Joe J. Tjandra

Which is the optimal bowel preparation for colonoscopy – a meta-analysis

Objective  To assess which bowel preparation agent is most effective.

Local excision of rectal cancer

PURPOSE: Although local excision of rectal cancers is a less morbid alternative to radical resection, its role as a curative procedure is unclear. The role of adjuvant therapy after local excision is also controversial. This review aims to examine current evidence on local excision of rectal cancers and how it fits into the management algorithm for rectal cancer. METHODS: A literature review was undertaken through the MEDLINE database and by cross-referencing previous publications, thus identifying 41 studies on curative local excision of rectal cancer published in English. Details of preoperative staging, surgical procedures, adjuvant therapy, follow-up, and outcome measures, including complications, survival data, recurrences, and salvage were examined. RESULTS: Preoperative staging of rectal cancers is variable. Digital rectal examination and computerized tomography are used in most studies. Endorectal ultrasound is used in some patients in 9 of 41 studies. Local excision preserves anorectal function, and seems to have limited morbidity (0–22 percent). Local excision alone is associated with local recurrences in 9.7 (range, 0–24) percent of T1, 25 (range, 0–67) percent of T2 and 38 (range, 0–100) percent of T3 cancers. The addition of adjuvant chemoradiotherapy after local excision yields local recurrence rates of 9.5 (range, 0–50) percent for T1, 13.6 (range, 0–24) percent for T2, and 13.8 (range, 0–50) percent for T3 cancers. Data on local excision after preoperative chemoradiotherapy for tumor down staging are limited. Factors other than T-stage that lead to higher local recurrence rates after local excision include poor histologic grade, the presence of lymphovascular invasion, and positive margins. Local recurrences after local excision can be surgically salvaged (84 of 114 patients in 15 studies), with a disease-free survival rates between 40 and 100 percent at a follow-up of 0.1 to 13.5 years. CONCLUSIONS: Local excision for rectal cancers is associated with a low morbidity and provides satisfactory local control and disease-free survival rates for T1 rectal cancers. There is, however, a need for a randomized, controlled trial for T2 cancers, comparing local excision with adjuvant chemoradiotherapy to radical resection.

Injectable Silicone Biomaterial for Fecal Incontinence Caused by Internal Anal Sphincter Dysfunction Is Effective

PURPOSEFecal incontinence caused by a weak or disrupted internal anal sphincter is common but there has been no effective treatment. This prospective study evaluates the medium-term clinical effects of an injectable silicone biomaterial, PTPTM (Bioplastique), used to augment the internal anal sphincter.METHODEighty-two patients (64 females; median age, 66 years) with severe fecal incontinence and a low anal resting pressure caused by internal anal sphincter dysfunction (defect, n = 11; intact, n = 71) were randomized to PTPTM injection into intersphincteric space and internal anal sphincter with (Group A, n = 42) or without (Group B, n = 40) guidance by endoanal ultrasound. Both groups were similar in terms of age, gender, past anorectal surgery, duration of follow-up (median, 6 months; range, 1–12 months), and baseline continence score. Sixty-two percent of Group A and 55 percent of Group B had prolonged pudendal nerve terminal motor latency.RESULTSThere was no significant complication. Two patients in Group A and four patients in Group B noted minor discomfort at injection sites. At one month postprocedure, endoanal ultrasound confirmed retention of silicone biomaterial without migration. In both groups, fecal continence was significantly improved by PTPTM implants 1 month after injection, but continued to improve significantly for up to 12 months in Group A and 6 months in Group B (P < 0.001). Improvement in fecal continence and maximum anal resting pressure was significantly greater in Group A, in whom injection was guided by endoanal ultrasound, than in Group B. At three months after injection, significantly more Group A patients than Group B patients achieved >50 percent improvement in Wexner’s continence score (69 percent vs. 40 percent; P = 0.014). Ninety-three percent of Group A and 92 percent of Group B had >50 percent improvement in global quality of life scores (visual analog scale). At a median follow-up of 6 months, all domains of the fecal incontinence quality of life scale improved significantly in both groups; however, the physical function and mental health scores of Short Form-12 only improved in Group A. A prolonged pudendal nerve terminal motor latency had no effect on functional outcome in either group.CONCLUSIONInjection of silicone biomaterial provided a marked improvement in fecal continence and quality of life in patients with internal sphincter dysfunction, despite the presence of pudendal neuropathy.

