Laparoscopic dorsal subsegmentectomy 8: Exploit the 3d technology to plan liver resection, and predict intraparenchymal pedicles. A case report. (With video explanation).

INTRODUCTION: Laparoscopic liver surgery is spreading, encouraged by technical and technological improvement. Both the obligated narrow space and the difficulty to modify it lead to a more complex approach to the lesions located in the posterosuperior portion of the liver. Surgical strategies such as the Caudal approach or the Diamond technique could ameliorate surgical procedure, but these areas remain a challenge and are still classified as complex. CLINICAL CASE: We discuss the case of a 68 year old man with metachronous liver metastasis in the dorsal part of segment 8. We used portal phase CT-scan Dicom data to create Three-dimensional reconstruction, which was able to show the more distal branches of intraparenchymal structures. The reconstructed images were subsequently used to plan laparoscopic liver resection. DISCUSSION: The capability of three-dimensional reconstruction to create a realistic image allows us to use ultrasound as a navigation tool. Exploiting these two technologies together, we arrived to regulate the resection stages by recognizing previously marked structures and searching them at every intervention phase. The strategy performed demonstrates both a high level of precision and the capability to predict intraparenchymal structures. CONCLUSION: The advantages obtained from three-dimensional reconstruction are numerous in terms of either anatomical comprehension and technical precision, suggesting a potential improvement in surgical skill. Three-dimensional technology should be encouraged and spread to understand, in every single aspect, the potential of its use.

Surgical coaching applied to laparoscopic TME for continuous professional development in rectal surgery: proof of concept.

BACKGROUND: Coaching is maturing as a strategy for surgeons' continuous professional development in different types of surgery. Laparoscopic total mesorectal excision (LAP TME) is one of the recognized difficult procedures in colorectal surgery. Aim of this trial is to introduce the surgical coaching as a tool for a continuous technical education of LAP TME for cancer in a consultant surgeon carrier. METHODS: Twelve Italian colorectal surgeons were enrolled as trainees in the AIMS Academy rectal cancer surgical coaching project and attended a face-to-face 90-min surgical coaching on a pre-edited 45-min-long video of a laparoscopic proctectomy according to pre-determined guidelines. At the end of the coaching, all mentors were asked to fill a questionnaire evaluating the trainee's skills. All trainees had to fill a post-coaching questionnaire addressing the appropriateness of the coaching with respect to their actual level. RESULTS: Trainees were more confident in performing the extra-pelvic part of the surgical procedures compared to the intra-pelvic dissection. The most challenging steps according to the trainees were the seminal vesicles identification and the pelvic floor dissection. Mentors found the trainees quite confident in the approach to the vascular structures, lymphadenectomy, stapler utilization and bleeding control. The sharpness and the efficacy of the dissection, the dissection of the surgical planes and the anastomosis fashioning were reported at a lower level of confidence. The higher grade of satisfaction reported by the trainee came from the attention that the mentors demonstrated towards them, from the availability of the mentors to take into consideration the surgical issues raised and from the willingness to apply the suggestions received during their next proctectomies. CONCLUSIONS: The surgical coaching applied to LAP TME should be considered as an innovative tool for continuous professional development.

Bowel obstruction in obturator hernia: A challenging diagnosis.

INTRODUCTION: The obturator hernia is a rare pelvic hernia that often comes in the shape of bowel obstruction caused by the presence of an intestinal segment, more often ileum, passing trough the obturator foramen of the pelvic wall (Fig. 1). This type of hernia accounts for 0.5-1.4% of all hernias. CASE PRESENTATION: We report the clinical case of a 84-year-old woman with no previous surgical interventions, who went to the emergency room complaining of vomit and nausea, bowels closed to gas and stool, which she had experienced for three previous days. Routine blood test showed impaired renal function and hydrohelectrolyte imbalance. A CT scan revealed a right ileal, strangulated obturator hernia. The patient underwent an emergency surgical intervention with laparoscopic trans-abdominal peritoneal approach (TAP): after the reduction of the herniated segment, a primary suturing of the parietal defect was performed without ileal resection. DISCUSSION: Because of the non-specific symptoms the diagnosis of this kind of hernia is often unclear; female are 6-9 times more likely than men to be subject to the aforementioned pathology, mostly occurring in multiparous, emaciated, elderly woman so it is also called "the little old lady's hernia". Risk factors are loss of weight, chronic pulmonary disease and ascites which increase the abdominal pressure. An unfrequent presenting sign is a palpable mass, or the Howship-Romberg sign- a pain radiating from the inner tigh and knee - but it could be misleading when confused with symptoms of gonarthrosis or lumbar vertebral disc pathology. CT scan has superior sensitivity and accuracy with respect to other radiological exams to assess the presence of an obturator hernia. CONCLUSION: Obturator hernia is a rare type of hernia due to his diagnosis, which is often unclear; a prompt suspect based for the non-specific symptoms is crucial for the diagnosis. Surgical management depends on early diagnosis and it is the only possible treatment for this pathology.

Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis on Liver Biopsy During Transplantation.

BACKGROUND: Assessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis. MATERIALS AND METHODS: Twenty consecutive intraoperative donor liver biopsy specimens were evaluated by a pathologist at the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service. The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6 (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB special stain. After a 3-week washout period, only the slides stained with H&E were re-assessed for fibrosis stage by the same pathologist blinded to donor patient data. RESULTS: Combination H&E-CAB staging fibrosis score was higher in 20%, lower in 10%, and the same in 70% of biopsy specimens as determined using only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain alone. CONCLUSIONS: CAB staining may be performed on frozen tissue from liver biopsy during a transplantation process without a significant delay in diagnosis. Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

What is the most accurate lymph node staging method for perihilar cholangiocarcinoma? Comparison of UICC/AJCC pN stage, number of metastatic lymph nodes, lymph node ratio, and log odds of metastatic lymph nodes.

BACKGROUND: We compared the prognostic performance of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) 7th edition pN stage, number of metastatic LNs (MLNs), LN ratio (LNR), and log odds of MLNs (LODDS) in patients with perihilar cholangiocarcinoma (PCC) undergoing curative surgery in order to identify the best LN staging method. METHODS: Ninety-nine patients who underwent surgery with curative intent for PCC in a single tertiary hepatobiliary referral center were included in the study. Two approaches were used to evaluate and compare the predictive power of the different LN staging methods: one based on the estimation of variable importance with prediction error rate and the other based on the calculation of the receiver operating characteristic (ROC) curve. RESULTS: LN dissection was performed in 92 (92.9%) patients; 49 were UICC/AJCC pN0 (49.5%), 33 pN1 (33.3%), and 10 pN2 (10.1%). The median number of LNs retrieved was 8. The prediction error rate ranged from 42.7% for LODDS to 47.1% for UICC/AJCC pN stage. Moreover, LODDS was the variable with the highest area under the ROC curve (AUC) for prediction of 3-year survival (AUC = 0.71), followed by LNR (AUC = 0.60), number of MLNs (AUC = 0.59), and UICC/AJCC pN stage (AUC = 0.54). CONCLUSIONS: The number of MLNs, LNR, and LODDS appear to better predict survival than the UICC/AJCC pN stage in patients undergoing curative surgery for PCC. Moreover, LODDS seems to be the most accurate and predictive LN staging method.

Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis.

BACKGROUND: The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. MATERIALS AND METHODS: Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. RESULTS: Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%). CONCLUSIONS: Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems.

ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice.

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aß-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aß oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.

Pancolitis with ischemic injury as a complication of immunosuppressive treatment in a patient with autoimmune hepatitis: a case report.

Ischemic colitis is a serious drug-induced adverse event. There are only few cases of immunosuppression-associated ischemic colitis described in the literature, but none with a pancolitis-like manifestation. We report the case of a 72-year-old female patient who developed a pancolitis with ischemic injury on immunosuppressive treatment with steroids and azathioprine for autoimmune hepatitis. The patient presented with massive rectal bleeding. Colonoscopy confirmed the diagnosis of pancolitis. The results of histological examination indicated drug-induced ischemic colitis involving the entire colon. This is the first case of ischemic pancolitis mimicking an inflammatory bowel disease (IBD) in a patient with immunosuppressive therapy.

Pancreatic endocrine tumours: mutational and immunohistochemical survey of protein kinases reveals alterations in targetable kinases in cancer cell lines and rare primaries.

BACKGROUND: Kinases represent potential therapeutic targets in pancreatic endocrine tumours (PETs). PATIENTS AND METHODS: Thirty-five kinase genes were sequenced in 36 primary PETs and three PET cell lines: (i) 4 receptor tyrosine kinases (RTK), epithelial growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), tyrosine-protein kinase KIT (KIT), platelet-derived growth factor receptor alpha (PDGFRalpha); (ii) 6 belonging to the Akt/mTOR pathway; and (iii) 25 frequently mutated in cancers. The immunohistochemical expression of the four RTKs and the copy number of EGFR and HER2 were assessed in 140 PETs. RESULTS: Somatic mutations were found in KIT in one and ATM in two primary neoplasms. Among 140 PETs, EGFR was immunopositive in 18 (13%), HER2 in 3 (2%), KIT in 16 (11%), and PDGFRalpha in 135 (96%). HER2 amplification was found in 2/130 (1.5%) PETs. KIT membrane immunostaining was significantly associated with tumour aggressiveness and shorter patient survival. PET cell lines QGP1, CM and BON harboured mutations in FGFR3, FLT1/VEGFR1 and PIK3CA, respectively. CONCLUSIONS: Only rare PET cases, harbouring either HER2 amplification or KIT mutation, might benefit from targeted drugs. KIT membrane expression deserves further attention as a prognostic marker. ATM mutation is involved in a proportion of PET. The finding of specific mutations in PET cell lines renders these models useful for preclinical studies involving pathway-specific therapies.

