Combined modality treatment for complex fistulating perianal Crohn's disease.

AIM: Perianal disease affects 33% (range 8-90%) of patients with Crohn's disease. Fistulae are often complex and their management is often difficult and unsatisfactory. This study was a retrospective assessment of a combination of surgical treatment with a standardized protocol of infliximab (IFX) therapy. METHOD: A consecutive series of patients with complex perianal Crohn's disease, presenting between January 2003 and June 2008, were included. Acute sepsis was initially treated with antibiotics and/or surgical drainage (MRI guided when appropriate) and loose seton insertion. IFX was given at 5 mg/kg, at 0, 2 and 6 weeks. End-points were complete, partial or no response. Setons were empirically removed after the second cycle of IFX. RESULTS: Forty-eight patients, average age 46 (range 24-82)years, with perianal Crohn's disease were identified. Three patients stopped IFX after the second infusion, either because of allergy (two patients) or for failure to respond (one patient). Fourteen patients were given maintenance IFX at 8-weekly intervals. Results were recorded for 48 patients, of whom 14 (29%) had a complete response, 20 (42%) had a partial response and 14 (29%) had no response to treatment. Outpatient follow-up was for a median of 20 months. CONCLUSION: Combining surgical procedures with IFX resulted in complete and partial remission in 29% and 42% of patients, respectively. No serious side effects occurred. Using a combined, intensive medico-surgical approach, good initial control of perianal disease was achieved safely.

A proposal for the annotation of recurrent colorectal cancer: the 'Sheffield classification'.

AIM: Current classification systems of large bowel cancer only refer to metastatic disease as M0, M1 or Mx. Recurrent colorectal cancer primarily occurs in the liver, lungs, nodes or peritoneum. The management of each of these sites of recurrence has made significant advances and each is a subspecialty in its own right. The aim of this paper was to devise a classification system which accurately describes the site and extent of metastatic spread. METHOD: An amendment of the current system is proposed in which liver, lung and peritoneal metastases are annotated by 'Liv 0,1', 'Pul 0,1' and 'Per 0,1' in describing the primary presentation. These are then subclassified, taking into account the chronology, size, number and geographical distribution of metastatic disease or logoregional recurrence and its K-Ras status. CONCLUSION: This discussion document proposes a classification system which is logical and simple to use. We plan to validate it prospectively.

Asymptomatic isolated coccygeal metastasis in low rectal carcinoma.

As well as being relatively rare, osseous metastases from colorectal cancer are frequently asymptomatic and represent a late manifestation of disease. We report a case of an unidentified, asymptomatic coccygeal metastasis discovered on histological processing of the resection specimen from a patient with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by radical abdomino-perineal resection with coccygectomy. The anatomical explanation for this finding may involve passage of tumour cells via the vertebral venous plexus.

Surgery for obstructed defaecation: does the use of the Contour device (Trans-STARR) improve results?

AIM: The objective of the study was to assess safety, efficacy and outcomes of stapled transanal rectal resection (STARR) procedure for obstructed defaecation syndrome (ODS) with two stapling devices, PPH01 and Trans-STARR. METHOD: Data were collected on all patients undergoing PPH01 or Trans-STARR over a 2 year period. Initially, all were treated using the PPH01 device and during the last 8 months using the Trans-STARR. RESULTS: During the analysis period, 25 consecutive patients were treated with PPH01 and 27 patients were treated with Trans-STARR. The median follow up was 12 months (range 3-12 months) for the PPH01 group and 6 months (range 3-12 months) for the Trans-STARR group. Although the resected specimen was larger in the Trans-STARR group (P < 0.001), there was no difference in early adverse events, time to discharge or late complications between the groups. In both groups, postoperative urgency was common (occurring more than occasionally in up to 40% at last review) but the incidence was high preoperatively. ODS and symptom severity scores improved with surgery (P < 0.001). However, the degree of improvement was similar with complete resolution of symptoms occurring in 64% of the PPH01 group and 67% of the Trans-STARR group. CONCLUSION: Our study shows that both procedures are safe and effective in the surgical treatment of obstructed defaecation but despite a larger resection the Trans-STARR procedure does not offer any additional benefit. A policy of individualizing techniques tailored to the extent of prolapse may be appropriate, but requires further evaluation.

