Genomic CGH-assessed structural DNA alterations in rectal carcinoma as related to local recurrence following primary operation for cure.

Several factors determine overall outcome and possible local recurrence after curative surgery for rectal carcinoma. Surgical performance is usually believed to be the most pertinent factor, followed by adjuvant oncological treatment and tumor histopathology. However, chromosomal instability is common in colorectal cancer and tumor clones are assumed to differ in aggressiveness and potential of causing local recurrence. The aim of this study was, therefore, to evaluate if genetic alterations in primary rectal carcinoma are predictive of local recurrences. A large clinical database with linked bio-bank allowed for careful matching of two patient groups (R0) resected for rectal carcinoma. One group had developed early, isolated local recurrences and the other group seemed cured after 93 months follow-up. DNA from the primary tumors was analysed with array-CGH (comparative genomic hybridization) including 55,000 genomic probes. DNA from all primary tumors in both groups displayed previously reported and well-recognised DNA aberrations in colorectal carcinoma. Significant copy number gains were confirmed in the 4q31.1-31.22 region in DNA from tumors with subsequent local recurrence. Twenty-two affected genes in this region code for products with high relevance in tumor biology (p53 regulation, cell cycle activity, transcription). DNA from rectal carcinoma displayed well-known aberrations as described for colon carcinoma with no obvious prediction of local rectal recurrence. Gains in the 4q31.1-31.22 DNA region are highly potential for local recurrence despite R0 resection to be confirmed in larger patient materials.

Long-term results of stapled haemorrhoidopexy in a prospective single centre study of 153 patients with 1-6 years' follow-up.

AIM: The long-term results of stapled haemorrhoidopexy for prolapsed haemorrhoids were assessed using uniform methods to acquire data and pre-set definitions of failure, recurrence, residual symptoms and impaired continence. METHOD: From October 1999 to May 2005, 153 patients underwent a stapled haemorrhoidopexy and were enrolled prospectively. They were assessed preoperatively, postoperatively and at the end of the study from replies to a questionnaire about symptoms and continence. Preoperatively, manual reduction of prolapse was required in 103 patients, skin tags were found in 115 patients (circumferential in 22) and impaired continence in 63. RESULTS: In all, 145 patients completed preoperative and long-term protocols and were analysed as paired data, at a mean follow-up of 32 months. Failure to control the prolapse or recurrence was seen in 19 (13%) patients including nine reoperations for prolapse. Symptoms improved from 8.1 to 2.5 points on a 15-point scale (P = 0.001). Symptoms were not controlled in 25 (17%) patients. Continence improved from 4.7 to 2.9 points on a 15-point scale (P = 0.001). Twenty-five (17%) patients still had a continence disturbance. Altogether 51 (35%) patients had a deficient outcome with respect to prolapse, symptoms or continence. There were no major adverse events. CONCLUSION: Restoration of the anal anatomy by stapled haemorrhoidopexy resulted in a significant improvement in haemorrhoid-associated symptoms and continence but a third of patients had poor symptom control including 13% with persisting prolapse.

Local recurrence of rectal cancer: a population-based cohort study of diagnosis, treatment and outcome.

AIM: Local recurrence is an important endpoint of rectal cancer treatment, but details of this form of treatment failure are less well described. The aim of this study was to acquire deeper knowledge of local recurrence regarding symptoms, diagnostic work-up, clinical management, health-care utilization and outcome. METHOD: Of 671 patients with rectal cancer, 57 were diagnosed with local recurrence within 5 years after surgery. Their records were analysed. RESULTS: At diagnosis of local recurrence 49 (86%) of 57 patients were symptomatic and 40 (70%) were diagnosed between scheduled follow-up visits. The predominant symptom was pain. Forty-five of the 57 (79%) had a palpable tumour. Most were deemed incurable at presentation and 10 (18%) were operated on with curative intent. Five years after the initial rectal cancer surgery, two patients were alive, with one free of disease. Despite the need for multiple interventions, including surgery, only four out of 40 patients were classified as being well-palliated in the terminal stage. CONCLUSION: Follow-up after rectal cancer surgery by annual clinical examination is not sufficient to detect local recurrence when it is asymptomatic. Local recurrence of rectal cancer is often associated with intractable symptoms. These patients require frequent interventions and can rarely be cured if diagnosed at an advanced stage. Strategies for early detection of local recurrence and the management thereof require improvement.

A phase I/II study of neoadjuvant chemotherapy with Pemetrexed (Alimta) in rectal cancer.

