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Biomedical subjects

I J Kodner

Publications and source records attributed to I J Kodner.

At least 37 records · Page 2Linked to original sources

Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer.

OBJECTIVE: To assess the potential role of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in patients with unexplained rising carcinoembryonic antigen (CEA) levels after the treatment of colorectal cancer. BACKGROUND: A rising CEA level after the resection of colorectal cancer is an early indicator of tumor recurrence. However, conventional imaging techniques have limited sensitivity for detecting recurrent disease in such patients. Especially after surgical intervention, FDG-PET is rapidly gaining an important role in establishing the extent of disease in the oncology patient. METHODS: Twenty-two patients with abnormal CEA levels and normal results of conventional methods of tumor detection were studied with FDG-PET. The PET results were compared with pathologic findings (n = 9) and long-term radiologic and clinical follow-up (n = 13). RESULTS: FDG-PET was abnormal in 17 of 22 patients. Tissue sampling was available in 7 of these 17 patients; all of these had recurrent disease. Definitive curative surgical intervention was performed in four patients. Subsequent dedicated imaging findings and clinical course confirmed the presence of extensive disease in 8 of the remaining 10 patients; the PET results in the other 2 patients were considered falsely positive. FDG-PET was negative in 5 of 22 patients. No disease was found by tissue sampling (n = 2) and clinical follow-up (n = 3). Overall, the positive-predictive value for PET was 89%, (15 of 17) and the negative-predictive value was 100% (5 of 5). CONCLUSIONS: When conventional examinations are normal, FDG-PET is a valuable imaging tool in patients who have a rising CEA level after colorectal surgery.

Adult↗

Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.

PURPOSE: Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer. METHODS: Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated. RESULTS: LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease. CONCLUSION: Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.

Adenocarcinoma↗

Mutations in MLH1 are more frequent than in MSH2 in sporadic colorectal cancers with microsatellite instability.

The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. Microsatellite instability is also seen in 10-16% of sporadic colorectal cancers. A limited number of MSH2 and MLH1 mutations have been described for sporadic colorectal cancers. In this study, we screened 12 primary sporadic colorectal cancers with microsatellite instability for mutations in MSH2 and MLH1 by using reverse transcription-polymerase chain reaction (RT-PCR) and single-strand-conformation-variant (SSCV) analysis. Eight mutations were identified in six tumors. One mutation in MLH1 was found to be present in the patient's germline DNA. Four tumors had somatic mutations in MLH1, and, in two of these tumors, two different mutations were identified. A single tumor had a somatic MSH2 mutation. Our observations suggest that MLH1 is mutated more frequently than MSH2 in sporadic colorectal cancers with microsatellite instability.

Adaptor Proteins, Signal Transducing↗

Aggressive surgical management of recurrent rectal cancer--is it worthwhile?

OBJECTIVE: The purpose of this study was to determine whether radical surgery in appropriately selected patients who have recurrent rectal cancer can produce significant disease-free survival. PATIENTS AND METHODS: This is a retrospective review of the management of all patients presenting with recurrent local and metastatic rectal cancer at a single institution during an 11-year period. RESULTS: Of 489 patients who underwent curative surgery for primary rectal cancer during the period reviewed, 44 (9 percent) developed recurrent disease at a median interval of 18 (range, 3-60) months after curative surgery. Local pelvic recurrence alone was present in 28 (5.7 percent) patients. Overall survival after diagnosis of recurrent disease was 41 percent (18/44) at a median interval of 15 (range, 2-60) months. Curative resection was performed in 14 (32 percent) patients with a disease-free survival of 86 percent (12/14) at a median of 25 (range, 9-60) months after curative surgery. In comparison, survival in patients who underwent palliative treatment was significantly less (25 vs. 12 months; P < 0.05; 95 percent confidence interval, 10, 23 (Mann-Whitney U test)); 20 percent survival at a median of 12 months ranged from 2 to 36 after diagnosis of recurrent disease. Of six patients in the curative group who developed second recurrences, four underwent further curative surgery and are disease-free at a median of 19.5 (range, 12-29) months after surgery. Palliative surgery provided good symptomatic relief and improved quality of life in 11 patients in the palliative group, although there was no survival advantage over those who underwent nonsurgical palliative treatment (n = 19). CONCLUSION: In appropriately selected cases, aggressive surgical therapy produces significant disease-free survival in patients with recurrent rectal cancer.

Disease-Free Survival↗

Detection of recurrent and metastatic colorectal cancer: comparison of positron emission tomography and computed tomography.

BACKGROUND: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). METHODS: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. RESULTS: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. CONCLUSION: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.

Adult↗

Prognostic value of chromosome 1p allelic loss in colon cancer.

