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Objective: Thymosin beta 4 (Tβ4) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation. Recently, a role for Tβ4 has been proposed in experimental and human carcinogenesis, including gastrointestinal cancer. This study was aimed at evaluating the relationship between Tβ4 immunoreactivity and the initial steps of carcinogenesis., Methods: In total, 60 intestinal biopsies, including 10 hyperplastic polyps, 10 sessile serrated adenomas/polyps, 15 colorectal adenomas with low-grade dysplasia, 15 adenomas with high-grade dysplasia, 15 adenocarcinomas and 10 samples of normal colon mucosa, were analyzed for Tβ4 expression by immunohistochemistry., Results: Weak cytoplasmic reactivity for Tβ4 was detected in the normal colon mucosa. No reactivity for Tβ4 was found in hyperplastic and sessile serrated polyps/adenomas. Tβ4 expression was observed in 10/15 colorectal adenocarcinomas. In adenomas with low-grade dysplasia, Tβ4 immunoreactivity was mainly detected in dysplastic glands but was absent in hyperplastic glands. Tβ4 immunoreactivity was characterized by spot-like perinuclear staining. In high-grade dysplastic polyps, immunostaining for Tβ4 appeared diffuse throughout the entire cytoplasm of dysplastic cells. Spot-like perinuclear reactivity was detected in adenocarcinoma tumor cells., Conclusions: Our study shows for the first time that Tβ4 is expressed during different steps of colon carcinogenesis. The shift of Tβ4 immunolocalization from low-grade to high-grade dysplastic glands suggests a role for Tβ4 in colorectal carcinogenesis. However, the real meaning of Tβ4 reactivity in dysplastic intestinal epithelium remains unknown.

Background: The objective of this study was to evaluate pretreatment clinical parameters as predictive factors for complete pathological response after long-term chemoradiotherapy (RCT) for rectal cancer. Tumor downstaging after RCT for rectal cancer can be obtained in half of cases, whereas a complete pathological response (CPR) is reported to range between 15 and 30%. It is not possible to foresee before therapies who will respond., Methods: Patients with stage II-III rectal cancer that had undergone RCT and rectal resection between January 1995 and October 2010 were considered. Patients were divided in those who achieved a CPR, "CR" group, and those who did not achieve a CPR, "NCR" group. Univariate and multivariate analyses between groups were performed considering the clinical parameters: gender, age, ASA score, preoperative hematic CEA, tumor grading; distance of the tumor from the anal verge, maximum tumor diameter, TNM stage, and neoadjuvant treatment details., Results: Among 260 patients, 43 (16.5%) achieved a CPR. The two groups resulted homogeneous for age, sex, pretreatment status, and tumor stage. A CEA <5 ng/dl and distance from anal verge >5 cm were correlated with CPR at multivariate analysis. Patients with both these conditions presented a significantly higher CPR rate (30.6%) as well as improved 5-year survival. CPR was also correlated with improved survival., Conclusions: Very low tumors with a high serum CEA are very unlikely to reach a CPR. The predictive value of these easily available clinical factors should not be underestimated, and better therapeutic strategies for these tumors are needed.

Objective: Thymosin β 4 (Tβ(4)) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation during embryogenesis. Recently, a role for Tβ(4) has been proposed in experimental and human carcinogenesis. This study was aimed at evaluating the correlation between Tβ(4) immunoractivity and colorectal cancer, with particular attemption to tumor cells undergoing epithelial-mesenchymal transition., Methods and Results: 86 intestinal biopsies were retrospectively analyzed including 76 colorectal adenocarcinomas with evident features of epithelial-mesenchymal transition, and 10 samples of normal colorectal mucosa. Paraffin sections were immunostained for Tβ(4) and for E-cadherin. Total RNA was isolated from frozen specimens obtained, at surgery, from the normal colon mucosa, the deeper regions and the superficial tumor regions in four cases of colon cancer. Tβ(4) immunoreactivity was detected in the vast majority (59/76) of colon carcinomas, showing a patchy distribution, with well differentiated areas significantly more reactive than the less differentiated tumor zones. We also noted a zonal pattern in the majority of tumors, characterized by a progressive increase in immunostaining for Tβ(4) from the superficial toward the deepest tumor regions. The strongest expression for Tβ(4) was frequently detected in invading tumor cells with features of epithelial-mesenchymal transition. The increase in reactivity for Tβ(4) matched with a progressive decrease in E-cadherin expression in invading cancer cells. At mRNA level, the differences in Tβ(4) expression between the surrounding colon mucosa and the tumors samples were not significant., Conclusions: Our data show that Tβ(4) is expressed in the majority of colon cancers, with preferential immunoreactivity in deep tumor regions. The preferential expression of the peptide and the increase in intensity of the immunostaining at the invasion front suggests a possible link between the peptide and the process of epithelial mesenchymal transition, suggesting a role for Tβ(4) in colorectal cancer invasion and metastasis.

