Causes of Mortality in a Population of Marine-Foraging River Otters (Lontra canadensis).

Retrospective analysis of diagnostic findings from 30 marine-foraging river otter (Lontra canadensis) carcasses opportunistically acquired between 2003 and 2013 revealed trauma as the most common cause of mortality (47%). Within this focal population, causes of trauma included vehicular, gunshot, and one case of suspect intraspecific aggression. Other causes of death included idiopathic (20%), infectious (13%), metabolic (10%), nutritional (7%), and neoplasia (3%). One case of neoplasia, a pancreatic islet cell adenoma, was identified in a 12-yr-old female. In six animals, diffuse renal interstitial fibrosis and multifocal glomerulosclerosis of unknown clinical significance were noted.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.

BACKGROUND: Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. METHODS: Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. RESULTS: Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease. CONCLUSION: Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and functional status of the pNET.

Postoperative Complications, In-Hospital Mortality and 5-Year Survival After Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review.

Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000-2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75%. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45%; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14-14-58%. Delayed gastric emptying rates were, respectively, 5-5-18-16%. Postoperative hemorrhage rates were, respectively, 6-1-7-4%. In-hospital mortality rates were, respectively, 3-4-6-4%. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85-93%. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80%. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.

Examining the accuracy and clinical usefulness of intraoperative frozen section analysis in the management of pancreatic lesions.

BACKGROUND: Intraoperative frozen section analysis is often performed in the surgical management of pancreatic lesions. This test is used to obtain histologic diagnosis, to assess resectability because of unanticipated locoregional spread, and to ensure negative margins after resection. We sought to define the accuracy and clinical usefulness of intraoperative frozen section analysis in patients with pancreatic lesions and to determine the impact on long-term outcomes. METHODS: A retrospective database review was performed for all patients who underwent pancreatic resection at our institution from 2002 to 2011. Patient demographics, indications for frozen section analysis, final pathology, and long-term outcomes were analyzed. Five-year survival was compared using the Kaplan-Meier method. RESULTS: Sixty-eight patients were identified (mean age 65 ± 14 years, 52% female). Malignancy was identified on final pathology in 38 (56%) patients. Intraoperative frozen section analysis was performed in 59 (87%) patients. Frozen section analysis was performed for histologic diagnosis in 6 (10%) cases, to determine resectability in 15 (25%) cases, and to evaluate margin status in 58 (98%) cases. Frozen section analysis for histologic diagnosis was associated with a sensitivity of 80%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 50% with an overall accuracy of 83%. Frozen section analysis for the determination of resectability was associated with a sensitivity of 38%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 58% with an overall accuracy of 66%. Intraoperative frozen section analysis for the determination of the final margin status was associated with a sensitivity of 33%, specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 97% with an overall accuracy of 97%. There were no false-positive results on frozen section analysis. Errors on frozen section analysis interpretation did not negatively impact survival outcomes (mean survival = 2.2 years in those with concordant frozen section analysis vs 1.7 years in those with discordant frozen section analysis, P = .69). CONCLUSIONS: Although intraoperative frozen section analysis is helpful for ensuring negative final margins, its usefulness for obtaining histologic diagnosis and determining resectability is limited by low negative predictive potential. These results highlight the importance of preoperative staging and intraoperative surgical judgment for questionable resectable disease.

Hypoxia inducible factor-1α is necessary for invasive phenotype in Vegf-deleted islet cell tumors.

In the mouse model of pancreas endocrine tumor, loss of Vegf (VKO) results in dramatically decreased tumor progression; however, the residual microscopic lesions show increased invasion into surrounding exocrine tissue. Double KO mice of Vegf and hypoxia inducible factor-1α (Hif-1α) showed increased life span and suppressed tumor growth due to increased apoptosis. The increased invasiveness of tumors in VKO mice was diminished in DKO mice to the levels of wild-type mice. Compared to VKO mice, DKO mice also exhibited smaller changes in the expression levels of adhesion molecules, including E-cadherin, N-cadherin, and NCAM. These changes of adhesion molecules were not observed in the primary culture of the tumor cells under hypoxic conditions. Thus, the invasive phenotype observed under angiogenesis inhibition requires Hif-1α, but is not directly caused by acute hypoxia.

Hedgehog inhibition with the orally bioavailable Smo antagonist LDE225 represses tumor growth and prolongs survival in a transgenic mouse model of islet cell neoplasms.