BACKGROUND & AIMS: Current evidence suggests that there may be a tumor-suppressor gene on chromosome 1p associated with colorectal cancer. The aim of the present study was to determine whether allelic loss on chromosome 1p is of prognostic value in colorectal cancer. METHODS: Polymerase chain reaction was used to assess allelic loss of five chromosome 1p microsatellite markers in tumor specimens. Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 116 patients who had undergone curative treatment for adenocarcinoma of the colon. Allelic loss was correlated with disease-free interval and survival. RESULTS: Deletion of 1p sequence was detected in 22 of 82 tumors. Deletions of the microsatellite markers D1S228 (1p36) and HY-TM1 (1p32) were significantly associated with poor survival (P < 0.05): relative risk, 4.1; 95% confidence interval, 1.25-9.23 for D1S228; and relative risk, 6.6; 95% confidence interval, 1.4-19 for HY-TM1. Loss of heterozygosity at D1S228 was also associated with shorter disease-free interval: relative risk, 4.5; 95% confidence interval, 1.3-11. CONCLUSIONS: Allelic loss in the 1p36 and 1p32 regions of chromosome 1 appears to be an independent predictor of poor prognosis in patients with adenocarcinoma of the colon.

Adult↗

Laparoscopic-assisted ileocolic resections in patients with Crohn's disease: are abscesses, phlegmons, or recurrent disease contraindications?

BACKGROUND: Because of the inflammatory nature of Crohn's disease, ileocolic resections are often difficult to perform, especially if an abscess, phlegmon, or recurrent disease at a previous ileocolic anastomosis is present. Our goal was to determine whether the above factors are contraindications to a successful laparoscopic-assisted ileocolic resection. METHODS: Between 1992 and 1996, 46 laparoscopic-assisted ileocolic resections were attempted. Fourteen patients had an abscess or phlegmon treated with bowel rest before operation (group I), 10 patients had recurrent Crohn's disease at the previous ileocolic anastomosis (group II), and 22 patients had no previous operation and no phlegmon or abscess associated with their disease (group III). These groups were compared with each other and with 70 consecutive open ileocolic resections for Crohn's disease during the same time period (group IV). RESULTS: Operative blood loss and time were greater in group IV than in groups I, II, and III (245 versus 151, 131, and 195 ml, respectively, and 202 versus 152, 144, and 139 minutes, respectively). Conversion to open procedure occurred in 5 patients (group I, 1 [7%]; group II, 2 [20%]; group III, 2 [9%]). Morbidity was highest in group IV (21% versus 0%, 10%, and 10%, respectively). Only one patient died (group IV, 1%). Length of hospital stay was longest in group IV (7.9 versus 4.8, 3.9, and 4.5 days, respectively). CONCLUSIONS: The laparoscopic-assisted approach to Crohn's disease is feasible and safe with good outcomes. Co-morbid preoperative findings such as abscess, phlegmon, or recurrent disease at the previous ileocolic anastomosis are not contraindications to a successful laparoscopic-assisted ileocolic resection in select patients.

Abdominal Abscess↗

Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system.

PURPOSE: An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. METHODS AND MATERIALS: The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. RESULTS: The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. CONCLUSIONS: An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.

Brachytherapy↗

Laparoscopic-assisted and minilaparotomy approaches to colorectal diseases are similar in early outcome.

OBJECTIVE: The purpose of this study was to compare laparoscopy with minilaparotomy approaches to colorectal diseases. METHOD: Outcomes after minilaparotomy and laparoscopy were prospectively compared for a 12-month period. RESULTS: Minilaparotomy was performed in 35 patients to achieve right colectomy (14), left colectomy (8), total colectomy (2), low anterior resection (6), abdomino-perineal resection (2), colostomy (1), and ileal resection (1). Laparoscopic techniques were used in 52 patients to perform right colectomy (20), left colectomy (11), low anterior resection (5), abdominoperineal resection (7), total colectomy (3), ileal resection (1), colostomy (3), transverse colectomy (1), and colostomy closure (1). Mean operative times were 69 minutes for minilaparotomy (range, 33-180) and 173 minutes for laparoscopy (range, 60-300). Mean incision lengths were 12 (range 8-18) cm and 8 (range, 0-25) cm; mean time to bowel movement was four (range, 1-7) days and 3.9 (range, 0-8) days; mean day of discharge was 6.9 (range 3-15) days, and 6 (range, 1-15) days postoperatively, respectively. Laparoscopy procedures were completed in 39 of 52 patients (75 percent); mean time to bowel movement was 3.5 (range, 0-6) days, and mean day of discharge was 5.3 (range, 1-14) days (P = <0.005). CONCLUSION: The use of a small incision, whether by minilaparotomy or by laparoscopy, results in similar early return of function and discharge.