Purpose: MET, the tyrosine kinase receptor for hepatocyte growth factor, is frequently overexpressed in colon cancers with high metastatic tendency. We aimed to evaluate the role of its negative regulators, miR-1 and miR-199a*, and its transcriptional activator, the metastasis-associated in colon cancer 1 (MACC1), in controlling MET expression in human colon cancer samples., Experimental Design: The expression of MET, miR-1, miR-199a*, and MACC1 was evaluated by real-time PCR in 52 matched pairs of colorectal cancers and nontumoral surrounding tissues. The biological role of miR-1 in controlling MET expression and biological activity was assessed in colon cancer cells either by its forced expression or by AntagomiR-mediated inhibition., Results: MiR-1 was downregulated in 84.6% of the tumors and its decrease significantly correlated with MET overexpression, particularly in metastatic tumors. We found that concurrent MACC1 upregulation and miR-1 downregulation are required to elicit the highest increase of MET expression. Consistent with a suppressive role of miR-1, its forced in vitro expression in colon cancer cells reduced MET levels and impaired MET-induced invasive growth. Finally, we identified a feedback loop between miR-1 and MET, resulting in their mutual regulation., Conclusions: This study identifies an oncosuppressive role of miR-1 in colorectal cancer in which it acts by controlling MET expression through a feedback loop. Concomitant downregulation of miR-1 and increase of MACC1 can thus contribute to MET overexpression and to the metastatic behavior of colon cancer cells.

Aims and Background: The MutY human homologue gene (MUTYH) is responsible for about a quarter of attenuated familial adenomatous polyposis. Occasionally, it has been associated with hyperplastic polyps and serrated adenoma. We report a family where the same MUTYH mutation determined four different phenotypes, including a case of hyperplastic polyposis syndrome., Patients and Methods: A family with a history of right-sided colon cancer and multiple colonic polyposis was investigated. Genetic tests were correlated with clinical findings to define phenotypic manifestations of MUTYH mutations. The pertinent English-language literature was reviewed to evaluate the risk of malignancy of MUTYH and the role of prophylactic surgery., Results: Three male siblings carried a biallelic MUTYH mutation (G382D-exon13), while the fourth was heterozygote. One developed an isolated cecal cancer at the age of 48. Another, aged 38, was diagnosed with numerous minute colonic and rectal polyps and underwent a proctocolectomy, with final pathology showing a picture of hyperplastic and lymphoid polyposis. The third biallelic brother, 46 years old, developed four hyperplastic lesions, while the heterozygote brother had a large flat serrated adenoma of the right colon removed at the age of 50., Conclusion: Many aspects of MUTYH mutation still need to be clarified and one of them regards the different phenotypic expressions. Although the majority of reported cases manifested attenuated adenomatous polyposis, hyperplastic polyps and serrated adenomas appear to be more common than expected. Presenting hyperplastic polyposis syndrome is very unusual and may represent a clinical dilemma for correct management. Current evidence suggests to handle MUTYH-associated polyposis as typical FAP.

Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole derivative 33 was further tested in vivo for its anti-inflammatory activity in rats. This compound showed greater inhibitory activity than ibuprofen. Other compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced inflammation. The latter compounds showed a weak capacity to inhibit the proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.

Background: Accurate preoperative staging is the key to correct selection of rectal tumors for local excision. This study aims to assess the accuracy of endorectal ultrasound (ERUS) at our institution., Patients and Methods: Retrospective analysis was carried out of patients treated by transanal endoscopic microsurgery (TEM) from 1996 to 2008. TEM was considered the treatment of choice for uT0-1/N0 lesions located between 2 and 12 cm from the anal verge. It was also proposed in selected uT2-3 patients. Preoperative staging was compared with histopathologic findings., Results: Eighty-one patients (46 males, mean age 66 years) underwent TEM. Mean distance of the tumor from the anal verge was 6.6 cm (range 2-12 cm). ERUS staged 15 of 27 adenomas (55%) as uT1. Of 54 carcinomas, 5 were pT0 because TEM was performed to remove resection margins of a malign polyp already snared. Five of 19 pTis (26%) were overstaged uT1, while 7 of 17 pT1 (41%) were understaged. Overall, ERUS enabled distinction between early and advanced rectal lesion with 96% sensitivity and 85% specificity, giving accuracy of 94% (65/67). Thirteen patients had advanced lesions (eight pT2 and five pT3). Only in two of them (15%) was depth of invasion underestimated by ERUS (one uT0, one uT1) and thus was subsequent salvage surgery necessary., Conclusions: ERUS is useful to confirm the diagnosis of adenoma and predict depth of mural invasion in early rectal cancer. Differentiation between T0/is and T1 lesions remains challenging, however this does not usually influence surgical strategy.

