Treatment Of Recurrent Colorectal Cancer Research Articles

A case in which TAS-102 produced disease control without severe adverse events in a patient with recurrent colorectal cancer and dihydropyrimidine dehydrogenase deficiency

Fluoropyrimidine is commonly used to treat unresectable cases of metastatic colorectal cancer or as an adjuvant therapy for colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down >80% of standard doses of 5-fluorouracil (5-FU). Reductions in DPD activity increase the half-life of 5-FU, resulting in excess 5-FU accumulation and toxicity, which can lead to life-threatening side effects. There have been several published case reports about DPD deficiency in colorectal cancer patients from Western countries. However, case reports of DPD deficiency in Japanese colorectal cancer patients are rare because the measurement of DPD activity is not covered by the public medical insurance system in Japan, and DPD activity is not currently measured in daily clinical practice. Furthermore, there have not been any reports about anticancer drug therapy for Japanese patients with DPD deficiency. In this report, we describe a case in which a Japanese patient with colorectal cancer was diagnosed with DPD deficiency. The DPD deficiency arose as a severe adverse effect of mFOLFOX6/CapOX treatment for recurrent colorectal cancer, and the patient was subsequently treated with TAS-102, without experiencing any severe adverse effects. We report this case along with a review of the literature.

Surgical Treatment of Recurrent Colorectal Cancer: Short and Long Term Outcomes

Surgical Treatment of Recurrent Colorectal Cancer: Short and Long Term Outcomes

Surgical Treatment of Recurrent Colorectal Cancer: Short and Long Term Outcomes

Surgical Treatment of Recurrent Colorectal Cancer: Short and Long Term Outcomes

Premedication with fast-acting oxycodone hydrochloride hydrate effectively reduced oxaliplatin-induced severe vascular pain

Oxaliplatin is a platinum-based chemotherapeutic agent that holds a prominent position in the treatment of colorectal and gastric cancers. However, severe oxaliplatin-related vascular pain can be problematic for patients. Here we describe seven patients who experienced severe vascular pain caused by oxaliplatin administration. All seven patients were treated with capecitabine and oxaliplatin or capecitabine plus oxaliplatin with bevacizumab as an adjuvant or a treatment for recurrent colorectal cancer, respectively. Patients experienced intolerable vascular pain during oxaliplatin administration, which continued for several days. Moreover, vascular pain also induced insomnia and appetite loss in all patients. We recommended implantation of a central venous (CV) port to the patients; however, all patients declined this treatment. In addition, various known countermeasures were taken, but were ineffective. Therefore, patients were orally administered oxycodone hydrochloride hydrate (Oxinorm®) 45min prior to oxaliplatin administration. This pretreatment successfully reduced vascular pain and improved subsequent chemotherapy. Oxinorm® is a fast-acting opioid that can be an effective and practical option for severe vascular pain induced by oxaliplatin. The present report is the first description that emphasizes the usefulness of Oxinorm® to overcome the vascular pain induced by administration of oxaliplatin via a peripheral vein.

The possibilities of treatment of recurrent colorectal cancer with sacral invasion

To describe current methods of surgical treatment of rare form of recurrent rectal cancer with sacral invasion. The article presents the methodology for the treatment of patients with recurrent colorectal cancer and sacral invasion using preoperative chemoradiotherapy followed by high-tech surgery of recurrent tumor removal with sacral resection at various levels (including high intersection at S1 level). It was concluded that chemoradiotherapy is indicated in patients with recurrent colorectal cancer if it was not made at the first stage of treatment. Additional radiotherapy up to optimum overall focal dose prior to surgery is advisable in those patients who previously underwent radiotherapy with partial dose. This type of operations has high risk of complications and requires a personalized approach to the selection of patients. However, R0-resection is associated with favorable long-term prognosis, significantly increased survival and overall quality of life. Combined surgery for recurrent tumors with sacral invasion should be performed by multidisciplinary surgical team in specialized centers using current possibilities of anesthesiology and intensive care.

Intraoperative radiotherapy with low energy photons in recurrent colorectal cancer: a single centre retrospective study.

