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Martin Weiser

Publications and source records attributed to Martin Weiser.

10 recordsLinked to original sources
PubMed2006

A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography.

BACKGROUND: Preoperative combined-modality therapy (CMT) is the preferred treatment for locally advanced rectal cancer (endorectal ultrasonography [ERUS] T3-4, N1, or clinically bulky) and achieves a pathologic complete response (pCR) in 4% to 33% of patients. However, the prognostic significance of pCR remains unclear. METHODS: A prospectively collected database was queried to identify 200 patients with locally advanced disease treated from 1992 to 2002. The pCR group was defined as having no evidence of viable tumor on pathologic analysis. The no-downstaging group was defined as no difference between the pre-CMT ERUS stage and the pathologic stage. Those achieving some downstaging but not pCR were excluded. Patients were treated with CMT (5040 cGy of radiation and 5-fluorouracil-based chemotherapy) followed by surgery, and 51 (85%) in the pCR group and 129 (92%) in the no-downstaging group (P = .1) received postoperative chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were determined by using the Kaplan-Meier method. RESULTS: The median follow-up was 38.6 months (range, 18.2-124.9 months). The pCR (n = 60) and control (n = 140) groups were similar in age (P = .6), sex (P = .4), distance of the tumor from the anal verge (P = .3), pre-CMT ERUS stage (P = .2), and comorbidities (P = .2). The 5-year RFS was 96% and 54% in the pCR and control groups, respectively (P < .00001); the 5-year OS was 90% and 68% (P = .009). Sphincter-preservation rates were higher in the pCR group (P = .01). CONCLUSIONS: Rectal cancer patients with pCR after preoperative CMT have improved RFS, OS, and sphincter preservation compared with patients without downstaging. Because pCR seems to be associated with better outcome, an understanding of the factors governing the response to CMT should be pursued.

Adenocarcinoma↗
PubMed2006

Ten-year results of preoperative radiation followed by sphincter preservation for rectal cancer: increased local failure rate in nonresponders.

BACKGROUND: The primary objective of this study was to determine the long-term outcome of sphincter preservation with preoperative radiation therapy (RT) and surgical resection in the treatment of distal rectal adenocarcinoma. PATIENTS AND METHODS: Between April 1988 and December 1996, 36 (cT2, n=9; cT3, n=27) patients with rectal adenocarcinoma were enrolled on a phase I/II trial of preoperative RT followed by surgical resection. All patients had distal tumors that were clinically judged to require an abdominoperineal resection and received preoperative RT (50.4 Gy) followed by surgery. The median follow-up was 94.5 months (range, 4-187 months). RESULTS: Of the 35 patients in this study who underwent resection, 77% were able to undergo sphincter preservation after preoperative RT. The pathologic complete response rate for these patients was 14%. The 10-year rates of overall survival and local failure for patients undergoing sphincter preservation were 54% and 21%, respectively. The 10-year local failure was 26% in patients with cT3 disease who underwent sphincter preservation. All local failures in this study occurred in patients with cT3 disease undergoing sphincter preservation; however, none of the patients with cT3 disease that was downstaged by preoperative RT experienced local failure. In contrast, 10-year local failure was 67% in the patients with cT3 disease that was not downstaged by RT. Sphincter function was good or excellent in 85% of patients at the time of last follow-up. CONCLUSION: This approach provides excellent long-term results in all patients with cT2 disease and those with cT3 disease that is downstaged by RT. However, patients with cT3 disease that is not downstaged by RT have an increased risk of local failure. These data underscore the impact of tumor response to radiation on long-term oncologic outcome.

Adenocarcinoma↗
PubMed2005

Distal cT2N0 rectal cancer: is there an alternative to abdominoperineal resection?

