case). Another inconsistency was related to the application of different stage prognostic groupings between both systems. In conclusion, the discrepancies between ENETS and AJCC-UICC staging systems for pNENs are relatively frequent and heterogeneous. We believe that they should be rigorously recognized. This is necessary for the evaluation of prognostic factors and the effectiveness of therapeutic options used in patients with pNENs.

Clinical Value of Serum Neopterin, Tissue Polypeptide-Specific Antigen and CA19-9 Levels in Differential Diagnosis between Pancreatic Cancer and Chronic Pancreatitis

Background: Neopterin and tissue polypeptide-specific antigen (TPS) have been suggested to be useful in differential diagnosis between pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The aim of our study was to compare the clinical usefulness of CA19-9, neopterin and TPS serum levels in patients with PA and CP. Methods: The study included 85 patients with PA, 72 with CP and 50 healthy controls. The serum concentrations of neopterin, TPS and CA19-9 were measured (DRG International, USA). The associations of the analyzed markers and clinical data at diagnosis have been evaluated. Results: Serum levels of neopterin, TPS and CA19-9 were higher in PA patients compared to CP (p < 0.001). TPS and CA19-9 levels were also elevated in patients with CP compared to the control group (p < 0.001). In contrast, there was no difference between neopterin serum levels in CP patients and the control group (p > 0.05). Neopterin showed the best sensitivity and specificity (91.8 and 87.5%) in PA diagnosis compared to CA19-9 (respectively 83.5 and 75%) and TPS (75.3 and 65.3%). Conclusion: Our results indicate that neopterin may be potentially useful in differential diagnosis between PA and CP. Assessment of TPS probably adds no significant information to that obtained with CA19-9 and neopterin.

Different approaches to assessment of lymph nodes and surgical margin status in patients with ductal adenocarcinoma of the pancreas treated with pancreaticoduodenectomy.

Aim: To develop a method of gross examination of pancreaticoduodenectomy specimens with pancreatic ductal adenocarcinoma, allowing adequate assessment of the entire pancreatic surface as a surgical margin, which would not affect the lymph node yield. Methods: We retrospectively compared the R1 rates (i.e., proportions of patients with microscopic residual tumour at surgical margins) and lymph node yield in a series of 67 consecutive cases of pT3 ductal adenocarcinomas diagnosed in pancreaticoduodenectomy specimens during three different periods of time and sampled using three different approaches: (1) period 2006–2007, when the pancreatic surface (except for the transection margin and superior mesenteric artery margin) was not examined; (2) period January–September 2008, when the posterior pancreatic surface (posterior circumferential radial margin) was examined using an improved method based on sampling of 2.0–2.5 mm thick consecutive slices perpendicular to the duodenal axis; and (3) period October 2008 – June 2009, when the whole surface of the pancreatic head was sampled using the approach mentioned above. Results: The R1 rates in three consecutive time periods were 23.5%, 40% and 53.8%, respectively. Median numbers of retrieved peripancreatic lymph nodes were 11.0, 12.0 and 14.0, respectively. Conclusions: The newly proposed approach allowed adequate assessment of the entire pancreatic head surface as a surgical margin and reduced the risk of under‐detection of R1 status. Moreover, this approach did not affect the number of peripancreatic lymph nodes examined.

Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours)

An increased interest in gastro-entero-pancreatic neuroendocrine neoplasms (GEP NENs) has recently been observed. These are rare neoplasms and their detection in recent years has improved. Over 50% of GEP NENs are carcinoids, and they are usually found incidentally during surgery in the small intestine and appendix and at diagnosis in distant metastases, mainly to the liver. There is a need for co-operation between specialists in various disciplines of medicine in order to work out the diagnostic and therapeutic guidelines. In this publication, we present general recommendations of the Polish Network of Neuroendocrine Tumours for the management of patients with GEP NENs, developed at the Consensus Conference which took place in Kamień Śląski in April 2013. Members of the guidelines working groups were assigned sections of the 2008 guidance to update. In the subsequent parts of this publication, we present the rules of diagnostic and therapeutic management of: - neuroendocrine neoplasms of the stomach and duodenum (including gastrinoma); - pancreatic neuroendocrine neoplasms; - neuroendocrine neoplasms of the small intestine and the appendix; - colorectal neuroendocrine neoplasms. The proposed recommendations by Polish and foreign experts representing different fields of medicine (endocrinology, gastroenterology, surgery, oncology, nuclear medicine and pathology) will be helpful in the diagnosis and treatment of GEP NENs patients.

Utility of serum IgG, IgG4 and carbonic anhydrase II antibodies in distinguishing autoimmune pancreatitis from pancreatic cancer and chronic pancreatitis.

PURPOSE Autoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. The aim of our study was to compare IgG, IgG4 and anti-CAIIAb serum levels in patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) and to assess their clinical significance and utility in differential diagnosis of pancreatic diseases. PATIENT/METHODS The study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. Peripheral venous blood samples were obtained from all analyzed patients at the time of hospital admission and total IgG, IgG4 and anti-CAIIAB serum levels were measured using ELISA tests. RESULTS Serum levels of IgG, IgG4 and anti-CAIIAb were significantly higher in patients with AIP compared to PA and CP patients (p<0.001). In AIP patients the median IgG levels were 19.7 g/l, IgG4 levels - 301.9 mg/dl and anti-CAIIAb - 81.82 ng/ml, compared to 10.61 g/l, 123.2mg/dl and 28.6 ng/ml, respectively, in PA patients. IgG4 for the cut-off 210 mg/dl showed the best sensitivity and specificity (83.8% and 89.5%) in AIP diagnosis compared to IgG (69.3% and 87.3%, respectively) and anti-CAIIAb (45.3% and 74.3%). However, 16 (35.5%) patients with PA and 14 (25.4%) patients with CP had IgG4 levels greater than 140 mg/dl. Moreover, in 3 (6.67%) patients with pancreatic cancer those values were greater than 280 mg/dl. No patients with CP had IgG4 more than 280 mg/dl. CONCLUSIONS IgG4 at cut-off 210 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and anti-CAIIAb, however elevations of serum IgG4 may be seen in subjects without AIP, including pancreatic cancer.

Pancreatic neuroendocrine neoplasms — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised diagnostic and therapeutic guidelines for the management of pancreatic neuroendocrine neoplasms (PNENs) proposed by the Polish Network of Neuroendocrine Tumours.These guidelines refer to biochemical (determination of specific and nonspecific neuroendocrine markers) and imaging diagnostics (EUS, CT, MR, and radioisotope examination with a 68Ga or 99Tc labelled somatostatin analogue).A histopathological diagnostic, which determines the further management of patients with PNENs, must be necessarily confirmed by immunohistochemical tests. PNENs therapy requires collaboration between a multidisciplinary team of specialists experienced in the management of these neoplasms. Surgery is the basic form of treatment. Medical therapy requires a multidirectional procedure, and therefore the rules of biotherapy, peptide receptor radionuclide therapy, chemotherapy and molecular targeted therapy are discussed.