BACKGROUND: This study was designed to evaluate the role of the hedgehog pathway in tumor progression of murine islet cell tumors. Blockade of aberrant hedgehog activation has recently been proposed as a therapeutic target, but effects in models of islet cell tumors with a new orally bioavailable Smoothened (Smo) antagonist LDE225 have not been examined. MATERIAL AND METHODS: To assess in vivo effects, transgenic Rip1Tag2 mice, which develop islet cell neoplasms, were treated with vehicle or LDE225 (80 mg/kg/d) from week 5 until death. The resected pancreata were evaluated macroscopically and microscopically by iummohistochemsistry. Quantitative real-time polymerase chain reaction was performed for hedgehog target genes with RNA from islet, isolated from treated and untreated Rip1Tag2 mice. RESULTS: LDE225 significantly reduced tumor volume by 95% compared with untreated control mice. Hedgehog inhibition with LDE225 significantly prolonged median survival in the used transgenic mouse model (105 vs 116 days; P = 0.02). Quantitative real-time polymerase chain reaction for downstream hedgehog target genes demonstrated significant downregulation in the islet cell tumors of Rip1Tag2 mice treated with LDE225, confirming the ability to achieve effective pharmacologic levels of LDE225 within the desired tissue site, in vivo. CONCLUSION: This is the first study to show that the orally bioavailable Smo antagonist LDE225 may provide a new option for therapy of islet cell neoplasms.

[Pancreatic endocrine tumors: clinical manifestations and predictive factors associated with survival].

BACKGROUND/AIMS: Since pancreatic endocrine tumors (PET) are rare and heterogeneous diseases, their survival and prognosis are not well known. Due to recent advances in CT/MRI technology, incidentalomas of the pancreas are detected with increasing frequency. This study presents results of clinical manifestations of PET and predictive factors associated with survival. METHODS: From year 1990 through 2006, medical records of 98 patients (56 men, 42 women) who were diagnosed as PET pathologically at Seoul National University Hospital were reviewed retrospectively. RESULTS: Ages ranged from 17 to 76 years (mean 51.6+/-1.3 years) with a mean follow-up of 3.6+/-0.4 years (range 0-10.1 years). Overall 5-year survival rate was 68.1%, and 5-year survival rate of the patients who had distant metastases at initial diagnosis was 43.9%. Functioning tumors [hazard ratio (HR) 0.229, 95% confidence interval (CI) 0.056-0.943, p=0.041] and lymph node or liver metastases (HR 5.537, 95% CI 2.106-14.555, p<0.001) were the significant prognostic factors associated with survival rate. However, tumor size and pathology showed no significant association with survival. CONCLUSIONS: Because small and pathologically benign nature do not predict good prognosis in PET, aggressive treatment such as curative resection would be considered initially even in the case of incidental PET.

Laparoscopic vs open resection of pancreatic endocrine neoplasms: single institution's experience over 14 years.

BACKGROUND: Laparoscopic resection of benign pancreatic endocrine neoplasms (PENs) has become the standard of care for tumors in the pancreatic tail. Over a 14-year period, we have resected both benign and malignant tumors of the entire pancreas laparoscopically and compared our survival and complication rates with open controls. MATERIALS AND METHODS: We collected our data retrospectively and reviewed our outcomes with an actuarial 5-year survival according to Kaplan-Meier. Patients who underwent minimally invasive techniques were compared to patients who were approached with open techniques. RESULTS: From April 1992 to September 2006, we operated on 31 patients for PENs: 13 (42%) were operated on using open techniques and 18 (58%) laparoscopically, and conversion occurred in one patient (6%). In the laparoscopic group, eight (47%) tumors were malignant compared to six (43%) in the open group. Operative times averaged 188 min for the minimally invasive approach and 305 min for the open approach (p = 0.02). Length of stay was 25 days (range 8-82) for the laparoscopic group compared to 20 days (range 6-63; p > 0.05). Overall morbidity and fistula rates ranged from 67 to 24% in the laparoscopic group to 69 to 38% in the open group (p > 0.05). There were no postoperative mortalities. The average follow-up was 63 months for the open group and 33 months for the laparoscopic group. The overall actuarial survival rates were both 90% at 5 years. CONCLUSIONS: Laparoscopic resection of benign and malignant PENs has similar overall complication and 5-year survival rates as the open technique; however, the laparoscopic approach is associated with shorter operative times.

