Low Local Recurrence Research Articles

Low local recurrence rate among node negative breast cancer patients with tumor size 5cm and larger treated with surgery and chemotherapy without radiation

Node-negative breast cancers with primary tumors size 5cm or greater occur infrequently and optimal management is challenging. While standard recommendations for these patients include chemotherapy in addition to surgery, the addition of radiation therapy for improved local control is debatable. Our recent survey indicated that 80% of practicing radiation oncolgists would give post-mastectomy radiation in this situation (Ceilley, E. et al., Int J Radiat Oncol Biol Phys 51:110, 2001, abstr. 197).

Radical resection with total mesorectal excision under the laparoscope in the treatment of rectal cancer

To evaluate the effect of radical resection with total mesorectal excision under the laparoscope in the treatment of rectal cancer. Under the laparoscope and with the ultrasonic scalpel, total mesorectal excision in 38 patients with rectal cancer was performed. In operation, alone the parietal layer of pelvic fascia and inside the autonomic nerve trunk, the mesorectum was excised. All patients were followed up for 2 years. All cases were underwent successfully and no complication was observed. Postoperative flatus and feces were passed at 32 hours and postoperational hospital stay were 7.5 days. No trocar port implantation and no death case was observed. Two local recurrence developed in 2 years follow-up. Radical resection with TME is a new progress of less damageable operation, which has advantages of low postoperative local recurrence rate and help for pelvic autonomic nerve.

Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.

Adjuvant radiochemotherapy in resectable stage II, III rectal cancer: Results of the FOGT-2 trial

3608 Background: In this phase III trial (FOGT-2) we studied whether one of the 5-FU modulations with either folinic acid (FA) or Interferon alpha-2a (IFNa) increased overall survival compared to the standard treatment in R0-resected rectal cancer, 5-fluorouracil (5-FU) plus levamisole (LEV) for 12 months, plus postoperative radiotherapy (RT). Methods: From 7/92 to 5/03 793 patients with resected rectal cancer stages UICC II (267 pts.) and UICC III (526 pts.) were randomized into three arms and stratified (N-stage, centers). After a postoperative loading course with 5-FU [450mg/ m2 d1–5 (arms A and C)] or 5-FU [450mg/m2 plus folinic acid (Rescuvolin, medac, Hamburg, Germany), 200 mg/ m2 d1–5 (arm B)], LEV was administered orally at 150 mg/d d1–3, q every 2 weeks. 4wks later treatment was continued weekly for up to 52 wks. RT was given over a 6-wks postoperative period in a 3-field technique up to a dose of 45–50,4 Gy in 1,8 Gy fractions 5x/wk with a 20% dose reduction of 5-FU. Arm A (280 pts.) was treated with 5-FU i.v. (450 mg/ m2 at d 1, q 1 w) plus LEV. 5-FU plus LEV was modulated in arm B (291 pts.) with FA (200mg/ m2 d1, q 1 w), and in arm C (222 pts.) with IFNa at 6 million units 3x/week, q 1 w. Arm C was closed early due to toxicity. Results: Toxic events WHO3,4, mainly diarrhea, leukopenia, occurred in 36% of all pts. (A, 31%, B,27%, C, 55%). Discontinuance rates were 34% (all), 33% (A), 31% (B), 39% (C). 80% of all pts. received treatment for at least 6 months. Overall relapse rates were 37% (all), 39% (A), 35% (B) and 37% (C). Tumors relapsed either locally (all: 6%; A, C:6%, B:5%) or distant (all: 26%; A: 27%, B, C: 26%) or both locally and distant (all: 5%; A: 6%, B, C: 5%). Death rates were 32% (all), 33% (A), 28% (B), and 34% (C), with no significant difference among arms in Kaplan-Meier analysis. There were 2 toxic deaths (A, C). Conclusions: Adjuvant postoperative radio-/chemotherapy with 5-FU +/- FA plus LEV for 12 months in more than 700 patients is safe, well tolerated and shows low local recurrence rates. IFNa-modulation of 5-FU (plus LEV) adds toxicity without therapeutic benefit. No significant financial relationships to disclose.

