Sphincter-saving Procedure Research Articles

Complications of elective surgery for rectal cancer

BACKGROUND: Standardization of surgery and new procedures have led to significant advances in the treatment of rectal cancer. METHODS: Review on avoidance and management of complications in rectal cancer surgery. RESULTS: Anatomical dissection of the mesorectum permits optimal local control and reduction of local recurrence. Sphincter preservation can be achieved by the technique of intersphincteric resection even for low tumours. A J-pouch or a recently designed coloplasty pouch improve functional results after coloanal anastomoses. Neoadjuvant treatments have a role in local control of the disease after TME surgery and in new strategies of sphincter-saving procedures. Although perioperative morbidity in elective surgery for rectal cancer is very low, radical local control of the disease and the patient's wish for sphincter preservation have to be weighed against possible complications. The literature was carefully reviewed to evaluate data on the procedure-specific complications in elective surgery for rectal cancer and the impact of neoadjuvant treatment regimens and perioperative management on postoperative morbidity. CONCLUSIONS: Meticulous attention to detail achieve low complication rates in modern rectal surgery. In experienced hands, the total mesorectal excision operation is not associated with increased postoperative morbidity and mortality.

Laparoscopic Pelvic Autonomic Nerve-Preserving Surgery for Patients with Lower Rectal Cancer after Chemoradiation Therapy

Laparoscopic Pelvic Autonomic Nerve-Preserving Surgery for Patients with Lower Rectal Cancer after Chemoradiation Therapy

A Defunctioning Stoma in the Treatment of Lower Third Rectal Carcinoma

Introduction: Total mesorectal excision (TME) is the accepted standard for rectal cancer treatment. However, there is an increased risk of symptomatic anastomotic leakage associated with TME as TME potentially endangers the blood supply of the remaining rectum. On top of this, many patients will receive neo-adjuvant radio-chemotherapy. A defunctioning stoma helps in avoiding severe complications of anastomotic failure.Material and mehods: We prospectively collected data of all patients with a rectal carcinoma within reach of the palpating finger, operated on in our department between December 2000 and January 2005. There were 70 patients (42 men and 28 women, median age 70 (range 32–95)).Results: In 40 patients (40/70 = 57%) a sphincter-saving procedure was performed. Eleven patients were diagnosed with anastomotic leakage or failure. Seven patients had neo-adjuvant radio-chemotherapy, 4 had no neo-adjuvant therapy. In 4 patients signs of anastomotic leakage were seen on the barium-enema that is routinely performed before closing the defunctioning stoma. Seven patients (7/40 = 17,5%) had clinical signs of anastomotic leakage. Three of them could be treated conservatively with antibiotics and parenteral nutrition. Two of these patients did not have a defunc-tioning stoma. Four patients needed re-intervention and were treated in intensive care for several days. Three of these patients did not have a defunctioning stoma.Conclusion: Neo-adjuvant radio-chemotherapy and TME resection are two factors in the treatment of rectal cancer that might interfere with anastomotic healing in the case of a sphincter-saving procedure. The construction of a defunctioning stoma helps in limiting the complications of anastomotic leakage or failure.

The clinical staging of rectal cancer.

Abstract The ability of rectal digital examination to recognize significant stages of local extent and lymph node involvement in adenocarcinoma of the lower two-thirds of the rectum was investigated. Seventy patients with a palpable rectal cancer were examined by 2 or 3 out of a panel of 10 clinicians including 2 consultants and 8 registrars. A defined protocol was used and the results were recorded on a proforma. Clinical findings were compared with the results of pathological examination of the resected specimen or the final surgical assessment when the growth was not removed. In 38 patients computed tomography of the primary growth was performed and the results were also compared to the pathological findings. Four groups of cases with different degrees of extent of spread were recognized by digital examination in 67–83 per cent by consultants and in 44–78 per cent by registrars. Computed tomography correctly identified growths with extensive local spread in 89 per cent of cases, but was no more reliable than digital examination in the assessment of other degrees of spread or of lymph node involvement. Based on the results, a clinical staging system is proposed, comprising four stages of local extent as follows—stage 1: confined to rectum; stage 2: confined to rectum or slight extrarectal spread; stage 3: moderate or extensive extrarectal spread; stage 4: involvement of other organs or unresectability. Two stages of lymph node involvement are also proposed: namely, node negative and node positive. Each stage corresponds to different survival and local recurrence rates after surgery. Combined with other factors, such as level and size of tumour, histological grade and the general state of the patient, the clinical staging system may facilitate the choice of treatment. It might extend the use of major sphincter-saving procedures, indentify many patients suitable for local treatment and define those with a considerable risk of local recurrence where combined surgery and radiotherapy might be considered.

