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Biomedical subjects

C Pasquali

Publications and source records attributed to C Pasquali.

At least 19 recordsLinked to original sources

RASSF1A promoter methylation and 3p21.3 loss of heterozygosity are features of foregut, but not midgut and hindgut, malignant endocrine tumours.

The Ras-association domain family 1A (RASSF1A) tumour suppressor gene is inactivated in a variety of solid tumours, usually by epigenetic silencing of the promoter and/or allelic loss of its locus at 3p21.3. RASSF1A induces cell cycle arrest through inhibition of cyclin D1 accumulation. In this work, 62 endocrine tumours from different sites in the gut were investigated for methylation of the RASSF1A promoter using the polymerase chain reaction, the presence of 3p21.3 deletions by loss of heterozygosity analysis, and cyclin D1 expression by immunohistochemistry. Methylation was found in 20/62 (32%) cases and was restricted to foregut tumours; deletion at 3p21.3 was found in 15/58 (26%) informative cases and restricted to malignant foregut tumours; cyclin D1 hyper-expression was found in 31/58 (53%) cases and correlated with RASSF1A methylation. Our data suggest that RASSF1A is involved in the development of endocrine tumours derived from the foregut only, and that the presence of both RASSF1A methylation and 3p21.3 deletion is associated with malignancy. These results may provide a rationale for foregut-targeted therapy for aggressive endocrine carcinomas entailing the use of demethylating agents.

Adult↗

Extent of lymphadenectomy in the resection of pancreatic cancer. Analysis of the existing evidence.

Pancreaticoduodenectomy is considered the standard procedure for the surgical treatment of the pancreatic head cancer. However, the extent of lymph node clearance associated to the procedure is still largely debated. Arguments in favour of an extended lymphadenectomy are the regular progression of lymph node invasion, without skip metastases, and the removal of the extrapancreatic neural plexus that is invaded in 52-72% of patients. Arguments against the extended lymphadenectomy are the failure of extended lymphadenectomy to improve survival in other cancers, and the severe diarrhoea that follows the skeletonisation of the superior mesenteric artery. After Ishikawa's paper, several retrospective studies supported a longer survival after an extended than after a standard lymphadenectomy, but as much retrospective studies failed to demonstrate any difference. Only three prospective randomised controlled trials have been performed so far. Unfortunately all are underpowered, and the substantial differences in the surgical procedures, in the adjuvant treatment, and in the length of follow-up make the comparison impossible. Only one study reports a significantly longer survival for lymph node positive patients who underwent an extended lymphadenectomy, but adjuvant treatment was not performed. Furthermore, the difference was of minimal clinical impact. At least two adequately powered prospective Randomised Controlled Trials including a true extended lymphadenectomy, and a standardised adjuvant treatment, would be required to answer the question. Unfortunately, we have not yet a standardised adjuvant (or neoadjuvant) treatment, and we do not know the impact of such treatment on the expected statistical difference in the survival after a standard or extended lymphadenectomy. The lot of work required to perform such trials probably doesn't worth the expected results.

Humans↗

Acetyl-L-carnitine shows neuroprotective and neurotrophic activity in primary culture of rat embryo motoneurons.

We evaluated the role of acetyl-L-carnitine (ALCAR) in protecting primary motoneuron cultures exposed to excitotoxic agents or serum-brain derived neurotrophic factor (BDNF) deprived. To exclude that ALCAR works as a metabolic source, we compared its effects with those of L-carnitine (L-CAR), that seems to have no neurotrophic effect. A concentration of 10 mM ALCAR, but not L-CAR, significantly reduced the toxic effect of 50 microM N-methyl-D-aspartate (NMDA, % viability: NMDA 45.4+/-2.80, NMDA+ALCAR 90.8+/-11.8; P<0.01) and of 5 microM kainate in cultured motoneurons (% viability: kainate 40.66+/-10.73; kainate+ALCAR 63.80+/-13.88; P<0.05). The effect was due to a shift to the right of the dose-response curve for kainate (EC50 for kainate 5.99+/-1.012 microM; kainate+ALCAR 8.62+/-1.13 microM; P<0.05). ALCAR, but not L-CAR, significantly protected against BDNF and serum-deprivation reducing the apoptotic cell death (% viability respect to control: without BDNF/serum 61.8+/-13.3: without BDNF/serum+ALCAR 111.8+/-13.9; P<0.01). Immunocytochemistry showed an increase in choline acethyltransferase and tyrosine kinaseB receptors in motoneurons treated with ALCAR but not with L-CAR. These results suggest that ALCAR treatment improves the motoneurons activity, acting as a neurotrophic factor.