A retrospective review of wide excision alone for ductal carcinoma in situ (DCIS) of the breast

785 Background: The standard treatment for ductal carcinoma in situ (DCIS) of the breast today is wide excision (WE) followed by radiotherapy.This is due to the results of 3 randomised trials .The major benefit is a 50–60% reduction in the risks of recurrence.The recurrence rates vary from centre to centre .Historically, some centres have had low local recurrence rates while treating DCIS with a policy of WE and selective mastectomy.They have questioned whether radiotherapy should be routinely done.We reviewed the DCIS patients at Worthing general hospital where the recurrence rates were thought to be low. Methods: We retrospectively reviewed 190 patients with DCIS treated by surgery alone from January 1989 to December 1998.These patients had 5–14 years follow up with a median follow up of 90 months.145 (75%) patients were given Tamoxifen for a minimum of 5 years. Results:83 (42.5%) patients underwent a mastectomy .8(4%) patients developed DCIS recurrence while 8(4%) went on to have an invasive recurrence.2(1%) patients died of bony secondaries with normal breasts and must have had occult invasive disease.9 patients died from causes unrelated to their disease.Overall mortality was 5.6% with disease specific mortality being 1%. Conclusions: The local recurrence rate for DCIS was 8% over a median follow up of about 71/2 years.The recurrence rate of 1% per patient-year is lower than that reported in major trials.However, a large number of patients had mastectomy and Tamoxifen .If the mastectomy patients are not included in the analysis, then the recurrence rate is 15% at 71/2 years(16/107) or 2% per patient-year.This is similar to that reported in the literature.Therefore, centres with low recurrence rates for DCIS are likely to have higher rates for mastectomy .The literature stresses the reduction of recurrences as the main benefit of radiotherapy in DCIS.Radiotherapy much more importantly reduces the mastectomy rate.However, 15 (107/16) patients need to be treated to prevent 1 local recurrence.Since the long term side effects of radiotherapy in DCIS are unknown and it has an excellent prognosis, we need a reliable prognostic system to use radiotherapy selectively after WE. No significant financial relationships to disclose.

A retrospective review of wide excision alone for ductal carcinoma in situ (DCIS) of the breast

785 Background: The standard treatment for ductal carcinoma in situ (DCIS) of the breast today is wide excision (WE) followed by radiotherapy.This is due to the results of 3 randomised trials .The major benefit is a 50–60% reduction in the risks of recurrence.The recurrence rates vary from centre to centre .Historically, some centres have had low local recurrence rates while treating DCIS with a policy of WE and selective mastectomy.They have questioned whether radiotherapy should be routinely done.We reviewed the DCIS patients at Worthing general hospital where the recurrence rates were thought to be low. Methods: We retrospectively reviewed 190 patients with DCIS treated by surgery alone from January 1989 to December 1998.These patients had 5–14 years follow up with a median follow up of 90 months.145 (75%) patients were given Tamoxifen for a minimum of 5 years. Results:83 (42.5%) patients underwent a mastectomy .8(4%) patients developed DCIS recurrence while 8(4%) went on to have an invasive recurrence.2(1%) patients died of bony secondaries with normal breasts and must have had occult invasive disease.9 patients died from causes unrelated to their disease.Overall mortality was 5.6% with disease specific mortality being 1%. Conclusions: The local recurrence rate for DCIS was 8% over a median follow up of about 71/2 years.The recurrence rate of 1% per patient-year is lower than that reported in major trials.However, a large number of patients had mastectomy and Tamoxifen .If the mastectomy patients are not included in the analysis, then the recurrence rate is 15% at 71/2 years(16/107) or 2% per patient-year.This is similar to that reported in the literature.Therefore, centres with low recurrence rates for DCIS are likely to have higher rates for mastectomy .The literature stresses the reduction of recurrences as the main benefit of radiotherapy in DCIS.Radiotherapy much more importantly reduces the mastectomy rate.However, 15 (107/16) patients need to be treated to prevent 1 local recurrence.Since the long term side effects of radiotherapy in DCIS are unknown and it has an excellent prognosis, we need a reliable prognostic system to use radiotherapy selectively after WE. No significant financial relationships to disclose.

Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer.

Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease. Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence. The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C ( P = 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C ( P = 0.0001). If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.

Total Mesorectal Excision Results in Low Local Recurrence Rates in Lymph Node-Positive Rectal Cancer

PURPOSE:: Most series report lymph node involvement as the main predictor for local recurrence. The principal lymphatic drainage of the rectum is to nodes in the mesorectum and then nodes along the superior rectal and inferior mesenteric arteries. If total mesorectal excision provides adequate block dissection of the lymphatics of the rectum, good local control with low rates of local recurrence should be achieved even in node-positive disease. METHODS:: Prospective data on all rectal cancers have been collected since 1978; 170 patients with Dukes C rectal cancer have undergone anterior resection and total mesorectal excision. We did not perform any internal iliac node dissections. Follow-up data were analyzed for local recurrence and distant recurrence. RESULTS:: The local recurrence rate was 2 percent for Dukes A cases, 4 percent for Dukes B, and 7.5 percent for Dukes C (P= 0.0127). The systemic recurrence rate was 8 percent for Dukes A, 18 percent for Dukes B, and 37 percent for Dukes C (P= 0.0001). CONCLUSIONS:: If surgical priority is given to the difficult task of excision of the whole mesorectum, anterior resection with total mesorectal excision in node-positive rectal cancer, local recurrence rates of < 10 percent can be achieved.

Primary Tumor Control in Patients With Stage 3/4 Unfavorable Neuroblastoma Treated With Tandem Double Autologous Stem Cell Transplants

To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.

Long-term review of a breast conservation series and patterns of care over 18 years.

Multiple randomized trials of breast conservation compared with mastectomy in early breast cancer have validated equivalence of survival. Overwhelmingly the standard management of breast conservation includes surgical removal of the tumour, axillary dissection, postoperative breast irradiation, and adjuvant systemic therapy as appropriate. The outcomes are reviewed of 832 women with early breast cancer treated by local resection and irradiation at Royal Prince Alfred Hospital over an 18 year period, with particular emphasis on the changing patterns of practice. Between September 1978 and May 1996, 832 women with early stage breast cancer were treated with conservative surgery and radiation therapy. The changes in patient, tumour and treatment factors were analysed over this time period. The outcomes of local recurrence and survival were recorded. Trends in patterns of these variables were evaluated by dividing the 18 years accrual period into three consecutive periods (1978-1983, n = 28; 1984-1990, n = 392; 1991-1996, n = 412). At a median follow up of 76 months, the 5 and 10 year actuarial local recurrence rates were 4% and 6%, respectively. Half of the local recurrences were at the primary site. Young age, extensive intraduct carcinoma, oestrogen receptor (ER) status and extranodal spread were predictive of local recurrence on multivariate analysis. The 5 and 10 year overall survival rates were 88% and 73%, respectively. Actuarial 5 year local recurrence (4%, 6%, 2%) and survival (96%, 88%, 92%) rates varied little across the three time intervals. There was an increase in median age from 46 to 56 years over the accrual period, with no change in median primary tumour size (1.5 cm). There were significant histopathological improvements in reporting margin status and ER status. Surgically, the median number of axillary lymph nodes retrieved (14) did not alter significantly. With respect to adjuvant therapies, irradiation of lymph nodes regions decreased over time. The proportion of patients receiving adjuvant hormones or chemotherapy increased significantly (18%, 35%, 54%). The low local recurrence rate and high survival are consistent with published literature for early breast cancer. Changes in practice during the accrual period included improvements in histopathological reporting, a reduction in irradiation of lymph node regions, and an increase in the use of systemic therapy. These changes parallel international recommendations regarding the optimal management of early breast cancer.

ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer

• The crude incidence of rectal cancer in the European Union is approximately 35% of the total colorectal cancer incidence, i.e. 15–25 cases/100 000 per year.• The mortality is 4–10 cases/100 000 per year with the lower figures valid for females, the higher for males. • Diagnosis is based on a clinical rectal examination including rigid proctoscopy with biopsy for histopathological examination. Tumors with distal extension to 15 cm or less (as measured by rigid proctoscopy) from the anal margin are classified as rectal, more proximal tumors as colonic. • Complete history and physical examination, complete blood count, liver and renal function tests, chest X-ray and computed tomography (CT) or magnetic resonance (MR) or ultrasound of liver should be performed. In fixed tumors, CT or MR of the pelvis should be done.• Complete colonoscopy should be done.• Histopathological examination should include a surgical specimen with proximal, distal and circumferential margins and regional lymph nodes (it is recommended that at least 12 nodes are examined).• TNM staging system should always be used. In addition Dukes’ staging system (A, B, C, D) may be used (Table 1):Table 1TNMStageExtension toModified Dukes’TisN0M00Carcinoma in situ–T1N0M0IMucosa or submucosaAT2N0M0IMuscularis propriaB1T3N0M0IISubserosa/perirectal tissueB2T4N0M0IIPerforation into perirectal tissue orinvasion of other organsB3T2N1M0/T2N2M0IIIT2, N1: 1–3/N2: ≥4 lymph nodesC1T3N1M0/T3N2M0IIIT3, N1: 1–3/N2: ≥4 lymph nodesC2T4N1M0IIIT4, N1: 1–3/N2: ≥4 lymph nodesC3Any T any NM1IVDistant metastasesD Open table in a new tab • Preoperative radiotherapy. Preoperative radiotherapy (e.g. 25 Gy, 5 Gy/fraction followed by immediate surgery) reduces local recurrence [I, A], and may improve survival compared with surgery alone and is recommended unless there is a very low risk of local failure.• Surgical procedure. Total mesorectal excision is strongly recommended as the method gives a low local recurrence rate (<10%) [II, A]. Whenever possible a low anterior resection should be employed.• Postoperative radio/chemotherapy. Postoperative radiotherapy (e.g. 50 Gy) with concomitant 5-fluorouracil (5-FU)-based chemotherapy is recommended [III, B] for patients with T3 and T4 (i.e. Dukes’ B2 and B3) tumors and for patients with nodal involvement (N1–2, i.e. Dukes’ C1–3), if preoperative radiotherapy has not been given. 5-FU-based chemotherapy may be continued for 2–4 months following radiotherapy. • Patients with fixed tumors or with local recurrence (if radiotherapy was not given in the primary situation) should receive preoperative radiotherapy with or without concomitant chemotherapy [II, A].• Attempted radical surgery should take place 4–8 weeks after radiotherapy [II, A]. • In selected cases, treatment may include surgery of isolated liver or lung metastases [II, A], surgical stenting [III, A] or radiotherapy should be considered as palliative procedures [II, A].• First-line palliative chemotherapy should be started early and consists of 5-FU in various combinations and schedules, e.g. infusional regimens. Frequently used schedules include 5-FU (425 mg/m2) + low-dose leucovorin (20 mg/m2) days 1–5, q4 weeks. Combination with oxaliplatin or irinotecan may be considered.• Second-line chemotherapy should be considered for selected patients with maintained good performance status. • Follow-up serves to identify patients in need of salvage surgery or palliative care and to prevent second colorectal cancers. There is no proof that regular follow-up after successful treatment improves the outcome of patients with rectal cancer. Provisional recommendations are as follows: history andrectosigmoidoscopy (with endosonography if available) every 6 months for 2 years [V, D]; history and colonoscopy with resection of colonic polyps every 5 years [I, B]; clinical, laboratory and radiological examinations are of unprovenbenefit and should be restricted to patients with suspicious symptoms [A]. Levels of Evidence [I–V] and Grades of Recommendation [A–D] as used by the American Society of Clinical Oncology are givenin square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty. Coordinating author for the ESMO Guidelines Task Force: K. M. Tveit,Ullevaal University Hospital, Oslo, Norway. Approved by the ESMO Guidelines Task Force: August 2002. Correspondence to: ESMO Guidelines Task Force ESMO Head Office Via La Santa 7 CH-6962 Viganello-Lugano Switzerland