Long-term failure and function after restorative proctocolectomy - a multi-centre study of patients from the UK National Ileal Pouch Registry.

OBJECTIVE: There is little information on the long-term failure and function after restorative proctocolectomy (RPC). The results of data submitted to a national registry were analysed. METHOD: The UK National Pouch Registry was established in 2004. By 2006, it comprised data collected from ten centres between 1976 and 2006. The long-term failure and functional outcome were determined. Trends over time were assessed using the gamma statistic or the Kruskal-Wallis statistic wherever appropriate. RESULTS: In all, 2491 patients underwent primary RPC over a median of 54 months (range 1 month to 28.9 years). Of these, 127 (5.1%) underwent abdominal salvage surgery. The incidence of failure (excision or indefinite diversion) was 7.7% following primary and 27.5% following salvage RPC (P < 0.001). The median frequency of defaecation/24 h was five including one at night. Nocturnal seepage occurred in 8% at 1 year, rising to 15.4% at 20 years (P = 0.037). Urgency was experienced by 5.1% of patients at 1 year rising to 9.1% at 15 years (P = 0.022). Stool frequency and the need for antidiarrhoeal medication were greater following salvage RPC. CONCLUSION: In patients retaining anal function after RPC, frequency of defaecation was stable over 20 years. Faecal urgency and minor incontinence worsened with time. Function after salvage RPC was significantly worse.

Direct photographic documentation of ileal mucosa in routine colonoscopy is not an independent valid or reliable proof of completion: quality assurance issues for the national colorectal cancer-screening programme.

INTRODUCTION: The implementation of bowel cancer screening in the UK requires the maintenance of high standards in colonoscopy. Part of this quality control requires the reliable documentation of complete colonoscopy that can be externally audited and assessed. It has been suggested that terminal ileal biopsy is the only definitive and reliable method of confirming caecal intubation, but it is not cost-effective and may now be contraindicated because of potential prion infection. OBJECTIVE: To determine how reliable routine terminal ileal images were as an independent predictor of complete colonoscopy and whether their interpretation was aided with water insufflation or indigo-carmine dye-spraying. Method Forty-nine histologically confirmed terminal ileal images were obtained from a single endoscopist's database; 19 were conventional white-light images, 15 were taken with water insufflation and 15 were taken using chromoscopy enhancement. The images were transferred onto CD-ROM and sent as a questionnaire to 42 colonoscopists who were asked to identify the images as terminal ileum or not. RESULTS: Twenty questionnaires were returned resulting in a total of 980 responses. Overall, the accuracy of positive identification was 53.4%. Water insufflation and chromoscopy improved the accuracy to 68.3% and 63% respectively. Experience of (> 1000 colonoscopies) did not increase overall accuracy. Less experienced endoscopists had an increased accuracy rate with dye-spraying (76.7%vs 59.3%, P < 0.05) but experienced endoscopists had an increased accuracy rate with water insufflation (67.4%vs 63.3%, P > .05). CONCLUSION: Currently, terminal ileal imaging is not a reliable mode of documenting complete colonoscopy. Using water insufflation or dye-spraying coupled with modifications in image acquisition technique may improve its reliability but these methods require further investigation before they can replace the use of caecal landmarks as completion parameters.

Salvage endoscopic submucosal dissection for residual or local recurrent intraepithelial neoplasia in the colorectum: a prospective analysis.

OBJECTIVE: A prospective technical feasibility study of cap assisted ESD for 'curative intent' in patients with residual or local neoplastic recurrence following EMR. Primary end points were second stage R0 resection rate, safety and recurrence. METHOD: Salvage ESD was performed using the Olympus GIF-XQ240 gastroscope and KD-630L insulation tipped knife. Thirty-day mortality, re-admission rates, complications and histological resection status were collected prospectively up to 9 months following index resection. RESULTS: Thirty patients met eligibility criteria. Index R0 resection was achieved in 25/30 (83%) lesions. One patient underwent surgical excision with a second receiving a curative second stage dissection. Ninety-six per cent (29/30) patients were discharged within 24 h of the procedure with a 0% 30-day mortality and re-admission rate. Bleeding occurred in 5/30 (16%) treated successfully with endoluminal haemostasis. There were no perforations. Overall 'cure' rates at short-term follow-up [median 6/12 (range; 3-18)] was 96%. CONCLUSION: This novel application of ESD for first line 'salvage' therapy in treating residual or locally recurrent neoplastic disease may be a safe, minimally invasive and cost effective alternative to direct surgical resection in a select patient cohort.

A selective approach to restorative proctocolectomy without ileostomy: a single centre experience.

OBJECTIVE: A single surgeon series on complications and functional outcomes following restorative proctocolectomy (RPC) is presented. METHOD: An ethically-approved database was used to collect data on all patients undergoing RPC at a single institution. Patient demographics, operative details, complications and functional outcomes were assessed. The impact of ileostomy omission on outcomes was also assessed. RESULTS: Two hundred patients undergoing RPC between 1987 and 2006 were included. There were 122 (61.0%) males and the mean age at surgery was 37.6 years. A J pouch was constructed in 199 (99.5%) patients and an ileostomy omitted in 160 (80.0%). Since adopting a selective policy after the 36th consecutive patient in the series, only 9 (5.5%) patients have had an ileostomy constructed at the time of pouch construction. Complications occurred in 112 (56.3%) patients, with anastomotic stricture (20.6%) and pouchitis (28.6%) being the most common. Anastomotic stricture was more common in those patients receiving an ileostomy (43.6%vs 15.0%, P < 0.001), as were pouch-cutaneous fistulae (5.1%vs 0.6%, P = 0.039) and pelvic sepsis (15.4%vs 5.0%, P = 0.023). Functional outcomes were good, with median 24-h stool frequency of five motions at 1 year. There was increased urgency to defaecate which in part may be due to a significant decline in the use of antidiarrhoeal medication during follow up. CONCLUSIONS: Selective omission of a covering ileostomy in most cases can produce good results following RPC with no increase in the risk of septic complications or pouch failure, and a decreased risk of anastomotic stricture, with maintenance of good function in the majority.

Nm23 protein expression in ductal in situ and invasive human breast carcinoma.

BACKGROUND: Mortality associated with human breast carcinoma is almost entirely due to subsequent metastatic disease, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. Expression of nm23, a putative metastasis suppressor gene, has been detected in human breast cancers, but studies have not consistently shown high levels of the Nm23 messenger RNA or protein to be associated with better histological differentiation. This inconsistency suggests that Nm23 protein may act independently as a metastasis suppressor. PURPOSE: The purpose of this retrospective study was to investigate the relationship of Nm23 protein expression with 1) histology in ductal breast carcinoma in situ and 2) the variables considered to be the major prognostic indicators in invasive breast carcinoma. METHODS: We obtained formalin-fixed biopsy specimens of breast tissue excised from 128 patients with breast lesions detected by mammography. Of these patients, 35 had been diagnosed with benign breast disease, 26 with ductal carcinoma in situ (DCIS), and 67 with invasive carcinoma. Tissue sections were embedded in paraffin blocks, and immunohistochemical staining was used to determine Nm23 expression. Specimens were rated positive if all lesional epithelium was stained and negative if any lesional epithelium was unstained. Statistical analysis was performed by multiple regression analysis because of nonorthogonality of the data. RESULTS: All 35 examples of benign breast disease showed uniform epithelial cell staining. The seven cases of comedo DCIS were negative for Nm23 protein; all 18 noncomedo types were positive. Nm23 negativity was significantly associated with worsening invasive ductal carcinoma grade and advancing lymph node stage but not with tumor diameter or vascular invasion. Despite the putative antimetastatic role of the nm23 gene, no statistically significant association was found between Nm23 protein expression and vascular invasion. CONCLUSIONS: The precise role of the nm23 gene remains to be established, but our simplified immunohistochemical rating system shows an association between Nm23 protein expression and the two most significant prognostic factors relating to histologic grade and stage. Nm23 negativity distinguished comedo ductal carcinoma in situ from the other histological types, a finding consistent with the fact that comedo histology is known to have a higher likelihood of becoming invasive and of having higher cell proliferation rates and higher expression of growth factor (c-erb B2) receptor.

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

BACKGROUND: Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. METHODS: Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. KEY RESULTS: Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. CONCLUSIONS & INFERENCES: Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration.

Wire-directed localization biopsy of the breast: an audit of results and analysis of factors influencing therapeutic value in the treatment of breast cancer.

Fine-wire localization biopsy is an accurate technique for diagnosis of mammographically-detected breast abnormalities, and may also be therapeutic in the management of impalpable malignant lesions. A number of factors were therefore examined regarding their influence upon therapeutic success in a consecutive series of 129 localization biopsies. Factors included type of radiological abnormality, method and accuracy of wire localization and pre-operative cytology. Primary malignancy was detected at initial localization in 64 cases (malignant:benign ratio, 1.11:1); 26 (41%) achieving adequate local tumour excision margins without further surgery, and 38 undergoing further surgery to clear margins (mastectomy in 23, further wide excision in 15). Therapeutic success was related to the accuracy of pre-operative needle localization (needle hook within 1 cm of target lesion in 26/26 (100%) therapeutic biopsies, compared to 29/38 (76%) non-therapeutic biopsies (P<0.01, Fisher's exact test)); and to pre-operative cytology (suspicious/malignant cytology in 15/24 therapeutic, compared with only 9/29 non-therapeutic biopsies (P=0.013, chi-squared)). Localization biopsy has a high diagnostic success rate and a therapeutic value dependent upon accurate pre-operative cytological diagnosis, supplemented by precise needle localization of the target lesion.

Gastric carcinoma in siblings with Friedreich's ataxia.

Friedreich's ataxia is a hereditary neurological condition characterized by severe ataxia. We report the cases of two siblings with this condition, both of whom developed signet ring cell adenocarcinoma of the stomach at a young age. This association has not been previously described and it suggests the presence of an unidentified aberrant gene.

A prospective audit of simple mastectomy under local anaesthesia.

The treatment options for breast cancer in elderly or unfit patients can be complicated by their coexistent medical problems. This study assesses the feasibility of simple mastectomy under local anaesthesia by means of a prospective audit on 36 patients with breast carcinoma and an ASA grade of 3 or worse. In 27 patients the tumour had escaped from tamoxifen control, no patients having had previous radiotherapy. Operation time ranged from 40 to 70 min, average blood loss was 200 ml and an average inpatient stay of 5 days. Only two patients had a resection margin less than 1 cm and in none was there significant morbidity or mortality despite the patients' poor pre-operative medical condition. This confirms the potential of using local anaesthetic for simple mastectomy. Eliminating the morbidity/mortality due to general anaesthesia widens the range of treatment available (especially to medically unfit patients) giving them the option of a rapid resolution to what could be a distressing protracted condition.

The management of persistent and recurrent chronic anal fissures.

There are numerous definitive reviews concerning aetiology and management of acute and chronic anal fissures. The problem of persistence and recurrence after surgical and nonsurgical therapy has not been specifically addressed and there is little evidence-based guidance for the management of this difficult group of patients. A review of the literature with particular reference to persistence and recurrence of chronic anal fissures is presented and an algorithm of management incorporating evidence-based data is suggested.

Effects of hormone replacement therapy on fine needle aspiration cytology of the breast.

To investigate the possibility that hormone replacement therapy (HRT) might induce morphologic changes in breast cytology simulating malignancy, we determined the subjective interpretation and objective morphometric features of 39 fine needle aspiration cytology samples from women who were using a variety of HRT preparations. Cases were matched for age and final diagnosis (assessed by a triple approach) with women who had never used HRT. Cytocentrifuge preparations stained with Papanicolaou stain were assessed by two observers for cellularity and diagnosis. Although diagnostic accuracy was slightly higher in HRT than non-HRT samples, there was no significant difference in the assessments of cellularity and diagnosis between the two observers or between HRT and non-HRT samples. Nuclear areas in HRT samples were larger than in non-HRT samples, measured using computerized image morphometry; this difference did not induce the observer to diagnose malignancy more frequently. HRT had no adverse effect upon the accuracy of interpreting breast fine needle aspiration cytology samples.