Effective treatment of locally advanced endocrine tumors of the pancreas with chemoradiotherapy.

BACKGROUND/AIMS: The use of chemoradiation in the management of locally advanced pancreatic endocrine tumors has not been reported in the medical literature. Patients with unresectable tumors are often included in trials of systemic chemotherapy, and use of external beam radiation has been only described in few case reports. Given the sensitivity of pancreatic endocrine tumors to cytotoxic agents including streptozocin, doxorubicin and 5-FU, we have hypothesized that the combination of concurrent and sequential chemotherapy and radiation will yield higher response rates than acheivable with chemotherapy alone. METHODS: Six patients with locally advanced pancreatic endocrine tumors were treated with a protocol consisting of radiation concurrent with infusional 5-FU (or capecitabine) along with induction and consolidation chemotherapy (streptozocin and doxorubicin). We retrospectively determined the objective radiographic response rate. RESULTS: The objective response rate was 80%. With a median follow-up of 29 months, all six patients in the study have had continued reduction in tumor size from the time of the first posttreatment scan to the most recent scan. None of the patients have experienced local or metastatic disease progression. Treatment was well tolerated with minimal toxicity. CONCLUSION: The combination of concurrent and sequential chemoradiotherapy appears to be a highly effective treatment for locally advanced pancreatic endocrine tumors.

Metastatic neuroendocrine hepatic tumors: resection improves survival.

BACKGROUND: The optimal treatment for hepatic metastases from neuroendocrine tumors remains controversial because of the often indolent nature of these tumors. We sought to determine the effect of 3 major treatment modalities including medical therapy, hepatic artery embolization, and surgical resection, ablation, or both in patients with liver-only neuroendocrine metastases, with the hypothesis that surgical treatment is associated with improvement in survival. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: Patients with metastatic liver-only neuroendocrine tumors were identified from hospital records. INTERVENTIONS: Patients were subdivided into those receiving medical therapy, hepatic artery embolization, or surgical management. MAIN OUTCOME MEASURES: Effect of treatment on survival and palliation of symptoms was analyzed. RESULTS: From January 1996 through May 2004, 48 patients with liver-only neuroendocrine metastases were identified (median follow-up, 20 months), including 36 carcinoid and 12 islet cell tumors. Seventeen patients were treated conservatively, which consisted of octreotide (n = 7), observation (n = 6), or systemic chemotherapy (n = 4). Hepatic artery embolization was performed in 18 patients. Thirteen patients underwent surgical therapy, including anatomical liver resection (n = 6), ablation (n = 4), or combined resection and ablation (n = 3). No difference was noted in the percentage of liver involved with tumor between the 3 groups. An association of improved survival was noted in patients treated surgically, with a 3-year survival of 83% for patients treated by surgical resection, compared with 31% in patients treated with medical therapy or embolization (P = .01). No difference in palliation of symptoms was noted among the 3 treatment groups (P = .2). CONCLUSION: In patients with liver-only neuroendocrine metastases, surgical therapy using resection, ablation, or both is associated with improved survival.

Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression.

Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1alpha, HIF-2alpha and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm(-2), respectively, P < 0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1alpha expression. Poorly differentiated carcinomas were associated with nuclear HIF-1alpha and membranous CA9 expression. Low MVD (P = 0.0001) and membranous CA9 expression (P = 0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours.

Surgical treatment of nonfunctioning islet cell tumor: report of 41 cases.

BACKGROUND: Nonfunctioning islet cell tumor (NIT) as a rare pancreatic endocrine neoplasm is characterized by unspecific clinical symptoms and is hard to diagnose. In China, NIT accounts for 15%-41% in pancreatic endocrine neoplasms just next to insulinoma. In this study, we evaluated the surgical modalities of NIT. METHODS: From January 1978 through February 2002, 41 patients with NIT were treated at the Department of Surgery of the First Affiliated Hospital, China Medical University, Shenyang, China. Tumors in the head of the pancreas were noted in 28 patients, and in the body or in the tail in 13 patients. The mean diameter of the tumors was 10.7 cm. Fifteen patients underwent enucleation and 21 received pancreatectomy. Tumors were unresectable in 5 patients because of extensive infiltration. The mean diameter was 9.6 cm in patients treated by enucleation, 13.1 cm in those by pancreaticoduodenectomy, 9.9 cm in those by distal pancreatectomy, and 11.6 cm in those with unresectable tumors. RESULTS: The curative resection rate was 88% (n=36), and the complication rate after enucleation and pancreatectomy was 33% (n=5) and 14% (n=3), respectively. No local recurrence was found after both enucleation and pancreatectomy. Liver metastases occurred in 3 patients treated by enucleation. CONCLUSIONS: Both enucleation and pancreatectomy are effective for NIT of the pancreas. No local recurrence has been found in patients treated by the two surgical procedures. The complication rates of the two modalities are comparable.

