Claudio Mattana

Preoperative Chemoradiation for Extraperitoneal T3 Rectal Cancer: Acute Toxicity, Tumor Response, and Sphincter Preservation

PURPOSE To evaluate whether or not an intermediate dose of preoperative external radiation therapy intensified by systemic chemotherapy could improve the tumor response, sphincter preservation, and tumor control. METHODS AND MATERIALS Between March 1990 and December 1995, 83 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. RESULTS Total Grade 3-4 acute toxicity during chemoradiation was observed in 11 (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two patients had no surgery: 1 died before surgery from septic complications after Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no postoperative mortality and the overall perioperative morbidity rate was 25%. The analysis of tumor response involved 81 patients. Overall, 9% (7) of 81 patients had a complete pathologic response. Comparing the stage at the diagnostic workup with the pathologic stage, tumor downstaging was observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected significantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The distance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after the sphincter-saving procedure. CONCLUSION Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able to tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphincter preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate recorded, a more aggressive schedule should be applied in these resectable tumors.

Impact of Emergency Surgery in the Outcome of Rectal and Left Colon Carcinoma

The negative results in terms of morbidity, mortality and survival among emergency treated patients affected by colorectal cancer are well known. The specific contribution of emergency surgery to adverse outcome is not clear because of the presence in all series of other possible determinants of a poor prognosis. We used a case-control study design to compare a group of 50 patients operated on for cancer of the rectum and left colon presented as emergencies in our department during the last 14 years, and an equal number of patients who underwent elective procedures during the same period. All records of these patients were reviewed and matched for age, stage, tumor location, and medical comorbidities (coronaropathy, diabetes mellitus, cerebral vascular deficiency, chronic obstructive pulmonary disease). Outcome measures included length of hospital stay, morbidity, mortality, and actuarial 5-year survival. Univariate and multivariate analysis of factors potentially influencing survival was performed on the entire population of 100 patients. Age, tumor location, stage of disease, and medical comorbidities were well matched by intent of the study design. Overall surgical morbidity (44% versus 12% P = 0.0004), length of hospital stay (16, 64 versus 10, 97 days P = 0.0026) and postoperative mortality (4% versus 0% P = 0.4949) resulted higher in the emergency group. Actuarial overall 5-year survival was not different between the two groups. The only variables independently predictive of survival in multivariate analysis were age and rectal location of the tumor. Postoperative surgical mortality and long-term survival appear not to be influenced by emergency presentation of colorectal cancer; the negative impact of the emergency procedures is confined to the immediate postoperative period and is probably connected to the acute medical pathology often presented by patients in emergency situations. Dealing with this kind of patient’s accurate preoperative assessment and solution of acute medical pathologies before surgical treatment are mandatory.

Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: A prospective evaluation of a single institutional experience

BACKGROUND Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods. METHODS Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome. RESULTS 100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4-136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival. CONCLUSION A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated.

Site, emergency, and duration of symptoms in the prognosis of colorectal cancer

Four prognostic factors,i.e., site of the tumors, mode of presentation, duration of symptoms, and pathologic staging, were correlated to the results of surgical treatment,i.e., curative resectability, postoperative complications and mortality, and five-year survival, in 161 patients operated upon for colorectal cancer.Only 31 (19 per cent) of the growths were right-sided; 71 patients (44 per cent) had symptoms less than six months. Fifty-four of them had a localized cancer; a radical procedure was performed in 114 (71 per cent), and postoperative complications occurred in 42 cases (26 per cent). The overall crude five-year survival was 38 per cent (53 of the 140 followed-up patients).The length of the clinical history did not correlate with the pathologic staging, which greatly influenced curability and survival.A statistically significant poorer prognosis was observed in patients with left-sided tumors, with an emergency presentation and with a duration of symptoms shorter than six months.A better prognosis can be achieved by means of a presymptomatic diagnosis.

Long-Term Results After Neoadjuvant Radiochemotherapy for Locally Advanced Resectable Extraperitoneal Rectal Cancer

PurposeThis study was designed to evaluate long-term outcome in locally advanced resectable extraperitoneal rectal cancer treated by preoperative radiochemotherapy.MethodsEighty-three consecutive patients who developed locally advanced resectable extraperitoneal rectal cancer underwent preoperative concomitant radiochemotherapy followed by surgery, including total mesorectal excision.ResultsMedian follow-up was 108 (range, 10–169) months. The living patients underwent complete follow-up of, at least, nine years. Fourteen patients developed local recurrence. The time to detection was longer than two years in eight cases and longer than five years in four. Twenty-one patients developed metastases, 19 within the first five years from surgery. At the univariate analysis, clinical stage at presentation, lymph node involvement at clinical restaging after neoadjuvant therapy, and pTand pN stage were found positively correlated to the incidence of metastases. At the multivariate analysis, the only factors which confirmed a positive correlation were pT stage and pN stage. The actuarial overall survival at five, seven, and ten years was 75.5, 67.8, and 60.4 percent, respectively. The same figures for cancer-related survival were 77.9, 70, and 65.8 percent. At the univariate analysis, factors directly correlated with worse survival were: TNM stage at clinical restaging after neoadjuvant therapy (in particular lymph node involvement) pTNM, pT, and pN. At the multivariate analysis the only factors that confirmed a correlation with worse survival were pTNM, pT, and pN.ConclusionsLong- term follow-up allows to individuate 28 percent of all local relapses after the first five years from surgery. Postoperative stage is highly predictive of prognosis.

