Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Patient-tailored treatments with anti-EGFR monoclonal antibodies in advanced colorectal cancer: KRAS and beyond.

Personalized medicine emphasizes the practice of considering individual patient characteristics as opposed to that centered on standards derived from epidemiological studies which, by definition, do not take into account the variability of individuals within a given population. When applied to oncology, personalized medicine is an even more complex concept because it extends the variability beyond the individual patient to the individual tumor. Indeed, the great genotypic and phenotypic variability (both in primary and metastatic sites of cancer) the development of targeted therapies, and the growing availability of biological assays complicate the scenario of personalized medicine in the oncological field. In this paper we review the results of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy in metastatic colorectal cancer (mCRC) in the context of tumor biology, delineating the future prospects of patient-tailored medicine in this area. In particular, we deal with EGFR inhibition by Cetuximab, a chimeric mouse human IgG1 mAb, and panitumumab, a fully human IgG2 mAb. We discuss the clinical impact of anti-EGFR mAbs on wild-type (WT) KRAS mCRC, also taking into account the feasibility of novel multi-marker approaches to treatment decision-making, aimed at increasing the predictive power of pre-therapy biomarkers. Experimental topics and fields of ongoing research, such as targeting microRNAs (miRNAs) with novel anticancer drugs and epigenetics in CRC are also addressed.

Total mesorectal excision with radiofrequency in rectal cancer: open versus laparoscopy approach.

AIM: The aim of this study was to compare the safety, efficacy and oncologic results in the low rectal resection with total mesorectal excision with radiofrequency (Ligasure™, Covidien, Boulder, CO, USA) in laparoscopic surgery. METHODS: From July 2005 to December 2008, 227 patients underwent colorectal resection for cancer at S. Martino Hospital in Genoa. Sixty-one patients underwent curative rectal resection for mid or low rectal cancer using Ligasure™ device applied on smaller vessels and for the execution of total mesorectal excision. Forty-six patients underwent open laparotomy (OL), 15 laparoscopic surgery. There were no differences concerning demographics data and diagnosis, but only regarding staging (P=0.009). Primary goal was to evaluate major complications, operating time, hospital stay, distal margin of the tumor and number of nodes harvested in specimen. Secondary goal was to assess the average time of survival in the short period. RESULTS: The mean operative times were shorter in the OL group (188 vs. 246 min) overall. This difference was significant (P=0.004). In particular two parameters of specimens were analyzed: the total number of nodes and distal clearing from cancer, excluding abdominoperineal resection. An average number of 16.6 nodes in the OL group and 13.9 in the VL group (P=ns) were detected; mean distal clearing in the OL group was 30.7 mm and 48.1 mm in the VL group (P=ns). There were no differences concerning major complications in either group. The hospital stay in the VL group was shorter than in the OL group, but the differences were not significant. CONCLUSION: The Ligasure™ device does not reduce operating time in laparoscopy rectal cancer resection but it allows to get correct oncologic results in patients submitted to total mesorectal excision.

Gastric Abrikosoff tumor (granular cell tumor): case report.

Granular Cells Tumor (GCT), also called Abrikosoff tumor, is very uncommon lesion of neural derivation. It is characterized by the presence of granular cell; benign and malignamt counterparts are known, even if the second ones are rare. It has a slight predominance in female sex and black race; the age range is wide, with peak between fourth and sixth decades of life. Any localisation is possible, although surface lesions (head, neck, trunk, extremities) are far more common than visceral ones (esophagus, stomach, small and large bowel, larynx, bronchi, gallbladder and biliary tract). Surgical en-block excision is curative for both benign an malignant forms. Radiotherapy and chemotherapy are not effective. We report the case of a 45 year old man who had a cytologic diagnosis of fusocellular stromal tumor of the gastric fundus during examination for gastritis. He underwent a wedge resection of the gastric wall: at the histological examination neoplastic cells had a granular cytoplasm and immunoassay was positive for S100 protein, PGP 9.5 and NSE. Complete excision guarantees from recurrence and metastases: however a long term endoscopic follow-up is necessary.

Survival in surgical palliative resection of stage IV colorectal cancer: short term results in a single institution.

