Adrenomedullin in pancreatic carcinoma. a case-control study of 22 patients

Pancreatic carcinoma is a leading cause of cancer-related death. Reduction of the diagnostic delay is mandatory. Adrenomedullin (AM) is overexpressed in pancreatic cancer. A case-control study including 12 patients with pathological diagnosis of pancreatic carcinoma and 10 healthy controls was conducted at our Institution. Blood samples were obtained at the time of hospitalization and post-operatively for cases. Controls’ samples were obtained from healthy volunteers. AM was measured by using enzyme immunoassay method. AM showed significant increase in pancreatic carcinoma patients vs controls (4.51 ng/ml vs 1.91 ng/ml, p value = 0.04) regardless of tumor stage, differentiation, resecability/unresecability, diabetes. A cut-off of 1.75 ng/ml reaches a sensibility of 83% and a specificity of 70% (p value = 0.0147; CL 95%; AUC 0.767). The increase of AM didn’t correlate with the increase of other common tumor markers (CA 19-9 and CEA), nor direct bilirubin. These data confirm the utility of studying the role of AM in pancreatic cancer, in order to achieve an early diagnosis in high risk populations

Management of duodenal stump fistula after gastrectomy for gastric cancer: systematic review

AIM: To identify the most effective treatment of duodenal stump fistula (DSF) after gastrectomy for gastric cancer. METHODS: A systematic review of the literature was performed. PubMed, EMBASE, Cochrane Library, CILEA Archive, BMJ Clinical Evidence and UpToDate databases were analyzed. Three hundred eighty-eight manuscripts were retrieved and analyzed and thirteen studies published between 1988 and 2014 were finally selected according to the inclusion criteria, for a total of 145 cases of DSF, which represented our group of study. Only patients with DSF after gastrectomy for malignancy were selected. Data about patients' characteristics, type of treatment, short and long-term outcomes were extracted and analyzed. RESULTS: In the 13 studies different types of treatment were proposed: conservative approach, surgical approach, percutaneous approach and endoscopic approach (3 cases). The overall mortality rate was 11.7% for the entire cohort. The more frequent complications were sepsis, abscesses, peritonitis, bleeding, pneumonia and multi-organ failure. Conservative approach was performed in 6 studies for a total of 79 patients, in patients with stable general condition, often associated with percutaneous approach. A complete resolution of the leakage was achieved in 92.3% of these patients, with a healing time ranging from 17 to 71 d. Surgical approach included duodenostomy, duodeno-jejunostomy, pancreatoduodenectomy and the use of rectus muscle flap. In-hospital stay of patients who underwent relaparotomy ranged from 1 to 1035 d. The percutaneous approach included drainage of abscesses or duodenostomy (32 cases) and percutaneous biliary diversion (13 cases). The median healing time in this group was 43 d. CONCLUSION: Conservative approach is the treatment of choice, eventually associated with percutaneus drainage. Surgical approach should be reserved for severe cases or when conservative approaches fail

Recurrence following anastomotic leakage after surgery for carcinoma of the distal esophagus and gastroesophageal junction. a systematic review

BACKGROUND: Esophageal cancer is the ninth most common cancer. The only potentially curative treatment is surgical resection, which unfortunately is still associated with major complications, the most important being anastomotic leakage, currently with an overall rate of up to 26% morbidity. The aim of this systematic review was to evaluate the relationship between anastomotic leakage and recurrence of disease. MATERIALS AND METHODS: A literature search was systematically performed. Seven out of 312 articles dated between 2009 and 2018 fulfilled the selection for a total of 5,433 patients. RESULTS: The frequency of anastomotic leakage ranged from 7.2 to 11.2%. Patients affected by anastomotic leakage had a recurrence rate of 9-56%. CONCLUSION: Closer follow-up or even more aggressive oncological therapy should be considered for patients affected by anastomotic leakage after surgery for carcinoma of the distal esophagus and gastroesophageal junction

Treatment options for PNET liver metastases. a systematic review

Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs

Cancer rate of the indeterminate lesions at low or high risk according to italian system for reporting of thyroid FNA

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome. Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study. Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories. Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy

Misdiagnosed esophageal perforation treated with endoscopic stent placement: a case report

Esophageal perforation has a high rate of mortality. Many strategies have been advocated for its management. Therapeutic options are surgical repair or resection, endoscopic placement of self-expandable metallic stents or, in selected cases, conservative management

Neoadjuvant treatment in pancreatic cance. Evidence-based medicine? A systematic review and meta-analysis

Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16-18.26 months); for resected patients OS was 22.78 months (95% CI 20.42-25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84-10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting

SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer

Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation andmigration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.Peer reviewe

Emergency laparotomy for misdiagnosed biliary cystadenoma originating from caudate lobe

BACKGROUND: Biliary cystadenoma is a rare benign neoplasm, which is often misdiagnosed for a hepatic abscess or a hydatid cyst that tends to recur and is at risk for progression to malignant neoplasm. CASE PRESENTATION: This case describes a 30-year-old woman admitted to our institution in an emergency setting. The patient was originally misdiagnosed as affected by a hepatic hydatid cyst at another hospital, and then emergently treated at our Institution for severe abdominal pain. Histologic evaluation of the cyst showed that it was a biliary cystadenoma and, therefore, the patient underwent a hepatic resection in order to completely remove the lesion. CONCLUSION: Complete excision of any suspicious hepatic cystic lesion remains the best method for diagnosis and treatment of cystadenoma. Incomplete excision of most biliary cystadenoma results in a higher rate of recurrence and the risk of malignant transformation. We report this case to elucidate the clinical presentation, preoperative evaluation, and surgical treatment of these rare lesions

Distal Pancreatectomy with Celiac Axis Resection: Systematic Review and Meta-Analysis

Background: Major vascular invasion represents one of the most frequent reasons to consider pancreatic adenocarcinomas unresectable, although in the last decades, demolitive surgeries such as distal pancreatectomy with celiac axis resection (DP-CAR) have become a therapeutical option. Methods: A meta-analysis of studies comparing DP-CAR and standard DP in patients with pancreatic adenocarcinoma was conducted. Moreover, a systematic review of studies analyzing oncological, postoperative and survival outcomes of DP-CAR was conducted. Results: Twenty-four articles were selected for the systematic review, whereas eleven were selected for the meta-analysis, for a total of 1077 patients. Survival outcomes between the two groups were similar in terms of 1 year overall survival (OS) (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.34 to 1.31, p = 0.24). Patients who received DP-CAR were more likely to have T4 tumors (OR 28.45, 95% CI 10.46 to 77.37, p < 0.00001) and positive margins (R+) (OR 2.28, 95% CI 1.24 to 4.17, p = 0.008). Overall complications (OR, 1.72, 95% CI, 1.15 to 2.58, p = 0.008) were more frequent in the DP-CAR group, whereas rates of pancreatic fistula (OR 1.16, 95% CI 0.81 to 1.65, p = 0.41) were similar. Conclusions: DP-CAR was not associated with higher mortality compared to standard DP; however, overall morbidity was higher. Celiac axis involvement should no longer be considered a strict contraindication to surgery in patients with locally advanced pancreatic adenocarcinoma. Considering the different baseline tumor characteristics, DP-CAR may need to be compared with palliative therapies instead of standard DP