Morbidities of adjuvant chemotherapy and radiotherapy for resectable rectal cancer

PURPOSE: Although adjuvant chemoradiotherapy may improve outcomes after surgery for high-risk rectal cancer, its toxicities are not well documented. This is a review of complications associated with adjuvant therapy in randomized, controlled trials. METHODS: A MEDLINE and literature search was performed for randomized, controlled trials of adjuvant therapy for rectal cancer. Modalities of adjuvant therapy evaluated included preoperative radiotherapy, preoperative chemoradiotherapy, postoperative radiotherapy, and postoperative chemoradiotherapy. All documented complications were analyzed, including any effect on pelvic floor function and quality of life. RESULTS: Short-term (acute) complications of preoperative radiotherapy include lethargy, nausea, diarrhea, and skin erythema or desquamation. These acute effects develop to some degree in most patients during treatment but are usually self-limiting. With preoperative radiotherapy the incidence of perineal wound infection increases from 10 to 20 percent. The acute toxicities after postoperative radiotherapy for rectal cancer occur in 4 to 48 percent of cases, and serious toxicities, requiring hospitalization or surgical intervention, occur in 3 to 10 percent of cases. Postoperative radiotherapy is associated with more complications than preoperative radiotherapy. The main problems with postoperative radiotherapy are small-bowel obstruction (5–10 percent), delay in starting radiotherapy caused by delayed wound healing (6 percent) and postoperative fatigue (14 percent), and toxicities precluding completion of adjuvant therapy (49–97 percent). The morbidity and mortality of both preoperative and postoperative radiotherapy are higher in elderly patients and when two-portal rather than three-portal or four-portal radiation technique is used. Meticulous radiation technique is important, and multiple fields of irradiation are mandatory. After combined adjuvant chemotherapy and radiotherapy acute hematologic and gastrointestinal toxic effects are frequent (5–50 percent). Delayed radiation toxicities include radiation enteritis (4 percent), small-bowel obstruction (5 percent), and rectal stricture (5 percent). Pelvic floor function and quality of life have not been well evaluated in randomized, controlled trials. CONCLUSION: Adjuvant therapy for rectal cancer has considerable adverse effects. Adverse effects on bowel and sphincter function and quality of life have not been defined.

Monoclonal antibodies reactive with mucin expressed in breast cancer

Three murine monoclonal antibodies (BC 1, BC2 and BC3) were developed against human milk fat globule membrane (HMFGM). By immunoperoxidase staining, it was found that the antigenic determinants had a predominant distribution in breast cancer tissue. In addition, the antibodies reacted preferentially with mucin derived from human milk rather than that derived from the breast cancer cell line ZR75; they also recognized polymorphic high molecular weight components (MW ≥ 230 000) in serum and in human milk fat globule membrane. Thus the antibodies appear to react with a component of the family of mucins found in breast cancer and human milk and it appears likely that at least part of each epitope is protein in nature. Antibodies BC1, BC2 and BC3 recognized related but not identical epitopes, and they appear to be co‐expressed on the same molecules as 3E1·2‐defined antigen (mammary serum antigen, MSA) which is also a member of the family of breast cancer‐related mucin. However, the 3E1 2 epitope is distinct and non‐cross‐reactive with those described for BC1, BC2 and BC3. The BC2 and BC3 defined epitopes were examined for their value in serum assays. Immunoassay was developed with a combination of two antibodies, using antibody BC3 for antigen capture and antibody BC2 or 3E1·2 for antigen detection and gave reasonable sensitivity (~85%) and specificity (~95%) in such serum tests for breast cancer. In a limited study, these tests appeared to complement the MSA test in the detection of breast cancer.

Cronic radiation proctitis

Background: Increasing use of radiation therapy in pelvic malignancy has led to an increase in the incidence of chronic radiation proctitis. The commonest presenting complaint is rectal bleeding.

Sacral nerve stimulation: an emerging treatment for faecal incontinence

Faecal incontinence is common, distressing to the patient and socially incapacitating. The treatment options depend on the severity and aetiology of incontinence. For mild cases of faecal incontinence, medical management and pelvic floor physiotherapy may be adequate. For more severe cases, surgery is often required. Patients who have a distinct sphincter defect are amenable to surgical repair. In many cases, there is a combination of diffuse structural damage of the anal sphincters with pudendal neuropathy. Conventional surgical repairs have a modest degree of success and the results tend to deteriorate with time. Neosphincter procedures such as artificial bowel sphincter and dynamic graciloplasty are potentially morbid and technically complex. Sacral nerve stimulation is innovative and has had a medium‐term success with improvement of quality of life in over 80% of patients treated for faecal incontinence. These results are superior to other techniques in treating patients with severe refractory faecal incontinence, where current maximal therapy has failed. The technique is unique because there is a screening phase, which has a high predictive value. It is also associated with minimal complications that are usually minor. However, most published reports of sacral nerve stimulation for treatment of faecal incontinence were case studies and methods of assessing outcome were variable. Criteria for patient selection are evolving and are yet to be defined. The present paper critically reviews the publications to date on sacral nerve stimulation for treatment of faecal incontinence. This will form the basis for future evaluation of this emerging treatment of severe, intractable faecal incontinence. Randomized clinical trials like that of the Melbourne trial will further clarify the role and indications of sacral nerve stimulation for faecal incontinence.