PURPOSE: Patients with cT2N0 distal rectal cancer do not require adjuvant therapy. However, when a patient refuses an abdominoperineal resection (APR), is there an alternative? The purpose of this trial is to determine whether preoperative external-beam radiation therapy can increase the rate of sphincter preservation for patients with distal cT2N0 adenocarcinoma of the rectum. PATIENTS AND METHODS: Between April 1988 and October 2003, 27 patients with distal rectal adenocarcinoma staged T2 by clinical and/or endorectal ultrasound who were judged by the operating surgeon to require an APR were treated with preoperative pelvic radiation alone (50.4 Gy). Surgery was performed 4 to 7 weeks later. If pathologic positive pelvic nodes were identified, postoperative adjuvant chemotherapy was recommended. The median follow-up was 55 months (range, 9 to 140 months). RESULTS: The pathologic complete response rate was 15% and 78% of patients underwent a sphincter-sparing procedure. The crude incidence of local failure for patients undergoing a sphincter sparing procedure was 10% and the 5-year actuarial incidence was 13%. The actuarial 5-year survival for patients undergoing sphincter preservation was as follows: disease-free, 77%; colostomy-free, 100%; and overall, 85%. Using the Memorial Sloan-Kettering Cancer Center sphincter function score, 54% of those undergoing a sphincter-sparing procedure had good/excellent bowel function at 12 to 24 months after surgery, and 77% had good/excellent function at 24 to 36 months after surgery. CONCLUSION: Our data suggest that for patients with cT2N0 distal rectal cancer who require an APR, preoperative pelvic radiation improves sphincter preservation without an apparent compromise in local control or survival.

Adenocarcinoma↗
PubMed2005

Rectus flap reconstruction decreases perineal wound complications after pelvic chemoradiation and surgery: a cohort study.

BACKGROUND: A major source of morbidity after abdominoperineal resection (APR) after external beam pelvic radiation is perineal wound complications, seen in up to 66% of cases. Our purpose was to determine the effect of rectus abdominus myocutaneous (RAM) flap reconstruction on perineal wound morbidity in this population. METHODS: The study group consisted of 19 patients with anorectal cancer treated with external beam pelvic radiation followed by APR and RAM flap reconstruction of the perineum. A prospectively collected database was queried to identify a control group (n = 59) with anorectal cancer treated with similar radiation doses that subsequently underwent an APR without a RAM flap during the same time period. Comparison of percentages was performed with a two-sided Fisher's exact test, and comparison of means was performed with Wilcoxon's test. RESULTS: Perineal wound complications occurred in 3 (15.8%) of the RAM flap patients and 26 (44.1%) of the control patients (P = .03). The incidence of other complications was not different between groups (42.1% vs. 42.4%; P = .8). Despite an increased number of anal squamous tumors, an increased vaginectomy rate, increased use of intraoperative radiotherapy, and an increased proportion of cases with recurrent disease, the flap group had a significantly lower rate of perineal wound complications relative to the control group. CONCLUSIONS: Perineal closure with a RAM flap significantly decreases the incidence of perineal wound complications in patients undergoing external beam pelvic radiation and APR for anorectal neoplasia. Because other complications are not increased, RAM flap closure of the perineal wound should be strongly considered in this patient population.

Adenocarcinoma↗
PubMed2004

Fully adaptive propagation of the quantum-classical Liouville equation.

In mixed quantum-classical molecular dynamics few but important degrees of freedom of a dynamical system are modeled quantum-mechanically while the remaining ones are treated within the classical approximation. Rothe methods established in the theory of partial differential equations are used to control both temporal and spatial discretization errors on grounds of a global tolerance criterion. The TRAIL (trapezoidal rule for adaptive integration of Liouville dynamics) scheme [I. Horenko and M. Weiser, J. Comput. Chem. 24, 1921 (2003)] has been extended to account for nonadiabatic effects in molecular dynamics described by the quantum-classical Liouville equation. In the context of particle methods, the quality of the spatial approximation of the phase-space distributions is maximized while the numerical condition of the least-squares problem for the parameters of particles is minimized. The resulting dynamical scheme is based on a simultaneous propagation of moving particles (Gaussian and Dirac deltalike trajectories) in phase space employing a fully adaptive strategy to upgrade Dirac to Gaussian particles and, vice versa, downgrading Gaussians to Dirac-type trajectories. This allows for the combination of Monte-Carlo-based strategies for the sampling of densities and coherences in multidimensional problems with deterministic treatment of nonadiabatic effects. Numerical examples demonstrate the application of the method to spin-boson systems in different dimensionality. Nonadiabatic effects occurring at conical intersections are treated in the diabatic representation. By decreasing the global tolerance, the numerical solution obtained from the TRAIL scheme are shown to converge towards exact results.

Journal Article↗
PubMed2004

Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection.

