Local Recurrence Of Rectal Cancer Research Articles

Association of PTEN loss and local recurrence in stage II-III colon cancer.

399 Background: Activation of the PI3K/Akt signaling pathway by PIK3CA mutations has been associated with increased risk for local recurrence (LR) in rectal cancer patients (pts). We hypothesized that loss of expression of PTEN, a tumor suppressor gene and negative regulator of the PI3K/Akt pathway, may also be associated with increased rates of LR in colon cancer. Methods: We studied 156 pts with stage II-III colon cancer resected from 1/1990 to 12/2002, including pathology review, PTEN immunohistochemistry, microsatellite instability (MSI) status, 18q loss of heterozygosity (LOH) status and clinical follow-up. PTEN expression with a CLIA-compliant protocol (DAKO antibody) was determined in a tissue microarray with four cores from each tumor and with non-neoplastic mucosa. PTEN loss was defined as complete absence of expression in malignant epithelium with preserved expression of adjoining non-neoplastic tissue serving as a positive control. LR was defined as anastomotic or pericolic peritoneal disease. Results: 83 M and 73 F pts with median age of 63 were included, with median follow-up of 7.6 yrs. PTEN loss was identified in 26 (16.7%) pts. There were no significant differences in age, sex, T stage, N stage, tumor differentiation, tumor site, lymphovascular invasion (LVI), mucinous component, MSI status or 18q LOH between the PTEN-lost and PTEN-intact groups. The overall survival, relapse-free survival, and distant metastases rate were similar. However, PTEN loss was associated with higher rates of LR (15.4% vs. 4.6%, p = 0.041), and the time to LR was shorter for pts with PTEN loss in their tumor than in PTEN-intact pts (HR 3.3, p = 0.049 by log-rank). LR was associated with LVI, R-sided tumor, 18qLOH, and PTEN loss in univariate analysis. In a multivariate analysis, PTEN loss was associated with a 10.6 fold increased risk of LR (95% CI: 1.7-64.8, p = 0.011). Conclusions: PTEN loss is associated with a higher rate of and shorter time to LR after resection of colon cancer. This result is consistent with a prior report on the role of PI3K pathway in LR of rectal cancer and suggests that PTEN alteration is a prognostic indicator and that the PI3K/Akt pathway is a potential therapeutic target for these pts. No significant financial relationships to disclose.

Pathology Studies of Combined Radical Resection of Seminal Vesicle in the Treatment of Rectal Cancer

To inhibit local recurrence of rectal cancer, it is very important to ensure that there is a sufficient circumferential resection margin. We evaluated pathology studies of combined radical resection of seminal vesicles in the treatment of rectal cancer. We analyzed data from 7 cases of combined radical resection of the seminal vesicle in the treatment of rectal cancer; we also analyzed data from 35 control cases without seminal vesicle resection. The circumferential resection margin averaged 5.97 mm for cases that had combined radical resection of the seminal vesicle, and this was significantly longer than for cases without resection (P < 0.001). Local recurrence was not seen in cases that had combined radical resection of the seminal vesicle, whereas 3 cases (5.9%) occurred in the group that did not undergo resection. Combined radical resection of the seminal vesicle in patients with rectal cancer ensures that the distance of the circumferential resection margin is sufficient to inhibit local recurrence.

Patterns of local recurrence in rectal cancer after a multidisciplinary approach

Improvements in surgery and the application of combined approaches to fight rectal cancer have succeeded in reducing the local recurrence (LR) rate and when there is LR it tends to appear later and less often in isolation. Moreover, a subtle change in the distribution of LRs with respect to the pelvis has been observed. In general terms, prior to total mesorectal excision the most common LRs were central types (perianastomotic and anterior) while lateral and posterior forms (presacral) have become more common since the growth in the use of combined treatments. No differences have been reported in the current pattern of LRs as a function of the type of approach used, that is, neo-adjuvant therapies (short-term or long-course radiotherapy, or chemoradiotherapy versus extended lymphadenectomy, though there is a trend towards posterior or presacral LR in patients in the Western world and lateral LR in Asia. Nevertheless, both may arise from the same mechanism. Moreover, as well as the mode of treatment, the type of LR is related to the height of the initial tumor. Nowadays most LRs are related to the advanced nature of the disease. Involvement of the circumferential radial margin and spillage of residual tumor cells from lymphatic leakage in the pelvic side wall are two plausible mechanisms for the genesis of LR. The patterns of pelvic recurrence itself (pelvic subsites) also have important implications for prognosis and are related to the potential success of salvage curative approach. The re-operability for cure and prognosis are generally better for anastomotic and anterior types than for presacral and lateral recurrences. Overall survival after LR diagnosis is lower with radio or chemoradiotherapy plus optimal surgery approaches, compared to optimal surgery alone.