Results of anal or low rectal anastomosis and pouch construction for megarectum and megacolon.

Over a 16-year period 34 patients underwent surgery for idiopathic megarectum or megacolon; 18 had megarectum with or without megasigmoid, one megacolon only and 15 megarectum and total megacolon (nine with a previous colectomy). Ten patients underwent low rectal or anal anastomosis without pouch formation (colodistal proctostomy, eight; coloanal anastomosis, two), eight had colonic pouch-anal anastomosis (J pouch) and 14 had an ileal J pouch after restorative proctocolectomy; one underwent subtotal colectomy with ileorectal anastomosis and one loop ileostomy alone. There was one death, from intestinal obstruction 24 months after operation. Twenty-seven of 32 evaluable patients without a stoma became fully continent following resection and sphincter-saving procedures. Three of 18 had a poor result after resection for megarectum because of recurrent constipation. One of 14 patients became incontinent after restorative proctocolectomy for megacolon and megarectum and in a further four persistent abdominal distension and pain was treated by pouch excision.

The future of external beam irradiation as initial treatment of rectal cancer

Several trials have demonstrated that pre-operative irradiation for rectal cancer decreases significantly the incidence of pelvic recurrence. However, this method is far from being generally accepted. It is now possible to enhance the effectiveness of external beam irradiation and to use it to extend the field of sphincter-saving and conservative procedures. Our protocol consists of a split-course regimen with a short course of cobalt-60 arc rotation (3000 cGy in 12 days). After 2 months rest, the second stage of treatment depends upon the pressure of residual disease and the site of the tumour. It consists of either radical surgery (82 cases) or conservative treatment by intracavitary irradiation in the event of a favourable initial response or in the case of poor risk patients (73 cases). In the radiotherapy-surgical group, the subsequent operative specimens were tumour free in 17 per cent of cases and assigned to Dukes' A category in 32 per cent of cases. Of 91 patients with T2 or T3 tumour involving the lower third of the rectum (followed up for more than 3 years) 72 (84 per cent) had no recurrence. Thirty-three of these patients (46 per cent) underwent a colostomy while 39 (54 per cent) had normal anal function. These results demonstrate the major place that a properly planned external beam irradiation can have in the curative management of cancers of the low rectum.

Diffuse cavernous hemangioma of the rectosigmoid colon

Diffuse cavernous hemangioma of the rectosigmoid colon is an uncommon benign vascular lesion. We report 5 cases of diffuse cavernous hemangioma, focusing on the clinical features, diagnosis procedure and treatment. Five patients have undergone sphincter-saving procedures, 3 cases had coloanal sleeve anastomoses and 1 patient each had pull-through anastomosis and lower anterior resection. During the follow-up, which ranged from 3 to 10 years, 3 patients had no further anal bleeding and 2 patients had minor intermittent anal bleeding. Continence for normal stool was satisfactory in all patients. In conclusion, sphincter-saving procedure is most appropriate and curative approach for the treatment of diffuse cavernous hemangioma. Imaging study plays an important role in the diagnosis, preoperative staging and follow-up.

Good colorectal cancer surgery

Adenocarcinoma of the colon and rectum is currently diagnosed in about 783,000 new cases annually and 437,000 patients will die of the disease each year worldwide. Colorectal cancer presents as an emergency situation (obstruction, bleeding or perforation) in approximately 25% of cases and with more or less obvious chronic symptoms in the rest of cases. Rectal cancer patients, with a T1 tumour can be offered local excision whereas patients with more advanced cancer must be offered a more radical abdominal procedure. In large bulky tumours (T3 or definitely T4), MRI should guide the choice of preoperative radiotherapy. Three major indications for radiotherapy are reduction of local recurrences in mobile rectal cancer in order to improve survival, down-staging of the tumour in primary irresectable tumours, and downsizing of low-lying tumours in an attempt to perform a sphincter-saving procedure. The surgical strategy is to remove the tumour-bearing bowel segment with, if possible, a locoregional curative procedure, to restorate bowel continuity, and to ensure an optimal quality of life. In most situations, it is possible to achieve local radical resection. In rectal cancer surgery, the main problem is to stick to the embryological planes during the whole procedure. The whole mesorectum is taken out as a packet down to the level of division. This TME procedure dramatically reduced the local recurrence rate to 3%-7%. Surgeon case volume may be an important factor in cancer surgery success. Laparoscopic surgery for colorectal cancer has stimulated a great deal of interest in recent years, but there are concerns regarding this type of surgery. In conclusion, modern surgery for colorectal cancer is a well-defined technique where the anatomical planes have to be identified. Care must be taken to learn all the essential steps. Data from the literature strongly support that the surgeon is the most important factor for an excellent outcome.