Increased risk for non-autoimmune hypothyroidism in young patients with congenital heart defects.

CONTEXT: Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels. OBJECTIVE: Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD. DESIGN AND SETTING: We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology. PATIENTS: Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD. INTERVENTION: Subjects underwent hormonal and genetic screening. MAIN OUTCOME MEASURES: Serum TSH and thyroid hormone levels were assessed. RESULTS: Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 µU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 µU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence. CONCLUSIONS: CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.

Acoustic radiation force impulse (ARFI) ultrasound imaging of pancreatic cystic lesions.

PURPOSE: To evaluate the ARFI ultrasound imaging with Virtual Touch tissue quantification in studying pancreatic cystic lesions, compared with phantom fluid models. MATERIALS AND METHODS: Different phantom fluids at different viscosity or density (water, iodinate contrast agent, and oil) were evaluated by two independent operators. From September to December 2008, 23 pancreatic cystic lesions were prospectively studied. All lesions were pathologically confirmed. RESULTS: Non-numerical values on water and numerical values on other phantoms were obtained. Inter-observer evaluation revealed a perfect correlation (rs=1.00; p<0.0001) between all measurements achieved by both operators per each balloon and fluid. Among the pancreatic cystic lesions, 14 mucinous cystadenomas, 4 pseudocysts, 3 intraductal papillary-mucinous neoplasms and 2 serous cystadenomas were studied. The values obtained ranged from XXXX/0-4,85 m/s in mucinous cystadenomas, from XXXX/0-3,11 m/s in pseudocysts, from XXXX/0-4,57 m/s in intraductal papillary-mucinous neoplasms. In serous cystadenomas all values measured were XXXX/0m/s. Diagnostic accuracy in benign and non-benign differentiation of pancreatic cystic lesions was 78%. CONCLUSIONS: Virtual Touch tissue quantification can be applied in the analysis of fluids and is potentially able to differentiate more complex (mucinous) from simple (serous) content in studying pancreatic cystic lesions.

Cathepsin-k as a diagnostic marker in the identification of micro-granulomas in Crohn's disease.

Crohn's disease is a chronic inflammatory bowel disease, whose aetiology and pathogenesis are still unknown. The occurrence of epithelioid granulomas is one characteristic feature of the disease since these lesions are found in the bowel wall in 50-87% of colectomy specimens. Although granulomas are not pathognomonic, their identification is considered a relevant element for diagnosis. Cathepsin-k, a papain-like cysteine protease, is involved in bone remodelling, and has been widely used as a immunohistochemical marker for the in situ detection of osteoclasts. Interestingly, the expression of this potent protease is also significantly increased in stimulated tissue macrophages, epithelioid cells and granulomas, but is not expressed in resident tissue macrophages. In the present study, we evaluated Cathepsin-k expression as a diagnostic tool in the identification of small granulomas in Crohn's disease. Formalin-fixed and paraffin-embedded samples of 10 cases of Crohn's disease were collected from surgical ileo-colic resections followed by comparison of Cathepsin-k and CD68 immunoreactivity. Granulomas were identified in 4 of 10 cases examined in haematoxylin & eosin preparations. Cathepsin-k enabled the identification of small granulomas (with a diameter between 100 and 200 microm) in 6 of 10 cases, mainly localized within the submucosa and muscular layers. When compared to CD68, Cathepsin-k immunoreactivity was generally absent or only weakly expressed in resting tissue macrophages, thus allowing better identification of activated epithelioid cells. Based on these results, Cathepsin-k appears to be a reliable tool for the precise and rapid identification of small epithelioid granulomas in Crohn's disease.

Resectable pancreatic adenocarcinoma: is the enhancement pattern at contrast-enhanced ultrasonography a pre-operative prognostic factor?

