Surgical margins for duodenopancreatectomy.

Microscopic residual tumor (R1) affects prognosis of resected pancreatic head cancer patients. Surgeon's ability, caseload and accuracy of pathological staging affect the rate of R1 resections. The goal of this study was to verify if a standardized histopathological workup of the specimen affects the rate of microscopic residual tumor after PD for cancer. Two groups of specimens were managed with (Group 1, Standardized Group, SG) or without (Group 2, Non Standardized Group, NSG) a standardized histopathological workup reported by the Royal College of Pathologists. Group 1 included 50 cases of PD for periampullary cancer treated between October 2010 and July 2012. Group 2 included 50 cases of PD for periampullary cancer treated between September 2005 and September 2010. The primary endpoint of the study was to verify the differences in terms of R1 rate in the two groups. Correlation between presence/absence of microscopic residual tumor status and local recurrence was also evaluated. The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma (PDAC) (SG: 35; NSG: 31), 15 distal common bile duct cancer (SG: 9; NSG: 6) and 19 cancer of the ampulla of Vater (SG: 6; NSG: 13). The rate of R1 resections resulted higher in the SG (66% vs 10%, p < 0.05). The rate of local recurrence did not differ in the two groups (NSG 23.4%, SG 27.6%). No relationships were found between R1 status and development of local recurrence in both groups. Local recurrence occurred in 20% of R1-NSG and in 34.3% of R1-SG. Our study showed that the standardized method determines a significant increase of R1 resection if compared with other non-standardized methods. This difference is due to the different definition of minimum clearance (0-mm- vs 1-mm rule). Even if not significantly, the standardized method seems to better discriminate the patients in terms of local recurrence risk after R1 vs R0 in SG (34 vs 11%) in comparison with R1 vs R0 in NSG (20 vs 27%).

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

Complete pathological response after FOLFIRINOX for locally advanced pancreatic cancer. The beginning of a new era? Case report and review of the literature.

Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.

Complementary use of local excision and transanal endoscopic microsurgery for rectal cancer after neoadjuvant chemoradiation.

BACKGROUND: Neoadjuvant therapies have significantly improved local control and survival of patients with rectal cancer. Nevertheless, although a complete pathologic response can be achieved in 30% of cases, a transabdominal surgical resection is always required. This study aimed, for the first time, to test in the literature the feasibility of local excision combined with transanal endoscopic microsurgery (TEM) as a surgical option for patients treated with neoadjuvant chemoradiation. METHODS: Between July 1997 and December 2002, 30 patients with rectal cancer affected by an extraperitoneal tumor entered a protocol consisting of neoadjuvant chemoradiation followed by surgery. The surgical treatment, consisting of open surgery, local excision, or TEM, was planned according to the patient's clinical response after chemoradiation and distance from the anal verge. RESULTS: A significant clinical downstaging was observed in eight patients. Five of these patients underwent TEM, and three had local excision. Consequently, open surgery was performed for 22 patients. Histology showed six cases of complete pathologic response: three in the open surgery group and three in the transanal excision group. After a mean follow-up period of 47 months, the disease-free survival rate was 77% in the open surgery group and 100% in TEM or local excision group. CONCLUSIONS: The findings suggest the complementary feasibility of TEM and local excision after neoadjuvant chemoradiation. However, randomized trials are needed to confirm the oncologic safety of this approach.

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.

Prognostic factors after surgery for locally recurrent rectal cancer: an overview.

PURPOSE: Local recurrence of rectal cancer occurs in a considerable group of patients who have undergone radical treatment for primary tumour. The treatment of choice is surgical resection but the prognosis remains poor, as a negative margin excision is possible in only a small subset of patients. A review of prognostic factors for locally recurrent rectal cancer (LRRC) after surgery is presented. METHODS: We systematically reviewed the literature for reports on prognostic factors after surgical excision of LRRC. These reports were identified through a review of the Medline database from 1982 to 2004. RESULTS: This review highlights the most important prognostic factors for LRRC patients treated with surgery. Data are grouped on the basis of the prognostic factors investigated. CONCLUSIONS: R0 resection seems to be the only reliable prognostic factor; however, symptoms, pre-operative CEA doubling time, performance status and pre-operative radiotherapy can help patient selection before surgery. The results of this review provide the basis for improved outcome, aiming to assess patients who would benefit from reoperation.