Acetylcarnitine↗

Epidemiology of pancreatic cancer in Northeastern Italy: incidence, resectability rate, hospital stay, costs and survival (1990-1992).

BACKGROUND: The incidence of pancreatic cancer and relative hospital stay and costs are not well known. AIMS: To define the incidence, hospital stay and cost of pancreatic cancer in a well-defined area of Italy. PATIENTS AND METHODS: Each new case of pancreatic cancer diagnosed between 1990 and 1992 among 669,703 inhabitants in the Veneto Region of Northern Italy was recorded and followed until death or for 5 years after diagnosis. Four types of hospital stay were defined. Type 1: undiagnosed pancreatic cancer; type 2: first diagnosis of pancreatic cancer, treatment excluded; type 3: main treatment; and type 4: follow-up and disease-related complications. Data were analysed for hospital stay-related procedures, costs and survival. RESULTS: Pancreatic cancer was diagnosed in 253 patients (12.6/100,000 per year), 43 patients (17.7%) underwent surgical resection, and 93 (36.8%) palliative surgery. The mean duration of type 3 hospital stay was similar for resection, palliative and exploratory surgery. The estimated hospital cost was significantly higher for surgical resection, almost the same for palliative and exploratory surgery, and only slightly lower for medical treatment. Each patient spent a mean of 57.7 days in the hospital. The hospital mortality rate was 4.6% for surgical resection, 22.1% for palliative surgery, and 18.7% for exploratory laparotomy. Overall, the 1-, 2-, 3- and 5-year survival rates were 20.9%, 5.1%, 2.9% and 1.2%, respectively. CONCLUSIONS: Pancreatic cancer is an expensive, almost incurable disease. Integrated treatments in specialized Centres should reduce the mortality rate and costs.

Costs and Cost Analysis↗

Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress.

Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1--10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

Animals↗

p27: a potential main inhibitor of cell proliferation in digestive endocrine tumors but not a marker of benign behavior.

The immunohistochemical expression of the inhibitors of cyclin-dependent kinases p21 and p27 was investigated in 109 endocrine tumors of the pancreas and gastrointestinal tract and compared with that of Ki67 and p53. p21 was found to be scarcely expressed without significant differences between benign and malignant or between differentiated and undifferentiated tumors. This suggests no relationship between changes in p21 levels and clinical behavior in these endocrine tumors. p27 was found to be highly expressed in differentiated neoplasms and proved to be inversely related to Ki67 labeling (P =.02), which was usually low. These data indicate that p27 may have an important inhibiting role on the low proliferation rate of the tumors. Moreover, the protein may have a role in the resistance of differentiated endocrine tumors to chemotherapeutic agents. p27 high-expressor neoplasms were frequent in either benign (70.6%) or malignant (81.4%) differentiated tumors, thus not allowing the use of this protein for the differential diagnosis of malignant neoplasms as suggested for endocrine tumors of parathyroid and pituitary. Poorly differentiated endocrine carcinomas, which differred from the differentiated tumors for their very high Ki67 levels and frequent p53 expression, showed low or absent p21 and p27 in most cases. Classical midgut carcinoids were characterized by a sharp discrepancy between malignant behavior and very bland proliferative pattern, with Ki67 and p27 expressions similar to that of benign tumors.

Adenoma, Islet Cell↗

Value of 18-fluorodeoxyglucose positron emission tomography in the management of patients with cystic tumors of the pancreas.