Nonfunctioning pancreatic endocrine tumors: a multicenter clinical study.

OBJECTIVES: Nonfunctioning pancreatic endocrine tumors (NFPTs) are rare neoplasms that have been the object of few studies that have involved only small numbers of patients. This study was carried out to obtain a comprehensive and up-to-date clinical picture of these tumors. METHODS: A total of 184 patients with NFPT admitted to three Italian hospitals in the last 15 yr were studied. The diagnosis of NFPT was confirmed histologically using conventional and immunohistochemical techniques. Data were obtained from the medical charts or directly from the patients. RESULTS: There were 85 men (46.2%) and 99 women (53.8%). The mean age at diagnosis was 55.2 yr (range 17-82 yr). The percentage of smokers and alcohol drinkers was similar to that in the general population. Seven patients (3.9%) had a family history of exocrine pancreatic carcinoma. In 120 cases (65.2%), the diagnosis was made after workup for pain or other symptoms, in the remaining 64 cases (34.8%), the tumor was discovered incidentally by ultrasound; in this group survival was significantly greater than it was for the symptomatic patients (p=0.0043). Survival was also found to be improved by tumor resection (p<0.0001), absence of metastases (p<0.0001), and small tumor size (< or =3 cm) (p<0.0007). CONCLUSIONS: NFPTs were slightly more frequent in women and were diagnosed most often in middle-aged individuals. No risk factors other than a family history of exocrine pancreatic carcinoma were found. Tumor discovery while patients were still asymptomatic, tumor resection, absence of metastases, and tumor size < or =3 cm significantly prolonged survival.

Pancreaticoduodenectomy for islet cell tumors of the head of the pancreas: long-term survival analysis.

Pancreaticoduodenectomy (PD) has been performed infrequently for islet cell tumors of the pancreas because of the perceived perioperative morbidity and the relatively protracted natural history of those tumors. To determine whether the improved safety of PD affects long-term outcome of patients with islet cell tumors, we reviewed our experience. All consecutive patients who underwent PD or total pancreatectomy for islet cell tumors between 1980 and 1995 were analyzed. Diagnoses were based on histologic findings and endocrine (biochemical) manifestations of the tumors. Patients were followed by outpatient clinic visits and mail correspondence. Clinical and pathologic factors were analyzed for prognostic risk. Survival and recurrence curves were generated using the Kaplan-Meier method, and the log-rank test was used for comparison (p <0.05 was significant). We identified 29 patients who fulfilled the inclusion criteria with an even distribution by gender (14M:15F). Mean age of patients was 56 years (SD +/- 14 years); mean tumor size was 4.4 cm (SD +/- 2.6 cm). Most tumors were nonfunctioning (n = 20); there were 4 somatostatinomas, 3 insulinomas, and 2 gastrinomas. Operating time was 316 minutes (SD +/- 75 minutes), median transfusion requirement was 0 units (mean 1.5 units). Standard Whipple resection was performed in 20 patients; the pylorus-preserving Whipple procedure, in 7; and total pancreatectomy, in 2. Regional lymph nodes were involved by tumor in 16 patients. The complication rate was 31%, and operative mortality was 10% (n = 3). Length of hospital stay was 17 days (SD +/- 8.8 days). Overall survival was 81% and 70% at 5 and 10 years. Recurrence-free survival was 76% at 5 and 10 years. There was a trend toward greater recurrence-free survival for node-negative patients (88% vs 65% at 5 years, p = 0.13), and overall survival was greater for node-negative patients (100% vs 67% at 5 years, p = 0.04). Mean follow-up was 8.8 years. PD is an appropriate strategy for selected malignant islet cell tumors of the pancreas, which offers extended survival with a low recurrence rate and control of endocrine symptoms.

Telomerase activity in pancreatic endocrine tumors.

OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr +/- 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type I and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.

