Theo Wiggers

Regression analysis of prognostic factors in colorectal cancer after curative resections

The clinical, laboratory, and pathologic data of 310 patients who had curative resections were prospectively collected and analyzed in a multiple step wise regression model. Although several factors (i.e., venous invasion) were of importance in univariate analysis, the following conclusions reflect the outcome and relative importance of the regression analysis only. Blood loss as an initial symptom and duration of symptoms were associated with a better prognosis. Location of the primary tumor, age, and sex did not appear to have prognostic value. Observations during operation such as palpable lymph nodes, fixity to adjacent organs, and tumor spill were related to a diminished tumor-free survival. Laboratory data (hemoglobin, leukocytes, ESR, GGTP, SGOT, SGPT, LDH, total protein, CEA) were tested for their potential prognostic values. Only a preoperative low protein level or an elevated CEA level were associated with an increased risk of death due to recurrent tumor. The histopathologic features (stage and grade), with the exception of venous invasion, were of relative importance in the determination of prognosis. The aforementioned variables can be included in a prognostic index on the base of which high-risk groups suitable for adjuvant studies can be identified.

Comparison of intraoperative radiation therapy-containing multimodality treatment with historical treatment modalities for locally recurrent rectal cancer

PURPOSE: Treatment protocols for patients with locally recurrent rectal cancer have changed in the last two decades. Subsequently, treatment goals shifted from palliation to possible cure. In this retrospective study, we explored the treatment variables that may have contributed to the improvement in outcome by comparing three treatment modalities from two collaborating institutions in patients with similar tumor characteristics. METHODS: Ninety-four patients were treated with electron-beam radiation therapy only (1975–1990), 19 with combined preoperative electron-beam radiation therapy and surgery (1989–1996), and 33 with intraoperative radiation therapy-multimodality treatment (1994–1999). Intraoperative radiation therapy was delivered either as intraoperative electron-beam radiotherapy (10–17.5 Gy) in 20 patients or as intraoperative high-dose-rate brachytherapy (10 Gy) in 13 patients. No patient had received prior electron-beam radiation therapy. RESULTS: The three-year survival, disease-free survival, and local control rates were 14, 8, and 10 percent, respectively, in the electron-beam radiation therapy-only group and 11, 0, and 14 percent, respectively, in the combined electron-beam radiation therapy-surgery group. The overall intraoperative radiation therapy-multimodality treatment group showed significantly better three-year survival, disease-free survival, and local control rates of 60, 43, and 73 percent, respectively, compared with the historical control groups (P<0.001). CONCLUSION: The outcome of patients with locally recurrent rectal cancer was improved after the introduction of intraoperative radiation therapy-multimodality treatment.

Surgery for local recurrence of rectal carcinoma

PURPOSE: This study was designed to evaluate results, especially mortality and morbidity, of surgical resection with curative intent for patients with a local recurrence of rectal cancer, in combination with radiotherapy. METHODS: Consecutive medical records of 163 patients with local recurrence of rectal carcinoma after previous “curative” therapy for primary rectal cancer were reviewed. Although 35 patients had an exploratory laparotomy, only 27 had local recurrence amendable to resection (6 irresectable locoregional recurrences and 2 distant metastases found at laparotomy). Twenty-one patients received radiotherapy. There was no perioperative mortality. Median follow-up time was 42 (range, 22–92) months. RESULTS: Local rerecurrence occurred in 16 (59 percent) patients. Ten patients are alive, of whom nine have good local control. Estimated five-year survival (Kaplan-Meier) is 20 percent. Survival was significantly better in patients without a second recurrence, but radicality of the resection was not influential. Good local control could be obtained in 12 (44 percent) patients, and 1 patient is living with symptoms. CONCLUSIONS: In selected patients with local recurrence of rectal carcinoma, reoperation with irradiation may result in good palliation and possibly cure.

Abdominosacral resection for primary irresectable and locally recurrent rectal cancer

