A Case of Radiation-induced Rectal Cancer Developing after a Long-term Follow-up

A case of radiation-induced rectal cancer is presented. In November,1971, a 58-year-old woman had a stage II squamous cell carcinomain the uterine cervix. She underwent a hysterectomy and postoperativeradiotherapy. External pelvic irradiation of 10 MV x-ray wascarried out in 15 fractions of 2 Gy daily, with a total doseof 30 Gy, and intracavitary radium insertion with a total doseof 960 mg hours (20 mg x 48 hours). She had been followed-upin our department since 1972, when rectal bleeding occurred.Proctoscopy and periodical biopsies were performed when thepatient visited our hospital. There was no evidence of malignanttumor cells nor of recurrent cervical cancer from 1973 to 1989.In August, 1990, a biopsy specimen taken from a rectal ulcerrevealed a malignant mucinous adenocarcinoma. The time intervalbetween the radiotherapy and the development of the rectal cancerwas 19 years. Microscopically, the main lesion was situatedin the granulation tissue covered with the regenerating mucosalepithelium, and histologically was found to be a mucinous adenocarcinoma.Other radiation damage was additionally found including colitis,endarteritis and intestinal wall fibrosis. The evidence stronglysuggested the present case to be one of radiation-induced rectalcancer.     

Utility of arterial infusion chemotherapy and radiation therapy for the pelvic local recurrence of rectal cancer

We treated 3 cases of local pelvic recurrence due to a rectal cancer post operation by arterial infusion chemotherapy with 5-FU and levofolinate calcium and also by radiation therapy. The result of imaging analysis showed that a recurrent tumor was decreased effectively in 2 cases by chemo-radiation therapy. We confirmed the cancer pain and tumor bleeding were gone for all of the 3 cases. As for side effects of arterial infusion chemotherapy and radiation therapy, we confirmed a paralysis of the pelvic nerve in 1 case and dermatopathy in 1 case. This therapy seemed to be an effective treatment for elderly patients with inoperable cases.     

Clinicopathological study on rectal cancer after sphincter-saving operation in conjunction with preoperative radiation therapy

In an attempt to clarify the effect of preoperative radiation on rectal cancer after sphincter-saving resection, radiation group (10 cases) and non-radiation group (22 cases) were studied clinicopathologically. A rate of local recurrence was 36.4% and 10.0% in radiation and non-radiation group, respectively. In cumulative 5-year-survival, non-radiation group showed 70.7%, however, all cases were alive in radiation group. Histological examination demonstrated that such factors predictive of local recurrence as depth of invasion a2, ew (distance between tumor invasion and surgical surface) less than 2 mm, have reduced in radiation group. As a result, it was shown that irradiation had an effect of lowering local recurrences even in cases with high risk factors of local recurrence prescribed above. On the contrary, AW (distance between tumor invasion and anal stump) and frequency of lymph node metastasis had no association with local recurrence, and have not changed favorably even after irradiation. It was also thought to be important to avoid radiation colitis as carefully as possible in radiation therapy for rectal cancer.     

Racial differences in prostate cancer related to loss of heterozygosity on chromosome 8p12-23