OBJECTIVE: To assess the reliability of 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) in distinguishing benign from malignant cystic lesions of the pancreas. SUMMARY BACKGROUND DATA: The preoperative differential diagnosis of cystic lesions of the pancreas remains difficult: the most important point is to identify malignant or premalignant cysts that require resection. 18-FDG PET is a new imaging procedure based on the increased glucose metabolism by tumor cells and has been proposed for the diagnosis and staging of pancreatic cancer. METHODS: During a 4-year period, 56 patients with a suspected cystic tumor of the pancreas underwent 18-FDG PET in addition to computed tomography scanning, serum CA 19-9 assay, and in some instances magnetic resonance imaging or endoscopic retrograde cholangiopancreatography. The 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value. The accuracy of 18-FDG PET and computed tomography was determined for preoperative diagnosis of a malignant cyst. RESULTS: Seventeen patients had malignant tumors. Sixteen patients (94%) showed 18-FDG uptake with a standard uptake value of 2.6 to 12.0. Twelve patients (70%) were correctly identified as having malignancy by computed tomography, CA 19-9 assay, or both. Thirty-nine patients had benign tumors: only one mucinous cystadenoma showed increased 18-FDG uptake (standard uptake value 2.6). Five patients with benign cysts showed computed tomography findings of malignancy. Sensitivity, specificity, and positive and negative predictive values for 18-FDG PET and computed tomography scanning in detecting malignant tumors were 94%, 97%, 94%, and 97% and 65%, 87%, 69%, and 85%, respectively. CONCLUSIONS: 18-FDG PET is more accurate than computed tomography in identifying malignant pancreatic cystic lesions and should be used, in combination with computed tomography and tumor markers assay, in the preoperative evaluation of patients with pancreatic cystic lesions. A positive result on 18-FDG PET strongly suggests malignancy and, therefore, a need for resection; a negative result shows a benign tumor that may be treated with limited resection or, in selected high-risk patients, with biopsy, follow-up, or both.

Adult↗

Pancreatic head resection for noninflammatory benign lesions of the head of the pancreas.

INTRODUCTION: Duodenum-preserving pancreatic head resection (DPPHR) has been safely performed in patients with chronic pancreatitis. The procedure has rarely been used to remove benign or borderline lesions of the head of the pancreas. AIMS: To review our experience with 13 patients who underwent DPPHR and to review reports in the literature on the same subject. METHODOLOGY: From October 1991 to September 2000, 13 patients underwent DPPHR to resect endocrine pancreatic tumors (n = 4), beta cell hyperplasia (n = 1), pancreatic pseudocysts (n = 2), serous cystadenomas (n = 3), congenital (n = 1) and choledochal (n = 1) cysts, and intraductal papillary mucinous tumor (n = 1). The Kocher maneuver was performed in seven patients (group 1) and avoided in six (group 2). Type 1, 2, and 3 DPPHR were defined depending on the amount of pancreatic tissue left at the inner surface of the duodenum. Ten patients underwent evaluation that included an oral glucose tolerance test and exocrine pancreatic function test. RESULTS: The mortality rate was zero; the complication rate was 69%. Patients in whom the Kocher maneuver was not performed (group 2) experienced fewer complications, shorter stay on nasogastric tube and abdominal drain(s), and earlier water intake and discharge. Type of DPPHR did not influence the postoperative course. One patient died 3 months after surgery of unrelated disease. Twelve patients were alive and well 2 months to 8 years after surgery. CONCLUSION: DPPHR is a low-risk procedure in patients with benign or borderline noninflammatory lesions of the head of the pancreas in whom pylorus-preserving pancreaticoduodenectomy is otherwise indicated. Whenever possible, the Kocher maneuver should be avoided.

Adult↗

Multiple endocrine neoplasia type 1 and adrenal lesions.