Prognostic Value of Quality of Life and Pain in Patients with Locally Recurrent Rectal Cancer

Care of patients with locally recurrent rectal cancer (LRRC) requires careful patient selection. While curative resection offers survival benefits, significant trade-offs exist for the patient. Knowledge of patient-reported outcomes will help inform treatment decisions. Quality of life (QOL) and pain were prospectively assessed in 105 patients treated for LRRC at a single institution, using the validated Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Brief Pain Inventory (BPI) questionnaires. In 54 patients enrolled and followed from diagnosis of LRRC, relationship between pretreatment pain, QOL, and overall survival (OS) were examined. Patients underwent curative surgical resection (C, 59%), noncurative surgery (NC, 12%) or nonsurgical treatment (NS, 28%). Median OS was 7.1, 1.4, and 1.9years, respectively (C versus NC: p<0.001; C versus NS: p=0.006; NC versus NS: p=0.261). Physical well-being QOL differed over time (p=0.042), with greatest difference between C and NC surgery patients (p=0.049). The remaining QOL domain scores and pain scores demonstrated no significant time or treatment effect. For the 54 patients assessed from diagnosis, median OS was independently predicted by treatment group (C, NC, NS: 4.3, 1.7, versus 2.4years; p<0.001) and pretreatment pain intensity (score≤4 versus>4: 3.8 versus 2.0years; p=0.001). Curative surgery offered prolonged survival, but significant pain exists among long-term survivors and should be a focus of survivorship care. Noncurative surgery did not offer apparent advantages over nonsurgical palliation. Patient's pretreatment pain has prognostic value, and should be assessed, treated, and considered in treatment decisions.

Postoperative Follow-Up of Rectal Cancer and Biopsy Techniques

Local recurrence of rectal cancer after treatment is a significant problem despite recent advances in surgery and adjuvant therapy. Appropriate follow-up is a cornerstone of early detection of local recurrence in hopes of timely treatment. Endorectal ultrasound is a readily available technique that can be performed in the outpatient's setting during regular follow-up and allows the detection of early and asymptomatic local recurrences. Endorectal ultrasound can also be used to obtain tissue diagnosis on the lesion in question. Other imaging modalities, including magnetic resonance imaging and positron emission tomography scanning, have been shown to be beneficial in both preoperative as well as postoperative settings. Although additional research is needed, successful detection of early recurrences most likely lies in close follow-up and combination of various imaging techniques.

Clinicopathological Assessment of Locally Recurrent Rectal Cancer and Relation to Local Re-Recurrence

Local re-recurrence after R0 resection of local recurrence of rectal cancer (LRRC) is not rare. The purpose of this study was to examine the pathological features of LRRC and determine the prognostic factors. Twenty-one patients underwent R0 resection of LRRC without preoperative therapy from 2000 to 2008. Tumor progression patterns were classified into three types: A, expanding type; B, infiltrating type; and C, intermediate type. Distant isolated cancer cells (DICCs) were defined as cancer cells present in isolation and at a distance (>1mm) from the tumor edge. Venous invasion was identified in all but one patient (95%). DICCs were observed in 11 of 21 cases. Type A patients had a significantly lower local re-recurrence rate (0/5) compared with type B and/or C patients (11/16, P=0.012) and a significantly lower incidence of distant metastasis compared with type B and C patients (0/5 vs. 13/16, respectively; P=0.0028). Multivariate regression analysis identified venous invasion of the primary lesion (P=0.027) and tumor progression patterns (P=0.039) as independent predictors of local re-recurrence. The main features of LRRC were infiltrating growth, venous invasion, and DICCs. Tumor progression patterns correlated with local re-recurrence and distant metastasis. Preoperative adjuvant therapy to terminate peri-tumor cancer cells may be required for better tumor control.