INTRODUCTION: Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy. Prolongation of the interval between preoperative combined modality therapy and surgery (RT-surgery interval) as a means of increasing pathologic complete response rate has not been fully examined. METHODS: One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified. All patients had endorectal ultrasound prior to combined modality therapy. Final pathology reports were reviewed for ypT and ypN stage and margin status. Medical records were reviewed for sphincter preservation, operative time, estimated blood loss, hospital stay, and morbidity (overall, anastomotic, and perineal). RESULTS: A pathologic complete response (ypT0N0) occurred in 24 patients (15 percent). Median RT-surgery interval was 44 (range, 15-206) days. A pathologic complete response occurred in 19 percent of patients with an interval >44 days, vs. 12 percent in those with an interval < or =44 days ( P = 0.27). Downstaging by three stages occurred more frequently in the long-interval group (15 percent vs. 6 percent, P = 0.11). The rates of sphincter preservation, positive margins, estimated blood loss, and operative time were not significantly different. Overall morbidity was similar between groups. CONCLUSIONS: Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval. However, sphincter preservation is not increased. Until prospective analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome, the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear.

Adult↗
PubMed2004

Residual mesorectal lymph node involvement following neoadjuvant combined-modality therapy: rationale for radical resection?

BACKGROUND: In order to evaluate the impact of preoperative radiation and chemotherapy (combined modality therapy, or CMT) on primary rectal cancer and mesorectal lymph nodes (MLNs), middle and lower third rectal cancers were resected with total mesorectal excision (TME) and assessed for frequency of MLN retrieval and residual MLN involvement. METHODS: Between 1990 and 2001, 187 consecutive patients underwent abdominoperineal resection (APR) or low anterior resection (LAR) for locally advanced (endorectal ultrasound [ERUS] stage, T3-4) mid and distal rectal cancer following preoperative CMT. Sphincter preservation was possible in 150 patients (80%). The mean number of retrieved MLNs was 10.6. Pre-CMT ERUS stage was compared with final pathologic stage. RESULTS: Comparison of pre-CMT ERUS stage with pathologic stage revealed a decrease in T stage in 93 patients (49%), as well as a decrease in the percentage of individuals with positive MLNs, from 54% to 27% (P <.0001). The overall incidence of positive MLN involvement was 27%, and incidence paralleled pathologic T stage (pT): pT0 = 7%, pT1 = 8%, pT2 = 22%, pT3 = 37%, and pT4 = 67%. CONCLUSIONS: Following preoperative CMT, the incidence of residual MLN involvement remains significant and parallels increasing pT stage. Therefore, the standard of care for locally advanced distal rectal cancer should continue to include formal rectal resection (TME).

Adult↗
PubMed2003

Adaptive integration of molecular dynamics.

This article presents a particle method framework for simulating molecular dynamics. For time integration, the implicit trapezoidal rule is employed, where an explicit predictor enables large time steps. Error estimators for both the temporal and spatial discretization are advocated, and facilitate a fully adaptive propagation. The framework is developed and exemplified in the context of the classical Liouville equation, where Gaussian phase-space packets are used as particles. Simplified variants are discussed briefly. The concept is illustrated by numerical examples for one-dimensional dynamics in double well potential.

Journal Article↗
PubMed2002

Radical resection of rectal cancer primary tumor provides effective local therapy in patients with stage IV disease.

BACKGROUND: The optimal use of radical surgery to palliate primary rectal cancers presenting with synchronous distant metastases is poorly defined. We have reviewed stage IV rectal cancer patients to evaluate the effectiveness of radical surgery without radiation as local therapy. METHODS: Eighty stage IV patients with resectable primary rectal tumors treated with radical rectal surgery without radiotherapy were identified. Sixty-one (76%) patients received chemotherapy; response information was available for 34 patients. RESULTS: Radical resection was accomplished by low anterior resection (n = 65), abdominoperineal resection (n = 11), and Hartmann's resection (n = 4). Surgical complications were seen in 12 patients (15%), with 1 death and 4 reoperations. The local recurrence rate was 6% (n = 5), with a median time to local recurrence of 14 months. Only one patient received pelvic radiotherapy as salvage treatment. One patient required subsequent diverting colostomy. Median survival was 25 months. On multivariate analysis, the extent of metastasis and response to chemotherapy were determinants of prolonged survival. CONCLUSIONS: For patients who present with distant metastases and resectable primary rectal cancers, radical surgery without radiotherapy can provide durable local control with acceptable morbidity. The extent of metastatic disease and the response to chemotherapy are the major determinants of survival. Effective systemic chemotherapy should be given high priority in the treatment of stage IV rectal cancer.

Adenocarcinoma↗