PURPOSE: There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with IBD and rectal cancer in order to determine the natural history of the disease as well as the effect and tolerance of pelvic irradiation. METHODS AND MATERIALS: A retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thirty-five patients had ulcerative colitis and 12 patients had Crohn's disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients, stage III in 13 patients, and stage IV in 9 patients. Surgical resection was performed in 44 patients. In two of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent postoperative adjuvant therapy (12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 patient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months). RESULTS: The 5-year actuarial results revealed an overall survival (OS) of 42%, a disease-free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5-year rate of 86% for patients with Tis-T2 disease compared to 10% for patients with T3-T4 disease (p < 0.0001). The presence of lymph node metastases also resulted in a decrease in DFS with a 5-year rate of 67% for patients with NO disease compared to 0% for patients with N1-N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grade with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respectively (p = 0.03). The T and N stages showed a statistically significant effect on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopathologic grade of the tumor did not significantly affect pelvic control. An analysis of high-risk patients (30) with T3-T4 or N1-N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26%, and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving RT (14 patients) with a 5-year PC of 60% compared to a rate of 23% for those patients not irradiated (16 patients). Acute complications (grade 3 or >) were noted in three patients (20%) receiving pelvic irradiation +/- chemotherapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastrointestinal toxicity. Two patients (13%) developed small bowel obstruction at 2 and 4 months, respectively, postirradiation which were managed conservatively. There were no long-term complications in patients irradiated. CONCLUSION: Treatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patients appeared to have a poorer outcome. In light of this finding and the ability of these patients to tolerate chemotherapy and pelvic irradiation, aggressive adjuvant therapy should be given to IBD-associated rectal cancer patients with high-risk features.     

Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline.

PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on colorectal cancer surveillance. RECOMMENDATIONS: Based on results from three independently reported meta-analyses of randomized controlled trials that compared low-intensity and high-intensity programs of colorectal cancer surveillance, and on recent analyses of data from major clinical trials in colon and rectal cancer, the Panel recommends annual computed tomography (CT) of the chest and abdomen for 3 years after primary therapy for patients who are at higher risk of recurrence and who could be candidates for curative-intent surgery; pelvic CT scan for rectal cancer surveillance, especially for patients with several poor prognostic factors, including those who have not been treated with radiation; colonoscopy at 3 years after operative treatment, and, if results are normal, every 5 years thereafter; flexible proctosigmoidoscopy [corrected] every 6 months for 5 years for rectal cancer patients who have not been treated with pelvic radiation; history and physical examination every 3 to 6 months for the first 3 years, every 6 months during years 4 and 5, and subsequently at the discretion of the physician; and carcinoembryonic antigen every 3 months postoperatively for at least 3 years after diagnosis, if the patient is a candidate for surgery or systemic therapy. Chest x-rays, CBCs, and liver function tests are not recommended, and molecular or cellular markers should not influence the surveillance strategy based on available evidence.     

根治术后盆腔复发直肠癌疗效及预后因素分析

目的 分析直肠癌根治术后盆腔复发规律以及放疗疗效和影响预后的因素.方法 回顾分析2000-2006年直肠癌根治术后盆腔复发接受放疗患者93例,分别为单纯放疗21例、放化疗56例、放疗结合手术和(或)化疗16例.放疗采用60Co或加速器X线,中位剂量59.4Gy,其中90例采用常规分割技术.68例患者放疗后接受了1～8个(中位数3个)疗程化疗,42例行同步放化疗,多为氟尿嘧啶为主的化疗方案.16例患者在放疗后接受了复发灶切除术,其中RO切除7例,姑息性肿块切除9例.结果 全组共132处复发,常见复发部位为直肠周围(31.8%)和骶前区(30.3%),髂外淋巴结和腹股沟淋巴结少见(1.5%和3.0%).总随访率为92%,随访满2、5年者分别为39、4例.有局部症状的84例患者中83%(70例)放疗后症状缓解.全组2、5年局部无进展率分别为49%、22%,2、5年生存率分别为46%、14%.多因素分析结果显示复发后治疗方法是影响直肠癌根治术后复发的局部无进展率的独立预后因素,复发灶最大径、无病间期、放疗后有无远处转移是影响直肠癌根治术后复发患者生存率的独立顶后因素.结论 直肠周围区、骶前区、髂内淋巴结区是直肠癌主要复发部位;放疗可明显改善直肠癌根治术后盆腔复发患者的症状和提高生存质量,放疗联合手术和(或)化疗可提高直肠癌根治术后复发的局部无进展率,复发灶直径＞5 cm、无病间期＜2年、放疗后有远处转移是影响预后的因素.     

