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Biomedical subjects

W E Enker

Publications and source records attributed to W E Enker.

At least 19 recordsLinked to original sources
PubMed2000

Current status of total mesorectal excision and autonomic nerve preservation in rectal cancer.

Two decades have passed since the late 1970s, which witnessed the introduction of total mesorectal excision (TME)-based operations for rectal cancers on both sides of the Atlantic. Since the introduction of TME, clinical experience has been reported widely in the form of single- and multisurgeon reports from wide geographic regions with multiple participants, and from specialty services with narrow focus and high levels of expertise. All of these published results conclude that in comparison with conventionally practiced blunt surgery for rectal cancer, TME-based (i.e., anatomically correct, sharply performed) operations are associated with significantly lower rates of pelvic (local) recurrences, a significantly higher rate of survival, and significantly lower long-term morbidity. The latter is accomplished through dramatically higher rates of sphincter preservation, and the preservation of both sexual and urinary functions. Overall, there is a remarkable similarity in the clinical results that have been reported from diverse centers. TME now forms the basis of large randomized clinical trials in which the role of adjuvant therapy is being reexamined. The current status of TME is reviewed, and the authors' clinical results of a consecutive series of 544 TME-based operations performed through 1998 are updated.

Autonomic Pathways↗
PubMed1999

Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients.

AIMS: Improved local control and survival in the treatment of rectal cancer have been reported after total mesorectal excision and after extended lymphadenectomy. Comparison of published results is difficult because of differences in patient populations and definitions. We compared three series of patients who underwent standardized surgery [i.e. total mesorectal excision (TME) or D3 lymphadenectomy] with patients who underwent conventional surgery, using actual patient data and uniform definitions. METHODS: TME was performed at Memorial Sloan-Kettering Cancer Center, New York, USA (n=254) and the North Hampshire Hospital, Basingstoke, UK (n=204). D3 lymphadenectomy was performed at the National Cancer Center, Tokyo (n=233). Conventional surgery was used in hospitals in Norway (n=366) and in hospitals of the Comprehensive Cancer Center West, The Netherlands (n=354). Only patients with a curatively resected primary TNM Stage II or Stage III rectal cancer within 12 cm from the anal verge were included. RESULTS: Five-year overall survival and cancer-specific survival were 62-75% and 75-80%, respectively, in the standardized surgery groups and 42-44% and 52%, respectively, in the conventional surgery groups. Local recurrence rates ranged from 4 to 9% in the standardized surgery groups and 32-35% in the conventional surgery groups. CONCLUSIONS: A 30% survival difference and 25% local recurrence difference is not likely to be caused by the shortcomings which are inherent in a non-randomized study: selection bias, assessment variability or stage migration. This study suggests that standardized surgery gives superior survival and local control when compared to conventional surgery.

Aged↗
PubMed1999

Safety and efficacy of low anterior resection for rectal cancer: 681 consecutive cases from a specialty service.

