Procalcitonin, as an early biomarker of colorectal anastomotic leak, facilitates enhanced recovery after surgery.

PURPOSE: Procalcitonin (PCT) is a biomarker used to help sepsis diagnosing and monitoring and guide antibiotic therapy. Anastomotic leak (AL) after colorectal surgery is a severe complication associated with relevant short- and long-term sequelae. The aim of our study is to assess the predictive value of PCT levels to early diagnose AL after colorectal surgery. METHODS: Between September 2011 and September 2012, a series of 99 patients underwent colorectal surgery in our institution. In all cases, white blood cell (WBC) count, C-reactive protein (CRP), and PCT levels were measured in first, third, and fifth postoperative day (POD). Anastomotic leaks and all other postoperative complications were recorded. RESULTS: We registered 7 ALs (7.1%). Decreased PCT levels had a significant negative predictive value (NPV) for AL in third and fifth POD (96.7% and 96.7%, respectively), compared with CRP and WBC. The best diagnostic performance was obtained with the combination of PCT and CRP measurements in third and fifth POD (area under the curve, 0.87 and 0.94, respectively). In 5th POD, PCT improves diagnosis, but not in a statistically significant way (area under the curve, 0.86). CONCLUSIONS: Compared with more established biochemical values such as CRP and WBC, PCT is an earlier, more sensitive, and reliable marker of AL. Increased PCT levels in early PODs after colorectal surgery may provide a more effective way to detect AL, before clinical symptoms appear. Moreover, normal PCT values might be also a useful marker to facilitate a safe and early discharge of selected patients after colorectal surgery.

The importance of lymph node retrieval and lymph node ratio following preoperative chemoradiation of rectal cancer.

AIM: Preoperative chemoradiation (CRT) for rectal cancer decreases the number of examined lymph nodes (NELN) found in the resected specimen. However, the prognostic role of lymph node evaluation including overall numbers and the lymph node ratio (LNR) in patients having preoperative CRT have not yet been defined. The study has assessed the influence of CRT on the NELN and on lymph node number and LNR on the survival of patients with rectal cancer. METHOD: Between 2003 and 2011, 508 patients with nonmetastatic rectal cancer underwent mesorectal excision. Of these 123 (24.2%) received preoperative CRT. Univariate and multivariate analysis was performed to define the role of NELN and LNR as prognostic indicators of survival. RESULTS: Neoadjuvant CRT significantly reduced the NELN (P < 0.0001). Disease-free survival (DFS) and overall survival (OS) of patients with fewer or more than 12 nodes retrieved did not differ statistically. Node-negative patients with six or fewer lymph nodes were significantly associated with a poor DFS and OS on univariate analysis (P = 0.03 and P = 0.03). LNR significantly influenced the DFS and OS on multivariate analysis [DFS, P = 0.0473, hazard ratio (HR) 2.4980, 95% confidence interval (CI) 1.2631-9.4097; OS, P = 0.0419, HR 1.1820, 95% CI 1.1812-10,710]. CONCLUSION: The cut-off of 12 lymph nodes does not influence survival and should not be considered for cancer-specific prediction of patients having neoadjuvant CRT. In contrast LNR is an independent prognostic predictor of DFS and OS in such patients.

Safety of a new biological adhesive after pancreatic resection.

AIM: Pancreatic fistula (PF) represents the main complication (10%-29%) after pancreatic surgery. Soft pancreatic texture with a not dilated pancreatic duct represent the major risk factors for PF. Mortality after pancreaticoduodenectomy (PD) is reported in several large series to be <5%. PF and local sepsis are the main causes of delayed arterial hemorrage with a high mortality rate (14-38%). Therefore, any effort should be implemented in order to reduce the incidence of PF. METHODS: In the present study we have extended the use of the biological adhesive Bioglue® to coat pancreatic resection surface after distal pancreasectomy (DP, N.=5) and pancreatico-jejunostomy (PJ) after PD (N.=18) in a RESULTS: Operative mortality was observed in 2 instances: one case after PJ leakage (1/18, 5.5%) and one case after DP not related to PF (1/5, 20%). PF has been documented in 7/23 (30,4%) after pancreatic resection, and in all cases after PD. In 3 cases PF has been successfully treated conservatively by NPO and octreotide. 2 patients required radiological percutaneous transhepatic biliary drainage and 2 patients required surgical drainage of multiple intrabdominal collections and radiological PTBD. CONCLUSION: On the basis of these observations Bioglue® can be safely utilized to coat pancreatic surface after DP and pancreatico-jejunostomy after PD. This experience warrants further larger controlled studies of the potential value of Bioglue® in reducing the incidence of PF after major pancreatic surgery.

miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.

Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC.