Management of perianal Crohn's disease

PURPOSE: Management of perianal Crohns disease is still controversial, and reports on large series are very few in the literature. The aim of this multicenter study was to investigate the outcome of both medical and surgical treatment in 225 patients. METHODS: Patients cared for at different institutions were followed up for a median of six years. Most of them had either anal fistula or an abscess (86 percent and 43 percent, respectively), but fissures were also present in 26 percent of the cases. Diarrhea and anal pain were the most common symptoms. Anal lesions preceded the onset of intestinal symptoms in 19 percent of cases. RESULTS: Medical treatment was curative only in 21 of 123 patients. Overall, medical and surgical treatment either cured or improved 62 percent of the cases. Fifty percent had an intestinal resection. Abscess drainage and fistulotomy were the most common anal surgeries. Rectovaginal fistulas (n=30) required intestinal surgery in 36 percent and anal surgery in 20 percent of the cases, 50 percent with good results. Of 166 patients who had anal surgery, 97 (58 percent) had a positive outcome. Recurrence of anal disease requiring further surgery occurred in 24.5 percent of the cases. CONCLUSIONS: Limited surgeries seem to achieve satisfactory results in more than one-half of the patients affected by perianal Crohns lesions, whereas medical treatment alone is curative in a small portion of them.

Rubber band ligation of hemorrhoids and rectal mucosal prolapse in constipated patients

Rubber band ligation was used in 160 patients with internal hemorrhoids; 43 of them also had rectal anterior mucosal prolapse; 13 had prolapse alone. Two thirds of the patients underwent a single rubber band ligation and one third a double rubber band ligation in one session without anesthesia. Ninety-four required repeated ligations. A follow-up of 25±16 months (mean ± SD) was carried out in 153 of them. Rubber band ligation was followed by prolonged bleeding in six patients and severe pain requiring removal of the rubber band in 12 patients. The complication rate decreased significantly (P<.05) in the last 80 patients. Compared with multiple ligation, single rubber band ligation in one sitting was followed by a lower compliction rate (P<.01). Long-term results were good in 71 percent of the patients. (A formal hemorrhoidectomy was needed within two years in 6 percent.) A significantly lower recurrence rate of 9 percent was noted in those with normal bowel habits, when compared with constipated subjects whose symptoms recurred in 85 percent (P<.001). Constipation seems to be a predictable factor in worsening the outcome of rubber band ligation. Rubber band ligation is followed by a lower complication rate when performed in a single ligation.

Concomitant preoperative radiochemotherapy in operable locally advanced rectal cancer

PURPOSE: The aim of this study was to examine the effectiveness of a combination of preoperative radiotherapy and chemotherapy for operable locally advanced rectal cancer (Stages II and III). METHODS: Chemotherapy and radiotherapy are started jointly on day one of the therapy. 5-Fluorouracil is given in a dosage of 1000 mg/ m2/day as a continuous 24-hour infusion for 4 days. Mitomycin C is given as a bolus intravenous at a dosage of 10 mg/m2 the first day. The radiation therapy is given to a total dosage of 37.8 Gy. Surgery is generally performed four to five weeks following completion of the radiation therapy. From March 1990 to April 1993, 34 patients with histologically documented adenocarcinoma of the rectum have been treated. Twenty-one lesions were located in the lower third of the rectum. Twenty-nine neoplasms were judged by initial clinical staging as Stage III. RESULTS: Patients compliance to the treatment have been 97 percent. Toxicity of treatment has been low (15 percent). Tumor sizes decreased 50 percent or more in about 80 percent of patients. Distance of the tumor from the anal canal increased in all but seven cases. Twenty-two anterior resections have been performed. The morbidity rate has been 24 percent. No postoperative mortality has been reported. Histologic examination of surgical specimens after integrated treatment showed in 10 cases a tumor confined to the rectal wall (T2), in 3 patients only a residual tumor limited to submucosa (T1), and in 5 (15 percent) patients no evidence of neoplastic cells (T0). CONCLUSIONS: We conclude that preoperative radiochemotherapy was generally well tolerated; in all cases we had a reduction of tumor sizes, surgery presented no technical difficulties, and there was the effect of stage reduction.

Clinical picture and pelvic floor physiology in the solitary rectal ulcer syndrome

Clinical examination, proctosigmoidoscopy, rectal biopsies, barium enema and pelvic floor physiology studies were performed in four patients with solitary rectal ulcer syndrome. All patients had chronic constipation and rectal bleeding. Resting tone and voluntary contraction were found to be decreased at anal manometry in two patients (maximal squeeze pressures were ten and 35 mm Hg, respectively). Balloon proctogram showed an increased rectoanal angle in these two patients (90° and 93° at rest, unchanged on squeezing) with a poor striated sphincter function at EMG; their deficient anal reflex, slight fecal incontinence and perineal descent seemed consistent with pudendal neuropathy. Fibromuscular obliteration of the lamina propria was found at histology. All subjects had successful conservative treatment, including topical corticosteroids in one patient; normalization of bowel habit was the most effective therapy for the disease. The present study seems to confirm the role of chronic constipation and abnormal pelvic floor physiology in the pathogenesis of the syndrome.

Peptic Ulcer in Gastric Heterotopia of the Gallbladder Without Evidence of Helicobacter pylori Infection

Gastric heterotopia has been described throughout the gastrointestinal tract, from the oral cavity to the rectum, including the liver and the gallbladder [1–6]. We report a case of peptic ulcer in heterotopic gastric mucosa of the gallbladder in a 56-year-old man submitted to laparoscopic cholecistectomy for chronic calculous cholecystitis. From the first case of gastric heterotopia of the gallbladder, reported in 1934 [7], we reviewed 49 cases, including our report. In nine cases gallstones were also found and in four cases a peptic ulcer was identified [8]. The case reported describes the first association between peptic ulcer in gastric heterotopia of the gallbladder and gallstones. The presence of HP was investigated in order to evaluate its possible role in the ethiology of the ulceration.