OBJECTIVE: To determine perioperative morbidity, survival, and local failure rates in a large group of consecutive patients with rectal cancer undergoing low anterior resection by multiple surgeons on a specialty service. The primary objective was to assess the surgical complications associated with preoperative radiation sequencing. SUMMARY BACKGROUND DATA: The goals in the treatment of rectal cancer are cure, local control, and preservation of sphincter, sexual, and bladder function. Surgical resection using sharp perimesorectal dissection is important for achieving these goals. The complications and mortality rate of this surgical strategy, particularly in the setting of preoperative chemoradiation, have not been well defined. METHODS: There were 1233 patients with primary rectal cancer treated at the authors' cancer center from 1987 to 1995. Of these, 681 underwent low anterior resection and/or coloanal anastomosis for primary rectal cancer. The surgical technique used the principles of sharp perimesorectal excision. Morbidity and mortality rates were compared between patients receiving preoperative chemoradiation (Preop RT, n = 150) and those not receiving preoperative chemoradiation (No Preop RT, n = 531). Recurrence and survival data were determined in patients undergoing curative resection (n = 583, 86%) among three groups of patients: those receiving Preop RT (n = 131), those receiving postoperative chemoradiation (Postop RT, n = 110), and those receiving no radiation therapy (No RT, n = 342). RESULTS: The perioperative mortality rate was 0.6% (4/681). Postoperative complications occurred in 22% (153/681). The operative time, estimated blood loss, and rate of pelvic abscess formation without associated leak were higher in the Preop RT group than the No Preop RT group. However, the overall complication rate, rate of wound infection, anastomotic leak, and length of hospital stay were no different between Preop RT and No Preop RT patients. With a median follow-up of 45.6 months, the overall actuarial 5-year recurrence rate for patients undergoing curative resection (n = 583) was 19%, with 4% having local recurrence only, 12% having distant recurrence, and 3% having both local and distant recurrence, for an overall local recurrence rate of 7%. The actuarial 5-year overall survival rate was 81%; the disease-free survival rate was 75% and the local recurrence rate was 10%. The overall survival rate was similar between Preop RT (85%), Postop RT (72%), and No RT (83%) patients (p = 0.10), whereas the disease-free survival rate was significantly worse for Postop RT (65%) patients compared with Preop RT (79%) and No RT (77%) patients (p = 0.04). CONCLUSION: The use of preoperative chemoradiation results in increased operative time, blood loss, and pelvic abscess formation but does not increase the rate of anastomotic leaks or the length of hospital stay after low anterior resection for rectal cancer. The 5-year actuarial overall survival rate for patients undergoing curative resection exceeded 80%, with a local recurrence rate of 10%.

Adult↗
PubMed1999

Total mesorectal excision with autonomic nerve preservation: a new foundation for the evaluation of multi-disciplinary adjuvant therapy in the management of rectal cancers.

Local and distant recurrence rates and disease-free and overall survival are markedly improved by total mesorectal excision, with little increase in morbidity, compared with other techniques of resection of rectal cancer. Adjuvant therapy is associated with significant morbidity and initial results suggest it may not be beneficial in the aggregate. Adjuvant therapy must be re-evaluated in trials using TME as standard operative technique. Different subgroups of patients, defined by clinical and pathological criteria will be best served by different forms of therapy and should be studied based on rates of local and distant recurrence. Selected groups of patients will be best served by undergoing no adjuvant therapy of any kind.

Chemotherapy, Adjuvant↗
PubMed1998

High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer.

PURPOSE: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). METHODS AND MATERIALS: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general, the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). RESULTS: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was 19% for those with positive margins (p = 0.02). The disease-free survival was 47% (71% for negative margins and 0% for positive margins) (p = 0.04). Prospective data gathering indicated that significant complications occurred in approximately 38% of patients and were multifactorial in nature, and manageable to complete recovery. CONCLUSION: HDR-IORT using our technique is versatile, safe, and effective. The local control rates for primary disease compare quite well with other published series, especially for patients with negative margins. For patients with recurrent disease, locoregional control and survival are especially encouraging in patients with negative resection margins. Further follow-up is needed to see whether these encouraging data will continue.

Adenocarcinoma↗
PubMed1997

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer.

PURPOSE: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. METHODS AND MATERIALS: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. RESULTS: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). CONCLUSION: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Adult↗
PubMed1997

Abdominoperineal resection via total mesorectal excision and autonomic nerve preservation for low rectal cancer.

We have examined the results of abdominoperineal resection (APR) for primary cancer of the rectum performed in accordance with the principles of total mesorectal excision (TME) and autonomic nerve preservation (ANP). TME is defined as sharp pelvic dissection under direct vision between the parietal and visceral planes of the pelvic fascia. TME results in the resection of all mesorectal disease with intact, negative lateral or circumferential margins of resection. Statistical analysis was done of survival, local recurrence, and both sexual and urinary functions in a prospective database of consecutive patients. Operative mortality was 2% (3/148) due to cardiac disease. Overall survival was 60%, significantly worse than consecutive patients from the same database who were able to undergo sphincter preservation (81%) (p = 0.0003). Poorer survival was statistically related to the presence of positive lymph nodes (p = 0.0009). Overall, local recurrence rates were 5% (8/148) in patients without distant metastases, and 15% to 21% in patients with positive nodes. Positive lymph nodes, N2 disease, lymphatic vascular invasion, and perineural invasion were independent significant risk factors for local recurrence. Sexual function was preserved in approximately 57% of patients undergoing APR versus 85% of patients undergoing sphincter preservation. No significant urinary morbidity was encountered. Low rectal cancer requiring APR seems to be a disease with more locally advanced disease and adverse pathologic features than are seen with mid-rectal cancers treatable by low anterior resection. APR when performed in accordance with the principles of TME and ANP ensures the greatest likelihood of resecting all regional disease while preserving both sexual and urinary functions. Preoperative combined modality treatment may be warranted in all T3 or greater low rectal cancers.

