Long-term pancreatic exocrine and endometabolic functionality after pancreaticoduodenectomy. Comparison between pancreaticojejunostomy and pancreatic duct occlusion with fibrin glue.

OBJECTIVE: Even if pancreatic pathologies, residual fibrosis, residual amount of parenchyma, and anastomotic patency are recognized as main causes of exocrine and glycemic impairment after pancreaticoduodenectomy (PD), few data are reported concerning the role of the different pancreatic remnant treatment techniques. The objective of the study is to assess and compare exocrine functionality, glycemic pattern, nutritional status, and quality of life (QoL) after PD between pancreaticojejunostomy (PJ) and pancreatic duct occlusion (PDO), both in an objective and a subjective manner. PATIENTS AND METHODS: Thirty-two patients (16 PJ and 16 PDO) were evaluated after a mean follow-up of 21 months after surgery. Exocrine insufficiency was objectively evaluated through the 13C-labelled mixed triglyceride breath test. Fasting glucose, fasting insulin, HbA1c and HOMA-IR values were used to assess glucose metabolism. For these two outcomes, anamnestic data were also collected. QoL was assessed with GIQLI, SF-36, EORTC-QLQ-C30, and EORTC-PAN-26 questionnaires. RESULTS: The 13C-labelled mixed triglyceride breath test detected a lipid digestive insufficiency in 56% of patients after PJ and 100% after PDO respectively (p = 0.007). However, no difference was observed between the two groups regarding postoperative necessity of substitutive pancreatic enzymes. Nutritional status, fasting plasma glucose, fasting insulin, HbA1c levels, HOMA-IR values and postoperative necessity of insulin or oral antidiabetic agents were comparable between the two groups. QoL measurements showed similar results. However, in the subdomains analysis, better outcomes were reported regarding digestive symptoms and physical functioning for PJ and PDO respectively. CONCLUSIONS: Even if an objective exocrine major impairment was evidenced after PDO, this result did not impact the need for a higher rate of postoperative substitutive enzymes. In terms of glycemic pattern, nutritional status, and QoL, the two techniques turn out to be comparable.

The hyperthermic intraoperative intraperitoneal chemotherapy in the treatment of advanced abdominopelvic cancer. Personal experience on 103 procedures during a seventeen year period in a single Italian center.

OBJECTIVE: Integration of different therapeutic strategies in cancer surgery in the last years has led from treating primary lesions to the surgical treatment of metastases. The purpose of this paper is to report a single Italian center experience of treatment of peritoneal carcinosis of the abdominopelvic malignancies. PATIENTS AND METHODS: 103 HIPEC procedures were performed in 17 years on 94 selected patients affected by abdominopelvic cancer. The PCI score was calculated at laparotomy. The CC score was calculated before doing HIPEC. HIPEC was carried out according to the Coliseum technique. RESULTS: The surgical cytoreduction allowed 89 patients to be subjected to HIPEC treatment with a CC score 0; 9 patients with a CC 1; 3 patients with a CC 2 and 2 patients with a CC 3. In 22 patients postoperative complications were recorded. No operative mortality occurred. The median follow-up of 53 months shows a rate of survival equivalent to 49 %, with a relapse in 46 patients, 29 of them reached exitus. CONCLUSIONS: The surgical resection alone for patients affected by advanced cancer with peritoneal carcinomatosis cannot be considered a sufficient treatment any longer and HIPEC would help to prolong survival in these patients.

Does CD10 expression individuate a GIST subgroup of patients?