AIM: The aim was to assess the feasibility of preoperative chemotherapy and possible tumour response using Pemetrexed (Alimta) in rectal cancer. METHOD: The study was a prospective, non-randomized, single-centre phase I/II feasibility trial. 37 patients with resectable rectal cancer were recruited and given three 3-week cycles of preoperative Pemetrexed therapy. Tumour size and stage were assessed by MRI scans before and after chemotherapy. Treatment tolerability and response such as changes in tumour size and symptoms were assessed. RESULTS: All patients completed the chemotherapy. Whilst mild side effects were frequent (grade 1, 34/37), the risk of severe effects was limited (grade 3 or 4, 4/37). Overall, there was a significant reduction in tumour size (p < 0.001). By RECIST criteria, one patient had tumour progression, 23/36 had stable disease and 12 patients had a response of up to 65%. There was also a significant decrease in the number of pre-treatment symptoms (p < 0.018) including reduction of bleeding and diarrhoea/constipation. CONCLUSION: Preoperative (Neoadjuvant) treatment with Pemetrexed was feasible in studied patients. Serious side effects were limited and a radiological tumour response or stable disease was seen in a majority of patients.

A study of lymph node ratio as a prognostic marker in colon cancer.

AIM: The aim of this study was to evaluate and describe the lymph node ratio (LNR) as a prognostic parameter for patients with colon cancer. As lymphatic involvement is the key, focus was set at stage III disease. Interest was directed at the possibility of identifying high-risk groups and the clinical implementation and consequence. METHOD: The study was retrospective using a database of clinical data of all cancer patients treated at our unit. It has been continuous in registration, inclusion and update since 1999 including survival and clinical features. All patients (n=265) diagnosed with stage III colon cancer during 1999-2003 were included for the study. LNR was calculated and quartile groups were created. LNR and associated parameters were analysed towards 3-year disease-free survival (DFS). Basic patient data as well as surgery, pathology and postoperative treatment were taken into consideration. RESULTS: Significant differences in disease-free survival were found for TNM N-status, tumour differentiation grade and LNR quartile group. There was a difference in 3-year DFS from 80% in LNR group 1 compared with less than 30% in group 4. These results were of prognostic interest both independently and in interaction with each other. High-risk groups could be identified and in the worst prognosis LNR group we also found a tendency towards more side effects with adjuvant chemotherapy. CONCLUSION: The lymph node ratio, the quota between the number of lymph node metastasis and assessed lymph nodes, is a highly significant (p<0.001) prognostic factor in stage III colon cancer. It can be an aid in identifying risk groups that could benefit from a more intense postoperative surveillance and possibly bring changes in adjuvant treatment strategy. More studies of clinical data, genetic and biochemical markers are needed in this patient group to understand the possible difference in tumour behaviour and tailor the treatment.

Stage migration in colorectal cancer related to improved lymph node assessment.

AIM: The aim of the study was to evaluate the clinical impact of improved cooperation between the treating surgeons and pathologists in a high volume surgical unit. As a measure we used the staging process with special focus on lymph node assessment. FINDINGS: Comparing two periods 5 years apart, we found a significant increase in the number of nodes examined and also an increase in the number of metastasis-positive nodes. Concurrently, we observed a trend in stage migration from stage I/II towards stage III, whilst stage IV remained unchanged. This was one factor that contributed to an increase in the number of patients treated with adjuvant chemotherapy. We also found that the number of assessed nodes had an impact on survival in stage II. The major change in practise was the implementation of a multidisciplinary team conference and the associated possibility of reciprocal feedback. CONCLUSION: Lymph node status has a key role in cancer staging and in the selection of further therapy. The quality and the standard of the assessment can be improved through multidisciplinary cooperation and it has an impact on the clinical decisions and can affect long-term survival. A correct node status should be mandatory in the evaluation of prognostic factors.

Local perianal block for anal surgery.

BACKGROUND: We refined a technique for local block of all terminal nerve branches to the anus. METHODS: A total of 30 consecutive patients with proctological disorders consented to ambulatory (n=29) or hospitalised (n=1) operation with local perianal block for skin tags, Milligan- Morgan haemorrhoidectomy, stapled haemorrhoidopexy or anocutaneous fistulae. Patients were operated prone. A total of 40 ml of a 4.75 mg/ml solution of ropivacaine (Narop; Astra, Sweden) was injected in 8 directions (5 ml each) into the ischiorectal fat immediately peripheral to the external sphincter as anaesthetic columns reaching from the skin to the levator. This injection scheme targets the terminal nerve branches of the anus rather than blocking the trunk of major nerves. The relaxation of a pain-free anus was obtained in 2-3 minutes with exposure similar to a general anaesthetic. Postoperative pain was evaluated on a 0 to 10 visual analogue scale (VAS). RESULTS: Patients were pain-free at discharge. However, mean postoperative VAS score at 24 hours was 3.2 following Milligan-Morgan haemorrhoidectomy, 4.8 following stapled haemorrhoidopexy and skin tags or polyps excision, and 2.7 after fistula lay-open. At telephone follow-up 1-2 weeks later, the patients were satisfied with the method of anaesthesia and would willingly accept it for any further anal surgery. CONCLUSIONS: The perianal block is easy to apply and effective as sole method of anaesthesia for proctological operations.