Adult↗
PubMed1997

Liver resection for colorectal metastases.

PURPOSE: More than 50,000 patients in the United States will present each year with liver metastases from colorectal cancers. The current study was performed to determine if liver resection for colorectal metastases is safe and effective and to evaluate predictors of outcome. MATERIALS AND METHODS: Data for 456 consecutive resections performed between July 1985 and December 1991 in a tertiary referral center were analyzed. RESULTS: The perioperative mortality rate was 2.8%, with a mortality rate of 4.6% for resections that involved a lobectomy or more. The median hospital stay was 12 days and only 9% of patients were admitted to the intensive care unit. The 5-year survival rate is 38%, with a median survival duration of 46 months. By univariate analysis, nodal status of the primary lesion, short disease-free interval before detection of liver metastases, carcinoembryonic antigen (CEA) level greater than 200 ng/mL, multiple liver tumors, extrahepatic disease, large tumors, or positive resection margin was predictive of poorer outcome. Sex, age greater than 70 years, site of primary tumor, or perioperative transfusion was not predictive of outcome. By multivariate analysis, positive margin, size greater than 10 cm, disease-free interval less than 12 months, multiple tumors, and extrahepatic disease were independent predictors of poorer outcome. Short disease-free interval or multiple tumors were nevertheless associated with a 5-year survival rate greater than 24%. CONCLUSION: Liver resection for colorectal metastases is safe and effective therapy and currently represents the only potentially curative therapy for metastatic colorectal cancer. The only absolute contraindication to resection is extrahepatic disease. A randomized trial to examine efficacy of surgical resection cannot ethically be performed. Liver resection should be considered standard therapy for all fit patients with colorectal metastases isolated to the liver.

Adult↗
PubMed1997

Total mesorectal excision--the new golden standard of surgery for rectal cancer.

Rectal cancer persists as a significant worldwide problem. Currently, surgery is associated with a poor prognosis, a high likelihood of permanent colostomy and a high rate of local recurrence in patients with regional disease (transmural penetration or involvement of regional mesenteric lymph nodes). Functional changes such as impotence and bladder dysfunction remain distressingly common consequences of conventional surgery. Over the past two decades, a fundamental change in operative technique has taken place. Conventional surgery (which is performed using blunt technique along undefinable tissue planes) has given way to sharp dissection along definable planes. The technique known as total mesorectal excision (TME) or complete circumferential mesorectal excision (CCME) produces the complete resection of an intact package of the rectum and its surrounding mesorectum, enveloped within the visceral pelvic fasia with uninvolved circumferential margins. As a result of TME, 5-year survival figures have risen from 45-50% to 75%, local recurrence rates have declined from 30% to 5-8%, sphincter preservation has risen by at least 20% for mid- and lower rectal cancers, and the rates of impotence and bladder dysfunction have declined from 50-85% to 15% or less. Patients with rectal cancer can now have a good prognosis, and intact image and high quality of life. The integration of multidisciplinary radiation therapy and chemotherapy into the care of patients undergoing TME or CCME for rectal cancer is presently under clinical trial.

Chemotherapy, Adjuvant↗
PubMed1996

Anatomical basis of autonomic nerve-preserving total mesorectal excision for rectal cancer.