Clinical-pathological features of gastrointestinal stromal tumors presenting associated with other neoplasms: a brief report.

AIM: Over the past 10 years, few authors reported the synchronous detection of gastrointestinal stromal tumors (GISTs) and other neoplasms in the 9-33% of GISTs series. The primary aim of the present study was of investigating the features of GISTs detected in patients with other malignancies. METHODS: From 1999 to 2010 the GISTs detected at surgical exploration or preoperative assessment for other malignancies plus primary-GISTs, were recorded and reviewed. RESULTS: All synchronous GISTs were positive for kit/CD34, resulting smaller in size, with a lower mitotic index and occurring in elderly patients, comparing with primary-GISTs (P<0.05). Moreover a prevalence of males and of lower-risk classifications were noted, not reaching, however, a statistical value. CONCLUSION: According with our findings, the synchronous GISTs are mainly asymptomatic/incidentally detected and display some of the low malignant features; we recommend, however, the surgical excision of GISTs occurring in patients with other malignancies in order to define the histology and risk features and since it might result in an incorrect management if misdiagnosed as a metastases.

Promptness of diagnosis is the main prognostic factor after colonoscopic perforation.

AIM: The authors present their experience of colonoscopic perforation and its management, with an analysis of factors affecting outcome. METHOD: During the last 10 years, 22 cases of colonoscopic perforation (CP) were identified in two different institutions. Multiple logistic regression analysis was used to identify significant predictors of morbidity and mortality. RESULTS: Morbidity and mortality rates were 31% and 13.6%, respectively. Prompt diagnosis was the most powerful predictor of outcome of CP. Multiple logistic regression analysis showed that morbidity and mortality were significantly related to a delay in diagnosis of more than 24 h (P = 0.03 and P = 0.04). CONCLUSION: The results emphasize the importance of prompt assessment of a patient who develops symptoms after colonoscopy.

Peritoneal washing cytology in gastric cancer. How, when and who will get a benefit? A review.

The most frequent cause of treatment failure following surgery for gastric cancer is peritoneal metastasis. The ability to predict the likelihood of peritoneal recurrence should improve the therapeutic approach to gastric cancer. Cytological analysis of peritoneal washings is thought to be useful for direct detection of free cancer cells in the peritoneal cavity. Intraperitoneal free cancer cells (IFCC) isolated during peritoneal washing in patients with gastric cancer, have been demonstrated to be significantly and independently related to the prognosis, influencing both early recurrence and poor survival, so that since 1998 the Japanese Classification of Gastric Carcinoma (JCGC) recommend peritoneal wash cytology (PWC) for the local staging. In Western countries PWC is not uniform practice, because of several controversies regarding the low sensitivity rate of conventional cytology, the correct application of molecular diagnosis (immunostaining and RT_PCR) and the exact role of PWC in the clinical practice. The authors examine the current apply of peritoneal washing in gastric cancer, emphasizing the clinical implication of peritoneal cytology by analyzing the different modality and techniques to perform it (conventional cytology, immunocytochemistry, RT-PCR), when to achieve it during the diagnostic or clinical work-up (at the staging or during the surgical treatment), and who will get a benefit (all patients or selected patients).

Peritoneal wash cytology in gastric carcinoma. Prognostic significance and therapeutic consequences.

BACKGROUND AND AIMS: The prognosis of patients with gastric cancer is poor, even following curative resection, and is related primarily to the extent of disease at presentation. In locally advanced gastric tumors, peritoneal lavage cytology (PLC) is a relevant prognostic factor. The Authors present their results of peritoneal washing cytology, evaluating the prognostic value of this technique, and discussing the clinical impact. PATIENTS AND METHODS: From July 2003 to May 2008, results of PLC in 64 patients with histologically proven primary gastric adenocarcinomas were analyzed. At laparotomy the abdomen was irrigated with 200 ml of normal saline, and ≥50 ml were aspirated and examined by means of cytology and immunocytopathology. RESULTS: PLC was positive in 7 cases (11%). Overall, 86% of patients with a positive PLC had a pT3/pT4 tumor and 100% with a positive PLC had an N-positive tumor (p < 0.001); 71% of patients with a positive PLC had a grade G3/G4 tumor (p = 0.001). At a median follow-up of 32 months, the cumulative 5-year survival was 28%. The median survival of patients presenting positive PLC (19 months) was significantly lower than that of patients with negative peritoneal cytology (38 months) (p = 0.0001). Multivariate analysis identified cytology as a significant predictor of outcome (p = 0.018). CONCLUSIONS: Results in the present series demonstrated that patients with a positive peritoneal cytology had advanced disease and poor prognosis, thus indicating that patients with locally advanced gastric cancer should undergo staging laparoscopy and PLC examination in order to select those requiring more aggressive treatment. Future therapeutic strategies should include PLC examination in preoperative staging, in order to select patients for more aggressive treatment.