Preoperative chemoradiotherapy has demonstrated to improve resectability and local control in locally advanced rectal cancer (LARC). 5-fluorouracil (5FU) has traditionally been the drug of choice in combination with radiation therapy. Early studies of capecitabine (CAP) have shown its potential to replace 5FU. Between March 2002 and April 2005, 31 patients with newly diagnosed LARC (T2 N+ 2 cases, T3 N0-N+ 25 cases, T4 N0-N+ 4 cases) received the combined treatment. Surgery was planned 6-8 weeks after chemoradiation. Adjuvant chemotherapy with 5FU plus leucovorin for 6 courses was given in pN+ patients. All patients completed the planned treatment. Grade 3 acute toxicity was observed in 5 patients (16%). Nineteen patients (61%) had a downstaging. A complete pathological remission was observed in 3 cases (10%). Median follow-up is of 23 months (range; 6-36 months). The results of this experience confirm the data of the literature about the feasibility and efficacy of a neoadjuvant treatment with radiation and CAP in LARC.

Oral delivery of toxin-negative derivatives of enterotoxigenic Escherichia coli (ETEC) that express colonization factor antigens (CFA) with deletions of the aroC, ompC, ompF, and toxin genes may be an effective approach to vaccination against ETEC-associated diarrhea. We describe the creation and characterization of an attenuated CFA/I-expressing ETEC vaccine candidate, ACAM2010, from a virulent isolate in which the heat-stable enterotoxin (ST) and CFA/I genes were closely linked and on the same virulence plasmid as the enteroaggregative E. coli heat-stable toxin (EAST1) gene. A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the aroC, ompC, and ompF chromosomal genes. A phase I trial, consisting of an open-label dose escalation phase in 18 adult outpatient volunteers followed by a placebo-controlled double-blind phase in an additional 31 volunteers, was conducted. The vaccine was administered in two formulations, fresh culture and frozen suspension. These were both well tolerated, with no evidence of significant adverse events related to vaccination. Immunoglobulin A (IgA) and IgG antibody-secreting cells specific for CFA/I were assayed by ELISPOT. Positive responses (greater than twofold increase) were seen in 27 of 37 (73%) subjects who received the highest dose level of vaccine (nominally 5 x 10(9) CFU). Twenty-nine of these volunteers were secreting culturable vaccine organisms at day 3 following vaccination; five were still positive on day 7, with a single isolation on day 13. This live attenuated bacterial vaccine is safe and immunogenic in healthy adult volunteers.

Aim: The aim of this study was to define the role of endorectal ultrasound in the evaluation of transphincteric fistula-in-ano treated with a seton., Methods: Fifty-one patients affected by complex fistula-in-ano and treated with the application of a drain seton at the Second Unit of General Surgery of the University of Cagliari were recruited for the study. Clinical and ultrasonographic (US) evaluation, with transanal scans, were performed in each case before operation. Intraoperative demonstration of a transphincteric track was an indication for a partial fistulotomy with the application of a seton, tied up loosely around the external sphincter. If clinical and US evaluation, during follow-up, revealed a good drainage of the fistula by the seton and its superficialization, definitive fistulotomy was performed., Results: Endoanal US had an 88.2% accuracy. Sclerosis around the seton was observed in 9 patients (17.6%); in other 9 cases a surgical toilette of the track was necessary because of the bad drainage carried out by the seton. Definitive fistulotomy was performed in 35 patients, whilst 16 are still bearer of the seton. After a mean follow-up of 39.5 months, 1 recurrence (2.9%) has occurred. Functional results were satisfactory: 55.9% of the patients has a perfect continence and 88.2% has a Wexner's incontinence score of up to 5., Conclusions: At skilled institutions, endoanal ultrasound allows to optimize the therapy of transphincteric fistula-in-ano treated with a seton and contribute to obtain good results in terms of recurrence and functional outcomes.

Pneumatosis cystoides intestinalis is a rare condition that can be located in any part of the gastrointestinal tract. It is usually associated with a wide variety of gastrointestinal or pulmonary diseases. The primitive form is much less frequent and usually involves the left colon. The pathogenesis of pneumatosis cystoides intestinalis is still unclear. The mechanical theory, which is the most accepted explanation, postulates that gas is forced into the bowel wall by breaks in the mucosa; this is more likely to occur when the intraluminal pressure is higher, as happens in obstructive conditions, during endoscopies, or during infections from gas-forming bacteria. Pneumatosis cystoides is often asymptomatic, representing an occasional finding during investigations for other abdominal conditions. Complications occur in about 3% of cases and include obstruction, intussusception, volvulus, haemorrhage and intestinal perforation. When presenting acutely or in association with other abdominal conditions the differential diagnosis is rarely a problem. More important is to diagnose asymptomatic primitive submucosal pneumatosis of the colon, in order to avoid unnecessary intestinal resections. The Authors present the case of a patient with pneumatosis coli who underwent laparotomy for a suspected colonic lipomatosis of the right colon.