Total mesorectal excision with autonomic nerve preservation for rectal cancer is based on the anatomy of the mesorectum and of the pelvic autonomic nerves. Cadaver dissections were performed to describe the relationship between these structures. Between the rectum and the sacrum a retrorectal space can be developed, lined anteriorly by the visceral leaf and posteriorly by the parietal leaf of the pelvic fascia. The hypogastric nerve runs anterior to the visceral fascia, from the sacral promontory in a laterocaudad direction. The splanchnic sacral nerves originate from the sacral foramina, posterior to the parietal fascia, and run caudad, laterally and anteriorly. After piercing the parietal layer of the pelvic fascia, approximately 4 cm from the midline, the sacral nerves run between a double layer of the visceral part of the pelvic fascia. The relationship between the hypogastric nerves, the splanchnic nerves and the pelvic fascia was comparable in all six specimens examined.

Autonomic Nervous System↗
PubMed1996

Aggressive versus conventional strategies in the treatment of rectal adenocarcinoma.

OBJECTIVE: Comparison of an aggressive approach (including total mesorectal excision and combined modality adjuvant therapy) with a conventional approach in the treatment of primary rectal cancer. DESIGN: Retrospective study. SETTING: Memorial Sloan-Kettering Cancer Centre, New York (MSKCC) and University Hospital Leiden, the Netherlands (UHL). SUBJECTS: One hundred and sixty-nine patients treated at MSKCC and 96 patients treated at UHL. INTERVENTIONS: Total mesorectal excision (MSKCC) and conventional resection (UHL). MAIN OUTCOME MEASURES: Overall survival and local recurrence-free survival. RESULTS: Five-year overall survival was 73% for MSKCC patients and 52% for UHL patients (P < 0.001). Five-year local recurrence-free survival was 83% for MSKCC patients and 72% for UHL patients (P=0.001). Relative risk of dying or developing a local recurrence was 3.37 and 2.61, respectively, for patients treated at UHL compared to patients treated at MSKCC (P<0.001 and P=0.008, respectively). CONCLUSIONS: These data suggest that an aggressive approach including total mesorectal excision and combined modality adjuvant therapy improves survival and local control compared to a conventional approach.

Adenocarcinoma↗
PubMed1996

Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum.

BACKGROUND: We performed a study to assess sexual and urinary function after total mesorectal excision with autonomic nerve preservation for primary carcinoma of the rectum. STUDY DESIGN: We studied retrospectively postoperative sexual and urinary function in 136 (78 percent) of 175 eligible patients (82 males and 54 females) who responded to a standardized questionnaire. RESULTS: The ability to engage in intercourse was maintained by 86 percent of the patients younger than 60 years of age, and by 67 percent of patients 60 years and older. Eighty-seven percent of male patients maintained their ability to achieve orgasm. The type of surgery (abdominoperineal resection compared to low anterior resection), and age equal to or greater than 60 years were significantly associated with male sexual dysfunction. Of the female patients, 85 percent were able to experience arousal with vaginal lubrication and 91 percent could achieve orgasm. The majority of patients had few or no complaints related to urinary function. Serious urinary dysfunction such as neurogenic bladder was not encountered. CONCLUSIONS: Autonomic nerve preservation in association with total mesorectal excision reduces the operative morbidity rate and is successful in minimizing sexual and urinary dysfunction in the operative treatment of patients with carcinoma of the rectum.

Adult↗
PubMed1996

Sphincter-preserving operations for rectal cancer.

Sphincter-preserving operations represent an important model for integrating the goals of surgery for rectal cancers. These goals--the achievement of cure and local control and the preservation of autonomic visceral pelvic functions--are inherently related. Sphincter-preserving procedures are possible for patients with mid-rectal cancers (6 to 10 cm from the anal verge) and for highly selected patients with distal rectal cancers (< or = 5 cm from the anal verge). Total mesorectal excision, a new concept in resection with negative circumferential margins, dramatically enhances both cure and local control. Total mesorectal excision can be combined with sphincter preservation. Perioperative adjuvant therapy protocols have been combined with sphincter-preserving operations in many investigative settings. Functional outcomes and recent survival data seem to favor preoperative over postoperative radiation therapy. The currently changing standards of surgery for rectal cancer, which result in improved local control, should enhance long-term sphincter preservation in the future.

Anastomosis, Surgical↗