One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer: analysis of outcomes and toxicity.

BACKGROUND: Concurrent chemoradiation with fluorouracil (5fu) and mitomycin C (mmc) is standard treatment for anal canal carcinoma (acc). The current protocol in Alberta is administration of 5fu and mmc during weeks 1 and 5 of radiation. However, administration of the second bolus of mmc has been based largely on centre preference. Given limited published data on outcomes with different mmc regimens, our objective was to compare the efficacy and toxicity of 1 compared with 2 cycles of mmc in acc treatment. METHODS: Our retrospective study evaluated 169 acc patients treated with radical chemoradiotherapy between 2000 and 2010 at two tertiary cancer centres. All patients were treated with 2 cycles of 5fu and with 1 cycle (mmc1) or 2 cycles (mmc2) of mmc. Acute toxicities, disease-free (dfs) and overall survival (os) were analyzed. RESULTS: Baseline demographics, performance status, and stage were similar in the groups of patients who received mmc1 (52%) and mmc2 (48%). Before treatment, median hematologic parameters were comparable, except for white blood cell count, which was higher in the mmc2 group, but within normal range. The 5-year os and dfs were similar (75.1% and 54.2% for mmc1 vs. 70.7% and 44.2% for mmc2, p = 0.98 and p = 0.63 respectively). On multivariate analysis, mmc2 was the factor most strongly associated with specific acute toxicities: grade 3+ leukopenia (hazard ratio: 4.82; p < 0.01), grade 3+ skin toxicity (hazard ratio: 4.76; p < 0.001), and hospitalizations secondary to febrile neutropenia (hazard ratio: 9.91; p = 0.001). CONCLUSIONS: In definitive chemoradiotherapy for acc, 1 cycle of mmc appears to offer outcomes similar to those achieved with 2 cycles, with significantly less acute toxicity.

Opening the black box of cancer surgery quality: WebSMR and the Alberta experience.

A web-based synoptic operative report, the WebSMR (Surgical Medical Record), was developed to define and improve the quality of cancer surgery. Surgeons accurately record the essential steps of an operation including important decision-making in an analyzable format. Outcomes can be reviewed with provincial aggregates for quality improvement and maintenance of certification. Future synoptic pathology and follow-up templates will open the "black box" of surgical processes to define quality indicators for the improvement of cancer outcomes.

Clinical rather than laboratory assessment predicts continence after anterior sphincteroplasty.

PURPOSE: Preoperative anorectal physiology studies have become part of the standard evaluation of fecal incontinence. This study was undertaken to see whether anorectal physiology results predicted surgical outcome after anterior sphincteroplasty. METHODS: Between 1985 and 1994, 191 females with a mean age of 37 (range, 20-74) years underwent anterior sphincteroplasty for anal sphincter disruption. A follow-up questionnaire was sent to all patients, and there were 158 respondents (83 percent). Mean follow-up was 43 (range, 6-120) months. Obstetric injuries accounted for incontinence in 91 percent of the 158 patients who responded to the questionnaire. Mean duration of incontinence was 4.2 years (range, 3 months-51 years) before surgery. Preoperatively, patients were incontinent to solid stool (53 percent), liquid stool (33 percent), gas (3 percent), and unspecified (11 percent). RESULTS: Subjectively, the results were as follows: 129 patients (82 percent) improved, 17 (11 percent) were initially improved but subsequently deteriorated, 7 (4 percent) were unchanged, and 5 (3 percent) were worse. Objectively, postoperative continence was classified as follows: excellent (normal) in 23 percent, good (incontinent to gas or minor stain) in 39 percent, fair (incontinent to stool an average of less than once per month) in 26 percent, and poor (incontinent to stool an average of greater than once per month) in 12 percent. Preoperative continence level (incontinent to solid vs. liquid stool) was predictive of postoperative continence classification. Preoperative anorectal manometry was not predictive of clinical outcome (n = 128). There was no significant difference in postoperative continence classification among patients with normal, unilaterally abnormal, and bilaterally abnormal pudendal latency (n = 89). CONCLUSIONS: Clinical rather than manometric assessment predicts continence after anterior sphincteroplasty.

Complications of dynamic graciloplasty: incidence, management, and impact on outcome.

PURPOSE: Dynamic graciloplasty can improve continence in patients with severe refractory fecal incontinence, but associated morbidity is high. The purpose of this study was to identify complications associated with dynamic graciloplasty and to characterize their treatment and impact on patient outcome. METHODS: In 121 patients enrolled in a prospective trial of 20 centers and eligible for safety analysis, all complications of dynamic graciloplasty were recorded at the time of their occurrence and followed up until resolution. Severe treatment-related complications were defined as those requiring hospitalization or surgical intervention. RESULTS: In 93 patients, 211 complications occurred. Of these, 89 (42 percent) in 61 patients were classified as severe treatment-related complications and resulted from the following: major infection, 19; minor infection, 10; thromboembolic events, 3; device performance and use, 13; pain, 16; noninfectious gracilis problems, 8; noninfectious wound-healing problems, 3; other surgery-related complications, 3. In addition, severe treatment-related complications resulted from constipation in ten and stoma creation or closure in ten. The recovery rate (full or partial) was 87 percent overall, and for severe treatment-related complications, was 92 percent. Of the types of complications, only major infections had an adverse effect on outcome. CONCLUSION: Severe complications occur frequently after dynamic graciloplasty, but are usually treatable. They often require one or more reoperations and can lead to significant delays in completion of therapy. In most cases therapy can be salvaged.

