[Modern classification of the lymph nodes groups in hepatopancreatobiliary zone, multifactorial criterion "T" and the lymphadenectomy extent in malignant diseases of pancreatic head].

Modern classifications of lymph nodes of the hepatopancreatobiliary zone organs, applied by domestic and leading foreign surgeons were analyzed. A modified classification of lymph nodes was proposed, basing on recommendations of Japanese society of pancreatologists (V edition). Basing on own experience, the results of studying of the lymph nodes groups and extent of lymphadenectomy in patients while presence of malignant tumors of pancreas and distal portion of common biliary duct were analyzed.

A new approach for evaluating the resectability of pancreatic and periampullary neoplasms.

OBJECTIVE: To establish a new standard for assessing the resectability of pancreatic and periampullary tumors by the Medical Image Three-Dimensional Visualization System (MI-3DVS). METHODS: Eighty cases of pancreatic and periampullary tumors were examined. The 64-slice multidetector CT (64-MDCT) images and patient data were processed by MI-3DVS. The main elements examined by MI-3DVS included tumor shape, size, and location; distribution of related vessels; luminal morphology of large vessels; distribution and morphology of the small peripancreatic veins; morphology, degree of dilation, and obstructive sites of bile and pancreatic ducts. Based on vascular characteristics of MI-3DVS findings, the cases were classified into five types. Type I and II were resectable, type III were potentially resectable or resectable with combined vascular resection and reconstruction, and type IV and V were unresectable. The outcome was then compared with corresponding CT angiography (CTA) analysis and actual surgical observations. RESULTS: Among the 80 cases, MI-3DVS indicated that 60 were resectable and the remaining 20 were not. In contrast, CTA indicated 50 resectable cases and 30 unresectable cases. For 57 cases of pancreatic ductal carcinomas and all 80 cases periampullary tumors, MI-3DVS assessment yielded a positive predictive value of 100%, negative predictive value of 100%, a sensitivity of 100%, a specificity of 100%, and an accuracy of 100%. While CTA generated corresponding values of 96%, 60%, 80%, 90%, 82.5%. The overall differences between the two methods were significant (P < 0.05). CONCLUSION: The new classification system is able to reliably assess the resectability of pancreatic and periampullary tumors.

Angiogenesis: a prognostic determinant in pancreatic cancer?

Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

[Pancreaticoduodenal resection in the treatment of malignant periampullar tumors].

The experience of performance of pancreaticoduodenal resection (PDR) in 412 patients in 1998-2009 yrs for malignant periampullar tumors was analyzed. In 296 patients a standard PDR was done and in 116, with tumoral affection of distal part of common biliary duct and duodenal large papilla - pylorus-preserving PDR Individualized approach was used, exploiting modern technologies of pylorus-preserving PDR: saving gastroduodenal artery, selective ligation of right branch of dorsal pancreatic and lower pancreatoduodenal artery, dorsal and translateral surgical approaches usage. In 26 patients PDR was accomplished with resection of vessels. In 12 patients a no-touch procedure of PDR was applied. There were analyzed the results of application of modified extended lymphadenectomy while PDR performance. Complications had occurred in 29.5% patients, lethality was 2.7%. The survival indices had constituted at average 24 mo--in pancreatic tumors, 48 mo--in tumors of a distal part of common biliary duct and 72 mo--for localized in duodenal large papilla. Introduction of a new methods of PDR would permit to improve an early and late results of treatment.

Computed tomography in diagnosing vascular invasion in pancreatic and periampullary cancers: a systematic review and meta-analysis.