[Pancreaticoduodenectomy for adenocarcinoma of the pancreatic head and papilla of Vater]. / Duodenocefalopancreatectomia per adenocarcinoma della testa del pancreas e della papilla di Vater.

AIM: The authors report their consecutive experience in the surgical management of adenocarcinoma (ADC) of head of pancreas and papilla of Vater, in order to review the available literature. METHODS: One hundred and seventy cases (131 in the head of pancreas and 39 in the papilla of Vater) were operated upon for ADC by radical pancreaticoduodenectomy in the period 1972-2005. The stomach was resected in 81 patients (47.7%) and the pylorus was preserved in 89 (52.3%). Follow-up was completed in all patients. RESULTS: Postoperative morbidity was reported in 66 patients (38.8%) and pancreatic fistulae were observed in 39 patients (22.9%). Postoperative mortality was 9.4% (16 patients), but in the last 10 years it was reduced to 4.1% (4/97 patients). Five-year survival for pancreatic ADC was 75% in stage IA, 43.9% in stage IB and IIA, 3.2% in stage IIB. In ADC of the papilla of Vater, for the same stages, the 5-year survival rates were 54.4%, 51.4%, 0% and 37.5%, respectively. None of the III-staged patients survived at a 5-year follow-up in both groups. CONCLUSIONS: Preoperative studies should include laparoscopy with cytological examination of peritoneal lavage, while preoperative biliary drainage is rarely indicated in case of obstructive jaundice. The Wirsung duct has to be anastomosed directly to the jejunum and the pancreatic section needs to be checked. Extended lymphadenectomy, in addition to the standard peripancreatic excision, is seldom indicated, there is no controindication to pylorus preservation and Wirsung drainage is not necessary. This operation should be performed in Centres with substantial experience.

Outcomes for early rectal cancer managed with transanal endoscopic microsurgery: a 5-year follow-up study.

BACKGROUND: This study aimed to evaluate the long-term risk of local and distant recurrence as well as the survival of patients with early rectal cancer treated using transanal endoscopic microsurgery (TEM). METHODS: The study reviewed 69 patients with Tis/T1/T2 rectal cancer treated using full-thickness excision between 1991 and 1999. The pathology T-stages included 25 Tis, 23 T1, and 21 T2. The median follow-up period was 6.5 years (range 5-10.2 years). RESULTS: The overall local recurrence rate was 8.7%. The 5-year local recurrence rate was 8% for Tis, 8.6% for T1, and 9.5% for T2. All six patients with recurrence were managed surgically. The 5-year disease-specific survival rate was 100% for Tis, 100% for T1, and 70% for T2. The overall cancer-related mortality rate was 7.2%. CONCLUSIONS: After local excision of early rectal cancer, a substantial local recurrence rate is observed. Patients with recurrent Tis/T1 cancers who undergo a salvage operation may achieve good long-term outcome. Local treatment without adjuvant therapy for T2 rectal cancers appears inadequate.

Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma.

BACKGROUND: Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. PATIENTS AND METHODS: 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). RESULTS: Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. CONCLUSIONS: Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.

Comparison between the fifth and sixth editions of the AJCC/UICC TNM staging systems for hepatocellular carcinoma: multicentric study on 393 cirrhotic resected patients.

AIMS: To compare the prognostic efficacy of the 5th and 6th edition of the TNM staging system for HCC. METHODS: We retrospectively applied the old and the new systems to 393 resected patients, comparing the efficacy of both in prognostic evaluation. RESULTS: The 1-, 3- and 5-year overall survival rates were 89.7, 71.1 and 56.3%, respectively. The 1-, 3- and 5-year disease-free survival rates were 79.4, 54.6 and 39.4%, respectively. Among the factors evaluated, Child's grade B and C (p=0.001) and presence of multiple nodules (p=0.01) were found to be related either to a worse long-term survival or to a worse disease-free survival. Stratifying patient survivals according to the old TNM system, we found significant differences only between stages II and IIIA (p=0.001); otherwise stages I and II (p=0.9) as well as stages IIIA and IVA (p=0.9) showed similar survival rates. Analysing the new TNM system, we found a more homogeneous staging stratification, with significant differences both between stage I and II (p=0.02) and between stage II and IIIA (p=0.05). CONCLUSIONS: In the present multicentric study, long term overall and disease-free survival after liver resection for HCC was strongly affected by the number of tumours and the underlying liver disease. Our results suggest that the new classification appears to achieve an accurate stratification of patients, simpler than the previous edition, as well as a more reliable comparative analysis of outcome after hepatic resection for HCC.