The aim of our study was to determine whether the enhancement pattern of pancreatic adenocarcinoma at contrast-enhanced ultrasonography (CEUS) is related to patient prognosis after resection. CEUS of 42 resected adenocarcinomas were retrospectively reviewed. Tumors were divided into two groups: group A=poorly vascularized (presence of avascular areas) or group B=well vascularized (absence of avascular areas). All lesions were resected and underwent pathological examination assessing tumor differentiation as: undifferentiated (poorly differentiated) or differentiated (moderately and well differentiated). Mean vascular density (MVD) was also evaluated. CEUS enhancement and pathology were correlated (Spearman's test). Survival was analyzed with the Kaplan-Meier method. Multivariate analysis was performed with the Cox regression model. There were 30 differentiated and 12 undifferentiated adenocarcinomas at pathology. At CEUS, 10 lesions were poorly vascularized, whereas 32 lesions were well vascularized. Positive correlation was observed between CEUS groups and tumoral differentiation (rs=0.51; p=0.001) and between CEUS and MVD (rs=0.74; p<0.0001). Median survival in patients with group A vascularization at CEUS was significantly lower than in group B (p=0.015). Cox proportional hazard model revealed the presence of poorly vascularized tumor at CEUS (p=0.0001) as a predictor of higher mortality. In conclusion, CEUS enables accurate depiction of the vascularization of adenocarcinoma, with positive correlation to histology grade and MVD.

Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas.

BACKGROUND: The role of debulking surgery in metastatic nonfunctioning pancreatic endocrine carcinomas (M-NF-PECs) with resectable primary tumour and unresectable liver metastases is debated. AIM: Aim of the study is to evaluate whether the resection of the primary tumour in metastatic nonfunctioning pancreatic endocrine carcinoma improves survival. PATIENTS AND METHODS: Fifty-one metastatic nonfunctioning pancreatic endocrine carcinoma patients with unresectable liver metastases were enrolled from 1990 to 2004 at the time of diagnosis. Nineteen patients underwent complete resection of the primary tumour whilst 32 were judged unresectable. All cases were classified according to the WHO 2000 classification. All clinico-pathological parameters, including grade of differentiation and the Ki-67 proliferation index were considered in univariate and multivariate models. RESULTS: Of the 19 resected patients, 14 (73.7%) underwent left-pancreatectomy and 5 (26.3%) pancreaticoduodenectomy. In the unresected group of 32 patients, 9 (28.1%) underwent surgical biliary and/or gastric by-pass. There was no postoperative mortality and the median survival was 54.3 months (95% CI: 25.7-82.9). No difference in survival was observed between the two groups [resected: median 54.3 months (95% CI: 25-83.6), unresected: median 39.5 months (95% CI: 5.4-73.6); p=0.74]. Upon multivariate analysis poor differentiation (HR 3.01; 95% CI 1.08-8.4; p=0.035) and a Ki-67 index > or = 10% (HR 4.4; 95% CI 1.2-16.1; p=0.023) were significant predictors of survival. CONCLUSIONS: Resection of the primary pancreatic tumour in metastatic nonfunctioning pancreatic endocrine carcinoma patients with unresectable liver metastases does not significantly improve survival. Resection can be considered as symptomatic palliative therapy in patients with well-differentiated endocrine carcinomas and a proliferative index lower than 10%.

Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours.

BACKGROUND: Non-functioning pancreatic endocrine tumours (NF-PETs) are an aggressive gastroenteropancreatic neoplasm. The present study assessed survival, value of World Health Organisation (WHO) classification and prognostic utility of clinicopathological parameters at diagnosis. PATIENTS AND METHODS: From 1990 to 2004, 180 patients with NF-PETs were entered in a prospective database, and predictors of prognosis were tested in uni- and multivariate models. RESULTS: There were 25 (14%) benign lesions, 38 (21%) neoplasms of uncertain behaviour, 100 well-differentiated carcinomas (56%) and 17 poorly differentiated carcinomas (9%). Radical resection was possible in 93 cases (51.6%). Overall 5-, 10- and 15-year survival rates were 67%, 49.3% and 32.8%, respectively, and were significantly higher in radically resected patients (93%, 80.8% and 65.2%, respectively; P < 0.00001). By multivariate analysis, poor differentiation [hazard ratio (HR) 7.3; P = 0.0001], nodal metastases (HR 3.05; P = 0.02), liver metastases (HR 3.29; P = 0.003), K(i)-67 >5% (HR 2.5; P = 0.012) and weight loss (HR 3.06; P = 0.001) were significantly associated with mortality. CONCLUSION: This study confirms the good long-term survival of patients with NF-PETs and the prognostic value of WHO classification, liver metastases, poor differentiation, Ki-67, nodal metastases and weight loss. These latter two parameters have a prognostic value similar to that of liver metastases and Ki-67.

Independent prognostic value of fascin immunoreactivity in stage III-IV colonic adenocarcinoma.

Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas.