An experience with video-assisted anal fistula treatment (VAAFT) with new insights into the treatment of anal fistulae.

BACKGROUND: The aim of this retrospective study was to assess our experience of 41 patients with anal fistulae treated with video-assisted anal fistula treatment (VAAFT). METHODS: Forty-one consecutive patients with cryptoglandular anal fistulae were included. Patients with low intersphincteric anal fistulae or those with gross perineal abscess were excluded. Eleven (27 %) patients had undergone prior fistula surgery with 5 (12 %) having had three or more previous operations. RESULTS: All patients underwent the diagnostic phase as well as diathermy and curettage of the fistula tracts during VAAFT. Primary healing rate was 70.7 % at a median follow-up of 34 months. Twelve patients recurred or did not heal and underwent a repeat VAAFT procedure utilising various methods of dealing with the internal opening. There was a secondary healing rate of 83 % with two recurrences. Overall, stapling of the internal opening had a 22 % recurrence rate, while anorectal advancement flap had a 75 % failure rate. There was no recurrence seen in six cases after using the over-the-scope-clip (OTSC(®)) system to secure the internal opening. CONCLUSIONS: VAAFT is useful in the identification of fistula tracts and enables closure of the internal opening. Adequate closure is essential with the method used to close large or fibrotic internal openings being the determining factor for success or failure. The OTSC system delivered the most consistent result without leaving a substantial perianal wound. Ensuring thorough curettage and drainage of the tract during VAAFT is also important to facilitate healing. We believe that this understanding will bring about a decrease in the high recurrence rates currently seen in many series of anal fistulae.

Young colorectal carcinoma patients do not have a poorer prognosis: a comparative review of 2,426 cases.

BACKGROUND: Colorectal cancer (CRC) in "young" patients under 50 years of age is uncommon. There have been conflicting reports regarding both the clinicopathological features of CRC in young patients and prognosis. The aim of this study was to review and compare the clinical characteristics, prognostic factors, and overall survival of patients in three different age groups (40 years and under, 41-50 years, over 50 years of age) and the prognosis of these patients. METHODS: A total of 2,426 consecutive patients who had undergone surgical resection for sporadic colorectal cancer at Singapore General Hospital in the period from 2000 to 2005 were retrieved from a prospectively collected computer database. There were 73 patients (3.0 %) in Group 1 (40 years old or less), 257 (10.6 %) in Group 2 (41-50 years old), and 2,096 (86.4 %) in Group 3 (>50 years old). Clinicopathological features were assessed using univariate analysis to evaluate significant differences, survival curves were constructed using the Kaplan-Meier method, and multivariate analysis was performed to evaluate the independent prognostic factors. RESULTS: Young CRC patients tend to present with a higher incidence of mucinous and signet ring cell tumors (Group 1-20.5 %, Group 2-8.2 %, Group 3-6.2 %, p < 0.001) and have more poorly differentiated tumors (Group 1-20.0 %, Group 2-9.7 %, Group 3-7.4 %, p = 0.014). Furthermore, young CRC patients tend to present with regional lymph node metastases (Group 1-65.7 %, Group 2-60.8 %, Group 3-51.0 %, p = 0.001) and distant metastases (Group 1-31.5 %, Group 2-24.1 %, Group 3-19.4 %, p = 0.006). Multivariate analysis reveals, however, that young age is not an independent prognostic factor for cancer-specific survival (CSS) (p = 0.392). Five-year CSS for Group 1 was 56.6 % (95 % confidence interval (CI) 44.8-68.4 %), Group 2 53.8 % (95 % CI 47.3-60.3 %), and Group 3 61.1 % (95 % CI 58.9-63.3 %). CONCLUSIONS: Although presenting with advanced tumors and with poorer prognostic factors such as presence of mucin and poor histological differentiation, young CRC patients do not have a worse prognosis.

Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients.

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited form of colorectal cancer (CRC) caused by mutation in the adenomatous polyposis coli (APC) gene. However, APC mutations are not detected in 10-50% of FAP patients. We searched for a new cancer gene by performing genome-wide genotyping on members of an APC mutation-negative FAP variant family and ethnicity-matched healthy controls. No common copy number change was found in all affected members using the unaffected members and healthy controls as baseline. A 111 kb copy number variable (CNV) region at 3q26.1 was shown to have copy number loss in all eight polyps compared to matched lymphocytes of two affected members. A common region of loss in all polyps, which are precursors to CRC, is likely to harbor disease-causing gene in accordance to Knudsen's "two-hit" hypothesis. There is, however, no gene within the deleted region. A 2-Mb scan of the genomic region encompassing the deleted region identified PPM1L, coding for a novel serine-threonine phosphatase in the TGF-beta and BMP signaling pathways. Real-time PCR analyses indicate that the 3'UTR of PPM1L transcript was down-regulated more than two-folds in all six polyps and tumors compared to matched mucosa of the affected member. This down-regulation was not observed in APC mutation-positive FAP patients. Our results suggest that the CNV region at 3q26 harbors an element that regulates the expression of an upstream candidate tumor suppressor, PPM1L, thus providing a novel mechanism for colorectal tumorigenesis in APC mutation-negative familial CRC patients.

The use of treosulfan and gemcitabine in the treatment of platinum-resistant ovarian cancer.

The combination of treosulfan and gemcitabine (TG) has been shown to have activity in ovarian cancer. These two agents are thought to be synergistic, with gemcitabine causing the persistence of treosulfan-induced DNA crosslinks. This study aimed to investigate the response rates, survival and toxicity in patients with platinum-resistant ovarian cancer treated with TG. A retrospective case note review of the patients treated with TG was performed in one cancer centre between May 1st, 2000 and November 1st, 2005. Estimates of cumulative survival were obtained using the Kaplan-Meier method. Forty-nine patients were identified; median age at diagnosis was 55 years (range, 31-72) and the median follow-up was 45.1 months (range, 12.2-118.3). TG was used as second-, third-, fourth- and fifth-line chemotherapy in 15, 19, 13 and 2 patients, respectively. Fifteen patients (30.6%) had stable disease; 25 (51%), a partial response; 1 (2%), a complete response and 8 (16.3%) had progressive disease. Median survival following diagnosis was 45.1 months and the median relapse-free survival was 12 months. The median survival time from the start of TG was 13.7 months with a relapse-free survival of 6.3 months. The median number of cycles given was 7. The most common toxicity recorded was myelosuppression. There were no treatment-related deaths. TG chemotherapy produced favourable response rates in a heavily pre-treated group of patients with platinum-resistant epithelial ovarian cancer. This doublet warrants further investigation in a phase III trial setting.

Ileo-anal j-pouch cancer: an unusual case in an unusual location.

Restorative proctocolectomy with ileal pouchanal anastomosis (IPAA) is the surgical treatment of choice for complicated ulcerative colitis. Development of ileal pouch-related cancer is a rare event and usually occurs in association with backwash ileitis or chronic pouchitis. We report a case of adenocarcinoma at the inlet of an ileal pouch in a 68-year-old Caucasian male, 14 years after restorative proctocolectomy for ulcerative colitis in the absence of severe chronic pouchitis or backwash ileitis. The operative technique is described, with a review of the literature on ileal pouch cancer.

A novel method of dealing with a large rectal enterotomy in an irradiated pelvis.

Pelvic irradiation as part of adjuvant therapy for rectal cancer is frought with many complications. We describe the case of a young man who presented with frequent intestinal obstruction after resection and radiotherapy for a low rectal cancer. Subsequent laparotomy and adhesiolysis resulted in a large defect at the previous anastomotic site. A loop of sigmoid colon was used to cover the pelvic brim in an effort to preserve the sphincter and intestinal continuity.

Localised extranodal non-Hodgkin's lymphoma of the gastrointestinal tract: Sheffield Lymphoma Group experience (1989-1998).

Extranodal non-Hodgkin's lymphoma (NHL) of the gastrointestinal tract accounts for about one third of all extranodal NHL. We retrospectively reviewed the clinical and histopathologic records of 71 patients with stage IE and IIE primary gastrointestinal NHL referred to the Sheffield Lymphoma Group (SLG) from 1989 to 1998. Cross-referencing with the Hospital Histopathology Department database revealed that only two-thirds of all cases were seen by the Group. The most common primary site was the stomach (45 patients, 63% of all cases), followed by the small intestine (16, 23%) and large intestine (9, 13%). The median age of patients was 62 years; the majority of patients presented with stage I (61%) and/or grade (65%) NHL. Mucosa-associated lymphoid tissue (MALT) lymphomas were the largest histologic subtype seen (57%), with 87% of these arising from the stomach; next most frequent was the diffuse large B-cell subtype (21% of all cases) most frequently arising from the intestine (60%). For treatment of gastric MALT lymphoma, a combined approach (surgery followed by chemotherapy, antihelicobacter therapy followed by chemotherapy) was favoured (22 cases). Five-year and 10-year overall survivals were 52% and 45% respectively. Knowledge of the Revised European American Lymphoma classification and the Helicobacter pylori/MALT association has influenced treatment approaches over the 10-year study period. For small intestinal lymphoma, surgery (with or without chemotherapy) gave 5- and 10-year survivals of 60%. Overall survival of patients with primary gastrointestinal lymphoma managed by the SLG is similar to that reported from other large series.