Fine needle aspiration of palpable breast lesions. Results obtained with cytocentrifuge preparation of aspirates.

The use of cytocentrifugation in the preparation of fine needle aspiration (FNA) specimens from the breast was evaluated. A total of 174 fine needle aspirates of breast masses were flushed into cytospin Collection Fluid, from which Papanicolaou-stained Cytospin preparations were made in the laboratory. Comparison of these preparations to conventional smears of aspirates showed no significant differences in the number or morphology of the cells. In 148 cases, the FNA cytologic study was followed up by excisional biopsy, Tru-Cut biopsy and/or a combination of mammography and clinical follow-up of two to nine months. Of 36 verified carcinomas, 31 (86%) were correctly diagnosed, with a zero false-positive rate. Among the 74 cytologically benign aspirates, 2 carcinomas were found on open biopsy, giving a false-negative rate of 3%. Lipomas were not diagnosable with this technique. This technique should be considered in institutions with a high turnover of junior staff members, which frequently results in a higher number of poorly smeared specimens or in poorly fixed/air-dried specimens that give suboptimal results with the Papanicolaou stain. With this method, there is less risk of creation of potentially hazardous aerosols and further preparations for additional studies may be made if required.

The surgical treatment of intestinal obstruction due to left sided carcinoma of the colon.

Forty two consecutive patients who underwent surgery for an obstructing carcinoma of the left colon over a 5 year period were studied retrospectively. Twelve patients underwent an initial defunctioning procedure with no hospital deaths but with four deaths after a mean follow-up of 25 months. Of the 30 patients who had a primary tumour resection, 7 died during the first hospital admission and a further 4 during a mean follow-up period of 23.7 months. The hospital mortality following primary resection was related to the site and timing of the anastomosis. During the first hospital admission 3 of 5 patients died after colocolic anastomosis, 3 of 10 died following ileocolic anastomosis, but only 1 of 15 died in those who did not have a primary anastomosis performed. The mean hospital stay of patients undergoing a delayed resection was 41 (s.e. (mean) 2.8) days compared to 24 (s.e. (mean) 2.8) days in those undergoing a primary resection. Primary tumour resection with a delayed anastomosis is recommended on the basis of these findings.

Who's afraid of informed consent?

OBJECTIVE: To test the assumption that patients will become unduly anxious if they are given detailed information about the risks of surgery in an attempt to obtain fully informed consent. DESIGN: Preoperative anxiety assessed before and after patients were randomly allocated an information sheet containing either simple or detailed descriptions of possible postoperative complications. SETTING: Four surgical wards at two Sheffield hospitals. SUBJECTS: 96 men undergoing elective inguinal hernia repair under general anaesthesia. MAIN OUTCOME MEASURE: Change in anxiety level observed after receiving information about potential complications. RESULTS: Detailed information did not increase patient anxiety (mean Spielberger score at baseline 33.7 (95% confidence interval 31.3 to 36.2), after information 34.8 (32.1 to 37.5); p = 0.20, paired t test). A simple explanation of the facts provided a statistically significant degree of reassurance (mean score at baseline 34.6 (31.5 to 37.6), after information 32.3 (29.8 to 34.9); p = 0.012), although this small effect is likely to be clinically important only in those whose baseline anxiety was high (r = 0.27, p = 0.05). CONCLUSIONS: In men undergoing elective inguinal hernia repair a very detailed account of what might go wrong does not increase patient anxiety significantly and has the advantage of allowing patients a fully informed choice before they consent to surgery, thus reducing the potential for subsequent litigation.

New thoughts on the aetiology of haemorrhoids and the development of non-operative methods for their management.

Haemorrhoids constitute a frequent clinical problem. A variety of conservative treatment options have been proposed, the majority of which can be safely performed on an outpatient basis. Haemorrhoidectomy, however, remains the ultimate treatment for large, third degree haemorrhoids.