Pathological study of distal mesorectal cancer spread to determine a proper distal resection margin

Local recurrence after curative surgical resection for rectal cancer remains a major problem. Several studies have shown that incomplete removal of cancer deposits in the distal mesorectum contributes a great share to this dismal result. Clinicopathologic examination of distal mesorectum in lower rectal cancer was performed in the present study to assess the incidence and extent of distal mesorectal spread and to determine an optimal distal resection margin in sphincter-saving procedure. We prospectively examined sepecimens from 45 patients with lower rectal cancer who underwent curative surgery. Large-mount sections were performed to microscopically observe the distal mesorectal spread and to measure the extent of distal spread. Tissue shrinkage ratio was also considered. Patients with involvement in the distal mesorectum were compared with those without involvement with regard to clinicopathologic features. Mesorectal cancer spread was observed in 21 patients (46.7%), 8 of them (17.8%) had distal mesorectal spread. Overall, distal intramural and/or mesorectal spreads were observed in 10 patients (22.2%) and the maximum extent of distal spread in situ was 12 mm and 36 mm respectively. Eight patients with distal mesorectal spread showed a significantly higher rate of lymph node metastasis compared with the other 37 patients without distal mesorectal spread (P = 0.043). Distal mesorectal spread invariably occurs in advanced rectal cancer and has a significant relationship with lymph node metastasis. Distal resection margin of 1.5 cm for the rectal wall and 4 cm for the distal mesorectum is proper to those patients who are arranged to receive operation with a curative sphincter-saving procedure for lower rectal cancer.

The surgical approach to locally recurrent rectal cancer

The incidence of rectal cancer recurrence after surgery is 5-45%. Predictive factors relating to local recurrence (LR) are the surgical experience, the location of the tumour, the tumour's pathology, the circumferential margins, the successful total mesorectal excision (TME) and the use of radiochemotherapy. The use of TME and preoperative radiotherapy reduce the risk of LR. Diagnosis is done using imaging techniques. Computed tomography with rectal contrast is the preferred imaging technique. The surgical strategy for LR at and around a previous anastomosis is the resection of the anastomosis with a sphincter-saving procedure. LR isolated to one side after anterior resection is an indication for en bloc resection of the rectum with a portion of the bladder. LR fixed to the sacrum requires a composite abdominosacral resection. Extrapelvic disease is a contraindication to curative resection. The composite sacropelvic resection is a reasonable alternative to palliative radiation with long-term survival of 20-30%.

Complete Pathologic Response Following Preoperative Chemoradiation Therapy for Middle to Lower Rectal Cancer Is Not a Prognostic Factor for a Better Outcome