Chemotherapy of gastric and rectal cancers incorporating non-radical irradiation during remission induction. 1

For the remission induction therapy of advanced gastric and rectal cancer, 25 cases were treated by non-radical irradiation (total doses: 3000-6000 rad) combined with tegafur, which minimized the tumor mass. For the reduction of tumor mass, a modified method of FAMT was employed and for the maintenance therapy of long-term chemotherapy a modified method of FAMT, MFE, MF or tegarfur alone were performed. Prolongation in survival was obtained with this combination therapy: Of 25 cases, 11 cases survived longer than one year and 6 cases longer then two years. One case of survived rectal cancer obtained disease-free for about 8 years with this treatment. But the observation period was too short to calculate one-year and two-year survival rates of all cases. The indications for application of this combination therapy were as follows; (1) Locally operable cases with myocardial infarct, heart insufficiency, poor risk or refusal of operation, (2) Very aged patients, (3) Locally inoperable cases without clinical metastasis, and (4) Primary lesion of gastric cancer with small metastasis controllable by tegafur. It was concluded that over 3000 rad of irradiation combined with tegafur was necessary to obtain the sufficient radiation effect. As for side effects, loss of appetite , leukopenia and a few case of gastric bleeding by radiation were noted. From the result this treatment modality appears to be valuable in the management of gastric and rectal cancer.     

Faut-il faire un curage ganglionnaire avant la radiothérapie d’un cancer prostatique localisé, et si oui lequel ?

Pelvic nodal irradiation has classically been recommended in all patients with a predicted lymph node invasion risk of 15% or greater. However, in view of the results of recent series of extended lymphadenectomy, this rule has been critically discussed. Moreover, the technological progress of radiotherapy has drastically decreased the risk of rectal and urinary injuries secondary to the pelvic irradiation. These two points have lead the teams who used to perform a staging lymphadectomy before radiation therapy in order to avoid a useless pelvic irradiation to the N0 patients, to question this attitude. The objective of this review is to discuss these points and to present the clinical situations in which a pelvic lymphadenectomy performed before the irradiation of a prostate cancer, either exclusive or associated to an androgen deprivation, keeps a potential benefit.     

Carcinoma of the large bowel after a single massive dose of radiation in healthy teenagers

Three healthy teenagers were exposed to a single pelvic x-ray irradiation as part of sterilization experiments performed in the Auschwitz concentration camp in 1943. Single and multiple carcinomas of the colon and rectum developed 40 years later in the radiation field. Histologic examination of surgical specimens revealed severe radiation-induced changes in all layers of tumor-adjacent areas. In contrast to previous reports of radiation-induced large bowel cancers, these women had not undergone repeated courses of radiation, had no known co-existing disease that might raise the risk for colonic and rectal malignancies, and had an extremely long and remarkably similar latency period. These cases emphasize the need for long-term surveillance in previously radiated patients. Since thousands of teenagers were subjected to similar sterilization experiments, awareness of this association might help in the early diagnosis of additional cases.     

Incontinence of urine and stool following treatment in infancy for embryonal rhabdomyosarcoma

A vaginal rhabdomyosarcoma which occurred in an 11-month-old infant was treated with conservative surgical excision, radiation therapy and chemotherapy. The long-term sequelae of this therapy included rectal stenosis, which required surgical correction, and urinary incontinence. The patient may have had fewer long-term complications if a more aggressive surgical procedure had been performed at the time of diagnosis because a gross and microscopically complete excision would have obviated the need of postoperative pelvic irradiation. Strong consideration of total surgical excision should be given to infants with pelvic rhabdomyosarcoma.     

Tamoxifen and malignant epithelial-nonepithelial tumours of the endometrium: report of six cases and review of the literature.