AIM: The aim of the study was to evaluate expression of CD10 in a series of gastrointestinal tumors (GIST) and to find its relationship with prognosis, biological and clinical behavior. GISTs represent the most frequent gastrointestinal (GI) mesenchymal tumors. Biological behavior of GIST cannot be easily predicted; for this reason many biomolecular factors are being investigated to predict prognosis. Recently the role of the CD10 as prognostic predictor in the carcinogenesis of the gastrointestinal carcinomas has been accurately studied. To our knowledge, no data regarding the role of CD10 in GISTs have been published to date. METHODS: CD10 expression was searched by immunohistochemistry in 29 histological specimens of proved GIST surgically treated. Patients' characteristics and all pathologic features of tumors were statistically reviewed and compared to CD10 expression. Survival analysis was also calculated respect to CD10 expression and relevant clinical or pathological features. RESULTS: CD10 was expressed in 24.1% of cases. There was no correlation between CD10 positivity and risk category, morphology, size or mitosis. The CD10 expression status did not prove to be statistically related to worse prognosis, advanced disease (metastasis) or recurrence, however it was significantly correlated to the tumor site. CONCLUSION: CD10 expression in our series seems to be associated to a small bowel origin of tumor. CD10 expression alone failed to reveal a statistically significant prognostic value. However survival analysis revealed worse prognosis in stomach tumours with mitotic count >10/50 HPF.

Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer.

BACKGROUND: The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery. METHODS: Data for patients who underwent neoadjuvant chemoradiotherapy followed by surgery for resectable rectal cancer from June 1992 to June 2009 were reviewed. The primary outcomes measured were the number of lymph nodes retrieved, their status, and patient survival. RESULTS: In total, 345 patients underwent neoadjuvant chemoradiotherapy followed by surgery, and 95 patients had surgery alone. Neoadjuvant chemoradiotherapy decreased both the median (range) number of lymph nodes retrieved (7 (1-33) versus 12.5 (0-44) respectively; P < 0.001) and the number of positive lymph nodes (0 (0-11) versus 0 (0-16); P = 0.001). After neoadjuvant chemoradiotherapy, the number of retrieved lymph nodes was inversely correlated with tumour regression, and with the interval between treatment and surgery. The 5-year overall and disease-free survival rates were 86.5 and 79.1 per cent respectively. After neoadjuvant therapy, lymph node status was found to be an independent predictor of survival, whereas the number of retrieved lymph nodes did not represent a prognostic factor for either overall or disease-free survival. CONCLUSION: Low lymph node count after neoadjuvant chemoradiotherapy for rectal cancer does not signify an inadequate resection or understaging, but represents an increased sensitivity to the treatment.

Complications related to hyperthermia during hypertermic intraoperative intraperitoneal chemiotherapy (HIPEC) treatment. Do they exist?

BACKGROUND AND OBJECTIVES: Hyperthermia, either alone or in combination with anticancer drugs, is becoming more and more a clinical reality for the treatment of far advanced gastrointestinal cancers, acting as a cytotoxic agent at a temperature between 40-42.5 degrees C. Although hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is demonstrated to have some benefit in selected patients with peritoneal seeding, there are not enough data on the risk of damage of normal tissue that increases as the temperature rises, with possible serious and, sometimes, lethal complications. MATERIALS AND METHODS: We searched on medline words like "intraoperative intraperitoneal chemohyperthermia and morbidity", focusing our attention on studies (published since 1990) which reported morbidity as bowel obstruction, bowel perforation or anastomic leak, during intraoperative intraoperitoneal chemotherapy in hyperthermia (HIPEC). RESULTS: Heat acts increasing cancer cell killing after exposure to ionizing radiation, inhibiting repairing processes of radiation-induced DNA lesions (radiosensitization), and also sensitizing cancer cells to chemotherapeutic drugs, particularly to alkylating agents (chemosensitization). The peritoneal carcinomatosis (a frequent evolution of advanced digestive cancer) represents one of the main indication to hypertermic treatment. In the last fifteen years, in fact, different methods were developed for the surgery treatment (peritonectomy) and for loco-regional chemotherapic treatment of the carcinomatosis (intraperitoneal intra/post-operative iper/normothermic chemotherapy) to act directly on neoplastic seeding. We found, as result of different studies, 9 articles, written about perforation after HIPEC. CONCLUSION: The aim of the present study is to present the review of the literature in terms of peri-operative complications related to the hyperthermia during intraoperative chemohyperthermia procedure.