A Case of Local Recurrence of Rectal Cancer

A Case of Local Recurrence of Rectal Cancer

Cost‐effectiveness of carbon ion radiation therapy for locally recurrent rectal cancer

The aim of this study was to evaluate the cost-effectiveness of carbon ion radiotherapy compared with conventional multimodality therapy in the treatment of patients with locally recurrent rectal cancer. Direct costs for diagnosis, recurrent treatment, follow-up, visits, supportive therapy, complications, and admission were computed for each individual using a sample of 25 patients presenting with local recurrent rectal cancer at the National Institute of Radiological Science (NIRS) and Gunma University Hospital (GUH). Patients received only radical surgery for primary rectal adenocarcinoma and had isolated unresectable pelvic recurrence. Fourteen and 11 patients receiving treatment for the local recurrence between 2003 and 2005 were followed retrospectively at NIRS and GUH, respectively. Treatment was carried out with carbon ion radiotherapy (CIRT) alone at NIRS, while multimodality therapy including three-dimensional conformal radiotherapy, chemotherapy, and hyperthermia was performed at GUH. The 2-year overall survival rate was 85% and 55% for CIRT and multimodality treatment, respectively. The mean cost was yen4 803 946 for the CIRT group and yen4 611 100 for the multimodality treatment group. The incremental cost-effectiveness ratio for CIRT was yen6428 per 1% increase in survival. The median duration of total hospitalization was 37 days for CIRT and 66 days for the multimodality treatment group. In conclusion, by calculating all direct costs, CIRT was found to be a potential cost effective treatment modality as compared to multimodality treatment for locally recurrent rectal cancer.

Origin of presacral local recurrence after rectal cancer treatment

The objective of this study was to obtain detailed anatomical information about the lateral lymph nodes, in order to determine whether they might play a role in presacral local recurrence of rectal cancer after total mesorectal excision without lateral lymph node dissection. Ten serially sectioned human fetal pelvises were studied at high magnification and a three-dimensional reconstruction of the fetal pelvis was made. Examination of the histological sections and the three-dimensional reconstruction showed that lateral lymph node tissue comprises a major proportion of the pelvic tissue volume. There were no lymph nodes located in the presacral area. Connections between the mesorectal and extramesorectal lymph node system were found in all fetal pelvises, located below the peritoneal reflection on the anterolateral side of the fetal rectum. At this site middle rectal vessels passed to and from the mesorectum, and branches of the autonomic nervous system bridge to innervate the rectal wall. The findings of this study support the hypothesis that tumour recurrence might arise from lateral lymph nodes.

Contrast-enhanced MRI and PET-CT in the evaluation of patients with suspected local recurrence of rectal carcinoma

This study aimed to evaluate the role of contrast-enhanced magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) in the assessment of local recurrence of rectal cancer. Among 200 patients scheduled for CT follow-up, 60 (48 low risk; 12 high risk) were selected due to CT findings suspicious for or suggestive of local recurrence. Patients underwent contrast-enhanced MRI and PET-CT within 2 weeks. Biopsy was considered the gold standard in 39 cases and follow-up at 6 and 12 months in the remaining 21. Local recurrence was confirmed by histology in 15 cases (7 low risk; 8 high risk) and was excluded in 21 cases by long-term follow-up and in 24 by histology. Sensitivity, specificity, positive and negative predictive value and accuracy were 86.7%, 68.9%, 48.1%, 93.9% and 73.3% for contrast-enhanced MRI and 93.3%, 68.9%, 50%, 96.9% and 75% for PET-CT. Contrast-enhanced MRI and PET-CT can help in the detection of local recurrence of rectal cancer, even though their roles in early detection remains debatable, as the value of these techniques in current surveillance protocols is still to be defined.

Multimodal salvage therapy for locally recurrent and re-recurrent rectal cancer.

3647 Background: Radical salvage surgery offers the only chance of potential cure for locally recurrent rectal cancer (LRRC). We examined predictors of outcome after multimodality salvage for LRRC and determined outcomes after secondary failure. Methods: A retrospective consecutive cohort study of patients (pts) undergoing surgical salvage for LRRC between 1988 and 2008 was conducted. Only pts who underwent radical resection for their primary rectal tumors were included. Cox regression analysis was performed to evaluate survival outcomes. Results: A total of 171 pts were identified. Median age was 59 years (interquartile range [IQR] 47-67); 97 pts (57%) were male. Salvage for LRRC required repeat rectal resection in 80 (47%), exenteration in 63 (37%), and radical pelvic tumor excision in 28 (16%) pts. Bone resection was needed in 50 (29%). The rate of R0 resection was 79%. Radiation was used in 109 (67%) prior to salvage, including 43 (47%) who had received prior pelvic radiation. Intraoperative radiotherapy was given to 57 (33%) and postoperative chemotherapy, to 48 (28%). At 5 years, overall survival (OS) was 42% and recurrence-free survival was 30%. Secondary failure occurred in 94 (55%) after a median interval of 11 months from salvage operation. The site of first failure was local only in 44 (25%), distant only in 33 (19%), both in 5 (3%). Second operative salvage was undertaken in 26 (28%) pts, including repeat pelvic resection in 21 (81%). Other treatments included chemotherapy, reirradiation, and brachytherapy. The 5-year OS with secondary failure was 37% (vs. 50% without failure; p = 0.036), but pts who underwent repeat salvage operation had significantly higher OS than those who did not: 46 vs. 33% (p = 0.049). In multivariate analysis, independent predictors of improved OS included: R0 resection margin status (p = 0.01) and recovery of lymph nodes during salvage surgery (p = 0.027). Conclusions: Prolonged survival and local control can be achieved by multimodality salvage therapy for LRRC. Repeat salvage after secondary failure is appropriate in select patients. Finding residual lymph nodes at salvage operation may suggest incomplete mesorectal resection at primary rectal cancer resection which correlated with improved salvageability. No significant financial relationships to disclose.