PURPOSE: We investigated the relationship of long-term pancreatic hormone hypersecretion with adrenal lesions in patients with multiple endocrine neoplasia type 1 and in those with sporadic pancreatic endocrine tumors. MATERIALS AND METHODS: We assessed the prevalence of adrenal lesions in 20 patients with multiple endocrine neoplasia type 1 and in a control group of 12 with sporadic pancreatic endocrine tumors. We also performed genetic testing for germline mutations of MEN1, the multiple endocrine neoplasia type 1 gene. RESULTS: Adrenal lesions were common in multiple endocrine neoplasia type 1, accounting for 35% of cases. All adrenal lesions were nonfunctioning and benign. The relative risk of adrenal tumors was higher in patients with multiple endocrine neoplasia type 1 than in controls (p <0.05). No apparent relationship was observed of hormonal pattern or genotype with adrenal disease. CONCLUSIONS: Hormone hypersecretion by pancreatic endocrine tumors is not the primary cause of the development of adrenal lesions and the role of the MEN1 gene in adrenal tumorigenesis remains unclear. Adrenal lesions follow a benign course in most multiple endocrine neoplasia type 1 cases but careful morphological and functional followup is advisable.

Adolescent↗

Analysis of glycosyl phosphatidylinositol-anchored proteins by two-dimensional gel electrophoresis.

The aim of this study was to characterize mammalian glycosyl phosphatidylinositol (GPI)-anchored proteins y two-dimensional gel electrophoresis using immobilized pH gradients. Analysis was performed on detergent-resistant membrane fractions of baby hamster kidney (BHK) cells, since such fractions have previously been shown to be highly enriched in GPI-anchored proteins. Although the GPI-anchored proteins were readily separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), these proteins were undetectable on two-dimensional (2-D) gels, even though these gels unambiguously revealed high enrichment of known hydrophobic proteins of detergent-resistant membranes such as caveolin-1 and flotillin-1 (identified by Western blotting and tandem mass spectrometry, respectively). Proper separation of GPI-anchored proteins required cleavage of the lipid tail with phosphatidylinositol-specific phospholipase C, presumably to avoid interference of the hydrophobic phospholipid moiety of GPI-anchors during isoelectric focusing. Using this strategy, BHK cells were observed to contain at least six GPI-anchored proteins. Each protein was also present as multiple isoforms with different isoelectric points and apparent molecular weights, consistent with extensive but differential N-glycosylation. Pretreatment with N-glycosidase F indeed caused the different isoforms of each protein to collapse into a single spot. In addition, quantitative removal of N-linked sugars greatly facilitated the detection of heavily glycosylated proteins and enabled sequencing by nanoelectrospray-tandem mass spectrometry as illustrated for the GPI-anchored protein, Thy-1.

Amino Acid Sequence↗

Mapping and identification of protein-protein interactions by two-dimensional far-Western immunoblotting.

Studies of protein-protein interactions have proved to be a useful approach to link proteins of unknown function to known cellular processes. In this study we have combined several existing methods to attempt the comprehensive identification of substrates for poorly characterized human protein tyrosine phosphatases (PTPs). We took advantage of so-called "substrate trapping" mutants, a procedure originally described by Flint et al. (Proc. Natl. Acad. Sci. USA 1997, 94, 1680-1685) to identify binding partners of cloned PTPs. This procedure was adapted to a proteome-wide approach to probe for candidate substrates in cellular extracts that were separated by two-dimensional (2-D) gel electrophoresis and blotted onto membranes. Protein-protein interactions were revealed by far-Western immunoblotting and positive binding proteins were subsequently identified from silver-stained gels using tandem mass spectrometry. With this method we were able to identify possible substrates for PTPs without using any radio-labeled cDNA or protein probes and showed that they corresponded to tyrosine phosphorylated proteins. We believe that this method could be generally applied to identify possible protein-protein interactions.

Adenocarcinoma↗

ME-PCR for the identification of mutated K-ras in serum and bile of pancreatic cancer patients: an unsatisfactory technique for clinical applications.