Aim of the studyIntraoperative radiotherapy (IORT) may improve outcome of surgical treatment of recurrent colorectal cancer (CRC). The aim of this study is to determine the feasibility, safety and long-term results of surgical treatment of recurrent CRC with orthovolt IORT.Material and methodsFifty-nine consecutive CRC patients with local recurrence (LR), undergoing surgery, were included in the retrospective analysis of prospectively collected data. The modified Wanebo classification was used to stage LR (Tr). Twenty-five (43%) patients received IORT using INTRABEAM® PRS 500. The complications were classified according to the Clavien-Dindo classification.ResultsThere were 32 males and 27 females, with a median age of 63 years. Multi-visceral resections were performed in 37 (63%) patients. Median hospitalization time after surgery with IORT was 7 days. One (1.7%) in-hospital postoperative death was reported. Grade 3/4 postoperative complications were found in 11 (19%) patients. Intraoperative radiotherapy had no effect on the postoperative hospitalization time, morbidity and mortality. Median survival after R0 resection was 32 months. Complete resection (R0), no synchronous liver metastases (M0), and no lateral and posterior pelvic wall involvement, were significant predictors of improved survival. Stage of LR was found to be an independent prognostic factor in the multivariate analysis (p = 0.03); Cox regression model). In patients with LR stage < Tr5, a 3-year overall survival (OS) rate was 52%.ConclusionsCombination of surgical resection and orthovolt IORT is a safe and feasible procedure that does not increase the risk of postoperative complications or prolongs the hospital stay. Despite aggressive surgery supported by IORT, the advanced stage of LR is a limiting factor of long-term survival.

Microwave ablation as palliative treatment of locally recurrent colorectal cancer.

Patients suffering local recurrence of colorectal cancer which cannot be surgically removed are troubled with severe pain and poor quality of life. The aim of this study is to evaluate the efficacy and safety of computed tomography (CT)-guided microwave ablation (MWA) as palliative treatment for recurrent unresectable colorectal cancer. Thirty-one patients were suffering locally recurrent colorectal cancer underwent MWA with CT guidance. The MWA power was set at 60-80 W, 6-8 min. Effectiveness was evaluated by visual analog scale (VAS) with a follow-up of 6-month. Complications were also recorded. Technical success was achieved in all patients. Mean VAS preprocedure was 7.10. Mean VAS postprocedure were as follows: 1 week, 2.65 (P < 0.001); 1 month, 0.81 (P < 0.001); 3 months 0.45 (P < 0.001); and 6 months 0.19 (P < 0.001). No serious complications were observed including intestinal fistulas, bladder fistulas, or peripheral vascular or nerve injury. CT-guided MWA as treatment of recurrent colorectal cancer can quickly and effectively relieve pain. It is a minimally invasive, safe, and efficient palliative treatment of recurrent colorectal cancer.

P2-33-2 - Successful Multimodal Treatment of Multiple Metastatic Rectal Cancer in an Elderly Patient with Chronic Renal Failure

A 75-year-old man, having history of angina pectoris and chronic renal failure (CKD stage4), was admitted due to melena. Colonoscopy revealed advanced rectal cancer and Miles operation was performed (pApN1M0, stageIIIa). Postoperative adjuvant chemotherapy using S-1 was introduced but was canceled because of nausea and general malaise. One year after the surgery, he revealed to have multiple lung and liver metastases detected by follow-up CT. Considering severe renal failure, he started 75% dose of FOLFOX6 therapy and a total of 13 courses had completed without severe adverse events. The status of lung lesions was PR (almost disappeared except for one lesion), but two liver lesions remained NC status. Subsequently, he underwent laparoscopic partial liver resection 21 months after the initial surgery. Despite of continuation of 75% dose FOLFOX6 therapy postoperatively, the remnant lung lesion became PD 33 months after the initial surgery, and he underwent radiation therapy (50Gy/25Fr). Soon after the radiation therapy, relapse of multiple lung metastases occurred. Since FOLFOX therapy was canceled due to peripheral neuropathy, he started half dose of oral uracil-tegafur and leucovorin therapy, maintaining the SD tumor status for 19 months, but finally discontinued the therapy due to drug eruption. Instead, bevacizumab and irinotecan therapy was administered every 3 weeks and SD status was maintained for additional 21 months until now. The patient is currently 80 years of age, 5 years after the initial surgery, and has maintained excellent performance status with good disease control.Standardization of chemotherapy or other therapeutic modalities has not been established for the treatment of recurrent colorectal cancer in elderly patients with chronic renal failure. We discussed efficacy of multidisciplinary treatment for such high risk colorectal cancer patients with the review of the literature.

