Biomedical subjects

M Gonen

Publications and source records attributed to M Gonen.

At least 19 recordsLinked to original sources

PubMed2006

A phase II trial of neoadjuvant cisplatin-fluorouracil followed by postoperative intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5-FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and leucovorin (LV) in patients with locally advanced gastric cancer. PATIENTS AND METHODS: Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2), continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days from surgery. RESULTS: Thirty-eight patients were treated. Both preoperative and postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment LAP versus surgical pathological stage) was seen in 23% of patients. The R0 resection rate was 84%. Neither an increase in postoperative morbidity nor operative mortality was noted. With a median follow-up of 43.0 months, 15 patients (39.5%) are still alive (median survival 30.3 months). Good pathologic response, seen in five patients (15%), was associated with better survival (P = 0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients, respectively. Quality of life seemed to be preserved. CONCLUSIONS: Neoadjuvant cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection and the survival rates are encouraging. An association between pathologic response and patient outcome was suggested.

Adenocarcinoma↗

PubMed2006

Treatment of cholangiocarcinoma with oncolytic herpes simplex virus combined with external beam radiation therapy.

Replication-competent oncolytic herpes simplex viruses (HSV), modified by deletion of certain viral growth genes, can selectively target malignant cells. The viral growth gene gamma(1)34.5 has significant homology to GADD34 (growth arrest and DNA damage protein 34), which promotes cell cycle arrest and DNA repair in response to stressors such as radiation (XRT). By upregulating GADD34, XRT may result in greater oncolytic activity of HSV strains deficient in the gamma(1)34.5 gene. The human cholangiocarcinoma cell lines KMBC, SK-ChA-1 and YoMi were treated with NV1023, an oncolytic HSV lacking one copy of gamma(1)34.5. Viral proliferation assays were performed at a multiplicity of infection (MOI, number of viral particles per tumor cell) equal to 1, either alone or after XRT at 250 or 500 cGy. Viral replication was assessed by plaque assay. In vitro cytotoxicity assays were performed using virus at MOIs of 0.01 and 0.1, with or without XRT at 250 cGy and cell survival determined with lactate dehydrogenase assay. Established flank tumors in athymic mice were treated with a single intratumoral injection of virus (10(3) or 10(4) plaque forming units), either alone or after a single dose of XRT at 500 cGy, and tumor volumes measured. RT-PCR was used to measure GADD34 mRNA levels in all cell lines after a single dose of XRT at 250 or 500 cGy. NV1023 was tumoricidal in all three cell lines, but sensitivity to the virus varied. XRT enhanced viral replication in vitro in all cell lines. Combination treatment with low-dose XRT and virus was highly tumoricidal, both in vitro and in vivo. The greatest tumor volume reduction with combination therapy was seen with YoMi cells, the only cell line with increased GADD34 expression after XRT and the only cell line in which a synergistic treatment effect was suggested. In KMBC and SK-ChA-1 cells, neither of which showed increased GADD34 expression after XRT, tumor volume reduction was less pronounced and there was no suggestion of a synergistic effect in either case. Oncolytic HSV are effective in treating human cholangiocarcinoma cell lines, although sensitivity to virus varies. XRT-enhanced viral replication occurs through a mechanism that is not necessarily dependent on GADD34 upregulation. However, XRT-induced upregulation of GADD34 further promotes tumoricidal activity in viral strains deficient in the gamma(1)34.5 gene, resulting in treatment synergy; this effect is cell type dependent. Combined XRT and oncolytic viral therapy is a potentially important treatment strategy that may enhance the therapeutic ratios of both individual therapies.

Animals↗

PubMed2006

Efficacy of dretler stone cone in the treatment of ureteral stones with pneumatic lithotripsy.