A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision.

Preoperative chemoradiation reduces tumor size and nodal metastasis in patients with rectal cancer. Tumor downstaging has been associated with an increased probability of a sphincter-saving procedure and with improved local control. However, pathologic complete response to chemoradiation has not been correlated with local control and patient survival. We studied the prognostic value of pathologic complete response to preoperative chemoradiation in rectal cancer patients. We have prospectively followed up 168 consecutive patients with ultrasound Stages II (46) and III (122) rectal cancer treated by preoperative chemoradiation followed by radical resection with mesorectal excision; 161 had a curative resection. Recurrence and survival were compared with tumor characteristics and pathologic complete response. Average follow-up was 37 months. Tumor downstaging occurred in 97 (58 percent) patients, including 21 (13 percent) patients who had a pathologic complete response. None of the clinical or pathologic variables was associated with pathologic complete response. The estimated 5-year rate of local recurrence was 5 percent; of distant metastasis, 14 percent. None of the patients with pathologic complete response has developed disease recurrence. We found no difference in survival among patients with pathologic Stages I, II, or III tumors. A pathologic complete response to preoperative chemoradiation is associated with improved local control and patient survival. For patients without pathologic complete response, the pathology stage does not have prognostic significance.

DCIS: Current Concepts in Diagnosis and Management

: The majority of published outcome studies for breast carcinoma, whether retrospective or prospective, are designed without specific standards for tissue analysis. These studies treat pathology practice as entirely uniform and reproducible; in fact, it is an enormous variable. Such variation has an unrecognized adverse impact on the results. The outcome of in situ carcinoma is highly dependent on pathologic characteristics, probably more so than on the details of treatment. The use of standardized tissue processing and orientation in addition to pathologic taxonomy is urged. Oncologic surgical principles can combine successfully with reconstructive techniques for patients with ductal carcinoma in situ (DCIS), and this combination may increase the number of women who can be treated with breast-conserving surgery rather than mastectomy by allowing surgeons to perform larger breast excisions with acceptable cosmetic results. Excellent outcome has been demonstrated with extremely low local recurrence rates after excision of DCIS with greater than 1 cm surgical margins without subsequent radiation, especially with smaller and lower-grade lesions. However, meticulous surgical approaches, tissue processing, and pathologic examination are all prerequisites in order to achieve these results. Managed care reimbursement guidelines generally do not allow most centers to attain these standards.

Local recurrence of rectal cancer after total mesorectal excision without preoperative radiotherapy.

At this moment, it is still debatable whether all patients with mobile rectal cancer who undergo surgical removal of the tumor should be treated with preoperative radiotherapy, since it is likely that only certain patients will benefit from this strategy. In this study, patients with mobile rectal cancer were immediately operated upon and only those with positive nodes or with incomplete resection received adjuvant radiotherapy. To investigate the local recurrence rate after the use of a selective policy of adjuvant radiotherapy and to determine risk factors for local recurrence. In a 5-yr-period, 178 patients with rectal cancer were referred to our institute. A total of 131 patients with mobile rectal cancer were treated with curative intent, which implied a microscopically radical resection and no signs of distant metastasis at operation. A retrospective analysis was undertaken to investigate the incidence of local recurrence in this curative group and to determine risk factors for local recurrence. The postoperative mortality in the curative group was 5.3%. Local recurrences were observed in 6 patients (4.6%) after a median period of 25 mo (range 11-37); two of them also had distant metastases detected at the same time. The highest local recurrence rates were seen in men (5.3%), in distal rectal cancers (6.9%), and in the node-positive group (8.7%). A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest using preoperative radiotherapy only for those patients who are at a higher risk for local recurrence. Staging techniques for selection of these patients are at this moments till inappropriate.