The aim of this study was to evaluate factors associated with pathologic tumor response following pre-operative chemoradiation therapy, and the prognostic impact of pathologic response on overall and disease-free survival. Between 1994 and 2002, 132 patients underwent chemoradiation therapy followed by surgery for middle to lower rectal cancer. After excluding 26 cases (metastatic cancer, n = 13; nonradical surgery, n = 6; local excision procedure, n = 4; non-5-fluorouracil-based chemotherapy, n = 2; incomplete data on preoperative chemoradiation therapy regimen used, n = 1), the remaining 106 patients were included in the study. Variables considered were the following: age, gender, tumor location, pretreatment T and N stage, modality of 5-fluorouracil administration, total radiotherapy dose delivered, chemoradiation therapy regimen used (Regimen A: chemotherapy (bolus of 5-fluorouracil and leucovorin, days 1-5 and 29-33) + radiotherapy (45 Gy/25 F/1.8 Gy/F); Regimen B: chemotherapy (5-fluorouracil continuous venous infusion +/- weekly bolus of carboplatin or oxaliplatin) + radiotherapy (50.4 Gy/28 F/1.8 Gy/F)), time interval between completion of chemoradiation therapy and surgery, postoperative chemotherapy administration, surgical procedures, pT, pN, and pTNM stage, and response to chemoradiation therapy defined as tumor regression grade, scored from 1 (no tumor on surgical specimen) to 5 (absence of regressive changes). Statistical analysis was performed by means of logistic regression analysis (Cox's model for overall and disease-free survival). Median age of the 106 patients was 60 (range, 31-79) years and the male:female ratio, 66:40. Median distance of tumor from the anal verge was 6 (range, 1-11) cm. Pretreatment TNM stage, available in 104 patients, was cT3T4N0, n = 41; cT2N1, n = 9; cT3N1, n = 39; and cT4N1, n = 17. The median radiotherapy dose delivered was 50.4 (range, 40-56) Gy; 58 patients received 5-fluorouracil by continuous venous infusion, and carboplatin with oxaliplatin was added to the chemotherapy schedule in 71 cases. Patients were given Regimen A in 47 cases and Regimen B in 59. The median interval between chemoradiation therapy and surgery was 42.5 (range, 19-136) days, and 94 patients underwent a sphincter-saving procedure. Tumor regression grade, available in 104 cases, was 1, n = 19; 2, n = 18; 3, n = 15; 4, n = 13; and 5, n = 39. At a median follow-up of 42 (range, 1-110) months, 11 patients had died, and 95 were alive. None of the patients had local recurrences, but 13 had distant recurrences. At logistic regression analysis, the chemoradiation therapy regimen used was the only independent predictor of tumor response following preoperative chemoradiation therapy (odds ratio = 0.29, 95% confidence interval = 0.13-0.67, P = 0.003). At Cox's regression analysis, pretreatment T stage was the only independent prognostic factor for both disease-free survival (relative risk = 7.13, 95% confidence interval = 2.3-21.8, P = 0.001) and overall survival (relative risk = 4.83, 95% confidence interval = 1.1-19.9, P = 0.029). Tumor response following preoperative chemoradiation therapy is mainly related to the preoperative regimen used. For patients receiving preoperative chemoradiation therapy, pretreatment T stage, but not tumor response to preoperative chemoradiation therapy, is prognostic for outcome (both disease-free and overall survival).

Localized radiation therapy and simultaneous chemotherapy with uft and low-dose leucovorin as neoadjuvant treatment in-patients with T3-T4 rectal cancer. a phase II study

The aim of the study was to determine pathologic complete response rate and toxicity profile of the combination of high-dose preoperative localized radiation therapy and chemotherapy with UFT and leucovorin given simultaneously in patients with T3-T4 rectal cancer. This combination has been demonstrated feasible in a previous phase I study (Hoff, et al, JCO 18: 3529–3534, 2000). Secondary objectives were to assess resectability and sphincter preservation rates. Eligibility included biopsy proven of rectal adenocarcinoma, T3-T4,N0-2,M0 lesions, performance status <2 (ECOG) and adequate liver, renal, hematological and cardiac functions. Staging work-up included colonoscopy or barium enema, chest X-ray, abdominopelvic CT and transrectal ultrasonography. Treatment consisted of radiation therapy at two dose levels: a)PTV1: GTV + 3–5 cm margin, TD 45 Gy at 1.8 Gy/d b)PTV2: GTV + 1–2 cm margin, TD 55 Gy at 2 Gy/d and simultaneously UFT 300 mg/m2/d and leucovorin 60 mg/d, daily during 6 weeks given orally. Surgical resection was performed within 4–6 weeks after treatment. Between January 2001 and November 2003, 40 patients were included into this study. Patients characteristics: age 35–79 (median 64.5); male/female 29/11; T3N0:23, T3N1:15, and T4N1:2. Thirty-seven patients received full dose of radiation (93%) and in one patient UFT was reduced to 150 mg/m2/d. Mean treatment time was 52 days (range 37–62). Overall, 7 patients (17.5%) had grade 3 acute toxicity being mucositis in 4 patients (10%) and anusitis in 3 (7.5%). There was no grade 4 toxicity. Only one patient developed grade 2 neutropenia. Mean time between radiochemotherapy and surgery was 37 days (range 31–55). At the time of analysis, 3 patients are in surgery and therefore are not evaluable for response. Of the 37 remaining patients, 8 achieved pathologic complete response (21,6%) and 20 downstaged (54%). There was microscopical residual tumor in 8 patients. Radical surgery with free margins could be performed in all 37 patients, being sphincter-saving procedures in 3 of the 9 patients with tumor <5 cm from anal verge. Simultaneous high-dose preoperative localized radiation therapy and UFT and leucovorin is feasible with a low toxicity profile. This schedule is highly effective and merits further investigation

