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I Kodner

Publications and source records attributed to I Kodner.

5 recordsLinked to original sources
PubMed1996

Carcinoma of the rectum. Possible cellular predictors of metastatic potential and response to radiation therapy.

BACKGROUND: Preoperative radiation therapy can markedly improve local control of rectal carcinoma. However, some tumors do not respond well to moderate doses of preoperative radiation and would be better served by more aggressive preoperative treatment (e.g., chemoradiotherapy). Cellular predictors of responsiveness to radiation can help to select lesions for more aggressive treatment. In addition, there is a need for cellular predictors of metastatic potential. This is particularly important in the setting of preoperative radiation-downstaging by preoperative treatment can obscure the true pathologic stage of a tumor and confound the usual selection criteria for postoperative chemotherapy. PURPOSE: This study was undertaken to determine if proliferating cell nuclear antigen (PCNA), p53, DNA ploidy, and S-phase fraction are associated with response to radiation and/or risk for distant metastatic disease and to determine if these cellular markers are best evaluated from preradiation biopsy specimen or the larger (but possibly altered) final surgical specimen. MATERIALS AND METHODS: Archival specimens from 23 cases of ultrasound T3 or T4 rectal carcinoma treated preoperatively with radiation therapy were reviewed. Eligible lesions had preradiation biopsy specimens of sufficient size for flow cytometric review of archival tissue. Factors considered included PCNA positivity, presence of mutant nuclear p53, more than 30 percent tumor cells in S-phase, and presence of aneuploidy. RESULTS: With a median follow-up of three years, overall freedom from relapse was 83 percent, with all but one failure being extrapelvic. PCNA positivity in the preradiation specimen was significantly (P = 0.025) associated with a greater risk of tumor recurrence. In addition, there was a trend to greater likelihood of "probable downstaging" (defined as surgical T stage less than preradiation ultrasound T stage) for lesions that were PCNA-negative or lesions with normal p53. Biomarkers measured in the postradiation surgical specimen were not associated with either freedom from relapse or response to radiation. Radiation treatment appeared to produce false-negatives in the final specimen. Thus, there were significantly more specimens converting from PCNA-positive to PCNA-negative after preoperative radiation than would be expected solely on the basis of sampling errors (P = 0.004). Similar results were found for abnormal p53 findings (P = 0.02). CONCLUSIONS: Prospective studies of biomarkers should be based on pretreatment specimens if preoperative radiation is given. For carcinoma of the rectum, PCNA and p53 may be useful predictors of both metastatic potential and responsiveness to radiation.

Adenocarcinoma↗
PubMed1995

Adjuvant radiation therapy for rectal carcinoma: predictors of outcome.