AIMS: To review the use of tamoxifen in malignant epithelial-nonepithelial tumours of the endometrium. Tamoxifen has been widely used for almost 20 years as adjuvant therapy for breast cancer. Large clinical trials have pointed out that long-term tamoxifen therapy increases the risk of uterine cancers. These tumours include endometrial carcinomas, stromal sarcomas, leiomyosarcomas as well as malignant mixed (epithelial-nonepithelial) tumours. METHODS: We report here six more cases of malignant epithelial-nonepithelial tumours which, in addition to those reported in the literature, makes a total of 36 presented cases. The pathogenesis of such tumours remains unclear, but it has been claimed that unopposed oestrogenic stimulation due to the agonistic effect of tamoxifen might be involved, as in the case of endometrial carcinomas. Pelvic irradiation has also been incriminated, especiallly in women under 55 years of age. RESULTS: Among 21 endometrial malignant epithelial-nonepithelial tumours associated with tamoxifen, seven occurred in women less than 55 years old. Five of them had previous pelvic irradiation. The data from the literature and from our series suggest that tamoxifen might favour the occurrence of malignant epithelial-nonepithelial tumours in women with breast cancer aged over 55 years, whereas in younger women both pelvic irradiation and tamoxifen might participate.     

Adjuvant radiation therapy for rectal cancer

Since 1976, 104 patients with rectal cancer have been treated with a new approach of combined pre- and postoperative radiation. All patients were given 500 rad preoperative irradiation on the day of or the day before surgery. Surgery in the majority of patients was an abdominal perineal resection. The disease was then staged pathologically according to Astler-Coller's modification of Duke's staging. Patients with early stage cancer (Stages A and B1) were followed with no further therapy. Patients with poor prognostic characteristics (Stages B2, C1, C2) were given postoperative pelvic irradiation (4500 rad in 5 weeks). Twenty-nine patients were found to have Stage A or B1 cancer and were followed with no further therapy. Of these 29 patients, 1 patient developed recurrence and one has died of metastatic disease. The excellent survival of patients with early tumors indicates that minimizing the role of adjuvant therapy in this group has not been detrimental to their survival. Fifteen were found to have liver metastases at laparotomy and had just a colostomy and palliative therapy. Sixty patients had Stage B2 and C disease. Thirty-one received postoperative irradiation as per protocol. Twenty-nine patients did not receive postoperative irradiation for a variety of reasons. Follow-up ranges from 1 to 7 years in these patients. Of the 29 patients with Stage B2 and C disease who should have but did not receive postoperative radiation, 10 patients (34%) have developed a recurrence in the pelvis, and 5 other patients (17%) have developed metastatic disease. Of 31 patients who received postoperative irradiation, only 2 patients (6%) developed a local recurrence and 4 patients (13%) have developed distant metastases. Survival at 3 years was 80% for patients receiving the combined treatment, as compared to 42% for those not receiving the postoperative part of the treatment protocol.     

A case of advanced rectal cancer responding to oral UFT and Leucovorin-based preoperative chemoradiation therapy

We report a case of a 44-year-old male with advanced lower rectal cancer that showed a significant effect after preoperative chemoradiation therapy. Preoperative radiation and chemotherapy included whole pelvis irradiation (30 Gy in total), oral UFT (500 mg/day), and Leucovorin (75 mg/day) was administered daily for 4 weeks. Consequently, the patient underwent a total pelvic exenteration with lymph node dissection (D 3). Histopathological findings showed: invasion to peritoneum(Ai); stage IIIa with n(-); and histological grading, Grade 2. Preoperative chemoradiation therapy appears to be effective for locally advanced lower rectal cancer.     

Rapid growth of microscopic rectal cancer as a determinant of response to preoperative radiation therapy

Purpose: To quantify the dose-time fractionation factors in preoperative radiation therapy for microscopic pelvic deposits of rectal cancer. This provides a biologic basis for understanding and improving the results of adjuvant therapies for this disease.

Methods: The reduction in incidence of pelvic relapses as a function of radiation dose and overall treatment time was determined from the literature. The displacement of dose-response curves to higher doses reflects the growth during radiation treatment of subclinical pelvic deposits which are beyond the future surgical margins.

