Laparoscopic ventral/incisional hernia repair: updated Consensus Development Conference based guidelines [corrected].

BACKGROUND: The Executive board of the Italian Society for Endoscopic Surgery (SICE) promoted an update of the first evidence-based Italian Consensus Conference Guidelines 2010 because a large amount of literature has been published in the last 4 years about the topics examined and new relevant issues. METHODS: The scientific committee selected the topics to be addressed: indications to surgical treatment including special conditions (obesity, cirrhosis, diastasis recti abdominis, acute presentation); safety and outcome of intraperitoneal meshes (synthetic and biologic); fixing devices (absorbable/non-absorbable); abdominal border and parastomal hernia; intraoperative and perioperative complications; and recurrent ventral/incisional hernia. All the recommendations are the result of a careful and complete literature review examined with autonomous judgment by the entire panel. The process was supervised by experts in methodology and epidemiology from the most qualified Italian institution. Two external reviewers were designed by the EAES and EHS to guarantee the most objective, transparent, and reliable work. The Oxford hierarchy (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence") was used by the panel to grade clinical outcomes according to levels of evidence. The recommendations were based on the grading system suggested by the GRADE working group. RESULTS AND CONCLUSIONS: The availability of recent level 1 evidence (a meta-analysis of 10 RCTs) allowed to recommend that not only laparoscopic repair is an acceptable alternative to the open repair, but also it is advantageous in terms of shorter hospital stay and wound infection rate. This conclusion appears to be extremely relevant in a clinical setting. Indications about specific conditions could also be issued: laparoscopy is recommended for the treatment of recurrent ventral hernias and obese patients, while it is a potential option for compensated cirrhotic and childbearing-age female patients. Many relevant and controversial topics were thoroughly examined by this consensus conference for the first time. Among them are the issue of safety of the intraperitoneal mesh placement, traditionally considered a major drawback of the laparoscopic technique, the role for the biologic meshes, and various aspects of the laparoscopic approach for particular locations of the defect such as the abdominal border or parastomal hernias.

WNT-pathway components as predictive markers useful for diagnosis, prevention and therapy in inflammatory bowel disease and sporadic colorectal cancer.

The key role of the Wnt/ß-catenin signaling in colorectal cancer (CRC) insurgence and progression is now recognized and several therapeutic strategies targeting this pathway are currently in developing. Wnt/ß-catenin signaling not only dominates the early stages of sporadic colorectal cancer (SCC), but could also represent the connection between inflammatory bowel diseases (IBD) and increased risk of developing SCC. The knowledge on the sequential molecular events of Wnt-signaling cascade in IBD and during colorectal carcinogenesis, might provide new diagnostic/prognostic markers and could be helpful for optimizing the treatment protocols, thus improving the efficacy of Wnt-targeting therapies. We performed a comparative evaluation of the expression of some crucial molecules participating to Wnt signaling in an animal model of chemically-induced CRC and in human tissues obtained from patients suffering from IBD or at sequential stages of SCC. Specifically, we analyzed upstream events of Wnt signaling including ß-catenin nuclear translocation and loss of E-cadherin and APC functions, and downstream events including c-Myc and Cyclin-D1 expression. We demonstrated that these crucial components of the Wnt/ß-catenin pathway, when evaluated by immunohistochemistry using a multiparametric approach that includes the analyses of both expression and localization, could be potent markers for diagnosis, prevention and therapy in IBD and SCC, also possessing a predictive value for responsiveness to Wnt-targeting therapies. Furthermore, we showed that the animal model of chemically-induced CRC mimics the molecular events of Wnt signaling during IBD and SCC development in humans and may therefore be suitable for testing chemopreventive or therapeutic drugs targeting this pathway.

Long-term analysis of gemcitabine-based chemoradiation after surgical resection for pancreatic adenocarcinoma.