Adult↗

Pudendal nerve terminal motor latency influences surgical outcome in treatment of rectal prolapse.

PURPOSE: This study was undertaken to document the effect of pudendal nerve function on anal incontinence after repair of rectal prolapse. METHODS: Patients with full rectal prolapse (n = 24) were prospectively evaluated by anal manometry and pudendal nerve terminal motor latency (PNTML) before and after surgical correction of rectal prolapse (low anterior resection (LAR; n = 13) and retrorectal sacral fixation (RSF; n = 11)). RESULTS: Prolapse was corrected in all patients; there were no recurrences during a mean 25-month follow-up. Postoperative PNTML was prolonged bilaterally (> 2.2 ms) in six patients (3 LAR; 3 RSF); five patients were incontinent (83 percent). PNTML was prolonged unilaterally in eight patients (4 LAR; 4 RSF); three patients were incontinent (38 percent). PNTML was normal in five patients (3 LAR; 2 RSF); one was incontinent (20 percent). Postoperative squeeze pressures were significantly higher for patients with normal PNTML than for those with bilateral abnormal PNTML (145 vs. 66.5 mmHg; P = 0.0151). Patients with unilateral abnormal PNTML had higher postoperative squeeze pressures than those with bilateral abnormal PNTML, but the difference was not significant (94.8 vs. 66.5 mmHg; P = 0.3182). The surgical procedure did not affect postoperative sphincter function or PNTML. CONCLUSION: Injury to the pudendal nerve contributes to postoperative incontinence after repair of rectal prolapse. Status of anal continence after surgical correction of rectal prolapse can be predicted by postoperative measurement of PNTML.

Adult↗

Anal sphincter reconstruction in the elderly: does advancing age affect outcome?

PURPOSE: This study was designed to determine whether advancing age affects outcome after anal sphincter reconstruction. METHOD: Anal sphincter reconstruction, performed on patients 55 years of age and older, was reviewed to determine if functional outcome was adversely affected by advancing age. A subgroup of patients was studied with anal manometry before and after repair and with pudendal nerve terminal motor latency (PNTML) before surgery. Results were compared with a younger group of patients. RESULTS: Between July 1986 and July 1991, 14 patients, ages ranging from 55 to 81, underwent anal sphincter reconstruction using an overlapping muscle repair. Ten patients were incontinent of solid stool and four of liquid stool. Improvement was seen in 13 of 14 patients: 7 (50 percent) complete control, 3 (21 percent) incontinent to flatus, and 4 (29 percent) incontinent to liquid stools (including the patient who failed to improve). Ten patients were studied with a continuous pull-out manometric technique and PNTML: one was not improved. There was minimum change in mean maximum resting pressure (35.0-37.9 mmHg). Mean maximum squeezing pressure increased from 66 to 75 mmHg overall. Patients with complete control had a mean maximum squeezing pressure of 81 mmHg compared with 60 mmHg in patients with residual incontinence. Mean anterior anal sphincter length increased from 2.92 cm to 3.31 cm. PNTML was normal (2.0 +/- 0.2) on one or both sides in all nine patients who improved (average, 2.1). The patient who failed to improve had abnormal nerve function bilaterally (2.4, 2.7). CONCLUSION: Anal sphincter reconstruction can be performed in elderly patients with improvements in the majority of patients. Total control can be achieved by restoring maximum squeezing pressure in a patient with normal pudendal nerve function.

Adult↗

Chronic effects of pelvic radiation therapy on anorectal function.

PURPOSE: The long-term effect of 4,500 cGy of preoperative radiation on anorectal function has not been prospectively evaluated. METHODS: Anal manometry was performed on 20 patients with rectal carcinoma before and four weeks after receiving 4,500 cGy of external radiotherapy. Four patients underwent proctectomies, three died, and three refused follow-up. Ten patients were available for long-term follow-up and underwent anal manometry at 14 to 42 (average, 35.5) months after initial radiotherapy. RESULTS: No significant difference in mean maximum squeeze or resting pressures was found after radiation therapy. The sphincter profile and minimum sensory threshold were unchanged. The rectoanal inhibitory reflex was present in all patients. Nine patients reported normal anal function. One patient who was incontinent before treatment remained incontinent. CONCLUSION: Preoperative radiation therapy has a minimal chronic effect on anorectal function. Incontinence after sphincter-saving operations for rectal cancer should not be attributed to preoperative radiation therapy.

Aged↗

Endorectal advancement flap repair of rectovaginal and other complicated anorectal fistulas.