Radical resection with total mesentery excision (TME) for the treatment of rectal cancer: a clinical analysis of 67 cases

Objective To discuss the clinical effect and the application value of total mesentery excision to the rectal cancerous patients. Methods The clinical data of 67 rectal cancerous patients who received the radical resection which following the TME principle,and with a 2 ～3 years follow-up were analyzed. Results All the 67 patients received the radical resection,including 1 anastomotic fistula,3 anastomotic stenosis, neither local recurrence nor distant metastasis. Conclusion TME played an important role in preventing the local recurrence of rectal cancer, and it met the standards of surgical treatment of rectal cancer better. Key words: Rectal neoplasms; Proctocolectomy, restorative

Focal dose escalation using FDG-PET-guided intensity-modulated radiation therapy boost for postoperative local recurrent rectal cancer: a planning study with comparison of DVH and NTCP

BackgroundTo evaluate the safety of focal dose escalation to regions with standardized uptake value (SUV) >2.0 using intensity-modulated radiation therapy (IMRT) by comparison of radiotherapy plans using dose-volume histograms (DVHs) and normal tissue complication probability (NTCP) for postoperative local recurrent rectal cancerMethodsFirst, we performed conventional radiotherapy with 40 Gy/20 fr. (CRT 40 Gy) for 12 patients with postoperative local recurrent rectal cancer, and then we performed FDG-PET/CT radiotherapy planning for those patients. We defined the regions with SUV > 2.0 as biological target volume (BTV) and made three boost plans for each patient: 1) CRT boost plan, 2) IMRT without dose-painting boost plan, and 3) IMRT with dose-painting boost plan. The total boost dose was 20 Gy. In IMRT with dose-painting boost plan, we increased the dose for BTV+5 mm by 30% of the prescribed dose. We added CRT boost plan to CRT 40 Gy (summed plan 1), IMRT without dose-painting boost plan to CRT 40 Gy (summed plan 2) and IMRT with dose-painting boost plan to CRT 40 Gy (summed plan 3), and we compared those plans using DVHs and NTCP.ResultsDmean of PTV-PET and that of PTV-CT were 26.5 Gy and 21.3 Gy, respectively. V50 of small bowel PRV in summed plan 1 was significantly higher than those in other plans ((summed plan 1 vs. summed plan 2 vs. summed plan 3: 47.11 ± 45.33 cm3 vs. 40.63 ± 39.13 cm3 vs. 41.25 ± 39.96 cm3(p < 0.01, respectively)). There were no significant differences in V30, V40, V60, Dmean or NTCP of small bowel PRV.ConclusionsFDG-PET-guided IMRT can facilitate focal dose-escalation to regions with SUV above 2.0 for postoperative local recurrent rectal cancer.

Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial

Aim of the study In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the effect of preoperative radiotherapy. Methods 1417 patients were analyzed; 713 were randomized into preoperative radiotherapy and total mesorectal excision (RT + TME), 704 into TME alone. Of the 114 patients with LR, the subsites of LR were determined and related to tumor and treatment factors. Results Overall 5-year LR-rate was 4.6% in the RT + TME group and 11.0% in the TME group. Presacral local recurrences occurred most in both groups. Radiotherapy reduced anastomotic LR significantly, except when after low anterior resection (LAR) distal margins were less than 5 mm. Abdominoperineal resection (APR) mainly resulted in presacral LR. Even after resection with a negative circumferential resection margin, LR-rates were high. Thirty percent of the patients had advanced tumors, which resulted in 58% of all LRs. Lateral LR comprised 20% of all LR. Presacral and lateral LR resulted in a poor prognosis, in contrast to anterior or anastomotic LRs with a relatively good prognosis. Conclusions RT reduces LR in all subsites and is especially effective in preventing anastomotic LR after LAR. APR-surgery mainly results in presacral LR, which may be prevented by a wider resection. In the TME trial many advanced tumors were included, rather requiring chemoradiotherapy instead of RT. Currently, with good imaging techniques, better selection can take place. Especially lateral LR might be a problem in the future.