PURPOSE: To evaluate the efficacy in terms of local control (LC) of 24 h infusion of gemcitabine plus radiotherapy after surgery for pancreatic cancer. METHODS: Weekly gemcitabine (100 mg/m(2)) was provided as a 24-hour infusion during the course of radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). Patients subsequently received five cycles of gemcitabine monochemotherapy (1,000 mg/m(2) 1, 8, q21). The primary end point of the study was to achieve a 2-year LC rate of ≥80 % with type I and II errors of 5 and 20 %. The study was designed to accrue a maximum sample size of 35 patients. Secondary end points were toxicity evaluation, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Data of 35 patients were available. Most of the patients (n = 27; 77.1 %) had duodeno-cephalo-pancreatectomy, 5 (14.3 %) distal pancreatectomy, and 3 (8.6 %) total pancreatectomy. The pathological stages were T1-T2 (n = 7; 20.0 %), T3-T4 (n = 28; 80.0 %), N0 (n = 17; 48.6 %), and N1 (n = 18; 51.4 %). Thirty patients (85.7 %) completed chemoradiation. Twenty-three patients (65.7 %) received further sequential chemotherapy. Acute toxicity was acceptable. No late toxicity occurred. The median follow-up period was 64 (range 24-118) months, and 2-year crude rate of LC was 83 (median not reached). Median MFS and OS were 26.5 and 22.5 months, respectively. CONCLUSIONS: The rate of LC met the main goal of the study. The regimen resulted in a high LC rate but failed to show a benefit in terms of OS or MFS, thus suggesting the need for a more intensified multimodal approach.

External beam radiotherapy plus 24-hour continuous infusion of gemcitabine in unresectable pancreatic carcinoma: long-term results of a phase II study.

PURPOSE: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). METHODS AND MATERIALS: Weekly gemcitabine (100 mg/m(2)) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m(2); 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. RESULTS: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). CONCLUSIONS: Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

MUC2 but not MUC5 expression correlates with prognosis in radically resected pancreatic cancer patients.

INTRODUCTION: 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 tumor. The present study investigated the prognostic role of MUC2 and MUC5 apomucin expression in a series of surgically resected pancreatic cancer patients. RESULTS: By univariate analysis, survival was influenced by MUC2 expression but not by MUC5 expression. The MUC2 overexpression was associated with better prognosis (p = 0.003). By a multivariate Cox regression analysis, MUC2 overexpression maintained the prognostic statistical value. In particular, patients with high MUC2 staining showed a longer survival. Moreover the present study does report the absence of a prognostic role of MUC5 expression in this type of cancer. MATERIAL AND METHODS: All patients affected by pancreatic ductal adenocarcinoma and treated with surgical resection from 1988-2003 were considered for the study. MUC2 and MUC5 expression were evaluated by immunohistochemical staining. Tumor specimens of 59 resected patients were included in the study. CONCLUSIONS: The study demonstrated the prognostic relevance of MUC2 expression in pancreatic cancer and underlined its potential role as target gene in the field of therapy research.

[Laparoscopic repair of incisional and ventral hernia]. / Trattamento laparoscopico delle ernie incisionali e ventrali della parete addominale.

The application of laparoscopic principles to ventral or incisional hernia repair has recently been shown to be a safe and effective alternative to open procedures. In this study we analyzed our recent experience with laparoscopic incisional-ventral hernia repair. The outcomes of 75 consecutive patients (January 2002 to July 2006) who underwent laparoscopic repair for incisional-ventral hernia were reviewed. Patient's demographics, hernia parameters, and intraoperative and postoperative data were collected. Of the 75 patients, 44 were females and 31 males. Mean age was 59.1 yrs (range 29-80 yrs). Mean BMI was 25.9 (range 19.4-36.7). Twenty-one patients had primary ventral hernias while 54 patients had an incisional hernia. Fifty-three patients had a single defect and 22 patients multiple defects. In 45 cases the incisional hernia was a primary hernia; in 4 cases it was a first recurrence; in 2 cases a 2nd recurrence; and in 3 cases a 3rd recurrence. The mean defect size was 52,7 cm2 (range 4-432). Laparoscopic hernia repair was successfully performed in 71 cases (94.7%). The mean mesh size was 211 cm2 (range 63-694). Mean operating time was 101 min (range 50-220 min). The mean hospital stay was 4.7 days. The postoperative morbidity rate was 14%. After a mean follow-up of 24.6 months (range 7-56) the recurrence rate was 7% (5/71). Laparoscopic repair of incisional-ventral hernias seems to be safe and effective. Medium-term outcomes were promising with a relatively low rate of conversion to open surgery, a low complication rate and a low risk of recurrence.

[Immediate and long-term results after laparoscopic primary ventral hernia repair]. / La chirurgia laparoscopica nelle ernie ventrali primitive della parete addominale: risultati immediati ed a distanza.

