Thymosin ß4 and ß10 are highly expressed at the deep infiltrative margins of colorectal cancer - A mass spectrometry analysis.

OBJECTIVE: Colorectal cancer (CRC) is a complicated tumor, involving several oncogenic signaling pathways, and with a molecular mechanism not fully understood yet. The implication of thymosin ß4 (Tß4) with tumor insurgence and in migration of CRC cells was evidenced in the past with different methodologies, while Tß10 connection with CRC has been sporadically investigated. This study focused on the implication of both types of thymosin in CRC progression and invasion by analyzing the changes in their levels according to different zones of the tumor, and to Dukes stage and budding index. PATIENTS AND METHODS: Tß4 and Tß10 were analyzed in deep and superficial tumor samples, and normal mucosa from 18 patients. Concentrations of Tß4 and Tß10 have been measured by high-pressure liquid chromatography (HPLC) coupled to electrospray-ion trap mass spectrometry (ESI-IT-MS). MS data were compared by t-test and ANOVA statistical analysis. Identification of thymosin and their proteoforms has been performed by HPLC-high resolution-ESI-IT-MSMS. RESULTS: Both Tß4 and Tß10, exhibited intra-tumoral quantitative differences, being upregulated in the deep part of the CRC. They exhibited, moreover, strong association with the Dukes stage and the budding grade, being more concentrated in patients at Dukes stage B and with budding index "2". CONCLUSIONS: The results obtained in the present investigation encouraged the hypothesis that the two thymosin are involved in colorectal cancer progression, and in promoting cancer invasion. Thus, they are good candidates to be diagnostic/prognostic biomarkers and therapy targets.

Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study.

BACKGROUND: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. METHODS: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. RESULTS: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25-10.16 and OR 6.43 95% CI 3.33-12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33-14.74 and OR 3.14 95% CI 1.68-5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78-7.62 and OR 2.09 95% CI 1.10-3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. CONCLUSIONS: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy.

Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer.

BACKGROUND: Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer. METHODS: This multicentre RCT included patients with rectal carcinoma who underwent low anterior resection followed by colorectal anastomosis. Patients were assigned randomly to receive a colonic J pouch or straight colorectal anastomosis. The main outcome measure was the occurrence of major anastomotic leakage. The incidence of global (major plus minor) anastomotic leakage and general complications were secondary outcomes. Risk factors for anastomotic leakage were identified by regression analysis. RESULTS: Of 457 patients enrolled, 379 were evaluable (colonic J pouch arm 190, straight colorectal arm 189). The incidence of major and global anastomotic leakage, and general complications was 14·2, 19·5 and 34·2 per cent respectively in the colonic J pouch group, and 12·2, 19·0 and 27·0 per cent in the straight colorectal anastomosis group. No statistically significant differences were observed between the two arms. In multivariable logistic regression analysis, male sex (odds ratio 1·79, 95 per cent c.i. 1·02 to 3·15; P = 0·042) and high ASA fitness grade (odds ratio 2·06, 1·15 to 3·71; P = 0·015) were independently associated with the occurrence of anastomotic leakage. CONCLUSION: Colonic J pouch reconstruction does not reduce the incidence of anastomotic leakage and postoperative complications compared with conventional straight colorectal anastomosis. Registration number NCT01110798 (http://www.clinicaltrials.gov).

Expression of oncogenic BARD1 isoforms affects colon cancer progression and correlates with clinical outcome.

BACKGROUND: Colon cancer predisposition is associated with mutations in BRCA1. BRCA1 protein stability depends on binding to BARD1. In different cancers, expression of differentially spliced BARD1 isoforms is correlated with poor prognosis and decreased patient survival. We therefore suspected a role of BARD1 isoforms in colon cancer. METHODS: We performed immunohistochemistry in 168 colorectal cancers, using four antibodies directed against differentially expressed regions of BARD1. We determined structure and relative expression of BARD1 mRNA isoforms in 40 tumour and paired normal peri-tumour tissues. BARD1 expression was correlated with clinical outcome. RESULTS: BARD1 isoforms were expressed in 98% of cases and not correlated with BRCA1. BARD1 mRNA isoforms were upregulated in all tumours as compared with paired normal peri-tumour tissues. Non-correlated expression and localisation of different epitopes suggested insignificant expression of full-length (FL) BARD1. Expression of N- and C-terminal epitopes correlated with increased survival, but expression of epitopes mapping to the middle of BARD1 correlated with decreased survival. Middle epitopes are present in oncogenic BARD1 isoforms, which have pro-proliferative functions. Correlated upregulation of only N- and C-terminal epitopes reflects the expression of isoforms BARD1δ and BARD1φ. CONCLUSION: Our results suggest that BARD1 isoforms, but not FL BARD1, are expressed in colon cancer and affect its progression and clinical outcome.

Routine preoperative chest computed tomography does not influence therapeutic strategy in patients with colorectal cancer.