Strategy to cope with local recurrence of rectal cancer

直肠癌局部复发(locally recurrent rectal cancer,LRRC)在临床上较为常见,但目前尚无规范和权威性的分类和分期.通常,临床上将LRRC分为3种类型,即直肠腔内复发、盆腔复发和会阴部复发.我国直肠癌在结直肠癌中的比例超过50%,而北美和欧洲在30%左右.由于直肠癌复杂的毗邻关系和狭小的手术操作空间,直肠癌手术后的局部复发率远高于结肠癌,可达2.6～20.0%不等.且中国人中低位直肠癌比例高,因此,LRRC愈来愈引起人们的重视.本文针对LRRC的处理谈谈个人之管见.

Barnsley Bottoms Sit on Their Symptoms

Barnsley Bottoms Sit on Their Symptoms

Low Rates of Rectal Cancer Local Recurrence Support Highly Selective Use of Preoperative Radiotherapy

Low Rates of Rectal Cancer Local Recurrence Support Highly Selective Use of Preoperative Radiotherapy

Current management of locally recurrent rectal cancer

A review of the literature was undertaken to provide an overview of the surgical management of locally recurrent rectal cancer (LRRC) after the introduction of total mesorectal excision (TME). A systematic literature search was undertaken using PubMed, Embase, Web of Science and Cochrane databases. Only studies on patients having surgery for their primary tumour after 1995, or if more than half of the patients were operated on after 1995, were considered for analysis. Studies concerning only palliative treatments were excluded. A total of 19 studies fulfilled the inclusion criteria. Locally recurrent rectal cancer still occurred in 5-10% of the patients and was a major clinical problem, due to severe symptoms and poor survival. In most studies, 40-50% of all patients with LRRC could be expected to undergo surgery with a curative intent and of those, 30-45% would have R0 resection. Thus, only 20-30% of all patients with LRRC would have a potentially curative operation. The postoperative complication rate varied considerably, from 15 to 68%. The rate of re-recurrence varied from 4 to 54% after curative surgery. The 5-year overall survival varied between 9 and 39% and the median survival between 21 and 55 months. Compared with previous studies, the proportion of potentially curative resections seems to have increased, probably due to improved staging, neoadjuvant treatment and increased surgical experience in dedicated centres, which has resulted in a tendency to improved survival.

Reoperation for patients with postoperative local recurrence of rectal cancer

Objective To assess the efficacy of surgical treatment and the prognostic factors predicting survival for patients with local recurrence of rectal cancer. Methods The clinical data of 43 rectal cancer patients who received reoperation at Beijing Cancer Hospital from November 1998 to April 2005 were retrospectively analyzed. The postoperative 5-year survival, incidence of complications, perioperative mortality were calculated. Postoperative survival was analyzed by Kaplan-Meier method and prognostic factors by univariate analysis and Cox proportional hazard regression model. Results Of all patients, 35 underwent radical resection, 8 underwent palliative resection or colostomy. The incidence of complications, perioperative mortality and postoperative 5-year survival were 26% (11/43), 2% (1/43) and 9% (4/43), respectively. Patients who received radical resec-tion, with primary tumor of TNM Ⅱ stage, with normal level of carcinoembryonic antigen, and with the time of recurrence within postoperative 24 months had better prognosis (χ~2 = 21.30, 14.17, 5.93, 5.53, P < 0.05). Modality of reoperation and TNM staging of primary tumor were the independent factors influcing the prognosis (χ~2 = 8.89, 6.96, P < 0.05). Conclusion Radical resection for patients with postoperative local recurrence of rectal cancer results in a favorable prognosis. Key words: Rectal neoplasms; Recurrence; Surgical procedures; Prognosis

Getting Knit-PI3Ky: PIK3CA Mutation Status to Direct Multimodality Therapy?

There is high morbidity associated with local recurrence of rectal cancer. However, the adjuvant therapies given to prevent such recurrences also have significant side effects and associated risks. The ability to select patients with the highest risk of recurrence and greatest therapeutic response will improve rectal cancer care.