PURPOSE: To review predictors of outcome, including sequencing of modalities and pretreatment findings for adjuvantly treated rectal cancer. METHODS AND MATERIALS: From 1975 through 1990, 307 patients with adenocarcinoma of the rectum underwent adjuvant radiation therapy. In 251 cases the radiation therapy was administered preoperatively, either 40-50 Gy (median dose 45 Gy) followed in 6-7 weeks by surgery (210 cases), or 20 Gy in five fractions immediately prior to surgery (41 cases). In 56 cases, patients were referred postoperatively for radiation (median dose 50 Gy). Adjuvant chemotherapy was never given concurrently with the preoperative radiation (RT), although 43 of the cases (including 14 of the preoperative RT cases) received postoperative chemotherapy. RESULTS: Multivariate analysis (Cox model) indicated that significant predictors of better overall freedom from disease were preoperative rather than postoperative RT (p < 0.001), low surgical stage (p < 0.0001), specialist surgeon (p = 0.007), low or moderate histologic grade (p = 0.026), and proximal lesion (p = 0.033). The significant predictors for better local control included use of preoperative RT (p < 0.001), low or moderate grade (p = 0.001), and low surgical stage (p = 0.015). The 5-year local control and freedom from disease for the preoperative RT patients were 90% +/- 2% and 73% +/- 3%, respectively. The selected cases that received the short course of 20 Gy preoperatively did well. Although 24 out of 41 patients proved to have Astler Coller B2 or C disease, local control at last follow-up was 39 out of 41 (95%). A second multivariate analysis of pretreatment factors was performed on the preoperative RT cases. The significant factors for both local control and overall freedom from disease were noncircumferential vs. circumferential tumor, proximal vs. distal lesion, and background of the surgeon. Additional negative factors on univariate analysis (although not achieving independent significance on multivariate analysis) included the finding of near-obstructing lesions and elevated carcinoembryonic antigen (CEA). Grade > or = 3 sequelae occurred in 8% of cases (including 3% bowel obstruction). The only significant factor for complications was background of the surgeon (4% for colorectal specialists vs. 12% for nonspecialists, p = 0.015). CONCLUSIONS: Significant factors for better tumor control included preoperative as opposed to postoperative RT and the experience of the surgeon. In selected cases, excellent results can be obtained with a short course of preoperative radiation. Concurrent chemotherapy need not be given routinely with preoperative radiation. Subgroups of preoperative RT cases at risk for distant metastases (who might benefit from postoperative chemotherapy), and at high risk for local failure (for whom concurrent preoperative chemotherapy and radiation might be considered), are identified.

Adenocarcinoma↗
PubMed1995

Carcinoma of the anal canal.

From 1975 to 1990 65 patients with carcinoma of the anal canal received radiation therapy alone or in conjunction with other modalities. Follow-up ranged from 12 to 171 months (mean: 59 months; median: 44 months). Actuarial disease-free survival (including salvage surgery) for T1-3 N0 lesions was 88% +/- 7% at 10 years. This was independent of T stage (91% for T1, 88% for T2, and 100% for T3). Disease-free survival was significantly worse for T1-3 N+ lesions (52% +/- 23% disease-free at 10 years, P = .025) and T4 lesions (0/8 disease free by 21 months, P < .001). Of the 57 patients with T1-3 lesions, 46 received low to moderate doses of radiation (< or = 5,000 cGy) in conjunction with infusional 5FU based chemotherapy. These were reviewed for treatment related factors. Among patients treated with low to moderate dose chemoradiotherapy the local control (including salvage surgery) was excellent: 100% for T1 lesions and 88% +/- 6% for T2, 3 lesions. There was a suggestion that increasing the dose of radiation to the tumor may reduce the need for surgery for T2, 3 lesions. For T2, 3 lesions the local control excluding surgery was 63% +/- 12% with 3,000 cGy plus chemotherapy, as opposed to 77% +/- 11% with 4,000-5,000 Gy (mean 4,600 cGy) plus chemotherapy. The most important factor for posttreatment toxicity was the addition of pelvic surgery to chemotherapy and radiotherapy. Eighteen patients who received chemoradiotherapy either had a history of prior pelvic surgery (five cases) or underwent APR following chemotherapy (13 cases). There were a total of nine grade 3 or 4 complications (including all five cases of small bowel obstruction) in this group. There was a significantly lower (P = .04) incidence of complications in the remaining patients: 2/47 (4%). It should be noted that no patient required a colostomy for management of treatment sequelae, the interventions taken were all successful in managing complications, and no complication was fatal. Nonetheless these results suggest that, for some T3 and T2 lesions, measures which reduce the need for salvage surgery might improve overall quality of life by reducing complications, although it may prove difficult to demonstrate an improvement in the excellent disease-free survival. In addition, measures should be taken to reduce the volume of irradiated bowel if a patient has a history of prior pelvic surgery.

Adult↗
PubMed1985

Preoperative tattooing of polypectomy site.

A simple method of marking polypectomy site is described. It involves submucosal injection of supravital dye via the colonoscope. It permits identification of site of pathology at the time of surgery.

Colon↗