Aim: Pilonidal sinus is a considerable source of problems in young patients both in terms of discomfort and in time off to work. Many procedures have been proposed for its treatment but most of them present substantial persistence/recurrence rates. Surgical procedures avoiding a wound in the midline are most likely to succeed. Bascom's technique is the simplest and successful method. The aim of this study is to retrospectively evaluate the results of the Bascom's procedure performed by the authors as to healing time and recurrence rate. All patients with chronic pilonidal disease, treated with Bascom's technique were re-viewed. Complications, healing time and long-term follow-up were considered., Results: A total of 74 patients (52 males, and 22 females), were admitted to the study. The mean age was 26 years; 69 had a small sinus with 1-2 tracks. Three patients (4%) had postoperative bleeding or wound infection. Mean healing time was 39 days but all patients were able to return to work within 1 week from the operation. The mean period of follow-up was 45 months. Six patients developed recurrence (9,2%). Only 3 of them, (because symptomatic) required a second operation., Conclusion: Bascom's technique is simple and suitable for one-day surgery with local anesthesia. It also gives favorable results as to return to work and rate of recurrence. Therefore, it is suggested as the procedure of choice in the initial treatment of symptomatic pilonidal disease.

Spigelian hernia (SH) is a rare partial abdominal wall defect; its manifestation is rare. Seven cases were observed--4 females and 3 males with mean age of 56.5 years (range 38-65)--in 857 patients operated for hernia (0.8%) between 1995 and 2003. Ultrasound examination avoid the diagnosis and marked the fascial defect, measuring diameter and sac contents. In all cases a surgical approach with an epicritic incision has be done and the fascia defect closed with properitoneal and subfascial polypropylene mesh (Prolene Hernia System, PHS). All patients underwent to follow-up demonstrating no recurrences or complications like mesh suppuration or dislocation.

Background: Local excision for T1 rectal cancers with Transanal Endoscopic Microsurgery (TEM) is an accepted standard of care. However for T2/T3 rectal cancers, the high local failure indicates that this is not a valid option., Materials and Methods: Between 1990 and 2000, 83 patients with rectal adenocarcinoma underwent complete full thickness local excision. The mean diameter of the tumor was 3.4+/-1.7 cm, 60% were located more than 5 cm from the anal verge; 43% of patients received radiation therapy (26 pre- and 10 postoperatively)., Results: Postoperative complications occurred in 15 patients (18%); there were no postoperative deaths. Mean follow-up was 37 months (range 18-118). The pathological stage was: Tis 9, T1 39, T2 23, T3 12. The overall local recurrence rate was 0% for Tis, 13% for T1, 17% for T2 and 50% for T3. Recurrence was managed surgically in 65% and nonsurgically in 35% because of advanced disease or poor general condition. Overall 5-year survival rates were 100%, 92%, 75% and 69% for Tis, T1, T2 and T3, respectively., Conclusion: Local excision with TEM is effective for early (Tis, T1) rectal cancers. Patients with T2 tumors can be treated with preoperative chemoradiation and subsequently local resection. Patients with T3 should not be treated with local excision unless they are unable to tolerate more extensive surgery.

The aim of the study was to assess the frequency of synchronous colorectal and renal cancers among our patients. To this end we reviewed 781 consecutive patients operated on for colorectal carcinoma in our institution. Three patients (0.4%) had diagnosis of synchronous renal-cell cancer during the work-up for their colorectal primary tumours. The colon and rectum are frequently affected by multiple malignant tumours. Second primaries are not frequently associated with colorectal cancer. On the other hand, renal cell carcinoma has been described as being associated with other synchronous malignancies in up to 27.4% of cases. A recent report has described a 4.8% incidence of synchronous colorectal and renal carcinomas, which is much higher than that previously reported in the literature (0.03-0.5%). We found a 0.4% incidence of simultaneous colorectal cancer and renal cell carcinoma. The latter was invariably asymptomatic and diagnosed during the work-up for the colorectal cancer. We are unable to confirm the observation of a higher than expected incidence of synchronous colorectal and renal neoplasms. Nevertheless, the surgeon should be conscious of this association, when considering renal lesions detected during the work-up for colorectal cancer.

Aim: To determine the results of elective surgical treatment for colo-rectal cancer in the elderly., Methods: A total of 746 patients were consequently operated on in elective conditions for colorectal cancer. Patients were divided into 4 groups, according to patient's age: Group A > or =80; Group B=70-79; Group C=60-69; Group D < or = 60., Results: Between older patients there was a higher percentage of right colon cancers (A: 26.3%; B: 13.9%; C: 16.6%; D: 20.6%) and stage D tumors (A: 34.4%; B: 28.3%; C: 21.4%; D: 26%), explaining the greater proportion of palliative surgical treatment in this group of patients (A: 34.7%; B: 28.2%; C: 28.6%; D: 25.7%). There were no differences in term of morbidity (A: 12.6%; B: 9.2%; C: 5.1%; D: 6.4%), mean hospital stay (A: 18.9+/-16.2 days; B: 17.2+/-15.8; C: 15.2+/-8.6; D: 16.8+/-21.8) and postoperative mortality (A: 3.1%; B: 2.3%; C-D: 0.4%); on the contrary, survival curve in group A was significantly shorter than in the other groups., Conclusion: Advanced age is not per se a negative prognostic factor and consequently does not represent a contraindication to surgery. In fact, long-term results have been proved to be similar both in young and old patients. Nevertheless, elderly patients have a lower capacity to react to postoperative complications; this needs an accurate evaluation of single patient, considering different parameters such as disease stage, possibility of cure or palliation, quality and expectancy of life.