PURPOSE: The purpose of this study was to present a technique of abdominosacral resection and its results in patients with locally advanced primary or locally recurrent rectal cancer with dorsolateral fixation. METHODS: Between 1994 and 1999, 13 patients with locally advanced primary rectal cancer and 37 patients with locally recurrent rectal cancer underwent abdominosacral resection as part of a multimodality treatment,i.e., preoperative irradiation, surgery, and intraoperative irradiation. After the abdominal phase, the patient was turned from supine to prone position to perform the transsacral phase of the resection. RESULTS: Margins were microscopically negative in 26 patients (52 percent), microscopically positive in 18 (36 percent), and positive with gross residual disease in 6 patients. Operation time ranged from 210 to 590 (median, 390) minutes, and blood loss ranged from 400 to 10,000 (median, 3,500) ml. No operative or hospital deaths occurred. Postoperative complications occurred in 41 patients (82 percent); most notable were perineal wound infections or dehiscence (n=24, 48 percent). Other complications were postoperative urinary retention or incontinence (n=9, 18 percent), peritonitis (n=4), grade II neuropathy (n=1), and fistula formation (n=3). Kaplan-Meier 3-year overall survival, disease-free survival, and local control rates were, respectively, 41 percent, 31 percent, and 61 percent. Completeness of the resection (negativevs. positive margins) was a significant factor influencing survival (P=0.04), diseasefree survival (P=0.0006), and local control (P=0.0002). CONCLUSION: The abdominosacral resection provides wide access and may be the therapeutic solution for the accomplishment of a radical resection for distally situated, dorsally or dorsolaterally fixed primary or locally recurrent rectal cancers.

Preoperative Radiotherapy Improves Outcome in Recurrent Rectal Cancer

PURPOSEWhen local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only.METHODSBetween 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database. Ninety-two patients were suitable for resection with curative intent. Preoperative radiation with a median dosage of 50 Gy was performed in 59 patients; 33 patients did not receive preoperative radiotherapy. The median age of the patients was respectively 66 and 62 years.RESULTSThe median follow-up of patients alive for the total group was 16 (range, 4–156) months. Tumor characteristics were comparable between the two groups. Complete resections were performed in 64 percent of the patients who received preoperative radiation and 45 percent of the nonirradiated patients. A complete response after radiotherapy was found in 10 percent of the preoperative irradiated patients (n = 6). There were no differences in morbidity and reintervention rate between the two groups. Local control after preoperative radiotherapy was statistically significantly higher after three and five years (Pn = 0.036). Overall survival and metastases-free survival were not different in both groups. Complete response to preoperative radiotherapy was predictive for an improved survival.CONCLUSIONSPreoperative radiotherapy for recurrent rectal cancer results in a higher number of complete resections and an improved local control compared with patients treated without radiotherapy. Preoperative radiotherapy should be standard treatment for patients with recurrent rectal cancer.

Prospective Evaluation of Quality of Life and Sexual Functioning After Laparoscopic Total Mesorectal Excision

PurposeThis study was designed to investigate how the quality of life of patients with rectal cancer changes with time after laparoscopic total mesorectal excision.MethodsPatients completed the Medical Outcomes Study Short Form 36 and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and a colorectal-specific European Organisation for Research and Treatment of Cancer quality of life questionnaire before laparoscopic total mesorectal excision, on discharge from the hospital and at 3, 6, and 12xa0months postoperatively. Patients were treated by laparoscopic low anterior resection or laparoscopic abdominoperineal resection.ResultsFifty-one patients (mean age, 64xa0years; 29 males (57 percent)) participated in this study, of whom 38 (75 percent) underwent laparoscopic low anterior resection and 13 (25 percent) laparoscopic abdominoperineal resection. Compared with preoperative scores on the Medical Outcomes Study Short Form 36, patients reported a deterioration in physical functioning (74 vs. 80; Pu2009=u20090.009), and improved mental functioning (76 vs. 70; Pu2009=u20090.007) at three months. Improvement in emotional well-being was reported both on the Medical Outcomes Study Short Form 36 (78 vs. 53; Pu2009=u20090.006) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (84 vs. 69; Pu2009<u20090.001). At one year, improvements in global quality of life (82 vs. 68; Pu2009=u20090.001) and symptoms, such as fatigue (18 vs. 32; Pu2009<u20090.001), pain (5 vs. 12; Pu2009=u20090.009), and appetite loss (3 vs. 13; Pu2009=u20090.01), were reported. Sexual functioning was worse from three months onward until one year after surgery (47 vs. 66; Pu2009=u20090.004). Patients who underwent low anterior resection experienced less sexual dysfunction than patients after abdominoperineal resection (21 vs. 56; Pu2009=u20090.004).ConclusionsOne year after laparoscopic total mesorectal excision for rectal cancer, patients reported improvement in some important quality of life outcomes, including global quality of life, despite a decrease in sexual functioning.