AIM: In this study, we analyze clinical parameters, survival and possible advantage of surgery in patients affected by symptomatic Dukes D colorectal cancer. METHODS: From July 2005 to December 2008 at our Oncological Surgery Unit we treated 69 symptomatic stage IV CRC, 46 of them resected at our Oncological Surgical Unit. Clinical variables were tested for their relationship to survival in a univariate prognostic analysis and revealed the interaction of the prognostic factors. RESULTS: In symptomatic stage IV CRC with non-curable resection, the most robust univariate predictor for poor prognosis was impossibility to cancer resection. It is associated with significative decrease of survival also in the short term. In our series we do not observe correlation between poor prognosis and age, gender, localisation of tumor, depth of invasion, 19.9 and surgeons. CEA more than 100 microg/L and impossibility to adiuvant therapy have a significative role and are associated with poor prognosis. CONCLUSION: Our results suggested that impossibility to perform cancer resection is associated with poor prognosis in symptomatic stage IV CRC and worse survival also in the short term.

[Leakage of colorectal anastomosis after neoadjuvant therapy with bevacizumab. Case report]. / Deiscenza di anastomosi colorettale dopo terapia neoadiuvante con bevacizumab. Case report.

BACKGROUND: Despite progresses achieved in last decades in treatment of rectal cancer, anastomotic leakage remains the main complication. PATIENTS AND METHODS: We report two cases of patients affected by distal rectal cancer. Both patients received neoadjuvant therapy according to ROCHE ML 18522 experimental protocol (Xeloda, Avastin and radiotherapy). After about respectively one and two months after anterior resection of the rectum, with transanal anastomosis and temporary colostomy, presacral abscess occurred. Patients were hospitalized and started antibiotic therapy. In one case it was necessary TC-guided drainage placement. RESULTS: Both patients had a favourable course and, after respectively 6 months and 1 year, underwent closure of colostomy. DISCUSSION: "Spontaneous" gastrointestinal microperforation (small leakage) is reported during treatment with bevacizumab, a monoclonal antibody against Vascular Endothelial Growth Factor (VEGF), also in patients with non gastrointestine tumours. Probably this results from inhibition of neoangiogenesis induced. CONCLUSIONS: Surgeons have to pay attention to adverse effects of combined neoadjuvant treatment of rectal cancer, considering temporary colostomy in presence of particular risk factors.

Factors predicting survival in surgical palliative resection of stage IV colorectal cancer.

AIM: Colorectal cancer (CRC) harbors accumulated genetic alterations with cancer progression, which results in uncontrollable disease. To regulate the most malignant CRC, we have to know the most dismal phenotype of stage IV disease. METHODS: A retrospective review of our Oncological Surgical Unit was performed (from 2005 to 2008) to extract the 52 resected stage IV CRC. Clinical variables were tested for their relationship to survival in a univariate prognostic analysis and revealed the interaction of the prognostic factors. RESULTS: In stage IV CRC with noncurable resection, the most robust univariate predictors for poor prognosis were preoperative high value of CEA. In our series we did not observe correlation between poor prognosis and depth of invasion, age, gender, pathologic lymph node metastasis status, Ca 19.9 and postoperative therapy. The mean average survival rate was 10.9 months. CONCLUSIONS: Our results suggested that only preoperative value CEA is associated with poor prognosis in stage IV CRC.

Lymphadenectomy in elective and urgency surgery for resective colorectal cancer.

AIM: The aim of this study was to analyze the factors affecting the number of lymph nodes examined in colorectal cancer specimens after elective or urgent surgery on the current clinical practice in our surgical unit. METHODS: The authors considered 120 patients who had undergone surgery for colorectal carcinoma from July 2005 to December 2007 divided into two groups, 102 elective oncologic resections (group A) and 18 performed in emergency (group B). All patients underwent laparotomic colorectal resection. The groups were similar in age, weight and body mass index, different in gender e in cancer stage. The authors analyze prognostic differences in number of examined lymph nodes and factors involved in differences between groups. RESULTS: There were no statistically significative differences in number of nodes harvested in specimen (15.85+/-8.17, CI 95% 14.25-17.46 for group A and 13.83+/-6.56, CI 95% 10.57-17.09 for group B, P-value 0.36). Operating time was shorter in group B (P-value 0.012). We not observed differences between groups in survival rate (P-value 0.62). CONCLUSIONS: The results of the study suggest that a correct lymphadenectomy and an adequate lymph node harvest in colorectal cancer surgery is essential also in resections performed in urgency, to allow a correct staging and an accurate selection of patients for adjuvant chemotherapy, with improvement of results at follow-up.

Total mesorectal excision with radiofrequency in rectal cancer.