Current evidence does not support routine adjuvant radiotherapy for rectal cancer

There is widespread support in the published literature for routine adjuvant radiotherapy for rectal cancer. In the present paper, the current evidence regarding adjuvant radiotherapy is reviewed, particularly the most recent studies of preoperative radiotherapy (usually including patients with Stage I, II and III disease) and postoperative radiotherapy (usually for Stage II and III disease), and meta-analyses. Two questions in particular are addressed: Does radiotherapy improve survival when surgeons are able to achieve low local recurrence rates with surgery alone? Does radiotherapy improve patients' quality of life? Radiotherapy has only been demonstrated to significantly improve survival in one individual study and one recent meta-analysis. The local recurrence rates in the no-radiotherapy arm of these studies were 27% and 21-36.5%, respectively. In more recent studies, with lower local recurrence rates reflecting modern surgical standards, no survival advantage has been found. It is currently unknown whether radiotherapy improves patients' quality of life. Studies have demonstrated that radiotherapy has acute and long-term detrimental effects on quality of life. While local recurrence can be very debilitating, it can also be asymptomatic, and the overall effect of the local recurrence statistics found in adjuvant therapy studies on quality of life has not been systematically investigated. The most recent studies demonstrate that 17-20 patients need to undergo adjuvant radiotherapy to prevent one local recurrence. Current evidence does not support the widespread advocacy for routine adjuvant radiotherapy as used in the treatment arms of recent trials.

The circumferential margin in rectal cancer: recommendations based on the Dutch Total Mesorectal Excision Study

A very low local recurrence rate in rectal cancer is possible with optimal staging, preoperative radiotherapy and the use of total mesorectal excision (TME). Data from a study where patients were randomised for preoperative radiotherapy (or not) and complete removal of the tumour and mesorectum were examined. A consensus meeting was held to discuss the data in which the following guidelines for implementation were made. Adequate imaging is necessary to increase the likelihood of a R0 resection. Advances cases (possible margin to the endopelvicfascie less than 2 mm) need a long course of preoperative radiotherapy. Primary resectable cases benefit from a short course of radiation directly followed by surgery. A continuous quality control of surgery is mandatory in order to maintain the skill for a TME. A complete pathology report is important for the quality control of the surgical treatment and to predict the outcome of treatment. All of the involved disciplines in the diagnosis and treatment of rectal cancer should focus on the circumferential margin to guide for optimal treatment. Multidisciplinary teams are important for the achievement of optimal treatment planning of rectal cancer patients and maintenance of the highest level of quality control.

How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery?