Development of human anti-murine antibody (HAMA) response in patients

Human anti‐mouse antibody (HAMA) response was determined in the scrum of 67 patients who received subcutaneously administered radiolabelled murine monoclonal antibodies (MoAb) (50 μg‐3 mg) for immunolymphoseintigraphy and of 10 patients with advanced colorectal cancer who received murine MoAb‐N‐acetyl melphalan (MoAb‐N‐AcMEL) conjugates (amount of MoAb ranged from 120 mg/m2 body surface area to 1000 mg/m2 body surfaee area) as therapy. A pre‐existing low level of apparent human anti‐mouse antibody reactivity could be detected in the serum of normal subjects and patients prior to administration of murine MoAb. Subcutaneous administration of low doses of murine MoAb, as used in immunolymphoscintigraphy, was associated with a low incidence (4/67 or 6%) of elevated HAMA response; the use of F(ab′)2 fragments was associated with the development of elevated HAMA response in one of three patients. By contrast, therapy with hepatic artery infusion of murine MoAb‐N‐AcMEL conjugates in three repetitive daily doses (each infusion lasting 2 h) elicited elevated HAMA responses in 10/10 (100%) patients, usually 1–3 weeks after the start of therapy. The HAMA response of patients in the therapy group was higher than those in the immunolymphoscintigraphy study and the use of steroids did not prevent the development of the HAMA response. Further administration of MoAb‐N‐AcMEL conjugates to a patient, who had already developed HAMA, led to ‘serum sickness’‐type symptoms and a transient reduction in the HAMA titres. The elevated HAMA response was polyclonal, containing increased levels of both immunoglobulin M and G (IgM and IgG) and was directed against mouse‐specific determinants, the isotype (presumed to be the Fc portion), the F(ab′)2 and the ‘idiotype’ of mouse immunoglobuiins.

Argon plasma coagulation is an effective treatment for refractory hemorrhagic radiation proctitis

INTRODUCTION: Chronic radiation proctitis complicating pelvic radiotherapy can be debilitating. It commonly presents with rectal bleeding, which can be difficult to control. Medical management of hemorrhagic radiation proctitis is not very successful, although surgery carries high risks. Thus, endoscopic treatments are preferred. The aim of this study is to assess the efficacy of argon plasma coagulation applied endoscopically to treat hemorrhagic radiation proctitis that has been refractory to topical formalin therapy. METHODS: Twelve patients who had ongoing bleeding from radiation proctitis, after previously failed formalin therapy, underwent endoscopic treatment using argon plasma coagulation. The efficacy of treatment was assessed by grading the frequency and severity of bleeding (0–4, 0 being no bleeding), hemoglobin level, and transfusion requirements. RESULTS: At a median follow-up of 11 months, ten patients (83 percent) had a significant reduction in the severity and frequency of bleeding, with complete cessation in six (50 percent). The presence of coexistent radiation-induced sigmoiditis in two patients was associated with reduced but persistent bleeding, because of difficulty in targeting the bleeding sites in the sigmoid colon. The median number of treatment sessions per patient was two (range, 1–3), with the number of sessions correlated with the extent of the proctitis. All patients had an improvement in their hemoglobin level, with the mean increasing from 11.2 to 12.3 g/dl. In the six months before starting therapy, all patients had been taking iron supplements, and four had required blood transfusions (median 3 units, range, 2–6). Iron supplements were ceased four weeks after the completion of therapy in all cases, and no further transfusions were required during the study period. None of the patients experienced any significant side effects or complications. CONCLUSIONS: Argon plasma coagulation is an effective and safe treatment for hemorrhagic radiation proctitis that has been refractory to topical formalin therapy.

Transanal repair of rectocele corrects obstructed defecation if it is not associated with anismus.

PURPOSE: Rectocele is often associated with anorectal symptoms. Various surgical techniques have been described to repair the rectocele. The surgical results are variable. This study evaluated the results of transanal repair of rectocele, with particular emphasis on the impact of concomitant anismus on postoperative functional outcome. METHODS: Fifty-nine consecutive females who underwent transanal repair of rectocele for obstructed defecation were prospectively reviewed. All 59 patients were parous with a median parity of 2 (range, 1–6) and a median age of 58 (range, 46–68) years. The median length of follow-up was 19 (range, 6–40) months. Anismus was detected by anorectal physiology and defecography. The functional outcome was assessed by a standard questionnaire, physical examination, anorectal manometry, neurophysiology, and defecography. The quality-of-life index was obtained using a visual analog scale (from 1–10, with 10 being the best). RESULTS: The functional outcome of transanal repair of rectocele was superior in patients without anismus. Forty (93 percent) of the 43 patients without anismus showed improved evacuation after repair compared with 6 (38 percent) of the 16 patients with anismus (P<0.05). The quality-of-life index improved (9vs. 4) if anismus was not present (P<0.05). There were minimal complications. Hemorrhage requiring blood transfusion (2 units) occurred in one patient and urinary retention in another. CONCLUSION: Transanal repair of rectocele is safe and, in the absence of anismus, effectively corrects obstructed defecation.