OBJECTIVE: Umbilical and epigastric hernias are relatively frequent amounting to about 10% of all primary hernias. The aim of this study was to evaluate the efficacy and safety of laparoscopic primary ventral hernia repair. MATERIAL AND METHODS: From January 2002 through July 2007 a total of 23 consecutive patients were treated by laparoscopy for primary ventral hernia. Main demographics, intraoperative and postoperative data were collected. RESULTS: There were 14 males and 9 females with a mean age of 53.1 yrs (range 28-70 yrs). Mean body mass index was 25.2 kg/m2 (range 19.4 - 35.2). Fifteen patients had an umbilical hernia, 6 patients had an epigastric hernia and 2 a Spigelian hernia. Mean defect size was 8,4 cm2 (range 1.7 - 81.6). Mean mesh size was 115.9 cm2 (range 62.8-310.8). Mean operating time was 76.1 min (range 50-130). Mean hospital stay was 3,4 days (range 2-8). The median postoperative pain score (evaluated by a visual analog scale - VAS) was 2 at day 1, 4 at day 3 and 1 at day 7. Morbidity rate was 4.3%. After a mean follow-up of 28.5 months none recurrences were observed. CONCLUSIONS: Our study confirmed the feasibility of laparoscopic repair in terms of postoperative morbidity and recurrence rate. Thus laparoscopic primary ventral hernia repair should be considered an effective alternative to open techniques.

COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters.

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.

Apoptotic index or a combination of Bax/Bcl-2 expression correlate with survival after resection of pancreatic adenocarcinoma.

In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl-2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty-seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl-2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico-pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumor's overexpression of both Bax and Bcl-2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl-2 represents the strongest prognostic factor.

Cavernous hemangioma of the gallbladder. Case report and review of the literature.

UNLABELLED: Hemangiomas are common benign tumors; they frequently occur in the liver but very rarely in the gallbladder, with only seven cases reported in the scientific literature to date. We here report an additional patient, a 49-year-old white woman presenting with an echogenic lesion of the gallbladder that was incidentally discovered. Cholecystectomy was performed after computed tomography had revealed a gallbladder neoplasm; pathological examination showed the mass to be a cavernous hemangioma. No postoperative complications occurred and the patient is alive and free of recurrence five years after the operation. We present a review of the literature on this topic with special emphasis on the diagnostic and therapeutic challenges these lesions may entail. Hemangiomas of the gallbladder may have extremely variable presentations (from non-specific abdominal pain to acute syndromes resembling cholangitis or choledocholithiasis) and can mimic different lesions (liver tumors, sarcoma). Only surgical exploration can provide a correct diagnosis. Excision is indicated as these lesions may grow to huge sizes, compress adjacent structures or bleed. CONCLUSIONS: Gallbladder hemangiomas are uncommon benign tumors. A preoperative diagnosis is difficult to make. Surgical excision is mandatory both in reaching a final diagnosis and in preventing bleeding or compression of vital structures.

Gastric adenocarcinoma associated with granulomatous gastritis. Case report and review of the literature.

AIMS: We describe the fourth reported case of granulomatous gastritis associated with gastric adenocarcinoma, with a review of the literature and considerations about the prognostic implications of this association. RESULTS: A 48-year-old woman who had been suffering from gastritis for ten years was admitted to our institute for increasing left epigastric pain associated with vomiting. After an endoscopic biopsy had revealed an ulcerated signet ring cell carcinoma, the patient was submitted to subtotal gastrectomy with regional lymph node dissection. Pathological examination of the resected specimen revealed a superficial signet ring cell carcinoma (early cancer) associated with multiple granulomas. The granulomas, which were observed within the mucosa and the submucosa at the periphery of the carcinoma, were composed of CD68-positive, CD15-negative epithelioid and giant cells of the Langhans type, confirming their true histiocytic nature, and were also extensively found within the dissected lymph nodes. Since no ocular, skin, pulmonary or other gastrointestinal lesions were found and the granulomas were negative for acid-fast and fungal stain, a diagnosis of granulomatous gastritis was made. CONCLUSIONS: To the best of our knowledge this is the fourth example of gastric adenocarcinoma and granulomatous gastritis. These cases suggest an association between granulomatous gastritis and early gastric cancer.