Background: The indication for elective nephron-sparing surgery (NSS) in renal cell carcinoma (RCC) is under discussion in the urological literature. The main problem of NSS is the multifocality of RCC. The presented study was preformed to assess the accuracy of pre-and intraoperative ultrasound (US), and computerized tomography (CT) in determination of tumor size and detection of multifocal lesions. Materials and methods: Tumor size was measured by preoperative US and CT and compared with the tumor diameters in gross sections of the neoplastic kidneys. Multifocality was determined by 3-mm step sectioning of the nephrectomy specimen, and the results were correlated with preoperative US and CT on the one hand, and the ex situ sonography of the nephrectomized kidney on the other hand. Results: US and CT show similar results in the determination of the tumor size. In only 22.9%, preoperative US and CT were able to detect multifocal tumors. Ex situ sonography had a sensitivity of 40.0% and a specificity of 87.2% in this regard. Conclusions: In preparation for nephron-sparing surgery of renal cell carcinoma, neither preoperative routine imaging, nor intraoperative ultrasound can safely predict multifocal lesions of renal cell carcinoma. Commentary Local tumor recurrence following nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) may be due to incomplete resection of the primary tumor, occult multicentric disease or the development of a new primary or metastatic focus of RCC in the renal remnant. The risk of multicentric disease in RCC has been evaluated and debated extensively in the literature. RCC generally occurs as a discrete focal lesion rather than an infiltrative process which is seen in carcinoma of the prostate. At issue is whether the molecular events that give rise to malignant transformation affect a discrete segment of the kidney or a broader segment of the renal tubular epithelium. A high incidence of multicentric RCC has been reported in patients with germ line mutations such as those that exist in von Hippel Lindau disease and other forms of hereditary RCC suggesting a global predisposition to malignant degeneration throughout the entire renal parenchyma. The incidence of multicentricity in sporadic RCC has been less clear. Emerging cytogenetic and molecular data suggest that satellite lesions may occasionally arise from the same malignant clone as their corresponding primary lesion and may therefore represent biologically significant intra-renal metastasises. A recent review of published studies comprising over 1100 cases of sporadic RCC indicated an aggregate incidence of 15.2% of tumor multifocality (range 6.5%–28%)[1]. It is important to remember that these studies represent a diverse group of patients and that RCC is in fact a heterogenous group of tumors. The risk of multicentricity is not equal in all patients and appears to be related to other prognostic variables such as tumor histology, stage and grade. For example, papillary RCC is known to be associated with a higher incidence of multifocality than the more common clear cell variant. The risk of multifocal disease also increases with larger tumors, particularly those that extend beyond the renal capsule (pT3+). Finally, some microfocal tumors are of unknown biological significance such as the finding of satellite adenomas. Of importance when considering relative indications for elective NSS is the incidence of multifocality when the primary or index tumor is ⩽ 4 cm. A recent review of the literature indicated that the incidence of multifocality in this setting is approximately 5%. The most worrisome implication of multifocal RCC is that this will predispose to an increased risk of local tumor recurrence following NSS. Although this potential risk must be considered, the relationship between multifocality and local recurrence is neither linear or predictable as suggested by the low overall local recurrence rates reported following NSS in several large series. In nearly 1800 cases of NSS reported in the literature to date, the risk of local tumor recurrence has ranged from 0–10% and is clearly lowest among patients undergoing elective NSS for small (⩽ 4 cm) low stage lesions [1]. The true biologic significance of multicentric renal tumors and their implication for NSS therefore remain to be fully elucidated. [1] Uzzo RG, Novick AC. Nephron-sparing surgery for renal tumors: indications, techniques and outcomes. J Urol 2001;166:6–18. Andrew C. Novick, M.D.

Neoadjuvant external beam radiation and proctectomy for adenocarcinoma of the rectum.