A prospective phase II study was conducted to evacuate toxicity and results of preoperative radiochemotherapy in locoregionally advanced rectal cancer (LARC). A total of 33 patients entered the study and received 45 Gy to the pelvis plus a supplemental boost of 5.4-9 Gy concurrently with 5 FU c.i. at a dose of 225-275 mg/m2. Thirty patients were operated after 5-7 weeks (20 anterior resection and 10 abdominoperineal excision). In 14 patients (47%) a downstaging was observed, 5 patients experienced a complete clearance of the primary tumor. After a median of 14 months (range, 5-27), 23 patients, are alive and well. And 8 patients experienced a disease progression (4 local-regional and 4 distant). Our results provide further evidence of the utility and effectiveness of preoperative radiochemotherapy in LARC.

Background: Hydatid cysts may occur in any area of the body, but they usually localize to the liver and the lungs. Primary localization in muscle is not common, accounting for 2-3% of all sites; even rarer is the development of multiple cysts., Methods: The patient presented with a painless abdominal mass which gradually increased in size to a diameter of approximately 16 cm. Organ imaging scan revealed multiple hydatid cysts within the right psoas muscle. Because of the proximity of the lesions to the iliac vessels, ureter and nerves to the lower limb, percutaneous drainage and alcoholization under local anaesthesia were -performed with the aim of reducing the size of the cysts and sterilizing them prior to definitive surgery. This procedure was not effective. Two weeks after percutaneous treatment the patient underwent surgery., Results: At operation the cysts were localized and successfully removed under ultrasound guidance. Postoperative stay was -uneventful. Two years after surgery the patient has no evidence of recurrent hydatid disease., Conclusions: Ultrasonography is the preferred method for detecting muscular hydatid cyst and for guiding the surgeon during resection.

Local excision is a suitable approach for treating sessile adenomas and early adenocarcinomas of the rectum. The indication for transmural rectal carcinomas (T2 and T3) is a matter of debate and no randomized studies have been reported to date. The early and long-term results of a consecutive series of 160 patients who underwent local excision in our departments are reported. Sixty-three patients (39%) had adenoma and 97 patients (61%) carcinoma. Forty-seven patients with carcinoma (48%) received adjuvant therapy. Postoperative complications occurred in 25 patients (15%). The complication rates were 13% (8/63) for adenomas and 18% (17/97) for carcinomas. Only 1 patient died during the postoperative period as a result of unrelated causes. The overall local recurrence rates were 3% and 24%, respectively. Among the adenocarcinomas recurrence was related to staging, tumour clearance at the resection margins and use of chemo- and radiotherapy. No recurrences were reported among the T2 patients submitted to neoadjuvant treatment. A difference versus radical surgery was observed for T3 patients only. Local excision and transanal endoscopic microsurgery in particular is worthwhile in adenomas and T1 carcinomas of the rectum. Patients with T2 tumors should be treated with preoperative chemo- and radiotherapy. Patients with T3 tumors should be treated with transanal endoscopic microsurgery for palliative purposes only.

Spores of Bacillus species are being used commercially as probiotics and competitive exclusion agents. Unlike the more commonly used Lactobacillus-type probiotics, spores are dormant life forms. To address how spore probiotics might function we have investigated whether spores can germinate in the gastrointestinal tract by using a murine model. Using a genetically engineered chimeric gene, ftsH-lacZ, which is strongly expressed only in vegetative cells, we have developed a sensitive competitive reverse transcription-PCR assay which has enabled detection of as few as 10(2) vegetative bacteria in the mouse gut. Using this method we have administered doses of ftsH-lacZ spores to groups of mice and shown that spores can germinate in significant numbers in the jejunum and ileum. The levels of detection we obtained suggest that spores may colonize the small intestine, albeit briefly.