Pre-operative assessment of extramural invasion and sphincteral involvement in rectal cancer by magnetic resonance imaging with phased-array coil.

OBJECTIVE: Pre-operative staging of rectal cancer should identify patients with extrarectal spread, who might benefit from pre-operative radiotherapy, and patients with minimal sphincteral involvement, who can avoid permanent colostomy. The aim of this study was to assess the accuracy of Magnetic Resonance Imaging (MRI) to predict tumour stage and sphincter status. PATIENTS AND METHODS: Thirty-three patients with a rectal tumour were pre-operatively assessed by MRI with a phased-array coil. Imaging results were correlated with the final pathological findings. RESULTS: The overall accuracy of pre-operative staging with MRI was 88% (k = 0.75) for extramural tumour invasion and 59% (k = 0.26) for lymph node metastases. MRI correctly evaluated the infiltration of the anal sphincters in 87% of patients (7 of 8 patients with low rectal tumour). CONCLUSION: MRI provides the surgeon with valuable information regarding extramural tumour spread and sphincteral involvement, enabling appropriate selection of patients for pre-operative adjuvant therapy or sphincter-saving surgery.

[Solitary small bowel metastasis after resection of bile duct carcinoma]. / Metastasi ileale solitaria da neoplasia biliare extraepatica precedentemente resecata.

Small bowel solitary metastases are a very rare occurrence and are more frequently recognized only in the presence of a severe complication, such as intestinal hemorrhage or occlusion. We report the case of a 75 year-old man who was admitted with a recent history of mechanical ileus developed one year after the surgical removal of an endoscopically intubated carcinoma of the extrahepatic biliary tree (pT3 pN0 Mx). A solitary metastasis of the small bowel, 30 cm from the ileo-cecal valve, was excised during the emergency laparotomy and a side-to-side anastomosis was performed to reconstruct the intestinal continuity. Patient was, thereafter, discharged in the 9th postoperative day. Local recurrence and intrabdominal dissemination are often observed in patients treated for bilio-pancreatic carcinoma. Preoperative invasive (ERCP, FNA, PTBD, etc.) diagnostic procedures and surgical tumor manipulation are associated with a greater risk of metastasis implantation and intraabdominal dissemination. In accordance to the literature, the authors propose, in cases with resectable bilio-pancreatic neoplasms, the use of standard external low dose radiotherapy prior to any invasive diagnostic procedure and/or surgical removal.

[Ciliated hepatic foregut cysts: a case report]. / Cisti epatiche a derivazione dall'intestino primitivo. Caso clinico.

The ciliated hepatic foregut cysts (CHFC) are uncommon benign lesions with columnar ciliated epithelium covering a connective lapse tissue. They are solitary uniloculate cysts localized in the left lobe of the liver. The diagnosis is made occasionally during autopsy or imaging studies for not related symptoms. The Authors report a case of CHFC with a review of the literature that allowed them to find only 60 cases.

[Multidisciplinary treatment in Budd-Chiari syndrome: clinical case]. / Trattamento multidisciplinare nella sindrome di Budd-Chiari: caso clinico.

Budd-Chiari Syndrome (BCS) is characterized by obstruction of hepatic venous outflow. When obstruction is limited to the suprahepatic veins, portocaval shunting provides an immediate relief of symptoms. If the obstacle results also from narrowing of the inferior vena cava (IVC), multimodality treatments seem to offer safer and easier alternative. In the patient herein reported, combination of side-to-side portocaval anastomosis with a cavo-atrial shunt through an expandible metallic stent provided immediate relief of symptoms. The patient is doing well after 85 months from combined treatment. In conclusion infracaval stenting combined to side-to-side portocaval shunting should represent the treatment of choice in acute or subacute forms of BCS.

Hepatic resections for hepatocellular carcinoma (HCC): short and long-term results on 106 cirrhotic patients.

To evaluate the short and long term outcome of liver resections for hepatocellular carcinoma in cirrhotic patients. A retrospective analysis was performed on 106 consecutive cirrhotic patients with hepatocellular carcinoma resected between June 1974 and September 2002 at the Department of Surgery "Pietro Valdoni" - University of Rome "La Sapienza" and at the Liver and Multivisceral Transplant Unit of the University of Modena. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumour recurrence appeared in 25 patients (23,5%). The 1-, 3-, and 5-year overall survival rates were 86,6%, 70,3%, and 60,6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86,3%, 58,1%, and 40,7%. On univariate analysis, viral ethiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) were found to be related to a worse long-term survival. At the multivariate analysis only the viral ethiology of cirrhosis and the presence of multiple nodules were confirmed as indipendent prognostic factors. Early results after hepatic resection for HCC can be improved by using a limited surgical approach. The viral ethiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.