Safety and efficacy of dynamic graciloplasty for fecal incontinence: report of a prospective, multicenter trial. Dynamic Graciloplasty Therapy Study Group.

PURPOSE: Dynamic graciloplasty has been used for intractable fecal incontinence, and good results have been reported. The aim of this study was to assess prospectively the safety and efficacy of dynamic graciloplasty for intractable fecal incontinence in a prospective, multicenter trial. METHODS: A total of 123 adults were treated with dynamic graciloplasty at 20 institutions. Continence was assessed preoperatively and postoperatively by use of 14-day diaries. RESULTS: There was one treatment-related death. One hundred eighty-nine adverse events occurred in 91 patients (74 percent). Forty-nine patients (40 percent) required one or more operations to treat complications. One hundred seventy (90 percent) events were resolved. Sixty-three percent of patients without pre-existing stomas recorded a 50 percent or greater decrease in incontinent events 12 months after dynamic graciloplasty, and an additional 11 percent experienced lesser degrees of improvement. Twenty-six percent were not improved, worsened, or exited. In patients with pre-existing stomas, 33 percent achieved successful outcomes at 12 months. This number increased to 60 percent at 18 months. Seventy-eight percent of patients had increased enema retention time, and mean anal canal pressures improved significantly at 12 months. Significant changes in quality of life were also observed. CONCLUSIONS: Objective improvement can be demonstrated in the majority of patients with end-stage fecal incontinence treated with dynamic graciloplasty. Reduction in incontinence episodes can be correlated with improved quality of life. Adverse events are frequently encountered, but most resolve with treatment.

"Sandwich" preoperative and postoperative combined chemotherapy and radiation in tethered and fixed rectal cancer: impact of treatment intensity on local control and survival.

PURPOSE: The present "sandwich" preoperative and postoperative chemotherapy and radiation study was undertaken to evaluate the impact of treatment intensity on the local control and survival in tethered or fixed rectal adenocarcinoma (T3, 4 NX M0). METHODS AND MATERIALS: Between 1990 and 1992, 27 patients were treated with this sandwich protocol. Preoperative therapy consisted of 4 weeks of concurrent radiation (40 Gy) and chemotherapy (mitomycin C on day 1, 5-fluorouracil infusion and leucovorin on days 1-4 and days 15-18, respectively), and one cycle of bolus 5-fluorouracil and leucovorin chemotherapy. After surgery, they received 2 additional weeks of radiation (18 Gy) and 4 days of similar chemotherapy. The outcome was compared to another 54 patients who were treated with our previous preoperative chemoradiation protocol (mitomycin C, 5-fluorouracil infusion and 40 Gy of pelvic RT). RESULTS: The complete resectability rate was improved from 91% in the preoperative protocol to 100% in the sandwich protocol, and the pathologic complete response rate (T0 N0 M0) was increased from 4 to 15%. There was no local recurrence in the sandwich protocol. The 4-year local failure rate was 23 vs. 0% (p = 0.005). The 4-year distant failure rate was 47 vs. 28% (p = 0.079). The 2-year and 4-year survival were 63 and 41% for the preoperative protocol, vs. 92 and 72% for the sandwich protocol, respectively (p = 0.014). There were more treatment-related Grade 2 diarrhea, but not Grade 3/4 diarrhea in the sandwich protocol. Two patients (7%) in the sandwich protocol developed late gastrointestinal complications. CONCLUSIONS: More intensive radiation and chemotherapy appeared to improve the resectability, local control, and survival in tethered and fixed rectal cancers. There was a moderate but acceptable increase in the bowel morbidity.

Jejunum is preferable for construction of a Bianchi bowel-lengthening procedure in swine short bowel.

This study compared the efficacy of a Bianchi bowel-lengthening procedure performed in residual ileum and jejunum of a 75% short bowel model. Eighteen female piglets underwent a 75% mid small bowel resection. After a 6-week period, animal weights were similar and pigs were randomly assigned to one of three treatment groups: (1) a control group receiving no further therapy; (2) a group receiving a Bianchi procedure in the residual jejunal segment; and (3) a group receiving a Bianchi procedure in the residual ileal segment. All were followed for a further 12 weeks. Jejunal Bianchi-treated short bowel animals demonstrated a greater final weight gain (78.8 +/- 4.9 kg) compared with nontreated short bowel (63.0 +/- 6.6 kg) and ileal Bianchi-treated short bowel groups (69.3 +/- 6.9 kg) in addition to a larger jejunal diameter. The increased weight gain in the jejunal Bianchi-treated group was not a consequence of initial bowel length, food intake, changes in bowel length, digestibility of nitrogen or fat, or nutritional status. Furthermore, kinetic constants for D-glucose absorption following 18 weeks of short-bowel syndrome demonstrated a lowered glucose maximal transport rate (Vmax) in animals with nontreated short bowel compared with sham-operated controls. Additionally, jejunal and ileal glucose Vmax was further lowered in the presence of a Bianchi procedure. We conclude that: (1) during short-bowel syndrome, body weight gain was significantly higher in animals when the Bianchi procedure was performed in jejunum; (2) the short-bowel syndrome decreased intestinal glucose absorption; and (3) the Bianchi procedure itself further impaired glucose transport.