Value of intraoperative radiotherapy in locally advanced rectal cancer

PurposeThis study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer.MethodsBetween 1987 and 2002, 123 patients with initial unresectable and locally advanced rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathologic reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed.ResultsAll patients were treated preoperatively with a median dose of 50xa0Gy radiotherapy. Surgery was performed six to ten weeks after radiotherapy. Twenty-seven patients were treated with intraoperative radiotherapy because margins were incomplete or ≤2xa0mm. Postoperative mortality was 2 percent. The median follow-up of all patients was 25.1xa0months. The overall five-year local control was 65 percent and the overall five-year survival was 50 percent. Positive lymph nodes and incomplete resections negatively influenced local control and overall survival. Intraoperative radiotherapy improved five-year local control (58 vs. 0 percent, P = 0.016) and overall survival (38 vs. 0 percent, P = 0.026) for patients with R1/2 resections.ConclusionsThe presented multimodality treatment is feasible with an acceptable mortality and a five-year overall survival of 50 percent. Addition of intraoperative radiotherapy for patients with a narrow or microscopic incomplete resection seems to overrule the unfavorable prognostic histologic finding.

Laparoscopic versus open total mesorectal excision: a case-control study

Background and aimsBecause definitive long-term results are not yet available, the oncological safety of laparoscopic surgery for treatment of rectal cancer remains unproven. The aim of this prospective non-randomised study was to assess the feasibility and short-term outcome of laparoscopic total mesorectal excision (LTME) after 25–30xa0Gy preoperative radiotherapy and to compare the results with a matched-control group of open TME (OTME).Materials and methodsA series of 41 patients with primary rectal cancer underwent LTME for rectal cancer and were matched with a historical control group of 41 patients who underwent OTME. Both groups received preoperative short-term radiotherapy.ResultsThere was no mortality in the LTME group and 2% mortality in the OTME group. The overall postoperative morbidity was 37% in the LTME group and 51% in the OTME group, including an anastomotic leakage of 9 and 14% in the LTME and OTME groups respectively. A positive circumferential margin was found in 7% of patients in the LTME group and in 12% of the patients in the OTME group.ConclusionThis study shows that LTME is technically feasible and can be performed safely. We show at least a similar surgical completeness using a laparoscopic technique compared with open surgery.

Impact of the number of histologically examined lymph nodes on prognosis in colon cancer : a population-based study in the Netherlands

PURPOSE: The impact of the reported number of lymph nodes at pathologic examination of colon specimens on survival was studied. METHODS: The data of 2,281 patients with localized colon cancer were retrospectively reviewed. The effect of tumor characteristics and surgical and pathologic factors on the number of lymph nodes and examined lymph node numbers on nodal status and survival were analyzed. RESULTS: The number of examined nodes increased with T stage, left-sided tumors, and mucinous morphology, but decreased with age. The proportion of node-positive patients increased with a larger number of nodes. A high number of examined nodes and high T stage affected nodal status. The five-year overall survival was 51.3 percent for node-positive patients vs. 68.2 percent for node-negative patients. Node-negative patients had a significantly higher five-year crude and relative survival when more lymph nodes were examined. This was not found for the node-positive group and for all patients combined. CONCLUSIONS: T stage, localization, and patient age were predictive for the number of nodes examined. A higher number of examined nodes was associated with an increase in node positivity. The survival benefit can be explained by stage migration. Eventually this may lead to an overall survival benefit, as more patients are classified as node-positive, and therefore will receive adjuvant therapy.

Multislice CT as a primary screening tool for the prediction of an involved mesorectal fascia and distant metastases in primary rectal cancer: a multicenter study.

PURPOSE: The purposes of this study were to assess whether multislice CT can identify tumors having a free or involved circumferential margin, to investigate the additional role of multislice CT as a one-stop shopping staging tool for staging nodal and distant metastases. METHODS: A total of 250 patients with adenocarcinoma of the rectum underwent multislice CT scans of the chest and abdomen before undergoing total mesorectal excision. The scans were scored by two teams. The main outcome was yes/no involvement of the mesorectal fascia. Histology was taken as the standard for determining the involvement. RESULTS: The overall sensitivity for predicting an involved mesorectal fascia was 74.2 percent and the overall specificity was 93.9 percent. The overall sensitivity for low tumors was 65.6 percent and the overall specificity was 81.5 percent. The overall sensitivity for mid-/high rectal tumors was 76.1 percent and the overall specificity was 96.3 percent. The interobserver agreement was substantial (&kgr; 0.695). The overall sensitivity for the prediction of liver metastases was 64.3 percent and the overall specificity was 94.4 percent with &kgr; 0.82. The accuracy in predicting lymph node metastases was low. CONCLUSIONS: Multislice CT can be used for the assessment of mesorectal fascia involvement in primary rectal cancer, especially those located in the middle rectum and the high rectum; however, in the prediction of an involved margin of tumors located in the distal rectum, the accuracy of multislice CT falls short.