Assessment of haemorrhoidal artery network using colour duplex imaging and clinical implications.

BACKGROUND: Dearterialization should reduce arterial overflow to haemorrhoids. The purpose of this study was to assess the topography of haemorrhoidal arteries. METHODS: Fifty patients with haemorrhoidal disease were studied. Using endorectal ultrasonography, six sectors were identified within the lower rectal circumference. Starting from the highest level (6 cm above the anorectal junction), the same procedure was repeated every 1 cm until the lowest level was reached (1 cm above the anorectal junction). Colour duplex imaging examinations identified haemorrhoidal arteries related to the rectal wall layers, and the arterial depth was calculated. RESULTS: Haemorrhoidal arteries were detected in 64·3, 66·0, 66·0, 98·3, 99·3 and 99·7 per cent of the sectors 6, 5, 4, 3, 2 and 1 cm above the anorectal junction respectively (P < 0·001). Most of the haemorrhoidal arteries were external to the rectal wall at 6 and 5 cm (97·9 and 90·9 per cent), intramuscular at 4 cm (55·0 per cent), and within the submucosa at 3, 2 and 1 cm above the anorectal junction (67·1, 96·6 and 100 per cent) (P < 0·001). The mean arterial depth decreased significantly from 8·3 mm at 6 cm to 1·9 mm at 1 cm above the anorectal junction (P < 0·001). CONCLUSION: This study demonstrated that the vast majority of haemorrhoidal arteries lie within the rectal submucosa at the lowest 2 cm above the anorectal junction. This should therefore be the best site for performing haemorrhoidal dearterialization.

Anorectal physiology is not changed following transanal haemorrhoidal dearterialization for haemorrhoidal disease: clinical, manometric and endosonographic features.

AIM: The effect of transanal haemorrhoidal dearterialization (THD) on continence and anorectal physiology has not yet been demonstrated. METHOD: Twenty patients suffering from 3rd degree haemorrhoids were enrolled and underwent THD, including both dearterialization and mucopexy. Clinical assessment, anorectal manometry, rectal volumetry and endoanal ultrasound were performed preoperatively and at 6 months postoperatively. RESULTS: Postoperatively two and six patients had transient rectal pain and tenesmus, respectively. No patient reported faecal urgency or minor or major incontinence. All patients remained able to discriminate gas from faeces. No significant variation of the mean values of anal manometric and rectal volumetric parameters was recorded at 6 months of follow-up compared with preoperative values. At 6 months both internal and external sphincters were endosonographically intact. CONCLUSION: THD does not cause trauma to the anal canal and rectum.

Transanal haemorrhoidal dearterialization (THD) for selected fourth-degree haemorrhoids.