Our aim was to assess the clinical reliability of mutated K-ras detection in serum or bile for the diagnosis of pancreatic cancer using ME-PCR. DNA was extracted from 1 ml serum obtained from 29 patients with pancreatic cancer and 12 control subjects. ME-PCR was optimized using a mixture of normal DNA added with different amounts of mutated DNA. The analysis of sera obtained from the 29 patients and of bile obtained from 11 pancreatic cancer patients demonstrated the presence of mutated K-ras in two (6.9%) and four cases (36%). By contrast K-ras was not amplifiable in any of the 12 serum samples obtained from healthy controls. In conclusion the DNA obtained from pancreatic cancer patients' sera is suitable for K-ras amplification and for the identification of codon 12 point mutations. However ME-PCR alone has an unsatisfactory sensitivity for the detection of pancreatic cancer using serum DNA as starting template.

Adult↗

Median pancreatectomy for tumors of the neck and body of the pancreas.

BACKGROUND: When enucleation is too risky because of possible damage of the main pancreatic duct, benign tumors located in the neck or body of the pancreas are usually removed by a left (spleno)-pancreatectomy or by a pancreatoduodenectomy. But standard pancreatic resection results in an important loss of normal pancreatic parenchyma and may cause impairment of exocrine and endocrine function. The aim of this study was to evaluate early and longterm results of median pancreatectomy, a limited resection of the midportion of the pancreas, in selected patients with benign or borderline tumors of the pancreas. STUDY DESIGN: Records of patients at Ospedale Busonera between November 1985 and September 1998 were reviewed. Ten patients with tumors of the neck or body of the pancreas underwent median pancreatectomy; the cephalic stump was sutured and the distal stump was anastomosed with a Roux-en-Y jejunal loop. Followup included clinical evaluation and routine laboratory tests: abdominal ultrasonography, exocrine and endocrine pancreatic function with fecal chymotrypsin, and an oral glucose tolerance test. RESULTS: Pathologic examination showed: insulinoma (n = 3), mucinous cystadenoma (n = 3), nonfunctioning endocrine tumor (n = 1), papillary-cystic neoplasm (n= 1), serous cystadenoma (n = 1), and intraductal mucinous tumor (n = 1). Operative mortality and morbidity were 0% and 40%, respectively; pancreatic fistula occurred in three patients. At mean followup of 62.7 months, no recurrence was found and no patient had exocrine insufficiency or glucose metabolism impairment. CONCLUSIONS: Median pancreatectomy is a safe and effective alternative to major pancreatic resection in selected patients with benign or low-malignant lesions of the pancreas. This procedure carries a surgical risk similar to that of the standard operation, but avoids extensive pancreatic resection and pancreatic function impairment.

Adolescent↗

Macrocystic serous cystadenoma of the pancreas: clinicopathologic features in seven cases.

BACKGROUND: Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. METHODS: Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. RESULTS: Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. CONCLUSION: When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.

Adult↗

Identification of syntenin as a protein of the apical early endocytic compartment in Madin-Darby canine kidney cells.

We used flow cytometry to sort and analyze apical and basolateral endocytic vesicles from filter-grown Madin-Darby canine kidney (MDCK) cells after membrane internalization of the lipophilic fluorescent probe trimethylamino-diphenylhexatriene. Western blot analysis of sorted fractions showed enrichment of the early endosomal markers transferrin receptor and the small GTPase Rab5. Two-dimensional gel analysis indicated that the apical and basolateral early endosomes differed significantly in their protein composition. We found nine polypeptides to be specifically enriched in apical or basolateral endocytic vesicles. An apical protein identified by microsequencing was the adaptor molecule syntenin. This protein contains two PDZ domains (PSD-95, Dlg, and ZO-1 homology) that bind syndecan and ephrin-B2 cytoplasmic domains. In MDCK cells, transiently overexpressed Myc-tagged syntenin localized to both plasma membrane domains and to an intracellular vesicular compartment. Syntenin positive vesicles colocalized with internalized transferrin in the perinuclear region. In addition, syntenin colocalized in the apical supranuclear region with Rab5 and Rab11; the latter is a marker for the apical recycling endosomes in MDCK cells.