Background: It is well known that mucosal concentrations of many pro and anti-inflammatory cytokines are elevated in diseased segments of colon in Crohn's colitis. The present study, showing preliminary results, aims to determine whether the IL-1beta, IL-6 and IL-8 levels are increased throughout the entire colon in patients with Crohn's colitis., Methods: Five patients with active Crohn's colitis and five controls were studied by mucosal biopsies. In the diseased patients IL-1beta, IL-6 and IL-8 levels have been measured in both pathologic and normal appearing colonic mucosa. The concentration of these cytokines was assessed using ELISA and compared. Histological sections were also performed to confirm diseased segment of colon., Results: The concentrations IL-1beta and IL-8 were much more higher in patients with Crohn's colitis when compared to controls. Moreover IL-1beta and IL-8 were more elevated in uninvolved colonic segments than on diseased segments., Conclusions: Our results confirm the finding of other authors that, although Crohn's colitis is a segmental disease, the concentration of IL-1beta and IL-8 in mucosal biopsies is increased throughout the entire colon. In particular our study shows that the concentrations of IL-1b and IL-8 is higher in uninvolved than involved colonic segments. These appearances favour the physio-pathologic hypothesis that Crohn's colitis involves the entire colon even when is not clinically or histologically apparent, and they suggest that uninvolved parts of colon may not be free of disease. Further studies are required to better understand the higher levels of cytokines found in macroscopically normal when compared to pathological mucosal in patients with Crohn's colitis.

Background: The aim of the study was to evaluate the clinical relevance of isolated metastases (MII) in unusual sites (different from liver and lung), synchronous and metachronous, in patients operated on for colorectal carcinoma (CCR)., Methods: The study was performed on 655 patients who underwent surgery for CCR during the period 1985-2000. Work out for distance metastases was performed (both during preoperative evaluation and follow-up) with physical examination and other few exams (CEA, chest X-ray, abdominal US scan). Other investigations were carried out if requested by clinical features. Metastases localized in sites different from liver and lungs were considered unusual., Results: Metastases in unusual sites usually are observed in patients with terminal neoplastic disease. MII was found in only 7 (1.07%) patients, all submitted to resection of the primary tumor. Sites of unusual metastases were bones (3), CNS (2), adrenal gland and anus; such lesions were easily diagnosed by clinical features or by few examinations. Curative treatment was feasible in only three patients, and actually it did improve neither survival, nor quality of life., Conclusions: Extra-abdominal MII are rare, generally they cannot be treated; therefore particular tests for early diagnosis of such lesions appear useless. Potentially curative surgery for splenic and adrenal metastases is described in the literature; anyhow these lesions are usually shown by routine investigations.

We present the case of a 50-year old patient, operated on for three adjoining annular strictures in the jejunum with proximal dilatation. He presented with a one-year history of recurrent cramping in the upper abdomen and vomiting, with two episodes of intestinal obstruction. Microscopic examination of the stricture revealed, in the submucosa, disorganised fascicles of smooth muscle derived from the muscularis mucosae, bundles of non-myelinated nerve fibres with scattered abnormal ganglion cells and haemangiomatous vessels. The pathological findings observed were similar to those described as neuromuscular and vascular hamartoma, a rare stricturing condition of the small intestine. Many authors have questioned the hamartomatous nature of this disorder, since identical features may be seen in Crohn's disease, in ischaemic enteritis, in radiation enteritis and in non-steroidal antiinflammatory drug-induced small intestinal strictures. On the basis of a review of the 5 previously described cases and of our own experience, we believe that neuro muscular and vascular hamartoma of the small bowel should be considered as a distinct entity if histological hallmarks of Crohn's disease are absent, in patients with no history of gastrointestinal disease, or of chronic ingestion of non-steroidal antiinflammatory drugs.

Newly hatched specific pathogen-free chicks were dosed with a suspension of Bacillus subtilis spores prior to challenge with Escherichia coli O78:K80, a known virulent strain associated with avian colibacillosis, 24h later. A single oral inoculum of 2.5x10(8) spores was sufficient to suppress all aspects of E. coli O78:K80 infection. Colonisation of deep organs was reduced by a factor of over 2log(10) whilst colonisation of the intestine, as measured by direct caecal count, was reduced over 3log(10). Shedding of E. coli O78:K80 was measured by semi-quantitative cloacal swabbing and was reduced significantly for the duration of the experiment, 35 days. B. subtilis persisted in the intestine although with decreasing numbers over the same period. Challenge with the same dose 5 days after pre-dosing with spores overcame any suppressive effect of the spores.

Herniation of small bowel trough a defect of the broad ligament is an extremely rare event, more over in women never had surgical operations. Pathogenetic hypothesis are considered. Differential diagnosis may be difficult. The Authors report a recent observation of such small bowel herniation trough the left mesosalpynx.

Neuromuscular and vascular hamartoma is an extremely rare stricturing condition of the small bowel. It consists of abnormal mixtures of intestinal tissues: disorganized fascicles of smooth muscle derived from the submucosa, bundles of nonmyelinated nerve fibers with scattered abnormal ganglion cells and hemangiomatous vessels, occurring focally and causing recurrent obstructive symptoms or occult chronic gastrointestinal bleeding. In this paper we report our experience with this tumor., (Copyright 2001 S. Karger AG, Basel)