BACKGROUND: Traditional treatment of fourth-degree haemorrhoidal disease (HD) is conventional haemorrhoidectomy and is frequently associated with significant pain and morbidity. In recent years, the use of transanal haemorrhoidal dearterialization (THD) for the treatment of HD has increased. The procedure aims to decrease the arterial blood flow to the haemorrhoids. Moreover, since a rectal mucopexy to treat the prolapsing component has become part of the THD technique, this treatment is also indicated for more advanced HD. The aim of this study was to assess the possible role of THD in the treatment of fourth-degree HD. METHODS: All patients with non-fibrotic fourth-degree HD were offered the THD procedure with mucopexy. Excision of skin tags was added to THD and mucopexy, when needed. A specific score was used to assess HD severity, ranging from 0 (no HD) to 20 (worst HD). The mean preoperative score was 18.1 ± 1.8. RESULTS: Thirty-five consecutive patients (mean age 50.4 ± 13.8 years; 19 men) with fourth-degree HD were prospectively enroled. An average of 6 arteries were identified and transfixed. Mucopexy was achieved with a 3-6 sector plication of rectal mucosa. Mean operating time was 33 ± 12 min. No intraoperative complications were recorded. Postoperative morbidity included 3 (8.6%) haemorrhoidal thromboses (1 requiring surgery) and 2 (5.7%) episodes of bleeding (1 requiring surgical haemostasis). Five patients (14.3%) had urinary retention requiring catheterization. At a median follow-up of 10 months (range 2-28 months), symptoms had resolved or significantly improved in 33 (94%) patients. Nine patients (25.7%) reported irregular bleeding, 3 patients (8.6%) mild anal pain, 4 patients (11.4%) transient anal burning and 4 patients (11.4%) tenesmus. Ten patients (28.6%) experienced some degree of residual prolapse, significant only in 2 (5.7%) who required further surgery. There was no anorectal stenosis, and no faecal incontinence was reported. At a median follow-up of 10 months, the symptomatic score was 2.5 ± 2.5 (P < 0.005). CONCLUSION: Transanal haemorrhoidal dearterialization seems to be a safe and effective treatment for fourth-degree HD providing a significant improvement of symptoms for the majority of patients. When present, persisting symptoms are mostly transient, occasional or limited in severity, and only a very few patients require further intervention. Larger series and longer follow-up to further assess the role of THD in this challenging group of pts.

International guidelines for prevention and management of post-operative chronic pain following inguinal hernia surgery.

PURPOSE: To provide uniform terminology and definition of post-herniorrhaphy groin chronic pain. To give guidelines to the scientific community concerning the prevention and the treatment of chronic groin and testicular pain. METHODS: A group of nine experts in hernia surgery was created in 2007. The group set up six clinical questions and continued to work on the answers, according to evidence-based literature. In 2008, an International Consensus Conference was held in Rome with the working group, with an audience of 200 participants, with a view to reaching a consensus for each question. RESULTS: A consensus was reached regarding a definition of chronic groin pain. The recommendation was to identify and preserve all three inguinal nerves during open inguinal hernia repair to reduce the risk of chronic groin pain. Likewise, elective resection of a suspected injured nerve was recommended. There was no recommendation for a procedure on the resected nerve ending and no recommendation for using glue during hernia repair. Surgical treatment (including all three nerves) should be suggested for patients who do not respond to no-surgery pain-management treatment; it is advisable to wait at least 1 year from the previous herniorraphy. CONCLUSION: The consensus reached on some open questions in the field of post-herniorrhaphy chronic pain may help to better analyze and compare studies, avoid sending erroneous messages to the scientific community, and provide some guidelines for the prevention and treatment of post-herniorraphy chronic pain.

Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases.

BACKGROUND: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). PATIENTS AND METHODS: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. RESULTS: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. CONCLUSIONS: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer.

BACKGROUND: "Cancer stem cells" (CSC) have been identified as a minority of cancer cells responsible for tumor initiation, maintenance and spreading. Although a universal marker for CSC has not yet been identified, CD133 has been proposed as the hallmark of CSC in colon cancer. The aim of our study was to assess the presence of a CD133+ cell fraction in samples of colon cancer and liver metastasis from colon cancer and evaluate their potential as tumor-initiating cells. METHODS: Tissue samples from 17 colon cancers and 8 liver metastasis were fragmented and digested using collagenase. Cell suspensions were characterized by flow cytometry using anti-CD133, CD45 and CD31 antibodies. CD133+ cells were also isolated by magnetic cell sorting and their tumor-initiating potential was assessed versus the remaining CD133- fraction by soft-agar assay. RESULTS: Our results confirmed the existence of a subset of CD133+ tumor cells within human colon cancers. Interestingly, CD133+ cells were detectable in liver metastasis at a higher percentage when compared to primary tumors. Soft-agar assay showed that CD133+ cell fraction was able to induce larger and more numerous colonies than CD133-cells. CONCLUSION: Our findings data that the CD133+ colon cancer cells might play an important role in both primary tumors as well as in metastatic lesions thus warranting further studies on the role(s) of this subset of cells in the metastatic process.