AIM: Patients with lung metastasis from colorectal cancer (CRC) may benefit from surgical resection. Chest computed tomography (CT) is often included in the preoperative staging. Interpretation of the nature of pulmonary lesions is not always easy and many question its clinical value. METHOD: Clinical data for all patients treated at our institution for CRC have been collected prospectively in a dedicated database. Since August 2008 chest CT has been routinely performed for preoperative staging. The outcome of 147 patients operated on since then (Group A) was compared with a numerically equal group of patients (147) (Group B) treated before the introduction of preoperative routine chest CT. RESULTS: Pulmonary lesions were identified in 45 (30%) patients in Group A and 10 (6.8%) in Group B. Ten and nine lesions, respectively, were interpreted as metastases. In 28 (19%) patients in Group A, the lesions were considered to be indeterminate and only four were confirmed as malignant. Overall metastases were present after 1 year of follow-up in 5 (50%) of 10 patients in Group A and 5 (55%) of 9 in Group B. The global incidence of synchronous and metachronous metastases was 6.8%, with no statistical difference between the two groups. CONCLUSION: This study shows that chest CT reveals a higher number of pulmonary lesions, only a small proportion of which were malignant. The investigation does not add value to routine staging methods in patients with CRC.

Does long-course radiotherapy influence postoperative perineal morbidity after abdominoperineal resection of the rectum for cancer?

AIM: The aim of the study was to define risk factors for perineal wound complications after abdominoperineal resection (APR), with particular reference to preoperative radiotherapy. METHOD: Patients undergoing APR at our institution between 1985 and 2009 were reviewed. Wound complications were classified according to the Center for Disease Control and Prevention classification of surgical site infection (SSI). Perineal complications were identified in patients who had preoperative long-course radiotherapy (Group 1) and those who had surgery alone (Group 2). RESULTS: One hundred and fifty-seven patients met the inclusion criteria. Preoperative radiotherapy was performed in 68 (44.7%) patients (Group 1), and 89 (65.3%) patients (Group 2) underwent surgery alone. The overall rate of perineal wound complications was 14.8%. The wound infection rate was similar in each group (Group 1, 10/68, 14.7%; Group 2, 13/89, 14.9%; P = 0.9). An elevated BMI (>30) was the only factor correlated with perineal morbidity on univariate analysis (P = 0.01). CONCLUSION: Preoperative radiotherapy does not influence perineal healing other than in patients with obesity.

[Role of endoanal ultrasound in the evaluation of fistula-in-ano treated with a seton]. / L'ecografia endoanale nella valutazione delle fistole trattate con setone.

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.

[Surgical treatment of pilonidal disease. Results with the Bascom's technique]. / Il trattamento del sinus pilonidalis: esperienza con la tecnica di Bascom.

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.

[Surgical treatment for colorectal cancer in patients over 80 years. Short and long term results]. / Il trattamento chirurgico del cancro colorettale nel paziente ultraottantenne. Risultati a breve termine e a distanza.

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.

Safety of primary anastomosis in emergency colo-rectal surgery.

BACKGROUND: The surgical management of left-sided large bowel emergency patients remains controversial. There has been an increasing trend towards primary reconstructive surgery. The main dilemma remains appropriate patient selection for primary anastomosis. METHODS: The records of 323 patients who presented as acute emergencies and underwent surgery between January 1990 and December 2000 for left-sided colorectal cancer and diverticular disease were reviewed, to compare the outcome of resection and primary anastomosis with Hartmann's procedure. Patients were stratified into 3 groups according to whether the presentation was with localized or generalized peritonitis, or with obstruction. RESULTS: Resection and anastomosis was carried out in 176 (55.7%) patients with a 30-day mortality of 5.7%. Anastomotic dehiscence occurred in 9 (5.1%) patients, with no difference between the three groups. Wound sepsis occurred in 8 (4.5%) patients, and the median hospital stay was 13 days. Hartmann's resection was associated with a higher incidence of systemic and surgical morbidity (39.5% and 24.3%, respectively). The mortality rates in those selected for primary anastomosis (5.7%) compared favourably with those undergoing Hartmann's resections (20.4%) (P < 0.001). CONCLUSION: Emergency primary anastomosis in left-sided disease can be performed with a low morbidity and mortality in selected patients, even in the presence of a free perforation with diffuse peritonitis. Patients selected for staged resection, were those with major comorbid disease.

[Levels of cytokines in mucosal biopsies of Crohn's colitis. Physiopatological observations]. / Contenuto delle citochine IL-1beta, IL-6 e IL-8 su prelievi bioptici di colite di Crohn. Considerazioni fisiopatologiche sull'estensione panintestinale della malattia.

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.

The impact of an incomplete preoperative colonoscopy in patients with colorectal cancer.

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.

[Recurrent esophageal obstruction by a foreign body: a case report and review of the literature]. / Ostruzione esofagea ricorrente da corpo estraneo: caso clinico e revisione della letteratura.

The Authors report a clinical case of a patient endoscopically treated for recurrent oesophageal obstruction by a foreign body. A review of the recent medical literature confirms that immediate endoscopic treatment is the best approach in the oesophageal retention of foreign bodies.