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.

A nationwide audit of the use of radiotherapy for rectal cancer in Italy.

BACKGROUND: There is good evidence that radiotherapy is beneficial in advanced rectal cancer, but its application in Italy has not been investigated. METHODS: We conducted a nationwide survey among members of the Italian Society of Colo-Rectal Surgery (SICCR) on the use of radiation therapy for rectal cancer in the year 2005. Demographic, clinical and pathologic data were retrospectively collected with an online database. Italy was geographically divided into 3 regions: north, center and south which included the islands. Hospitals performing 30 or more surgeries per year were considered high volume. Factors related to radiotherapy delivery were identified with multivariate analysis. RESULTS: Of 108 centers, 44 (41%) responded to the audit. We collected data on 682 rectal cancer patients corresponding to 58% of rectal cancers operated by SICCR members in 2005. Radiotherapy was used in 307/682 (45.0%) patients. Preoperative radiotherapy was used in 236/682 (34.6%), postoperative radiotherapy in 71/682 (10.4%) cases and no radiotherapy in 375 (55.0%) cases. Of the 236 patients who underwent preoperative radiotherapy, only 24 (10.2%) received short-course radiotherapy, while 212 (89.8%) received long-course radiotherapy. Of the 339 stage II-III patients, 159 (47%) did not receive any radiotherapy. Radiotherapy was more frequently used in younger patients (P < 0.0001), in patients undergoing abdominoperineal resection (APR) (P < 0.01) and in the north and center of Italy (P < 0.001). Preoperative radiotherapy was more frequently used in younger patients (P < 0.001), in large volume centers (P < 0.05), in patients undergoing APR (P < 0.005) and in the north-center of Italy (P < 0.05). CONCLUSION: Our study first identified a treatment disparity among different geographic Italian regions. A more systematic audit is needed to confirm these results and plan adequate interventions.

Phase II study of preoperative irradiation and chemotherapy with capecitabine in patients with locally advanced rectal carcinoma.

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.

Outcomes for early rectal cancer managed with transanal endoscopic microsurgery: a 5-year follow-up study.

BACKGROUND: This study aimed to evaluate the long-term risk of local and distant recurrence as well as the survival of patients with early rectal cancer treated using transanal endoscopic microsurgery (TEM). METHODS: The study reviewed 69 patients with Tis/T1/T2 rectal cancer treated using full-thickness excision between 1991 and 1999. The pathology T-stages included 25 Tis, 23 T1, and 21 T2. The median follow-up period was 6.5 years (range 5-10.2 years). RESULTS: The overall local recurrence rate was 8.7%. The 5-year local recurrence rate was 8% for Tis, 8.6% for T1, and 9.5% for T2. All six patients with recurrence were managed surgically. The 5-year disease-specific survival rate was 100% for Tis, 100% for T1, and 70% for T2. The overall cancer-related mortality rate was 7.2%. CONCLUSIONS: After local excision of early rectal cancer, a substantial local recurrence rate is observed. Patients with recurrent Tis/T1 cancers who undergo a salvage operation may achieve good long-term outcome. Local treatment without adjuvant therapy for T2 rectal cancers appears inadequate.

[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.

Is an antireflux procedure necessary in conjunction with parietal cell vagotomy in the absence of preoperative reflux?

During a 4 year period, we found no objective evidence that parietal cell vagotomy contributes to the production of gastroesophageal reflux. The fact that patients without reflux preoperatively achieved the same satisfactory clinical results whether parietal cell vagotomy was or was not accompanied by an antireflux procedure supports this view. Therefore, in the absence of reflux, we cannot recommend the prophylactic use of an antireflux procedure in combination with parietal cell vagotomy in the treatment of patients with duodenal ulcer. On the other hand, patients with duodenal ulcer should be evaluated for gastroesophageal reflux before operation because it is desirable to combine parietal cell vagotomy with an antireflux procedure if both conditions exist. Patients who have mild reflux preoperatively but no symptoms of reflux after parietal cell vagotomy alone, as in three of the four patients in Group IV, may have such symptoms subsequently. Therefore, we think that the combined procedure does not increase the morbidity over that of parietal cell vagotomy alone and recommend the combination of parietal cell vagotomy and an antireflux procedure for any patient undergoing operation for duodenal ulcer who also demonstrates an abnormal degree of gastroesophageal reflux.

Bacillus subtilis spores competitively exclude Escherichia coli O78:K80 in poultry.

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.

Experimental skeletal muscle revascularization by jejunal loop implant.

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.

The "ultraperipheral" revascularization in arteriosclerotic obstruction of tibial vessels. Experimental study.

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.

Carcinoma of the thyroid gland, adenoma of the adrenal cortex and peptic ulcer: an unreported association.

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.

[Neoadjuvant radiochemotherapy treatment in locally advanced rectal adenocarcinoma]. / Trattamento radiochemioterapico neoadiuvante negli adenocarcinomi del retto localmente avanzati.

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.

The mesenteric and antimesenteric location of colorectal cancer: the relationship with lymph nodes.

AIM: Purpose of the study was to evaluate if the circumferential location of colorectal cancer may be identified as a possible prognostic factor. The hypothesis is that tumours located on the antimesenteric (AM) side could have a better prognosis than tumours located on the mesenteric (M) side. METHODS: All patients undergoing curative resection for colorectal cancer were enrolled in the study. The specimens were sent to the pathologist to define the exact location of the tumour, the histological type, grading, T, N status as well as lymphatic, vascular and neural invasion, peritumoural lymphoid reaction, desmoplasia and microsatellite instability. Statistical analyses were performed using the test for proportions (with continuity correction), the Pearson Chi-square test and generalised linear models; p<0.05 were considered statistically significant. RESULTS: From August 2000 to August 2002, 255 patients were enrolled in the study. There was a significantly higher incidence of tumours located on the M (101) compared with the AM (37) site (p<0.0001). M located tumours were associated with higher numbers of metastatic lymph nodes (N1 and N2; p-value=0.014), whereas AM tumours were associated with involved lymph nodes in only 5/37 (13.5%) of tumours. There was no statistically significant relation between AM versus M location and T status: the Pearson Chi-Square test showed that the lymph node involvement and the location (M versus AM) are not statistically independent variables (p-value=0.014). CONCLUSIONS: Our preliminary results show that when M or AM tumour identification is possible, tumour location can be regarded as a prognostic factor. Further longer studies on recurrence rate and survival are required to validate these findings and the clinical usefulness of this putative prognostic factor.

[Immunosuppressive therapy in ulcerative rectocolitis. Long-term assessment of results]. / La terapia immunosoppressiva nella rettocolite ulcerosa.

The short and long-term efficacy of the combined administration of azathioprine and sulphasalazine in the treatment of ulcerative colitis was evaluated. A complete and durable remission of the clinical, the endoscopic and the histological signs of the disease was achieved in all the patients but one, who did not follow the domiciliary therapeutic regimen. No adverse effects referable to the long-term assumption of the azathioprine have been noted.

[Current trends of complementary therapy in radical surgery of colo-rectal cancer]. / Moderni orientamenti di terapia complementare nella chirurgia radicale del cancro colo-rettale.

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%.

[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.