Chemoradiation with raltitrexed (TOMUDEX) in preoperative treatment of stage II-III resectable rectal cancer: A phase II study

Purpose To evaluate the impact of preoperative chemoradiation with raltitrexed (Tomudex 1) on tumor response, sphincter preservation, and toxicity in patients with locally advanced rectal cancer. Methods and materials Between 1998 and 2002, 54 consecutive patients with Stage T3 or T2N+ resectable rectal carcinoma were treated with preoperative chemoradiation, i.v. bolus of raltitrexed on Days 1, 19, and 38 and concurrent 50 Gy external beam radiotherapy. Surgery was performed 6–8 weeks after the end of chemoradiation. Results No patients had Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 16.6% of cases and was hematologic in 6 patients and GI in 2. The overall clinical response rate was 88.8%, with a complete response in 5.5%, partial response in 83.3%, and no change in 9.2%. No patient showed disease progression. All patients underwent surgery. Sphincter saving was obtained in 83.3% of patients. No perioperative mortality occurred, and the perioperative morbidity rate was 5.5%. Of 20 resected patients (37%) who were candidates for abdominoperineal resection at diagnosis (anorectal ring distance ≤30 mm), 13 (65%) underwent a sphincter-saving procedure. At pathologic examination, 13 (24%) of 54 patients had a complete pathologic response (pT0) and 10 (18.5%) had rare isolated residual cancer cells (pT, microscopic foci). Overall, 42.5% had major downstaging. The tumor regression grade (TRG), using Mandard's score system, was also applied and was TRG1 in 13 patients, TRG2 in 11, TRG3 in 20, and TRG4 in 10 patients; no patient had TRG5. Conclusion The use of raltitrexed in a neoadjuvant chemoradiation schedule promoted high pathologic tumor downstaging and use of a sphincter-saving procedure. The low toxicity profile supports the rationale to explore raltitrexed combined with other drugs with different biologic targets.

Rectal cancer in the elderly: patients' perception of bowel control after restorative surgery.

The risk of incontinence is perceived as a relative contraindication to a sphincter-saving procedure in elderly patients with rectal cancer. To investigate this, we reviewed functional results one year after restorative surgery in patients older than aged 75 years. A total of 186 patients older than aged 75 years were diagnosed with rectal cancer during the study period. In 19 patients, no surgery was undertaken, and another 3 patients had a defunctioning stoma only. A local excision was performed in six patients. Of the remaining 158 having a major resection, 133 patients (84 percent) had a restorative anterior resection. The one-year, follow-up records of these patients were studied with particular reference to the patients' perception of bowel function and continence. At one year, 99 patients who had had an anterior resection were alive. In 92 patients, a stoma had been closed or avoided altogether, and these patients formed the study group. Significant problems with bowel function or continence were denied by 78 of 92 patients (85 percent). One patient had already reported severe difficulties and been given a definitive stoma for incontinence. The remaining 14 percent, although experiencing some problems with continence, did not consider the situation serious enough to contemplate a stoma. An elderly patient undergoing anterior resection for rectal cancer has a reasonable expectation of acceptable continence. Age alone should not be a contraindication to a restorative resection.

