Antonio Bolognese

Loop ileostomy versus loop colostomy for fecal diversion after colorectal or coloanal anastomosis: a meta-analysis

AbstractBackgroundSphincter-saving surgery for the treatment of middle and low rectal cancer has spread considerably when total mesorectal excision became standard treatment. In order to reduce leakage-related complications, surgeons often perform a derivative stoma, a loop ileostomy (LI), or a loop colostomy (LC), but to date, there is no evidence on which is the better technique to adopt.MethodsWe performed a systematic review and meta-analysis of all randomized controlled trials until 2007 and observational studies comparing temporary LI and LC for temporary decompression of colorectal and/or coloanal anastomoses.Clinically relevant events were grouped into four study outcomes: general outcome measures: dehydratation and wound infection GOMconstruction of the stoma outcome measures: parastomal hernia, stenosis, sepsis, prolapse, retraction, necrosis, and hemorrhageclosure of the stoma outcome measures: anastomotic leak or fistula, wound infection COM, occlusion and herniafunctioning of the stoma outcome measures: occlusion and skin irritation.ResultsTwelve comparative studies were included in this analysis, five randomized controlled trials and seven observational studies. Overall, the included studies reported on 1,529 patients, 894 (58.5%) undergoing defunctioning LI. LI reduced the risk of construction of the stoma outcome measure (odds ratio, OR = 0.47). Specifically, patients undergoing LI had a lower risk of prolapse (OR = 0.21) and sepsis (OR = 0.54). LI was associated with an excess risk of occlusion after stoma closure (OR = 2.13) and dehydratation (OR = 4.61). No other significant difference was found for outcomes.ConclusionOur overview shows that LI is associated with a lower risk of construction of the stoma outcome measures.

Estrogens stimulate the proliferation of human cholangiocarcinoma by inducing the expression and secretion of vascular endothelial growth factor

BACKGROUND Estrogens may induce the proliferation of neoplastic cells by activating neo-angiogenesis. AIM To evaluate the effect of estrogens on the expression of vascular endothelial growth factor (VEGF) and related receptors (VEGF-R) in human cholangiocarcinoma and the role played by VEGF in mediating the proliferative effects of estrogens. METHODS Seven biopsies of intra-hepatic cholangiocarcinoma and the HuH-28 cell lines were investigated. Cell proliferation was measured by both PCNA Western blot and MTS proliferation assay. RESULTS By immunohistochemistry, biopsies of human cholangiocarcinoma stained positively for VEGF-A and VEGF-C and related receptors. HuH-28 cells expressed VEGF-A, -C, and VEGFR-1, -2, -3 and, their protein level was enhanced by 17beta-estradiol in association with the stimulation of cell proliferation. 17beta-Estradiol-stimulated proliferation of HuH-28 cells was blocked by 70% by VEGF-TRAP, a receptor-based VEGF inhibitor. 17beta-Estradiol induced the secretion of VEGF in the supernatant of HuH-28 cells. The stimulatory effect of 17beta-estradiol on the protein expression of VEGF-A, VEGF-C and VEGFR-1, -2, -3 was blocked by antagonists of ER (Ici182,780) or insulin-like growth factor 1-receptor (alphaIR3). CONCLUSIONS With the limitations of experiments performed in a cell line, our study indicates that VEGF plays a major role in mediating the proliferative effects of estrogens on human cholangiocarcinoma.

Total mesorectal excision for surgical treatment of rectal cancer

The aim of our study was to retrospectively evaluate the results of 2 groups of patients admitted and treated for rectal cancer.