Tumornachsorge nach potentiell kurativerResektion eines Karzinoms

Surveillance programs have been recommended for colorectal and breast cancer patients in several countries, and appropriate surveillance guidelines have been issued by various societies. The Swiss Society of Gastroenterology consensus paper recommends a surveillance program for patients after curative resection of colorectal cancer (CRC), and the respective guidelines are updated regularly. Early detection of recurrent disease from CRC allows treatment with intention to cure. Five year survival rates after treatment for recurrent CRC can reach up to 50 % or more. Therefore tumor surveillance in CRC is important, and there is compelling evidence that patients benefit from intensive surveillance. In addition to clinical controls, measurements of carcinoembryonal antigen, colonoscopies and thoraco-abdominal CT scans should be performed on a regular basis. For surveillance of breast cancer (BC) patients, a regular schedule is recommended as well. However, this surveillance program is more focussing on the detection of possible loco-regional tumor relapse, as curative therapy of BC metastases is much less frequently possible than in CRC patients. Irrespective of the underlying tumor entity, surveillance is an important and challenging process that should be coordinated by one single physician. It is crucial that all involved physicians are aware of their responsibility and that they are informed about the respective surveillance program and its benefit to the patient.

Role of Repeated Hepatectomy in the Multimodal Treatment of Hepatic Colorectal Metastases

Multimodal treatment consisting of repeated hepatectomy and adjuvant systemic chemotherapy for liver-confined recurrence of colorectal cancer can yield long-term survival comparable with that associated with primary hepatectomy. Retrospective analysis. A prospective database at a tertiary referral cancer center. Review of 274 consecutive liver resections identified 64 patients who underwent resection of hepatic colorectal metastases without ablation followed by adjuvant irinotecan hydrochloride- or oxaliplatin-based systemic chemotherapy. Median and 5-year overall and disease-free survival after primary and repeated hepatectomy. At median follow-up of 40 months, median and 5-year overall survival after hepatectomy were 60 months and 53%, respectively; median and 5-year disease-free survival were 33 months and 25%, respectively. Multivariate analysis showed that less than 1 year between colectomy and liver resection (P = .001), more than 3 metastases (P = .001), no repeated hepatectomy (P = .01), and lymph node-positive primary colon cancer (P = .02) were independently predictive of worse survival. Of 28 patients (44%) with liver-confined recurrence, 19 (30%) underwent repeated hepatectomy; at median follow-up of 38 months, median and 5-year overall survival after repeated hepatectomy were 48 months and 44%, respectively. No risk factors were identified in multivariate analysis. In patients with recurrence, median and 5-year overall survival measured from primary hepatectomy were 70 months and 73%, respectively, with repeated hepatectomy vs 43 months and 43%, respectively, without repeated hepatectomy (P = .03). Multimodal treatment of recurrent colorectal cancer confined to the liver should begin with consideration of repeated hepatectomy.

Feasibility and Early Results of Interstitial Intensity-Modulated HDR/PDR Brachytherapy (IMBT) with/without Complementary External-Beam Radiotherapy and Extended Surgery in Recurrent Pelvic Colorectal Cancer

A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.

Decision-making: What Tests To Do? What Choices To Consider?

The treatment of recurrent colorectal cancer confronts the surgeon with a diagnostic and therapeutic challenge, particularly in cases involving the pelvis. Investigation and treatment in each case is tailored to the individual patient. Treatment is divided into those cases where an attempt at cure is possible and those where only palliation of symptoms is possible. This article seeks to help the surgeon confronted with this problem answer the following questions: Which patients with recurrent colorectal cancer are suitable for consideration of curative resection? What is the extent of disease recurrence? Is the disease resectable? The aim of this article is to offer advice in the logical and appropriate investigation and treatment of patients considered for curative or palliative therapy.