AIM: The aim of this study was to compare the safety, the efficacy and the oncologic results in rectal cancer with total mesorectal excision using Ligasure (LS), a modern bipolar vessel sealing system, with monopolar electrocoagulation or stitches (ME). METHODS: From July 2005 to December 2007 one hundred twenty-nine patients underwent colon resection for cancer at the San Martino Hospital of Genoa (Italy); 43 patients underwent rectal resection. All patients underwent laparotomy rectal resection with total mesorectal excision; 9 (21%, group LS) underwent total mesorectal excision with radiofrequency, 34 (79%, group ME) with monopolar electrocoagulations, vessels ligation or stitches. Patients of group LS were similar to patients of group ME in age, gender, weight and body mass index. Cancer stage was for group A 3 stage B, 5 stage C and 1 stage D, for group B 4 stage A, 15 stage B, 8 stage C, 6 stage D and 1 non-staged tumor. RESULTS: There were no differences in intraoperative or postoperative complications. Operating time was similar in both group. Oncological results was similar in both groups. The major cost in group LS were attributable to cost of service. CONCLUSION: The Ligasure device does not reduce operating time in laparotomy rectal cancer resection but permit correct oncological results in patients submitted to total mesorectal excision. The costs of device reserved its use to surgery of low-rectal cancer or laparoscopic approach.

Productive infection of HUVEC by HHV-8 is associated with changes compatible with angiogenic transformations.

Kaposi's Sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8) infection. We have characterized the morphologic and phenotypic modifications of HUVEC in a model of productive HHV-8 infection. HHV-8 replication was associated with ultra-structural changes, flattened soma and a loss of marginal folds and intercellular contacts, and morphologic features, spindle cell conversion and cordon-like structures formation. Phenotypic changes observed on cordon-like structures included partial loss and redistribution of CD31/PECAM-1 and VE-cadherin, uPAR up-regulation and de novo expression of CD13/APN. Such changes demonstrate the induction, in HUVEC, of an angiogenic profile. Most of these findings are directly linked to HHV-8-encoded proteins expression, suggesting that HHV-8 itself may participate to the initial steps of the angiogenic transformation in KS.

[Bochdaleck diaphragmatic hernia in adults. Case report]. / Ernia diaframmatica di Bochdaleck nell'adulto. Storia di un caso clinico.

The case of a 27-year-old woman, admitted to our surgical ward with symptoms of epigastric-ache, postmeal vomiting and significant weight loss, is reported. Clinical and radiographic suspicion of mesenterium commune, with duodenal compression due to bands, requested an explorative laparatomy that confirmed the mesenterium commune presence with left caecum and colon adhesion and left Bochdaleck hernia, which is rare in adult age.

An extraluminal leiomyosarcoma of the iliac vein without thrombosis--a case report.

Vascular leiomyosarcoma (LMS)is a rare malignant tumor arising from the muscle cells of the media of the vessels. Vascular LMS is often diagnosed as a result of the clinical manifestations of impaired venous flow such as edema and phlebothrombosis. The authors present a case of an LMS in a 72-year-old woman. Physical examination revealed a round mass deep in the left inguinal region close to the inguinal vessels, fixed and not pulsating. There was no sign of left lower-limb edema nor of articular impairment of the hip. Inguinal and distal pulses were normal. Results of laboratory analysis, including values for the oncologic markers, were normal. An ultrasound scan of the left inguinal fossa showed a 50-by-30 mm mass of mixed aspect that adhered to the left common iliac artery. An echo color Doppler showed conservative arterial flow. Thus, a thrombotic aneurysm of the left iliac artery was diagnosed. Chest x-ray showed no pathological findings. An abdominal computerized tomograph (CT) scan confirmed the location of the neoplasm and revealed a narrowing of the left iliac vein compressed behind the mass. The finding was interpreted as a colliquative lymph node. The patient underwent explorative laparotomy with midline incision. The finding was a neoplastic bilobed mass compressing and infiltrating the left iliac vein with no cleavage surface between the mass itself and the venous wall. An intraoperative frozen section revealed a necrotic mass with a cortex of ambiguous interpretation. Surgical procedure was then finished with no further venous resection. Histologic examination revealed the presence of leiomyosarcomatous tissue with nuclear pleomorphisms inside necrotic material limited by a thin fibrotic capsule. According to Coindre's classification the tumor was a G3. After six months the patient is fit and a CT scan showed no evidence of recurring disease.