Complications, continence and quality of life after an intensive preoperative radio-chemotherapy regimen for locally advanced rectal cancer: analysis of a phase I–II study

Complications, continence and quality of life after an intensive preoperative radio-chemotherapy regimen for locally advanced rectal cancer: analysis of a phase I–II study

First thousand rectal cancer cases: Local recurrence and survival

In the period 1990 - 2002, 1674 patients with colorectal carcinoma were operated in the First Surgical Clinic, Third Department for Colorectal Surgery. In 1264 cases (75.5%) rectal carcinoma was the indication for surgical treatment. Sphincter saving procedures (SSP) were performed in 824 (65.2%), abdominoperineal resections (APR) in 340 (26.9%) and resections of rectum with definitive stoma (Hartmann procedure) in 100 (7.9%) patients. We analyzed 1095 cases where curative SSP or APR were performed. All cases where curative resection was not possible because of liver metastases or inability to excise all macroscopic disease were excluded. In the group of patients where SSP was performed (767 cases), there were 26.6% high colorectal anastomoses (8cm from anal verge), 65.4% with low (4-8cm from anal verge) and 8.0% with intersphincteric coloanal anastomosis (cm from anal verge). Patohistological exam showed 5.3% Dukes A, 53.1% Dukes B, 36.5% Dukes C and 4.9% Dukes D. In the APR group (328 cases) there were 1.,5% Dukes A, 32.4% Dukes B, 62.1% Dukes C and 3.5% Dukes D. In this study we analyzed local recurrence and five-year survival in both groups. Recurrence of the disease was registered in 325 (29.6%) out of 1095 patients. Local recurrence was found in 81 (7.,4%) patients. In the SSP group recurrence occured in 215 (28.0%) out of 767 curative resections. Local recurrence alone was found in 53 patients (6.9%). SSP group was also divided into two subgroups; in the first group TME was performed and in second transection of mesorectum was carried out. Analyzing local recurrence in these two groups, in the TME group it was 7.6% and in the transection group 5.6%. In the APR group recurrence was registered in 110 (33.5%) out of 328 patients while local recurrence alone was found in 28 (8.5%) cases. Analyzing mortality we found that 234 (21.4%) out of 1095 patients died during follow-up. In the SSP group 154 out of 767 patients (20.1%) died. In the TME group mortality was 21.7% and in the transection group 16.9%. Mortality in the APR group showed that 80 out of 328 (24.4%) patients died during follow-up. Analysis by the Kaplan-Meier's test shows cumulative survival of 0.69 for all cases. In the SSP group cumulative survival is 0.72 and in the APR group 0.64 with statistically significant difference (p .001). In the TME group cumulative survival is 0.75 and in the transection group 0.,72 with statistically significant difference (p .05). We believe that performing SSP should be encouraged whenever it is possible because there is no difference in local recurrence rates and survival compared to APR. Transection of mesorectum can safely be performed in most cases with tumors located more than 8 cm form anal verge. We believe that exact preoperative staging and preoperative radiotherapy could improve results.

Improved sphincter preservation of low rectal cancer with high dose preoperative radiotherapy: the lyon R96-02 randomized trial

Purpose The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures. Patients and Methods Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or MO with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray. Results Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P = .004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival. Conclusion A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

243 Preoperative chemotherapy plus concomitant radiotherapy in rectal cancer patients (pts): updated results of a phase II study

To evaluate the impact of preoperative chemoradiation with raltitrexed (Tomudex1) on tumor response, sphincter preservation, and toxicity in patients with locally advanced rectal cancer.Between 1998 and 2002, 54 consecutive patients with Stage T3 or T2N+ resectable rectal carcinoma were treated with preoperative chemoradiation, i.v. bolus of raltitrexed on Days 1, 19, and 38 and concurrent 50 Gy external beam radiotherapy. Surgery was performed 6–8 weeks after the end of chemoradiation.No patients had Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 16.6% of cases and was hematologic in 6 patients and GI in 2. The overall clinical response rate was 88.8%, with a complete response in 5.5%, partial response in 83.3%, and no change in 9.2%. No patient showed disease progression. All patients underwent surgery. Sphincter saving was obtained in 83.3% of patients. No perioperative mortality occurred, and the perioperative morbidity rate was 5.5%. Of 20 resected patients (37%) who were candidates for abdominoperineal resection at diagnosis (anorectal ring distance ≤30 mm), 13 (65%) underwent a sphincter-saving procedure. At pathologic examination, 13 (24%) of 54 patients had a complete pathologic response (pT0) and 10 (18.5%) had rare isolated residual cancer cells (pT, microscopic foci). Overall, 42.5% had major downstaging. The tumor regression grade (TRG), using Mandard's score system, was also applied and was TRG1 in 13 patients, TRG2 in 11, TRG3 in 20, and TRG4 in 10 patients; no patient had TRG5.The use of raltitrexed in a neoadjuvant chemoradiation schedule promoted high pathologic tumor downstaging and use of a sphincter-saving procedure. The low toxicity profile supports the rationale to explore raltitrexed combined with other drugs with different biologic targets.