INTRODUCTION: Ureteroscopic pneumatic lithotripsy has been used to treat ureteral calculi for more than 10 years. Owing to its low price and high degree of effectiveness, it has become the most popular ureteroscopic lithotripsy device in use worldwide. The major limitation of the technique is the occurrence of proximal fragment migration during intracorporeal lithotripsy. The Dretler Stone Cone is a new device developed to prevent stone migration during ureteroscopic lithotripsy. The aim of this study was to assess the efficacy and safety of this device during ureteroscopic pneumatic lithotripsy. PATIENTS AND METHODS: Twenty-three consecutive patients having ureteral stones were treated with a 10-Fr semirigid ureteroscope, a Stone Cone Nitinol Retrieval Device, and a pneumatic lithotriptor. In all patients Stone Cones were placed under visual guidance through the working channel of the ureteroscope. Outcomes of this device were then compared with the outcomes of 23 previous patients with stones of similar sizes and locations who had undergone ureteroscopic pneumatic lithotripsy prior to the Stone Cone being available at our clinic. RESULTS: All patients in the study group were stone-free after the procedure. No stone fragments were noted to migrate to proximal segments. CONCLUSIONS: The Dretler Stone Cone effectively prevents proximal stone migration and facilitates stone fragmentation during pneumatic lithotripsy with no risk of ureteral injury. It has only a small extra cost.

Equipment Design↗

PubMed2006

A retrospective analysis of the impact of 18F-FDG PET scans on clinical management of 133 breast cancer patients.

AIM: While it is well-known that there is 18F-FDG uptake in breast tumors, clinical impact of (18)F-FDG PET in managing breast cancer patients is not well-studied. METHODS: One hundred and thirty-three consecutive breast cancer patients from May 1996 to June 2000 were studied. All patients were treated and being followed. Reasons of referral included equivocal conventional studies, staging/re-staging, clinical suspicion of recurrence, and elevated serum tumor markers. Clinical status at 6 months postPET is used as the gold standard in lesions of worsening versus stable or improving. RESULTS: PET was 69% sensitive and 80% specific in predicting clinical stage at 6 months. This 69% of the patients who got worse at 6 months was PET positive and 80% of the patients who were stable or improving at 6 months were PET negative. There was a significant association between PET results and clinical outcome, after adjusting for stage of disease (P=0.04), or for the treatment patients received (P<0.01). Negative PET results changed therapy as often as positive ones did. PET influenced treatment decisions in 74% of the patients referred for study. CONCLUSIONS: PET holds promise as a sensitive and specific modality in following treated breast cancer patients. PET results contain information on 6 month outcome that is independent of stage or past treatment and influence patient management.

Adult↗

PubMed2005

Comparison of the effects of amitriptyline and flunarizine on weight gain and serum leptin, C peptide and insulin levels when used as migraine preventive treatment.

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Adult↗

PubMed2004

Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64 cases.

Small-cell carcinoma (SmCC) of the gastrointestinal tract is a very rare and aggressive malignancy. To better define its clinicopathological features, the records of all patients with this disease seen at Memorial Sloan Kettering Cancer Center between 1980 and 2002 (n=64) were reviewed. The most common primary tumour locations were in the large bowel and oesophagus. Predisposing medical conditions for non-small-cell cancers, positive family cancer history, and metachronous tumours were common. In all, 37% had mixed tumour histology and 48% presented with extensive disease, according to the Veterans' Administration Lung Study group (VALSG) staging system used for small-cell lung cancer. Treatment outcome in limited disease (LD) suggested a role for surgery and chemotherapy. Platinum-based regimens resulted in a 50% response rate. The 2-year survival was 23% and two prognostic factors were identified, the extent of disease according to the VALSG system (P<0.01) and TNM stage (P=0.03). Anatomic location had no clinical impact. In conclusion, SmCC from various gastrointestinal sites can be viewed as one clinical entity. Mixed tumour histology is common and may affect therapy. Surgery, combined with chemotherapy, should be considered for LD. The value of the VALSG system was implied and possible differences from small-cell lung cancer were noted.