The aim of this study was to determine the survival rate, local failure, and perioperative morbidity in patients with adenocarcinoma of the rectum undergoing curative proctectomy who were felt to have transmural disease on preoperative assessment. Eighty-nine percent of these patients were treated with preoperative external beam radiotherapy. The records of 191 consecutive patients undergoing abdominal surgical procedures for primary treatment of rectal cancer were reviewed. The product-limit method (Kaplan-Meier) was used to analyze survival rate and tumor recurrence. One patient was excluded from survival analysis because of incomplete record of tumor stage. The study population comprised 109 males and 81 females, median age 64 (range, 33-91) years. Curative resection was performed in 152 of these 190 patients (80 percent), including low anterior resection with coloproctostomy or coloanal anastomosis (n = 103), abdominoperineal resection (n = 44), Hartmann's procedure (n = 4), and pelvic exenteration (n = 1). Mean follow-up of patients undergoing curative resection was 96 +/- 48 months. Palliative procedures were performed in 38 of 190 patients (20 percent). Perioperative mortality was 0.5 percent (1/190). Complications occurred in 64 patients (34 percent). The anastomotic leak rate was 4 percent (5/128). Disease-free five-year survival rate by pathologic stage was as follows: Stage I, 90 percent; Stage II, 85 percent; Stage III, 54 percent; Stage IV, 0 percent; and no residual tumor, 90 percent. Of the 152 patients treated with curative resection, disease-free survival rate was 80 percent at five years. Preoperative external beam radiation was administered to 135 of these 152 patients (89 percent). Tumor recurred in 32 of 152 patients (21 percent) treated with curative resection. The predominant pattern of recurrence was distant failure only. Kaplan-Meier overall local recurrence (local and local plus distant) at five years was 6.6 percent. The local recurrence rate paralleled tumor stage: Stage I, 0 percent; Stage II, 6 percent; Stage III, 20 percent; and no residual tumor, 0 percent. Preoperative external beam radiotherapy and attention to mesorectal dissection can achieve low local recurrence and excellent long-term survival rate in patients with adenocarcinoma of the rectum. Moreover, these goals can be obtained with low morbidity and mortality.

Amputation abdominopérinéale pour récidives locales des cancers du rectum après résection antérieure

Study aim: The aim of this retrospective study was to evaluate the short and long term results of abdominoperineal resection for local recurrence following low anterior resection of a rectal adenocarcinoma and to determine the prognostic factors. Patients and methods: From January 1978 to December 1996, 35 patients (17 women, 18 men) with a mean age of 59.4 years, underwent an abdominoperineal resection for local recurrence after low anterior resection of a rectal adenocarcinoma. The primary tumor was below the peritoneum in 29 cases, and the mean security marge was 3 cm under the tumor. Tumor staging at the time of primary surgery included 23 Dukes B, 11 Dukes C, and 1 Dukes D. The mean time elapsed between low anterior resection and local recurrence was 16.4 months. The histological diagnosis of recurrence was obtained preoperatively in 29 cases (82.8%). Results: Resection was curative in 12 patients and palliative only in 23 patients. The recurrence was intramural in 3 cases, extramural in 10 cases, and mixed in 22 cases. Ten patients had an extended « en bloc » resection including one or several adjacent organs, and a synchronous metastasis was resected in 2 cases. The mortality rate was 2.8% ( n=1) and the morbidity rate was 23% ( n=8). The 1-year and 5-year survival rates were respectively 77 and 30.2% with the univariate analysis of prognosis factors of survival, there were four pretherapeutic factors (age, staging of the primary tumor, delay of the recurrence, CEA rate) and four therapeutic factors (curative resection, extramural recurrence, staging of the recurrence, postoperative radiotherapy). The curative or not curative type of resection was the only independent predictor of survival with multivariate analysis. Conclusion: The results of this study seem to justify an abdominoperinal resection for local recurrence after low anterior resection whenever possible. Long-term results may possibly be improved by using adjuvant treatment.

Plexosarcoma: endoscopic ultrasound and electron-microscopic characteristics of a stromal tumor

Endoscopic ultrasound is useful for managing submucosal masses; however, some of these lesions can be difficult to classify except with full histological and electron microscopic evaluation. A 72-yr-old woman was seen with upper GI bleeding. Endoscopy showed a 1.7-cm sessile ulcerated submucosal mass in the duodenal bulb. Endoscopic ultrasound revealed an echolucent submucosal mass arising from the fourth echolayer, the muscularis propria of the duodenal wall. These findings suggested that the lesion was a leiomyoma. The patient eventually had the lesion resected because of recurrent bleeding. Histologically it was a spindle cell tumor that on electron microscopy showed neuronal elements consistent with a plexosarcoma, or gastrointestinal autonomic nerve tumor. These lesions account for some one third of all gastrointestinal stromal tumors. Despite their low grade malignant histologic appearance, local recurrence or hepatic metastases occur in about 70% of patients.