BACKGROUND: Surgical correction of rectovaginal and complicated anal-perineal fistulas has been associated with high rates of complications and failure of repair. METHODS: This paper reports on 107 patients treated during the past 10 years by endorectal advancement flap repair. Ninety-two percent of the patients were women with mean age of 38 years (range, 20 to 71 years). Seventy-one had low rectovaginal, 28 had anterior anal-perineal, and 8 had posterior anal-perineal fistulas. The causes were obstetric injury, 48; cryptoglandular abscess-fistula, 31; Crohn's disease, 24; and trauma or after operation, 4. The technique completely preserves the sphincter muscle, covers the internal opening of the fistula tract with healthy rectal wall, and provides counter drainage to aid healing. RESULTS: No deaths occurred in the series. Persistent or recurrent fistula occurred in 17 patients (16%). Nine patients whose initial operation failed underwent a secondary successful operation. Continence status was unchanged in 80%, improved in 18%, and was unknown in two patients who still had intestinal flow diversion. Recurrence of the fistula did not result in destruction of the sphincter mechanism in those patients who underwent simultaneous reconstructive operation. CONCLUSIONS: The endorectal advancement flap repair successfully treated 93% of the complicated anorectal fistulas, avoiding fecal diversion and improving, not injuring, sphincter function.

Adult↗

Radiation therapy as definitive treatment for selected invasive rectal cancer.

BACKGROUND: Eighty-four patients with invasive rectal adenocarcinoma were definitively treated with radiation during a period of 9 years in an attempt to achieve "local control" (eradication of rectal cancer and its associated morbidity) without radical resective surgery. METHODS: Initially, endocavitary radiation alone was used in 13 patients with "ideal" carcinomas and in six patients with aggressive cancers. To improve local control, 4500 cGy external radiation before the 6000 cGy endocavitary radiation was used to treat 28 ideal lesions, 15 "nonideal" but potentially curable cancers, 14 aggressive cancers, and 8 patients with incurable metastatic disease. RESULTS: Endocavitary radiation alone resulted in local control for 8 of 13 patients with ideal carcinomas (62%); eventually 11 of 13 (85%) had control after three successful salvage abdominoperineal resections. Local control was accomplished in none of six patients with aggressive cancers. Use of external radiation before endocavitary radiation achieved local control in 93% of patients with ideal lesions, eventually 100% after two salvage abdominoperineal resections. Of the 15 nonideal but potentially curable lesions, 100% had eradication of local disease with the combined modalities. Of the 14 with aggressive cancers and 8 with metastatic disease, 19 suffered failure of local control (86%). Eight of these had local salvage by surgical resection; the others died with local failure within 6 months. CONCLUSIONS: External radiation, combined with endocavitary radiation, is excellent, definitive treatment for selected, favorable, invasive rectal cancers; however, there is little place for nonresective management of aggressive rectal cancer, even for palliation, unless life expectancy is less than 6 months.

Humans↗

Laparoscopic anterior resection of the rectum using a triple stapled intracorporeal anastomosis in the pig.

Laparoscopic anterior resection of the rectum was performed in the porcine model. Colorectal anastomosis was accomplished with a closed triple staple technique using a circular stapler. The anvil and shaft were passed beyond the level of resection and retrieved through the proximal transverse linear cutter staple line. The stapler post was passed through the distal rectal staple line transanally. The resulting stapled anastomosis contained portions of three staple lines. There were no anastomotic leaks or strictures at one month follow-up autopsy. The triple-stapled anastomosis via a laparoscopic approach after an anterior resection of the rectum in a pig is a safe, reliable technique.

Anastomosis, Surgical↗

Accuracy of transrectal ultrasound in predicting pathologic stage of rectal cancer before and after preoperative radiation therapy.

Transrectal ultrasound (TRUS) and CT scan staging of rectal cancers before, and TRUS staging after, 45 Gy of irradiation were compared with the pathologic stage of the resected specimen in 19 patients. Accuracy of TRUS before and after irradiation, and of CT scan before irradiation, was 32 percent, 63 percent, and 53 percent, respectively. CT scan before and TRUS after irradiation predicted lymph node involvement in 79 percent and 68 percent of cases, respectively. Positive predictive value for lymph node involvement before irradiation was 60 percent for CT scan and 37.5 percent for TRUS; after irradiation, it was 50 percent for TRUS. Negative predictive value was 100 percent for CT scan and TRUS before radiation and 88 percent for TRUS after irradiation. Preoperative radiation therapy makes TRUS and CT scan less effective as staging techniques. The absence of lymph nodes on TRUS and CT scan before and after irradiation is reliable.

Female↗