Expression of CD44 variant isoforms and association to the benign form of endocrine pancreatic tumours.

BACKGROUND: The expression of CD44 and its isoforms have been shown in many neoplastic tissues to serve as prognostic indicators, therefore, the feasibility of using these as prognostic markers in endocrine pancreatic tumour patients was examined. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed on 26 tumour samples (5 gastrinomas, 3 glucagonomas, 10 non-functioning tumours, 6 insulinomas, 2 mixed insulinoma and glucagonomas) with monoclonal antibodies against CD44s (standard form) and variant isoforms (v4, v5, v6, v7, v7-8, v9, v10). Staining was correlated to the tumour proliferation, malignancy, metastasis and patients survival. RESULTS: There was variable expression of CD44s. All tumours showed complex expression of many isoforms. CD44v6 and CD44v9 were down regulated in malignant tumours. There was statistical significance of CD44v6 expression in benign tumours (P < 0.05) compared to malignant tumours and near significance in CD44v9 expression (P = 0.0574). Survival of the patients with CD44v6 positive staining was higher than those who were negative (P = 0.0822). Moreover, the expression was well correlated to the patients without any distant metastases (CD44v6, p < 0.001; CD44v9, P < 0.01). Tumour proliferation (Ki67 index) correlated directly to the malignancy (P < 0.05) and there was inverse correlation between Ki67 index and CD44v6 (P < 0.05) as well as v9 (P < 0.05). CONCLUSIONS: Endocrine pancreatic tumours express CD44s and isoforms differentially. Expression of the two isoforms of CD44, namely v6 and v9 seem to be related more to benign form of the tumour and could serve as a predictor of good prognosis.

Role of chemoembolization in synchronous liver metastases from pancreatic endocrine tumours.

Endocrine tumours of the pancreas, even in case of liver involvement, are generally characterized by a slower evolution and a better prognosis, if compared with ductal carcinoma. This fact gives reason to a radical surgical approach, whenever possible, and to the research of any effective adjuvant treatment. For this purpose, hepatic transarterial chemoembolization (TACE) has been proposed in recent years for the treatment of metastatic endocrine tumours. Out of 80 patients suffering from endocrine tumours of the pancreas, observed between January 1985 and December 1996, 28 (35%) presented liver metastases at the time of diagnosis. Twelve of these patients were submitted to palliative resection of pancreatic tumour and one or more cycles of TACE. Overall survival was 50% (6/12); median survival was 35.4 months (range 4-75). These results suggest that chemoembolization, combined with surgical resection of primary malignancy, appears to be able to control the disease for a certain time and to increase the survival rate.

Prognostic factors in patients with endocrine tumours of the duodenopancreatic area.

BACKGROUND: The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP. PATIENTS/METHODS: Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis. RESULTS: Twenty eight patients (34%) died within a median of 17 months (range 1-110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p < 0.00001), lack of complete resection of the primary tumour (p = 0.001), extranodular/extrahepatic metastases (p = 0.001), local invasion (p = 0.001), primary tumour size > or = 3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p < 0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively. CONCLUSION: Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.

Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and pathological aspects in 16 patients.

BACKGROUND: Nonfunctioning islet cell tumors (NFICTs) usually reach a large size prior to detection, at which stage patients have some symptoms or signs. Recently, NFICTs have been discovered in asymptomatic patients with increasing frequency owing to advances in diagnostic imaging techniques. This study investigated clinical, imaging and pathological features in recent cases of NFICT. METHODS: The medical records, radiographs and pathological specimens of 16 patients with NFICT who were evaluated between April 1991 and March 1996 were reviewed. RESULTS: Tumor sizes ranged from 0.8 to 17 cm (average, 5.2 cm). Five patients (31%) had some symptoms or signs at the time of diagnosis; however, the other 11 (69%) had no symptoms. Of 10 patients with a tumor of size 5 cm or less, nine were asymptomatic and all tumors were histologically benign. In contrast, in six patients with a tumor larger than 5 cm, four had some symptoms and five tumors were malignant. The detection rates of pancreatic tumor mass on ultrasonography and computed tomography were 94% (15/16) each. All 14 patients in whom the tumor was completely resected survived without recurrence; however, the remaining two patients with liver metastases died following recurrence. CONCLUSIONS: US and CT are useful in detecting NFICTs even if the tumor is small and the patient is asymptomatic. The detection of NFICTs of small size and their complete removal are essential for a successful cure.