Is the 2-cm size cutoff relevant for small nonfunctioning pancreatic neuroendocrine tumors: A French multicenter study.

BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are often discovered at a small size. No clear consensus exists on the management of NF-PNETs ≤ 2 cm. The aim of our study was to determine the prognostic value of indicators of malignancy in sporadic NF-PNETs ≤ 2 cm. METHODS: Eighty patients were evaluated retrospectively in 7 French University Hospital Centers. Patients were managed by operative resection (operative group [OG]) or observational follow-up (non-OG [NOG]). Pathologic characteristics and outcomes were analyzed. RESULTS: Sixty-six patients (58% women) were in the OG (mean age, 59 years; 95% CI, 56.0-62.3; mean tumor size, 1.6 cm; 95% CI, 1.5-1.7); 14 (72% women, n = 10) were in the NOG (mean age, 63 years; 95% CI, 56-70; mean tumor size, 1.4 cm; 95% CI, 1.0-1.7). All PNETs were ranked using the European Neuroendocrine Tumor Society grading system. Fifteen patients (19%) had malignant tumors defined by node or liver metastasis (synchronous or metachronous). The median disease-free survival was different between malignant and nonmalignant PNETs, respectively: 16 (range, 4-72) versus 30 months (range, 1-156; P = .03). On a receiver operating characteristic (ROC) curve, tumor size had a significant impact on malignancy (area under the curve [AUC], 0.75; P = .03), but not Ki-67 (AUC, 0.59; P = .31). A tumor size cutoff was found on the ROC curve at 1.7 cm (odd ratio, 10.8; 95% CI; 2.2-53.2; P = .003) with a sensitivity of 92% and a specificity of 75% to predict malignancy. CONCLUSION: Based on our retrospective study, the cutoff of 2 cm of malignancy used for small NF-PNETs could be decreased to 1.7 cm to select patients more accurately.

Salivary MicroRNA in Pancreatic Cancer Patients.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer death in Western countries, with the lowest 1-year survival rate among commonly diagnosed cancers. Reliable biomarkers for pancreatic cancer diagnosis are lacking and are urgently needed to allow for curative surgery. As microRNA (miRNA) recently emerged as candidate biomarkers for this disease, we explored in the present pilot study the differences in salivary microRNA profiles between patients with pancreatic tumors that are not eligible for surgery, precancerous lesions, inflammatory disease or cancer-free patients as a potential early diagnostic tool. METHODS: Whole saliva samples from patients with pancreatic cancer (n = 7), pancreatitis (n = 4), IPMN (n = 2), or healthy controls (n = 4) were obtained during endoscopic examination. After total RNA isolation, expression of 94 candidate miRNAs was screened by q(RT)PCR using Biomark Fluidgm. Human-derived pancreatic cancer cells were xenografted in athymic mice as an experimental model of pancreatic cancer. RESULTS: We identified hsa-miR-21, hsa-miR-23a, hsa-miR-23b and miR-29c as being significantly upregulated in saliva of pancreatic cancer patients compared to control, showing sensitivities of 71.4%, 85.7%, 85,7% and 57%, respectively and excellent specificity (100%). Interestingly, hsa-miR-23a and hsa-miR23b are overexpressed in the saliva of patients with pancreatic cancer precursor lesions. We found that hsa-miR-210 and let-7c are overexpressed in the saliva of patients with pancreatitis as compared to the control group, with sensitivity of 100% and 75%, and specificity of 100% and 80%, respectively. Last hsa-miR-216 was upregulated in cancer patients as compared to patients diagnosed with pancreatitis, with sensitivity of 50% and specificity of 100%. In experimental models of PDAC, salivary microRNA detection precedes systemic detection of cancer cells markers. CONCLUSIONS: Our novel findings indicate that salivary miRNA are discriminatory in pancreatic cancer patients that are not eligible for surgery. In addition, we demonstrate in experimental models that salivary miRNA detection precedes systemic detection of cancer cells markers. This study stems for the use of salivary miRNA as biomarker for the early diagnosis of patients with unresectable pancreatic cancer.

Pelvic exenterations for specific extraluminal recurrences in the era of total mesorectal excision: is there still a chance for cure?: a single-center review of patients with extraluminal pelvic recurrence for rectal cancer from March 2004 to November 2010.

BACKGROUND: The benefits in terms of curative resection and survival of pelvic exenterations for specific extraluminal pelvic recurrences from rectal cancer in the era of total mesorectal excision were assessed. METHODS: We conducted a single-center review of patients with extraluminal pelvic recurrence from colorectal cancer between March 2004 and November 2010. Twenty-seven pelvic exenterations (13 posterior and 14 total) were performed. Independent predicative factors such as age, sex, local control on first surgery, pelvic sidewall excision, initial International Union Against Cancer (UICC) staging, sphincter-preserving resection at first surgery, tumor presentation on computed tomography and magnetic resonance imaging (pelvis sidewall involvement, number of fixation sites, ureteral involvement), local disease-free interval, previous symptoms, and postoperative treatment were analyzed. RESULTS: No operative mortality was noted in this series. Overall morbidity rate was 74%; 22% of the patients developed severe complications. Complete surgical clearance (R0) was obtained in 63% of the patients. The rate of R0 resections was lower in total pelvic exenteration (57%) than in posterior pelvic exenteration (69%). Three years overall survival and disease-free survival were 76% and 59%, respectively. Curative resection (R0) was the only independent prognostic factor for overall survival (P = .0016) and disease-free survival (P < .0001). CONCLUSION: Pelvic exenterations for extraluminal pelvic recurrences from rectal cancer afford a high R0 resection rate with acceptable morbidity.

MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer.

Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma (PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients (80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are desperately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC.

Recurrence risk after Ivor Lewis oesophagectomy for cancer.

OBJECTIVE: The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy. METHODS: Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively. Univariate and multivariate survival analyses were performed. RESULTS: One hundred and twenty patients were analyzed. Fifty three patients (44%) presented recurrence during median follow-up of 58 months. Five-year relapse free survival (RFS) rate was 51% (95%CI = [46; 65%]). On multivariate analysis, pT stage > 2 (HR = 2.42, 95%CI = [1.22; 4.79] p = 0.011), positive lymph node status (HR = 3.69; 95% CI = [1.53; 8.96] p = 0.004) and lymph node ratio > 0.2 (HR = 2.57; 95%CI = [1.38; 4.76] p = 0.003) were associated with a poorer RFS and their combination was correlated to relapse risk. Moreover, preoperative tumor stenosis was associated with an increased risk of local recurrence (HR = 3.46; 95% CI = [1.38; 8.70] p = 0.008) whereas poor or undifferentiated tumor was associated with an increased risk of distant recurrence (HR = 3.32; 95% CI = [1.03; 10.04] p = 0.044). CONCLUSION: pT stage > 2, positive lymph node status and lymph node ratio > 0.2 are independent prognostic factors of recurrence after Ivor-Lewis surgery for cancer. Their combination is correlated with an increasing risk of recurrence that may argue favorably, in addition with preoperative tumor stenosis assessment, for adjuvant treatment or reinforced follow-up.

miRNA in clinical practice: pancreatic cancer.

To date, pancreatic cancer (PDAC) can't be diagnosed early. Consequently, a majority of patient (80%) display an advanced disease that results in a low resection rate leading to an overall median survival of 4 to 6months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are desperately needed to help alleviate the dismal prognosis of this disease. In this chapter, we review the translational studies demonstrating that miRNAs, alone or in combination, may soon translate into clinical applications as long-awaited screening tools for PDAC.