Role of CEA, TPA, and Ca 19-9 in the early detection of localized and diffuse recurrent rectal cancer

Sixty-six consecutive patients who underwent curative resection for rectal cancer were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue plasminogen activator (TPA), and carcinomatous antigen 19-9 (Ca 19-9) determinations in the early diagnosis of resectable recurrences. Thirty-three recurrences were detected between 6 and 42 months. CEA, TPA, and Ca 19-9 showed a sensitivity of 72.7 percent, 78.8 percent, and 60.1 percent, respectively, and a specificity of 60.6 percent, 60.6 percent, and 87.9 percent, respectively. In 23 cases the rise in the value of CEA and/or TPA and/or Ca 19-9 was the first sign of recurrences, and the diagnosis was established later by clinical methods. In this group, the lead time was two months for liver metastases and four months for disseminated metastases. As far as the relationship between localization of recurrence and marker level increase is concerned, of 16 hepatic metastases CEA, TPA, and Ca 19-9 showed a sensitivity of 94 percent (P<0.05), 69 percent, and 62 percent, respectively. Of six patients with local recurrences, CEA, TPA, and Ca 19-9 showed a sensitivity of 50 percent, 100 percent (P<0.05), and 83.3 percent, respectively. Of three patients with peritoneal carcinomatosis, CEA, TPA (P<0.05), and Ca 19-9 showed a sensitivity of 0 percent, 100 percent, and 0 percent, respectively. No significant differences were reported among the three markers according to multiple metastases and metachronous polyps. Fourteen patients (42.4 percent) underwent surgical treatment for recurrent disease, and eight of them (57 percent) showed a resectable disease, for a total resectability rate of 24.2 percent. The findings of our study indicate that a followup program based on CEA, TPA, and Ca 19-9 assays is related to an early diagnosis and a good resectability rate for both local and metastatic recurrences from rectal cancer.

Unusual breakage of a plastic biliary endoprosthesis causing an enterocutaneous fistula.

OBJECTIVE The objective of our study was to illustrate a case of endoscopically placed biliary stent breakage. METHODS A72-year-old woman with a prolonged history of cholangitis following laparoscopic cholecistectomy was referred to our institution 8 years ago. Dilatation of the intra- and extrahepatic biliary tree and a benign stricture at the cystic confluence were observed at US and endoscopic retrograde cholangiopancreatography (ERCP). A 12-F gauge plastic endoprosthesis was placed. In the absence of any symptoms, breakage of the stent was revealed 18 months later at plain radiology. Eight years later an enterocutaneous fistula occurred originating from a jejunal loop containing the indwelled distal part of the stent. Surgery was undertaken and the distal part of the stent removed with the perforated jejunal loop. The proximal part was successively endoscopically removed. CONCLUSIONS Disruption of a biliary endoprosthesis is observed in patients in whom the stent is kept in situ for a long period or consequent to exchange. The removal and exchange is mandatory when the stent disruption is followed by cholangitis. In the current case, because of the absence of any symptoms the removal of the stent was not attempted. Immediate endoscopic removal of the prosthetic fragments seems to be the treatment of choice for replacement of a new stent.

Prostate Apoptosis Response-4 Is Expressed in Normal Cholangiocytes, Is Down-Regulated in Human Cholangiocarcinoma, and Promotes Apoptosis of Neoplastic Cholangiocytes When Induced Pharmacologically

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that sensitizes cells to apoptosis; therefore, Par-4 modulation has therapeutic potential. No data currently exist on Par-4 expression in cholangiocarcinoma (CCA). We evaluated the expression of Par-4 in normal and neoplastic cholangiocytes and the effects of its pharmacological or genetic modulation. The study was performed in human and rat liver, CCA patient biopsies, and two CCA cell lines. PAR-4 was expressed in normal rat and human cholangiocytes, but its expression levels decreased in both human CCA and CCA cell lines. In both intrahepatic and extrahepatic CCA, Par-4 expression (as shown by immunohistochemistry) was inversely correlated with markers of proliferation (eg, proliferating cellular nuclear antigen) and directly correlated with apoptotic markers (eg, Bax and Bax/BCL2 ratio). Par-4 expression was decreased during CCA cell proliferation but was enhanced after apoptosis induction. Pharmacological induction of Par-4 expression in CCA cell lines by diindolymethane or withaferin A promoted activation of apoptosis and inhibition of proliferation. In contrast, specific Par-4 silencing by small-interfering RNA determined activation of CCA cell line proliferation. Par-4 is expressed in rat and human cholangiocytes and is down-regulated in both human CCA and CCA cell lines. Par-4 protein levels decrease during cell proliferation but increase during apoptosis. Pharmacological or genetic induction of Par-4 determines apoptosis of CCA cells, suggesting Par-4 targeting as a CCA treatment strategy.

KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

A study of sentinel node biopsy in T1 breast cancer treatment: experience of 48 cases.

Axillary clearance in breast cancer has been proven to be unnecessary in more than 50% of cases. Sentinel node biopsy (SNB) is a new technique that can be used to avoid unneccesary axillary clearance in breast cancer surgery. Our integrated team, consisting of surgeons, pathologists and nuclear medicine physicians, studied 48 cases of T1 breast cancer with lymphoscintigraphy-guided SNB. Before starting this study, the team performed 20 SNBs as a learning procedure. 500 μCi of 99mTc-nanocoll in 0.2 mL were injected around the lesion, under US or x-ray guidance if necessary. Static images in anterior, lateral and lateral oblique view collected at the end of a 20 min dynamic study were used to mark the SN on the skin. During surgery a gamma probe was used to guide SN resection, and node invasion was assessed with cytokeratin immunohistochemistry. In 14 patients tracer uptake was observed in a single node, in 30 patients in 2–4 nodes, whereas in four patients the nodes were scintigraphically missed. Surgical resection was possible in 42 nodes out of 54. All but two patients with negative immunohistochemistry for cancer cell clusters showed metastasis-free axillary nodes. All patients with positive SNBs (13) showed involved axilla. In four patients the lymphatic drainage was towards the intramammary chain; one node was juxtaclavicular and one node was intramammary in the upper outer quadrant. The overall sensitivity of the method was about 80%, the specificity about 90% with a diagnostic accuracy about 80%. SNB is a promising method for surgical decision-making regarding axillary clearance in breast cancer. Adequate training of an interdisciplinary team is needed in order to successfully perform SNB and assess SN invasion. Its unusual anatomic location can be encountered and technical care is necessary to correctly identify and remove them.

Preoperative Chemoradiotherapy in Elderly Patients with Locally Advanced Rectal Cancer

Purpose. To evaluate the treatment tolerance and clinical outcomes in patients aged 70 and older with locally advanced rectal carcinoma treated with multimodality approach. Methods and Materials. We retrospectively analysed 20 consecutive elderly patients, with histologically proven rectal adenocarcinoma, staged T3-4, and/or node-positive tumour, who received chemoradiotherapy and proceeded to surgical approach. Performance status score and adult comorbidity evaluation-27 score were calculated, and their influence on treatment tolerance and clinical outcomes was analysed. Results. All patients completed programmed chemoradiotherapy treatment. Gastrointestinal toxicity was the most common acute side effects: proctitis in 70% of patients and diarrhoea in 55%, classified as Grade 3 in 3 patients only. Radiation dermatitis was reported in 7 patients (35%) and it was graded G3 in one patient. There was no haematological toxicity. Eighteen patients out of 20 underwent surgery. Sphincter preservation was assured in 13 patients. Comorbidity index was related to higher severe acute toxicity (P = 0.015) but no influenced treatment outcomes. Conclusion. Treatment tolerance with combined modality is good in elderly patients. Due to age, no dose reduction for radiation therapy and chemotherapy should be considered.

Primary Osteosarcoma of the Breast

observed (Fig. 3). The presented case shows theimportance of team work and selection of the optimalirradiation technique in determining diagnosis, tumorstaging, and treatment of the patient. After histologi-cal classification, high-grade primary breast lympho-mas should be treated with combinationchemotherapy with or without radiation similar tosystemic lymphomas of a similar histological type.Reports on breast lymphoma treatment include fewor no details about the target volume and applied irra-diation technique and usually mention only the totalradiation dose. The delivery of radiotherapy was a sig-nificant predictor of improved overall survival in ourcase.