Results: Dose-response curves are steep if the effect of overall duration of radiation therapy is accounted for. The time-related displacement of these steep dose-response curves is consistent with a median doubling time for malignant clonogenic cells of about 4 or 5 days, much faster than the growth rate of the average primary tumor at diagnosis. This rapid growth is evident within the first few days of irradiation, implying that the natural growth rate of these microscopic deposits if fast, and/or that an acceleration of growth follows initiation of radiation injury with a very short lag time.

Conclusion: Subclinical pelvic deposits of rectal cancer grow rapidly during preoperative radiation therapy with an adverse influence on the rate of pelvic tumor control from protracting the duration of adjuvant treatment. Low doses only offer clinically relevant reduction in risk of pelvic relapses if the overall radiation treatment time is short. For a given overall treatment duration there is a relatively steep dose-response curve, predicting that significant improvements in tumor control are possible.     

放射线敏感性调节信号通路在癌症治疗中的作用研究进展

越来越多的证据表明信号转导异常使得放射线诱导的DNA损伤受阻,从而削弱放射线治疗癌症临床效果甚至起相反作用。对这些异常信号通路进行干预或阻断,将能够极大地改善放射线治疗效果。因此,研究放射线治疗前后癌细胞内关键信号通路的转变,并寻找干预方法或手段,对了解放射敏感性机制、解决临床放射线治疗抵抗或开发新型治疗方案都具有重要意义和应用价值。本综述通过对近十年来p53等关键信号通路在放射线敏感性调节中的作用研究进展进行综述,以期对我国相关研究领域或临床治疗进展提供有益线索或理论指导。     

Can radiotherapy alone be effective for treating anastomotic recurrence of rectal cancer? When the patient decides?

Among pelvic recurrences of rectal cancer following surgical resection, anastomotic recurrences are relatively rare; the literature reports an incidence between 2.4% and 12% of all patients who underwent colorectal anastomosis. The authors report the case of a patient already treated for an early rectal cancer who 1 year after surgery developed a 2 cm recurrence at the colorectal anastomosis. As he refused reoperation, he underwent radiation therapy only (54 Gy) with complete remission. After 8 years of follow-up, the patient is free of any further distant or local recurrence. The authors did not find, to the best of their knowledge, in the literature any similar case of a patient with anastomotic rectal recurrence who has been positively treated by radiotherapy only. The authors focus on its diagnostic and therapeutic problems: although surgical reresection is undoubtedly the best therapeutic option, in the case reported here, radiotherapy alone proved effective.     

Analysis of treatment modalities and their failures in stage IB cancer of the cervix

This is a retrospective analysis of 240 patients who had clinical Stage IB cancer of the cervix treated with radiation between 1969 and 1980. Of these, 186 patients were treated with a combination of external and intracavitary radiation therapy, and 54 patients received adjuvant postoperative radiation therapy. The minimum follow-up was 5 years. In the group who received only radiation therapy, the overall recurrence in 170 patients (excluding 16 patients found at laparotomy to have unresectable disease) was 17% (29 of 170); pelvic recurrence was 9% and distant metastases alone was 6%. In the group who received the adjuvant postoperative radiation therapy, 16 patients had a simple hysterectomy followed by vaginal ovoid and/or external pelvic irradiation for an unexpected Stage IB cancer of the cervix. Their overall recurrence was 37.5% (6 of 16). Pelvic recurrence was the most common treatment failure with a recurrence of 31%. Significant prognostic factors were depth of stromal invasion and status of surgical margins. Thirty-eight patients had a radical hysterectomy followed by postoperative radiation therapy because of positive pelvic lymph nodes and/or close surgical margins. In patients with positive pelvic lymph nodes, the overall recurrence was 39% (9 of 23); pelvic recurrence was 13%. Distant metastases, the most common treatment failure, was 26%. In seven patients with close surgical margins, five recurred in the pelvis. There was no distant metastases without pelvic failure. Five of eight patients with close paracervical margins recurred in the pelvis. All five of these patients were treated with vaginal ovoid irradiation alone. Whole pelvic irradiation plus vaginal ovoid irradiation is necessary in those with close paracervical margins. The vaginal ovoid irradiation alone should be limited to very selected patients with positive vaginal margins only.     