Unlabelled: Colonoscopic screening has been recommended in asymptomatic first-degree relatives of patients with colorectal cancer. In fact this population is believed to have an increased risk in developing colorectal neoplasia. The purpose of this study is to report the impact of colonoscopy in a series of completely asymptomatic first-degree relatives of patients operated on for colorectal cancer at our institution. A total of 480 individuals was requested to participate in a screening program based on faecal occult blood testing (FOBT) and colonoscopy in those with positive FOBT. Colonoscopy was also suggested to persons with negative FOBT. After the first 195 examined relatives, FOBT was abandoned because of continuously increasing acceptance of colonoscopy., Results: Two hundred fifty four subjects (52.4%) accepted to participate at the screening program. After the first 195 examined relatives, FOBT was abandoned because of continuously increasing acceptance of colonoscopy. A total of 142 colonoscopies was performed. Colonoscopy was completed in 112 relatives (78.9%). Thirty-three subjects (23.2%) had a positive colonoscopy: one had invasive adenocarcinoma, one had large villous adenoma and 31 had 54 polyps. Twenty-three lesions (40.3%) were located proximal to the splenic flexure. Of the 54 polyps, 45 (83.3%) were less than 1 cm in size. These findings confirm the utility of colonoscopic screening in asymptomatic first-degree relatives of patients with colorectal cancer. However, its feasibility with the current endoscopic facilities remains an unsolved question.

Total large bowel evaluation remains an essential step in the treatment of patients with colorectal cancer (CRC). Colonoscopy is the gold standard in the evaluation of the colon for colorectal tumors, but may be incomplete due to tumor obstruction, which is a frequent event in distal cancers. Double-contrast barium enema has a lower accuracy and is not ideal in the presence of signs of obstruction. In theory, intraoperative colonoscopy is a valid alternative, but its routine use is impeded by various practical limitations. Preoperative survey of the colon in 521 consecutive patients treated for CRC in our department was based on colonoscopy (92.5%). Our series was characterised by a high percentage of distal lesions (76.4%) and therefore by a high percentage of incomplete preoperative colonoscopies (50.4%) due to tumor obstruction. In the presence of an incomplete preoperative colonoscopy, we evaluated the entire colon with a double-contrast barium enema in selected cases (36.7%) and with a postoperative colonoscopy within 3 months of surgery in almost all patients (93.4%). The overall rate of complete endoscopic evaluation, either pre- or postoperatively, was 96.7%. The incidence of adenomas was significantly higher in the preoperative examinations as compared to early postoperative colonoscopy. This means that in distal cancer the vast majority of polyps will be located in the distal colon and therefore included in a standard resection. Four patients (0.8%), required a second operation for treatment of a missed lesion (2 benign and 2 malignant). The need for a repeat surgery apparently did not affect the therapeutic results in these four patients. On the basis of our experience, intraoperative colonoscopy would not appear to be a mandatory procedure in all cases of incomplete preoperative evaluation of the colon. However, in the absence of prospective, randomised trials comparing intraoperative vs early postoperative colonoscopy, the dilemma as to the strategy of choice remains.

An experience of surgical non-thoracic emergencies in patients admitted for chronic lung disease is herein presented. Fifty-four patients out of 10457 admitted in the four Departments of Pneumology of the Binaghi Hospital (Cagliari) between 1-1-1985 and 31-3-1993, were referred to our Department of General Surgery due to non-thoracic surgical emergencies. There was a considerable delay in the referral (only 25% of patients within 12 hours from the onset of symptoms): indeed predominant respiratory symptoms, hypoxia and hypercapnia made these patients no responsive to symptoms of surgical emergency. Surgical emergencies in causal correlation with respiratory disease (intestinal occlusion due to abdominal metastases of lung carcinoma, complicated peptic ulcer) had the worst prognosis (mortality: 52.9%). Those in chance connection, such as acute limb ischemia and preexisting abdominal disease, had a less adverse outcome. Mortality, however, was 37.5%: this datum outlines the role of chronic lung disease in defining operative risk. The authors call attention to three groups of observed patients: 1) three patients were operated on for intestinal occlusion due to unrecognized abdominal neoplasia, that showed itself in the course of hospitalization in the Department of Pneumology for lung metastases; 2) in 3 cases symptoms and signs of acute abdomen were observed without abdominal disease. The cause of acute pseudoabdomen was diaphragmatic pleural or basal pulmonary inflammation; 3) the eight patients with pulmonary embolism were all admitted in the Department of Pneumology with a wrong diagnosis of bronchopneumonia.

The efficacy of two methods of orthograde lavage preparation in elective colorectal surgery was tested in 133 consecutive patients: the results obtained with whole gut irrigation (50 patients, group A) were compared with the results of oral lavage solution (83 patients, group B). All patients received a parenteral association of antibodies (clindamycin in combination with a broad spectrum antibiotic, mainly II or III generation cephalosporins). Bacterial cultures were carried out at the end of the lavage in the rectal effluent (no statistically significant differences between the two groups) and in the intraoperative aspirate from the colon (the bacterial concentration was higher in group B). The total number of infections was 12 (9%), with 6 (12%) in group A and 6 (7.2%) in group B. The infectious complications involved perineal wound in 9 cases (in 2 patients in combination with abdominal wound infection), abdominal drainage in 2 and abdominal wound in 1. The type of broad spectrum antibiotic did not affect the infection rate significantly. Perioperative and infection site bacteriological cultures grew the same type of organism only in one case. The surgeons' judgement of the adequacy of the cleansing favored whole gut irrigation, although the results of the study revealed that both methods were safe and provided equally adequate bowel cleansing.