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients.

Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P = 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P = 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P = 0.0142). By a multivariate Cox regression analysis, both the nuclear (P = 0.002) and cytoplasmic (P = 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.

Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma.

BACKGROUND: There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma. AIMS: To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer. METHODS: All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p = 0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p = 0.001, p = 0.01, and p = 0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p = 0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p = 0.020). CONCLUSIONS: These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.

[Cerebellar metastasis from pancreatic adenocarcinoma: report of a clinical case]. / Metastasi cerebellare da adenocarcinoma del pancreas descrizione di un caso clinico.

We describe a case of a metacronous cerebellar metastasis from pancreatic adenocarcinoma occurred in a 67 years old male. Central nervous system metastases from pancreatic carcinoma are mostly autoptic findings. To our knowledge, this is the first case reported in literature of cerebellar metastasis from pancreatic cancer; furthermore, this case calls attention on vomit presentation that could be erroneously attributed to an abdominal relapse. Due to the increasing frequency of central nervous system metastases observed in recent years in other types of cancer, some authors speculate that this event could represent a consequence of the prolonged natural history as the result of improved survival.

Oxaliplatin may induce cytokine-release syndrome in colorectal cancer patients.

INTRODUCTION: Oxaliplatin, a third-generation platinum analogue, is a novel compound with proven anti-tumor activity in colorectal cancer. Moreover, oxaliplatin appears to be relatively well tolerated and easy to handle, even on an outpatient basis. PATIENTS AND METHODS: Five advanced colorectal cancer patients treated with oxaliplatin-based chemotherapy developed, after the end of oxaliplatin infusion, similar idiosyncratic reactions characterized by chills, high fever, hypotension, abdominal pain, nausea and often diarrhoea. Venous blood for IL-6 and TNF-alpha assessment was drawn just after the beginning of the reaction and 15 and 30 minutes later. After drawing the third venous sample, intravenous dexamethasone (8 mg) was administered and the drawing of other two venous samples was performed (180 and 360 minutes after the beginning of the reaction). RESULTS: TNF-alpha and IL-6 serum concentrations significantly decreased after steroid therapy administration. The decrease of TNF-alpha and IL-6 levels went along with the clinical complete regression of symptoms and signs in all the 5 patients. No statistically significant correlation was found between other laboratory parameters and basal cytokine levels or cytokine decrease after steroid therapy. DISCUSSION: Our results clearly show that that idiosyncratic reaction observed in colorectal cancer patients after oxaliplatin infusion may be due to a massive release of cytokines such as TNF-alpha and IL-6. Symptom regression following steroid therapy administration went along with significant decrease of cytokines levels, confirming that TNF-alpha and IL-6 play a role in the pathogenesis of this reaction.

Reducing the occupational risk of infections for the surgeon: multicentric national survey on more than 15,000 surgical procedures.

The objective of this study was to find the incidence of accidental exposures to blood and body fluids among surgeons during operations and to describe their dynamics. A probabilistic model was also used to predict the cumulative 30-year risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human immunodeficiency virus (HIV) infection and estimate the effect of preventive strategies in reducing this risk. A multicentric prospective survey, based on self-administered questionnaires, was conducted during a period of 6 months in 39 Italian hospitals. As accidental exposure to blood or body fluids occurred in 9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury, such as actual skin puncture or eye contamination, was suffered by the operating surgeon. A needle-stick injury was the commonest accident, and its occurrence was found to vary with the phase of the procedure and its length. The current lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is strongly recommended. The case is also made for the use of a face-shield combined with a permanent change in our surgical practice capable of reducing the current high rate of parenteral injuries.