BACKGROUND: Preoperative diagnosis of local vascular invasion is very important to the selection of therapeutic protocols and prediction of the prognosis of pancreatic and periampullary cancers. This meta-analysis was designed to evaluate the accuracy of computed tomography (CT) in diagnosing vascular invasion in patients with pancreatic and periampullary cancers. DATA SOURCES: English-language articles reporting diagnostic accuracy of CT for vascular invasion in pancreatic and periampullary cancers were searched from the MEDLINE and PubMed databases. A meta-analysis was conducted to estimate pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. RESULTS: Data were extracted from 18 studies that met the inclusion criteria. The pooled sensitivity and specificity of CT in diagnosing vascular invasion were 77% and 81%. Since CT technology improved in different periods, in the recent five years (2004-2008) CT has shown a higher diagnostic accuracy, and the pooled sensitivity and specificity increased to 85% and 82%, respectively. Subgroup analysis of CT studies was made to determine the involvement of different vessels, and the pooled sensitivities for the invasion of the venous system, portal vein, and arterial system were 75%, 75%, and 68%, and the pooled specificities were 84%, 91%, and 92%, respectively. For CT imaging with vascular reconstruction, the pooled sensitivity and specificity were 84% and 85%, higher than the estimates in studies without reconstruction. CONCLUSIONS: Developed CT technology with vascular reconstruction is used as an imaging modality for diagnosing vascular invasion at present. Further combined application of various imaging modalities may improve the accuracy of diagnosis, especially for smaller vessel involvement, such as the superior mesenteric vein or artery, which are difficult to demarcate.

Prognostic significance of vascular endothelial growth factor expression and microvessel density in carcinoma of ampulla of Vater.

BACKGROUND/AIMS: To investigate whether the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) are of prognostic significance in ampullary carcinoma. METHODOLOGY: Twenty-two resected tumor specimens from patients with ampullary carcinoma were immunohistochemically stained for VEGF and CD34 (surrogate for vessels) by streptavidin-peroxidase method. RESULTS: Expression of VEGF in tumor tissue was found in 50% of patients. The mean MVD for entire group was 26.4 +/- 12.8. A significantly higher MVD was observed in the tumors with positive VEGF expression (35.0 +/- 9.6) compared with that of negative VEGF expression (17.7 +/- 9.3) (p<0.01). The expression of VEGF and MVD were closely related lymph node status and tumor TNM stage. The positive expression rate of VEGF and the average MVD in patients with lymph node metastases were 85.7% and 33.1 +/- 10.8 respectively, which were significantly higher than those in patients without lymph node metastases (33.3% and 22.8 +/- 11.8 respectively) (p<0.05). The positive expression rate of VEGF and the average MVD in patients with stage III and were 75% and 36.3 +/- 8.4 respectively, which were significantly higher than those in patients with stage I (25% and 18.4 +/- 10.1 respectively) or stage II (50% and 23.8 +/- 13.4 respectively) (p<0.05). The Kaplan-Meier survival curves showed that the 3-year survival rate for patients with positive VEGF expression or a high MVD (9.1% and 10% respectively) were lower than those in patients with negative VEGF expression or a low MVD (63.64% and 58.33% respectively) (p<0.05). CONCLUSIONS: VEGF is positively correlated with MVD in ampullary carcinoma. VEGF and angiogenesis may play an important role in lymph node metastasis and progression of ampullary carcinoma. VEGF and MVD appear to be important prognostic predictor in patients with ampullary carcinoma.

COX-2 expression in ampullary carcinoma: correlation with angiogenesis process and clinicopathological variables.

BACKGROUND: There is evidence that the anti-neoplastic effect of non-steroidal anti-inflammatory drugs is attributable to cyclooxygenase-2 (COX-2) inhibition, but the exact mechanisms whereby COX-2 can promote tumour cell growth remain unclear. One hypothesis is the stimulation of tumour angiogenesis by the products of COX-2 activity. To data, there have been few clinicopathological studies on COX-2 expression in human ampullary carcinoma and no data have been reported about its relation with tumour angiogenesis. OBJECTIVE: To investigate by immunohistochemistry the expression of COX-2 and the angiogenesis process in a series of primary untreated ampullary carcinomas. METHODS: Tissue samples from 40 archival ampullary carcinomas were analysed for COX-2, vascular endothelial growth factor (VEGF), and an endothelial cell marker von Willebrand factor (vWF) by immunohistochemistry, using specific antibodies. RESULTS: COX-2 expression was detected in 39 tissue samples (97.5%), of which two (5%) were graded as weak, 26 (65%) as moderate, and 11 (27.5%) as strong. Only one lesion (2.5%) was negative for COX-2 expression. VEGF expression was detected in 36 tissue samples (90%). A significant positive correlation was found between COX-2 and VEGF expression. No statistic correlation was found between COX-2 expression and microvessel density. CONCLUSIONS: COX-2 is highly expressed in ampullary carcinomas. This suggests an involvement of the COX-2 pathway in ampullary tumour associated angiogenesis, providing a rationale for targeting COX-2 in the treatment of ampullary cancer.

[Reconstruction of visceral arteries with homografts in excision of the pancreas]. / Viszeralarterienrekonstruktionen mit Homografts bei Resektionen des Pankreas.

BACKGROUND: At present, surgical treatment with R(0) resection offers the only chance of cure for patients suffering from pancreatic cancer. Carcinomas of the pancreas are frequently diagnosed at an inoperable stage because of local tumor progression by vessel wall infiltration. In a small series of patients, efforts have been made to increase curative resection rates for advanced pancreatic cancer by excision and reconstruction of the involved visceral arteries. Whether this provides clinical benefit remains uncertain. METHODS: Since 2001 we have been employing "en bloc" tumor resection for advanced pancreatic carcinomas with extended infiltration of visceral vessels. Technical experience was gained previously by performing portal vein resection as well as arterial excision and reconstruction by direct anastomosis in the presence of malignant wall infiltration. A total of ten patients underwent vascular reconstruction by arterial homograft interposition. In six of ten cases, combined extended reconstructions of the hepatic and superior mesenteric arteries were performed. One patient died during the perioperative course due to fulminant bleeding. One patient developed severe diarrhea. During a 3- to 18-month follow-up, one case of liver metastasis and one case of local tumor recurrence were documented. CONCLUSIONS: In selective cases, operability and R(0) resection can be achieved in advanced pancreatic cancer by performing extended resection procedures with vascular reconstruction using arterial homografts. Vascular substitution of visceral arteries can be conducted without ischemic disturbances of the small bowel and liver. Only a few perioperative complications were observed.

Prognostic significance of intratumoural microvessel density (IMD) in resected pancreatic and ampullary cancers to standard histopathological variables and survival.

AIM: Angiogenesis is required for tumour growth. Its evaluation, by intratumoural microvessel density (IMD), has prognostic significance in many solid tumours. There is controversy regarding its use in pancreatic cancer and little is known about its role in ampullary tumours. The aim is to study IMD as a prognostic marker in resected ductal adenocarcinomas of head of pancreas and cancers of the ampullary region. METHODS: Forty-seven patients (23 pancreatic and 24 ampullary, mean age 62.0 years) surviving a potentially curative (R0/R1) resection were analysed. Paraffin-embedded sections of these tumours were immunohistochemically stained for CD-34 and IMD was determined (magnification x200). This was correlated with histopathological data and survival using Cox's multivariate analysis. RESULTS: Mean survival for the pancreatic cancer group was 18.4 months (SE=2.7) and 81.2 months (SE=9.9) for the ampullary cancer group. In the pancreatic cancer group, IMD was found to have independent prognostic significance to survival on multivariate analysis (P=0.002, Hazard Ratio (HR) 13.60) along with microscopic resection margin involvement (P=0.003, HR 15.18). For ampullary cancers, IMD was higher in those with lymph node metastasis (P=0.02, Mann-Whitney U -test). CONCLUSION: IMD in resected pancreatic cancers correlates with survival.

Significance of thymidine phosphorylase/platelet-derived endothelial cell growth factor in carcinoma of the papilla of Vater.

The expression of thymidine phosphorylase (TP) in carcinoma of the papilla of Vater was studied to clarify its significance in tumor progression and in determining prognosis. Fifty-nine cases of surgically resected carcinoma of the papilla of Vater were studied. Immunohistochemical staining was performed to evaluate the expression of TP, microvessel count and p53 overexpression. TP expression was demonstrated in tumor cells in 62.7% (37/59) of the cases. A higher frequency of regional lymph node metastasis was found in TP-positive tumors than in TP-negative tumors (P = 0.006). TP-positive tumors were more advanced than TP-negative tumors with regard to clinical stage (P = 0.035). TP-positive tumors had significantly higher microvessel density (27.6 +/- 10.1) than TP-negative tumors (20.4 +/- 10.0, P = 0.01). Moreover, TP expression was significantly correlated with a poor prognosis (P = 0. 02). These suggest that in carcinoma of the papilla of Vater, TP production by tumor cells is correlated with tumor progression through its regulatory effect on neovascularization.

Helical CT evaluation of arterial invasion in pancreatic tumors: comparison with angiography.

BACKGROUND: Although helical computed tomography (HCT) has been widely employed for the evaluation of pancreatic tumors, its capability in the diagnosis of peripancreatic arterial invasion has not been established. METHODS: HCT with a sequential cine-display was carried out in 34 patients with solid pancreatic tumors and 28 control subjects without angiographic abnormality. The HCT scans were compared with angiograms. RESULTS: All major arteries (celiac, superior mesenteric, splenic, gastroduodenal) and superoanterior pancreaticoduodenal arteries were well demonstrated by HCT in control subjects. However, posterior pancreaticoduodenal arcades and other smaller arteries were poorly identified. Although 19 major arterial invasions were equally diagnosed by HCT and angiography in patients with pancreatic tumors, only 4 of 11 minor arterial invasions were correctly diagnosed by HCT. CONCLUSIONS: Although HCT has some limitations in the evaluation of minor peripancreatic arteries, it can provide enough information for making a decision about conducting pancreatic surgery.

CT arterial portography vs pancreatic arteriography in the assessment of vascular involvement in pancreatic and periampullary tumors.

OBJECTIVE: Preoperative staging of pancreatic tumors is frequently accomplished through a combined effort of CT and arteriography. For tumor detection and delineation of disease extent CT is utilized routinely, with CT arterial portography (CTAP) being the single most accurate study for the detection liver metastases. Arteriography has remained the "gold" standard for assessing vascular involvement. The purpose of this study was to determine whether CTAP could become the single study of choice for assessing resectability in patients with pancreatic and periampullary tumors with particular emphasis on its accuracy in determining vascular involvement. MATERIALS AND METHODS: Radiologic studies and medical records were reviewed in 20 patients who had received both CTAP and arteriographic examinations for preoperative assessment of pancreatic and periampullary tumors. These findings were correlated with results from either surgery (12 cases) or percutaneous biopsy and follow-up (8 cases) in 12 nonresectable and 8 resectable tumors. RESULTS: Arteriography and CTAP correctly concurred in 75% of cases (15 of 20); CTAP correctly demonstrated vascular involvement not appreciated on arteriography in 15% (3 of 20) with an overall sensitivity and specificity of 90 and 100%, respectively. Arteriography was superior to CTAP in one patient (5%) with an overall sensitivity and specificity of 70 and 90%, respectively, for predicting vascular involvement by tumor. CONCLUSION: Our experience suggests that CTAP is more accurate than arteriography for demonstrating tumor involvement of major peripancreatic vessels. Because CTAP, additionally, has a high sensitivity for detecting liver metastases, no further studies may be necessary to determine operability of these patients.

[Combined digital subtraction angiography and cholangiography in assessing the spread of the tumor process in pancreatobiliary cancer]. / Sochetannaia digital'naia subtraktsionnaia angiografiia i kholangiografiia v otsenke rasprostranennosti opukholevogo protsessa pri pankreatobiliarnom rake.

The paper is concerned with comparative assessment of the efficacy of digital subtraction angiography and routine angiography in assessing tumor spreading in pancreatobiliary cancer. A combined method of digital subtraction angiography and cholangiography was developed and performed in 41 patients with pancreatobiliary cancer permitting maximum information on the topical location and spreading of a tumor process. The clinical importance of the obtained results permitted recommending simultaneous digital subtraction angiography and cholangiography in patients with hepatobiliary cancer.