Assessment of biomarkers in paired primary and recurrent colorectal adenocarcinomas

Purpose: Recurrent colorectal cancers respond poorly to anticancer treatment including radiotherapy. To better understand the biological characteristics of the recurrent colorectal tumor, we investigated various biomarkers regulating cell proliferation and cell loss in paired primary and recurrent colorectal tumor specimens within each individual. Methods and Materials: From a total of 11 colorectal adenocarcinoma patients, 22 specimens of paired primary and recurrent tumors were obtained for analysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragmentation. Other biomarkers including proliferating cell nuclear antigen (PCNA), p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistochemical stains. Results: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 recurrent tumors compared to primary tumors. Median PCNAI in primary and recurrent tumors were 33.5 and 48.3, respectively ( p = 0.16). In contrast, the apoptotic index (AI) decreased in 9 of 11 recurrent tumors compared to primary tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurrent tumors ( p = 0.04). The p53 expression increased in more than half of recurrent tumors compared to primary tumors. Mean staining score increased from 0.7 in primary tumors to 1.2 in recurrent tumors ( p = 0.059). WAF1 and cyclin B1 did not show significant change. In contrast, both cyclin D1 and p34cdc2 increased significantly in recurrent tumors. These two biomarkers showed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors, respectively, compared to their primary counterparts. Mean staining scores of both biomarkers in recurrent tumors increased by more than twofold compared to those in primary tumors and these differences were statistically significant (cyclin D1, p = 0.007; p34cdc2, p = 0.008). Conclusion: This study showed significantly decreased apoptosis in recurrent colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further study, it may be used for developing a new therapeutic strategy for the treatment of recurrent colorectal cancer.

Assessment of biomarkers in paired primary and recurrent colorectal adenocarcinomas

Purpose: Recurrent colorectal cancers respond poorly to anticancer treatment including radiotherapy. To better understand the biological characteristics of the recurrent colorectal tumor, we investigated various biomarkers regulating cell proliferation and cell loss in paired primary and recurrent colorectal tumor specimens within each individual. Methods and Materials: From a total of 11 colorectal adenocarcinoma patients, 22 specimens of paired primary and recurrent tumors were obtained for analysis. Apoptosis was evaluated by TUNEL labeling of apoptotic DNA fragmentation. Other biomarkers including proliferating cell nuclear antigen (PCNA), p53, WAF1, p34cdc2, and cyclins B1 and D1 were analyzed by immunohistochemical stains. Results: PCNA index (PCNAI) showed an increase in 6 and a decrease in 5 recurrent tumors compared to primary tumors. Median PCNAI in primary and recurrent tumors were 33.5 and 48.3, respectively (p 5 0.16). In contrast, the apoptotic index (AI) decreased in 9 of 11 recurrent tumors compared to primary tumors. Median AI decreased from 4.3 in primary tumors to 1.4 in recurrent tumors (p 5 0.04). The p53 expression increased in more than half of recurrent tumors compared to primary tumors. Mean staining score increased from 0.7 in primary tumors to 1.2 in recurrent tumors (p 5 0.059). WAF1 and cyclin B1 did not show significant change. In contrast, both cyclin D1 and p34cdc2 increased significantly in recurrent tumors. These two biomarkers showed increased expression in 8 (cyclin D1) and 7 (p34cdc2) recurrent tumors, respectively, compared to their primary counterparts. Mean staining scores of both biomarkers in recurrent tumors increased by more than twofold compared to those in primary tumors and these differences were statistically significant (cyclin D1, p 5 0.007; p34cdc2, p 5 0.008). Conclusion: This study showed significantly decreased apoptosis in recurrent colorectal tumors compared to their primary counterparts. The underlying regulatory mechanisms included increased expression of p53 and altered cell cycle regulators such as increased cyclin D1 and p34cdc2. With further study, it may be used for developing a new therapeutic strategy for the treatment of recurrent colorectal cancer. © 1999 Elsevier Science Inc.

Second-look operation for recurrent colorectal cancer based on carcinoembryonic antigen and imaging techniques.