Laparoscopic total mesorectal excision: a consecutive series of 100 patients.

To analyze total mesorectal excision (TME) for rectal cancer by the laparoscopic approach during a prospective nonrandomized trial. Improved local control and survival rates in the treatment of rectal cancer have been reported after TME. The authors conducted a prospective consecutive series of 100 laparoscopic TMEs for low and mid-rectal tumors. All patients had a sphincter-saving procedure. Case selection, surgical technique, and clinical and oncologic results were reviewed. The distal limit of rectal neoplasm was on average 6.1 (range 3-12) cm from the anal verge. The mean operative time was 250 (range 110-540) minutes. The conversion rate was 12%. Excluding the patient who stayed 104 days after a severe fistula and reoperation, the mean postoperative stay was 12.05 (range 5-53) days. The 30-day mortality was 2% and the overall postoperative morbidity was 36%, including 17 anastomotic leaks. Of 87 malignant cases, 70 (80.4%) had a minimum follow-up of 12 months, with a median follow-up of 45.7 (range 12-72) months. During this period 18.5% (13/70) died of cancer and 8.5% (6/70) are alive with metastatic disease. The port-site metastasis rate was 1.4% (1/70): a rectal cancer stage IV presented with a parietal recurrence at 17 months after surgery. The locoregional pelvic recurrence rate was 4.2% (3/70): three rectal cancers stage III at 19, 13, and 7 postoperative months. Laparoscopic TME is a feasible but technically demanding procedure (12% conversion rate). This series confirms the safety of the procedure, while oncologic results are at present comparable to the open published series with the limitation of a short follow-up period. Further studies and possibly randomized series will be necessary to evaluate long-term clinical outcome in cancer patients.

Preoperative concomitant radiochemotherapy with a 5-fluorouracil plus folinic acid bolus in the combined treatment of locally advanced extraperitoneal rectal cancer: a long-term analysis on 27 patients.

Many studies of preoperative chemoradiation in resectable rectal cancer have focused on down-staging and sphincter-saving procedures. The aim of this study was to evaluate long-term outcome in resectable rectal cancer treated with preoperative chemoradiation and surgery by only one surgical team irrespective of the tumor downstaging. From 1992 to 2001, in a cooperative study between the Institute of Semeiotica Chirurgica and the Division of Radiotherapy of the Catholic University of the Sacred Heart, 27 patients with locally advanced rectal cancer were treated with preoperative chemoradiation, followed by surgery after 4-6 weeks, and, just for 6 of them, by adjuvant chemotherapy. Seventeen patients were staged T3 N1 (63%), 4 patients T3N0 (15%), 4 patients T3N2 (15%) and 2 T4N2 (7.5%). Twenty-three patients (85.1%) had signs of nodal involvement at combined imaging. Radiation therapy was delivered to the posterior pelvis at a dose of 45 Gy to the tumor (clinical target volume) and the whole pelvis (planning target volume). Fractionation was conventional: 1.8 Gy/day, 5 fractions a week. Radiotherapy was started on Monday for all patients and was delivered with a linear accelerator. Concomitant chemotherapy consisted of 5-fluorouracil (350 mg/m2/day, as an intravenous bolus on days 1-5 and 29-33 of radiotherapy) and folinic acid (L-isomer) (10 mg/m2 as an intravenous bolus on days 1-5 and 29-33). This chemotherapy was generally administered about 1 hr before radiotherapy. Data were analyzed on July 2002; median follow-up was 59 months (range, 20-116 months). No patient was lost during the follow-up. All patients completed the treatment. Grade > 3 acute toxicity occurred in 11% of the patients and late toxicity was 15%. A pathologic complete response was recorded in 22% of patients; sphincter-preserving surgery was feasible in 44%. Seven patients died: 2 of them perioperatively, 1 patient died with local recurrence, and 1 died with distant metastases; 3 patients died during the follow-up for other causes. Five-year local control was 95% and overall survival was 84%. Our study, although limited in number, demonstrated good results in local control and disease-free survival with a limited toxicity.