Ultralow voltage, OTFT-based sensor for label-free DNA detection.

An organic ultralow voltage field effect transistor for DNA hybridization detection is presented. The transduction mechanism is based on a field-effect modulation due to the electrical charge of the oligonucleotides, so label-free detection can be performed. The device shows a sub-nanometer detection limit and unprecedented selectivity with respect to single nucleotide polymorphism.

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.

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.

[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.

[Spigelian hernia. Diagnosis and surgical treatment]. / Ernia di Spigelio: diagnostica e trattamento.

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.

[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.

[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.

[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.

Neuromuscular and vascular hamartoma of the small intestine.

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.

[Neuromuscular and vascular hamartoma of the small intestine. Report of a clinical case and review of the literature]. / L'amartoma neuromuscolare e vascolare dell'intestino tenue. Presentazione di un caso clinico e revisione della letteratura.

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.