The usefulness of postoperative carcinoembryonic antigen (CEA) monitoring and improvements in imaging techniques have renewed enthusiasm for second-look operations (SLO) as the most effective treatment for recurrent colorectal cancer by reresection following early detection. The aim of our study is to evaluate the role of CEA and imaging techniques-directed SLO. Seven hundred fifty-six patients with Dukes Stages B and C, who had undergone curative resection, were monitored postoperatively using CEA and imaging techniques. An SLO was performed on any potentially resectable recurrence, and in addition, an SLO was done when a persistently rising CEA value was detected. Recurrence developed in 18.8 percent (142/756) of patients, and 90.8 percent (129/142) of the recurrences were detected within the first three years following curative resection. When comparing carcinomas of the colon with that of the rectum, the former were associated with significantly more hepatic and intraabdominal recurrences, whereas the latter had significantly more locoregional and pulmonary recurrences. Seventy-two patients underwent SLO. Of these patients, 54.2 percent (39/72) had all of their disease resected, and 1.4 percent (1/72) had no detectable disease at the SLO. Among the 142 patients with recurrence, 71 (50 percent) patients underwent SLO. The resectable group at SLO carried a significantly better survival than the unresectable recurrence group (41.3 vs. 5.2 percent; P<0.01). Complete removal of colorectal cancer recurrences by SLO, on the basis of postoperative, follow-up CEA and imaging technique findings, results in improved survival.

Surgical treatment of recurrent colorectal cancer. Five-year follow-up.

Analysis of 81 consecutive patients with recurrent colorectal cancer was undertaken to evaluate the rationale and efficacy of surgical re-treatment. The disease-free interval after primary surgery and the diagnostic delay did not clearly differ between the modes of recurrences. Symptoms preceded the diagnosis of recurrence in 73% (59) of the cases, with pain being the most frequent symptom (n = 22). Of the patients, 58% (47) underwent reoperations, 38% (31) underwent reresections, and 10% (8) underwent radical resections. The overall postoperative mortality was 13%, and the postoperative morbidity was 45%. The postoperative relief of cancer symptoms after resective surgery was 8 months and, after nonresective surgery, 2 months. The median survival was 24 months for patients who underwent resections, 8 months for patients who were treated by nonresective surgery, and 15 months for patients who were treated conservatively. Radical resection clearly prolonged survival when compared with palliative resections and nonresective procedures. On the basis of these results, it was concluded that resective surgery, when possible, can improve survival and patient comfort after recurrence of colorectal cancer.

Diagnosis and Treatment of Recurrent Colorectal Cancer

In recurrent cancer of the large intestine, hepatectomy for localized liver metastasis and extensive total pelvic exenteration for pelvic local recurrence are often beneficial and prolongation of life can be achieved. Histological venous invasion of original tumor (v-factor) is an important parameter in the prediction of liver metastasis, and nuclear magnetic resonance (NMR) is useful for detecting liver metastases and determining the extent of local invasion. Early diagnosis and aggressive treatment of recurrent and metastatic cancer are as important as early and curative resection of initial malignant lesions. Oral administration of biological response modifier (BRM) and adjuvant adoptive immunotherapy after hepatectomy are considered to be promising approaches for the prevention of recurrence.

Comparison of Histologic and Colposcopic Findings in Des-Exposed Females

The complete autopsies of 145 patients dying of colorectal cancer are reviewed. Isolated local or distant metastases are infrequent, compared to disseminated disease. Solitary local recurrences are most common after resection of rectal tumors. Right colon tumors spread to local and distant sites in 90% of autopsies, and to distant sites alone in 10%. Rectal tumors spread locally only in 25% of cases, to distant site alone in 25%, and to both in 50%. Regardless of the origin of the primary tumor, the liver is the most common site of metastasis, followed by the regional lymph nodes and the lungs. Two-thirds of the patients with right colon lesions died of liver metastases, and three-quarters of those with rectal tumors succumbed to disseminated disease. The current curative and palliative treatment of recurrent colorectal cancer in clinical medicine by surgery, radiotherapy, and chemotherapy is reviewed. It is suggested that an understanding of the anatomic patterns of cancer recurrence will increase in importance as advances in the modalities of treatment are made,