Amino Acid Sequence↗

Subcellular fractionation, electromigration analysis and mapping of organelles.

Subcellular fractionation has provided the means required to analyze the composition and properties of purified cellular elements. In particular, subcellular fractionation has helped to define membrane boundaries and became necessary for the development of cell-free assays that reconstitute complicated cellular processes. Although cell fractionation techniques have improved over the last decades the purification of organelles to homogeneity is still a barely accessible goal in cell biology. In this article, we will first briefly review the basic principles of subcellular fractionation, and the establishment of different organelle fractions by density centrifugation, using tissue culture cells as a paradigm. Then we will discuss some of the intrinsic problems and will compare gradient purification of cellular extracts with electromigration analysis. Finally, we will describe alternative approaches, such as immunoisolation and flow cytometry to purify organelles from tissue culture cells.

Cell Fractionation↗

Loss of epithelial polarity is accompanied by differential association of proteins with intracellular membranes.

Cellular membranes play an important role in the formation and maintenance of epithelial polarity, which is lost early during carcinogenesis. We set out to identify membrane proteins which are altered during loss of cell polarity in mammary epithelium. As a model system we used murine mammary epithelial cells expressing the conditional oncoprotein c-JunER, which induces a reversible loss of polarity upon beta-estradiol-driven activation [1]. When grown either in the absence or presence of hormone, these cells exhibit a polarized or unpolarized phenotype, respectively. Different membrane fractions of polarized or unpolarized cells were analyzed by two-dimensional electrophoresis (2-DE) and differentially expressed membrane proteins were identified. To distinguish between transmembrane orientation and peripheral attachment of these proteins, were performed extractions with carbonate at high pH or with Triton X-114. In addition, cytosolic proteins of both states were analyzed to investigate their differential association with distinct membrane fractions. We found ten protein spots preferentially or exclusively in polarized cells and 17 other proteins as being upregulated during loss of polarity. Some of the peripheral membrane proteins were identified by microsequencing. The resident Golgi protein nucleobindin and fructose-bisphosphate aldolase were preferentially associated with membranes of polarized cells, whereas alphaB crystallin was detected exclusively and in high amounts in unpolarized cells.

Animals↗

General aspects of surgical treatment of pancreatic cancer.

BACKGROUND: Different results and opinions exist concerning the use of a standard or an extended lymphadenectomy, and about the indications for portal vein resection in the surgical treatment of pancreatic cancer. The site of recurrence of pancreatic cancer may help to define the usefulness of different treatments in avoiding local and/or distant recurrences. METHODS: From personal experience and a literature review, 841 patients who underwent portal vein resection were collected, and 29 papers reporting the results of extended lymphadenectomy in the surgical treatment of pancreatic cancer were analyzed. A review of the site of relapse according to the surgical treatment, with or without various adjuvant treatments, was performed. Personal experience on survival rate according to the site of relapse (local, distant, local and distant) is also reported. RESULTS: Portal vein resection has been performed without a significant increase in morbidity and mortality rate in a large number of patients. However, its usefulness for increasing the resectability rate and the long-term survival has yet to be established. Extended lymphadenectomy does not increase the morbidity and mortality rate, but conflicting results on long-term survival have been reported. Distant metastases, undetectable by the radiologist and the surgeon, usually kill more than 40% of the resected patients within 12 months. Only lymph node-positive patients with limited undetectable distant metastases seem to benefit from an extended lymphadenectomy. Although many data are lacking, the incidence of the different sites of relapse is the same whatever the surgical and/or adjuvant treatment performed. Overall survival and disease-free survival rate are not affected by the site of relapse. A significantly worse survival rate was observed after the radiological detection of local and distant metastasis than after an only local or only distant metastasis. CONCLUSION: Portal vein resection and extended lymphadenectomy can be performed without increasing the surgical morbidity and mortality rate. We still have insufficient data to decide which patient can benefit from a more extended procedure. Standardization of operations, terminology, pathological reporting, and follow-up, together with well-designed prospective studies, will help to decide the operation of choice for pancreatic cancer.

Humans↗