A case of long-term survival by combined modality therapy for liver and pulmonary metastasis of rectal cancer

We report a case of rectal cancer diagnosed in 2001, which enforced a rectal low anterior resection. Then, metastatic liver cancer and metastatic lung cancer recurred and we enforced an operation for both. Furthermore, metastatic lung cancer recurred again and enforced chemotherapy with radiation and systemic chemotherapy for approximately seven years. The metastatic lung cancer was reduced now in 2011, so that the chemotherapy has not been used since then. In our case, we mainly performed a surgical and radiation therapy for a local recurrent site therapy in the first half because we did not have much choice for a systemic chemotherapy like we have now. In the later half, we mainly performed a systemic chemotherapy to control the local recurrent site. A treatment policy for colon cancer recommends a surgical treatment by the guidelines, or even though chemotherapy has been developed at present, if a local therapy is practical. There were many cases where metastases had occurred right after surgery so a local site therapy by excision was good at all unconditionally. However, as a result of our case in a local site therapy combined with whole body chemotherapy, we report here that a long- term survival was obtainable. We also include a brief literature review.     

Unique considerations in the patient with rectal cancer

In the past two decades, substantial progress has been made in the adjuvant management of colorectal cancer. Chemotherapy has improved overall survival in patients with node-positive (N+) disease. In contrast with colon cancer, which has a low incidence of local recurrence, patients with rectal cancer have a higher incidence requiring the addition of pelvic radiation therapy (chemoradiation). Patients with rectal cancer have a number of unique management considerations: for example, the role of short-course radiation, whether postoperative adjuvant chemotherapy is necessary for all patients, and if the type of surgery following chemoradiation should be based on the response rate. More accurate imaging techniques and/or molecular markers may help identify patients with positive pelvic nodes to reduce the chance of overtreatment with preoperative therapy. Will more effective systemic agents both improve the results of radiation as well as modify the need for pelvic radiation? This review will address these and other controversies specific to patients with rectal cancer.     

Long-term survival and patterns of failure after postoperative radiation therapy for subtotally resected rectal adenocarcinoma

Between 1977 and 1984, 17 patients received external beam irradiation after subtotal resection of rectal carcinoma. Ten patients had microscopic residual disease and 7 had gross residual disease. In the group with microscopic residual disease, 4 had tumor cut through with pathologically involved margins, 5 had adjacent unresected structures that were biopsy positive, and 1 had tumor spillage into the pelvis. The patients with gross residual disease were noted by the surgeon to have visible tumor after maximal debulking. Nine of 17 cases had involved pelvic lymph nodes. Radiation was administered to the pelvis with 4, 6, or 10 MV photons. Doses ranged from 40 to 60 Gy, with a median dose of 50 Gy given at 1.8 to 2.0 Gy per fraction, 5 days per week. Three patients received bacillus Calmette-Guérin (BCG), 2 received 5-fluorouracil (5-FU), and 1 received hycanthone. Thirteen of the 17 patients (76%) experienced local failure and, of these, 10 also developed distant disease. No patients developed distant metastasis in the absence of local failure. Local control was achieved in 3 of 10 patients (30%) with microscopic residual and 1 of 7 (14%) with gross residual. Four of the 17 patients (24%) have remained free of disease for greater than 5 years. External beam irradiation is capable of producing long-term survival and local control in a minority of patients with rectal cancer after subtotal resection. Investigation of more aggressive forms of therapy such as the addition of intraoperative irradiation, brachytherapy, radiation dose modifiers, and chemotherapy is warranted.