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn's disease with anal endosonographic monitoring: a single-centre experience.

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.

Muscle myostatin signalling is enhanced in experimental cancer cachexia.

BACKGROUND/AIMS: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard. MATERIALS AND METHODS: Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. RESULTS: In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-alpha contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-alpha synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. CONCLUSIONS: These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia.

Sacral neuromodulation in the treatment of defecation disorders.

A large number of patients present with fecal incontinence due to idiopathic pelvic neuropathy or lesions of pelvic nerves, iatrogenic or secondary to other pelvic diseases or dysfunctions, involving sacral nerves. On the other hand, in many patients, constipation could be related to a peripheral neuropathy impairing normal defecation. Sacral neuromodulation (SNM) has been demonstrated as an effective approach in neuropathic defecation disorders. Its application is usually safe and easy, with a limited rate of complications or adverse events. The surgical procedure is made under local anesthesia. SNM effectiveness can be reliably tested during a short term period (up to 30 days) before the decision for a permanent implant. Results in most series show significant clinical improvement, with reduction in the number of incontinence episodes, decrease of incontinence score and improvement in patients' quality of life. A few reports suggest a potential and interesting application of SNM in constipation. Findings from anorectal manometry and other physiology examinations are not conclusive in order to define SNM mechanisms of actions and suggest that a multifactorial effect "modulates" the deficient neuromuscular system causing the defecation disorders.

[Indications and outcomes of surgical management of chronic pancreatitis: literature review]. / Indicazioni e risultati del trattamento chirurgico nella pancreatite cronica: revisione della letteratura.

Surgical management of chronic pancreatitis remains a challenge for surgeons. Last decades, the improvement of knowledge regarding to pathophysiology of chronic pancreatitis, improved results of major pancreatic resections, and new diagnostic techniques in clinical practice resulted in significant changes in the surgical approach of this condition. Intractable pain, suspicion of malignancy, and involvement of adjacent organs are the main indications for surgery, while the improvement of patient's quality of life is the main purpose of surgical treatment. The surgical approach to chronic pancreatitis should be individualized based on pancreatic anatomy, pain characteristics, exocrine and endocrine function, and medical co-morbidity. The surgical treatment approach usually involves pancreatic duct drainage procedures and resectional procedures including longitudinal pancreatojejunostomy, pancreatoduodenectomy, pylorus-preserving pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, duodenum-preserving pancreatic head resection (Beger's procedure), and local resection of the pancreatic head with longitudinal pancreatojejunostomy (Frey's procedure). Recently, non-pancreatic and endoscopic management of pain have also been described (splancnicectomy). Surgical procedures provide long-term pain relief, improve the patients? quality of life with preservation of endocrine and exocrine pancreatic function, and are associated with low mortality and morbidity rates. However, new studies are needed to determine which procedure is safe and effective for the surgical management of patients with chronic pancreatitis.

[Late complication after colon self-expandable metal stent placement: a case report]. / Complicanza tardiva dopo posizionamento colico di stent metallico autoespandibile: caso clinico.

Treatment of acute colorectal malignant obstruction, by using self-expandable metallic stents is useful for both palliative and decompressive therapy before the final surgical treatment. In this case, the patient may be benefit from a period of medical optimization prior to undergoing planned surgical resection by a colorectal surgeon. This is a minimally invasive procedure, relatively safe, which obviates the need for colostomy for evacuation relieving physical and psychological burden and contributing the improvement of quality of life. Furthermore, this method also has the advantage of being cost-effective. The previous experience in the benign biliary stenosis allowed the extension of using the metallic stents also for the treatment of benign colorectal diseases (diverticular occlusion, anastomotic strictures, colonic endometriosis). Complications of colon self-expandable metallic stents placement may occur during the procedure and soon after placement (early complications) or, rarely, late after insertion (late complications). These include bleeding, re-obstruction, pain, tenesmus, stent migration, and perforation. The authors report a case of an 81 year-old woman with inoperable rectal carcinoma with liver metastasis who underwent palliative treatment of self-expanding metallic stent endoscopic placement. One month later, the patient presented with acute abdomen at Accidents and Emergencies Department. The diagnosis was a late rectosigmoid junction perforation by stent placement.