The Authors report two cases of sub-peritoneal rupture of the duodenum following blunt abdominal trauma. The diagnostic difficulties are explained in detail. Emphasis is placed on the importance of prompt recognition of the duodenal injury and early surgical treatment to ensure a successful outcome.

A case of single splenic metastasis from large cell anaplastic carcinoma of the lung is described. The patient first underwent pulmonary lobectomy and then splenectomy. He is still alive 42 months after the first operation and 41 after the second. The case herein described is rather uncommon, due to the rarity of single splenic metastases, and the long survival of the patient. The latter point strongly suggests an aggressive surgical approach to single metastases, even if primary tumor has extremely poor prognosis.

In arteriosclerotic obstruction of the main tibial arteries, the tibial collateral vessels are usually patent, and about 70% of these arteries are potentially suitable for surgical revascularization. The present study aimed at investigating the practical feasibility of a selective revascularization procedure on these tibial muscular arteries (ultraperipheral revascularization). Six lower limbs amputated at thigh level for arteriosclerotic gangrene with complete obstruction of the main tibial arteries, were studied: the tibial collateral muscular vessels showed patency in 65% of cases. The authors propose a surgical technique for the revascularization of these peripheral vessels with the use of a vascular prosthesis. The "post-operative" angiographic studies showed that revascularization of these peripheral muscular arteries was possible.

Rupture of the right hemidiaphragm is an unusual event and often misunderstood. Failure to diagnose this lesion in the acute stage, in addition to contributing to its high mortality, means that it frequently becomes apparent only months or even years after the event. Even at this late stage, diagnosis is not always easy, especially when the history is not correctly weighed and proper investigation is thus lacking. Pneumoperitoneum and liver scintiscanning are recommended in this respect. A recently observed case is presented as a more or less typical example of this rare disease.

The possible onset of a vascular connection between the parietal network of a jejunal loop transposed into the crural region and the quadriceps muscle in hypoperfused condition has been experimentally studied. Ten dogs were included in this study. Sixty days after the operation the angiograms obtained by cannulating the artery of the implanted loop showed a rich neovascularity in the muscular area near the implant and the direct visualization of the venous outflow of the thigh. Histology of the specimens showed no substantial abnormalities of the muscular tissue. From these data the possible effective role of the skeletal muscle revascularization in the management of some severe ischemic conditions, after the failure of all the conventional reconstructive procedures, is suggested.

Large surgical series are agreed on the fact that the prognosis for radically operated colorectal cancer has improved little in the last twenty years. Reasons for these failures are, of course, local or remote recurrences. To improve the number of stable cures, experiments have been carried out with complementary or coadjuvant techniques whose purpose is to limit intra-operative dissemination of the tumour and to monitor the number of cancer cells that might remain after radical surgery. Such techniques have been applied at preoperative, intra-operative and post-operative phases. Results obtained so far have been uncertain but seem to point to the usefulness of intraoperative procedures in reducing the number of local recurrences and of postoperative chemotherapy with 5 FU which has improved five-year survival indices by 5-7%.

A 39-year-old man, operated on for duodenal ulcer, was found to have a papillary carcinoma of the thyroid, an aldosterone-producing adenoma of the adrenal cortex, and a recurrence of a peptic ulcer. The probable coincidental occurrence of these diseases in this patient is suggested. Nevertheless, careful investigation of the other endocrine glands in patients with endocrine tumors is recommended.

A considerable number of patients having aorto-femoral surgery for chronic obliterative atherosclerosis show evidence of obstructed run-off vessels. In this condition poorer long-term results were documented in many series. The present study was aimed at investigating the state of 33 small muscular arteries of 8 limbs amputated for atherosclerotic gangrene. Histological studies showed that 11 muscular arteries were completely free from atheromatous lesions and that another 11 with minor abnormal features could be considered susceptible of revascularization. The conclusive data from this study in a small series suggest that in generalized atherosclerotic obstruction of lower limbs, nearly 70 per cent of the muscular vessels distal to the obstruction are potentially suitable for revascularization.

Rupture of a hepatic artery aneurysm into the biliary tree is a rare cause of hemobilia. The dramatic nature of the disease and the difficulties in obtaining a preoperative diagnosis are the main causes of its high mortality rate. Progress in vascular radiology and surgery seems to be an important factor in improving the survival rates in patients with this type of hemobilia. A case of a patient with an aneurysm of the common hepatic artery ruptured into the common bile duct is reported. Preoperative arteriography revealed the aneurysm and the arteriobiliary fistula causing massive hemobilia. The patient was successfully treated by arterial ligation and is symptom free after 2 years.