[Clinical guidelines for the management of gastrointestinal stromal tumors]. / Raccomandazioni cliniche per la diagnosi, la terapia ed il follow-up dei tumori stromali gastrointestinali.

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.

Endoanal ultrasound-guided surgery for anal fistula.

BACKGROUND AND STUDY AIMS: Outcomes following surgical treatment of patients with anal fistula are related to eradication of tracts and the internal opening. In this study, the results of surgery based on endoanal ultrasound (EAUS) findings were evaluated. PATIENTS AND METHODS: A total of 102 patients with primary cryptogenetic anal fistula were prospectively examined with EAUS, using a 360-degree rotating 10-MHz probe, equipped with a three-dimensional (3-D) imaging system. Injection of hydrogen peroxide through the external opening was also used. Patients underwent operation on the basis of the EAUS findings. The agreement between findings from EAUS and from surgery was calculated. Clinical results were reported as treatment success, fistula recurrence, and fecal incontinence. RESULTS: Amongst 102 patients, the overall concordance between EAUS and surgical findings was 94.1 % for primary tracts, 91.2 % for internal openings, 96.1 % for secondary tracts, 100 % for abscesses, and 96.1 % for horseshoe tracts. Diagnostic accuracy was improved when hydrogen peroxide injection or 3-D imaging were used. Fistulotomy was performed in 46 patients (45.1 %), fistulectomy in 17 (16.7 %), fistulotomy plus seton placement in 19 (18.6 %), fistulectomy plus seton in 18 (17.6 %), and mucosal flap advancement in 2 (2.0 %). The operation was curative in 100 patients (98.0 %), and unsuccessful in 2 (2.0 %) due to recurrence of the fistula. Fecal continence was preserved in all patients. CONCLUSIONS: These data highlight the diagnostic accuracy of EAUS, particularly when hydrogen peroxide injection or 3-D imaging are used. Basing our surgical decision making on EAUS findings allowed us to carry out curative operations in a significantly large number of patients; the recurrence rate was very low. The accurate EAUS assessment of the relationship between fistulas and sphincters has been the main factor in choosing a sphincter-saving surgical procedure, avoiding fecal incontinence.

Skeletal muscle wasting in tumor-bearing rats is associated with MyoD down-regulation.

Cachexia is a syndrome characterized by profound skeletal muscle wasting that frequently complicates malignancies. A number of studies indicate that protein hypercatabolism, largely mediated by classical hormones and cytokines, is the major component of muscle depletion. Impaired regeneration has been suggested to contribute to the reduction of muscle size. In particular, it has been shown that the expression of MyoD, a muscle-specific transcription factor, is down-regulated by cytokines such as TNFalpha and IFNgamma in a NF-kappaB-dependent posttranscriptional manner. The present study investigated whether modulations of the transcription factor MyoD are associated with the onset of muscle wasting in a well established model of cancer cachexia. Rats bearing the Yoshida AH-130 hepatoma develop a condition of muscle protein hypercatabolism, largely dependent on TNFalpha bioactivity. In the gastrocnemius of these animals the expression of MyoD was markedly reduced, paralleling the decrease of muscle weight. This pattern is associated with increased nuclear translocation of AP-1, while DNA-binding assays did not detect any change in NF-kappaB activity. This is the first observation demonstrating that muscle depletion in tumor-bearing rats is associated with a down-regulation of MyoD levels. Although the underlying mechanisms remain to be clarified, this change is compatible with the hypothesis that a reduced expression of molecules involved in the regulation of the regenerative response may concur to muscle wasting in cancer cachexia.