Adult↗

PubMed2003

Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer.

PURPOSE: Patients who undergo resection of liver metastases from colorectal cancer have an average 2-year survival of 65%. With hepatic arterial infusion (HAI) plus systemic fluorouracil and leucovorin, 2-year survival increased to 86%. For further improvement in both local and systemic control, combinations of new systemic drugs with HAI are being explored. The purpose of this study was to determine the maximum-tolerated dose (MTD) of systemic irinotecan (CPT-11) and HAI floxuridine (FUDR) plus dexamethasone (DEX) as combination adjuvant therapy after liver resection. PATIENTS AND METHODS: Ninety-six patients who underwent complete resection of liver metastases from colorectal cancer were treated with six monthly cycles of HAI FUDR plus DEX for 14 days of each 4-week cycle plus escalating doses of systemic CPT-11. The primary end points of the phase I/II study were the MTD and efficacy of this regimen. RESULTS: The MTD for combined systemic CPT-11 and HAI FUDR was CPT-11 at 200 mg/m2 every other week and FUDR at 0.12 mg/kg x pump volume / pump flow rate. The dose-limiting toxicities were diarrhea and neutropenia. With a median follow-up time of 26 months, the 2-year survival rate is 89%. All of the 27 patients who were treated at the MTD are alive. CONCLUSION: In patients who undergo resection of liver metastases from colorectal cancer, adding systemic CPT-11 to HAI therapy in an adjuvant regimen is feasible. This regimen seems to have comparable activity to fluorouracil and leucovorin, but further studies are needed to assess whether it improves local control or decreases extrahepatic recurrences.

Adenocarcinoma↗

PubMed2003

The role of staging laparoscopy in hepatobiliary malignancy: prospective analysis of 401 cases.

BACKGROUND: Patients with potentially resectable hepatobiliary malignancy are frequently found to have unresectable tumors at laparotomy. We prospectively evaluated staging laparoscopy in patients with resectable disease on preoperative imaging. METHODS: Staging laparoscopy was performed on 410 patients with potentially resectable hepatobiliary malignancy. The preoperative likelihood of resectability was recorded. Data on preoperative imaging, operative findings, and hospital course were analyzed. RESULTS: Laparoscopic inspection was complete in 291 (73%) patients. In total, 153 patients (38%) had unresectable disease, 84 of whom were identified laparoscopically, increasing resectability from 62% to 78%. On multivariate analysis, a complete examination, preoperative likelihood of resection, and primary diagnosis were significant predictors of identifying unresectable disease at laparoscopy. The highest yield was for biliary cancers, and the lowest was for metastatic colorectal cancer. In patients with unresectable disease identified at laparoscopy, the mean hospital stay was 3 days, and postoperative morbidity was 9%, compared with 8 days and 27%, respectively, in patients found to have unresectable disease at laparotomy. CONCLUSIONS: Laparoscopy spared one in five patients a laparotomy while reducing hospital stay and morbidity. Targeting laparoscopy to patients at high risk for unresectable disease requires consideration of disease-specific factors; however, the surgeons' preoperative impression of resectability is also important.

Aged↗

PubMed2002

Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma.

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The area under the curve for a receiver operator characteristic curve on the basis of standardized uptake value (SUV) was 0.882 +/- 0.025. PET interpretation, SUV, and physical examination were independent predictors of relapse-free and overall survival in a time-dependent, multivariate proportional hazards model. An increase in SUV by one unit increased the relative risk (RR) of relapse by 11% and the RR of death by 14%. A positive PET interpretation increased the RR of relapse by four-fold and the RR of death by seven-fold. CONCLUSION: PET was a highly sensitive method of detecting recurrent HNSCC and provided important prognostic information for relapse-free and overall survival.

Adolescent↗

PubMed2002

Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer.

BACKGROUND: In vitro synergy between Oxal (oxaliplatin) and CPT-11 (irinotecan) has been reported. Oxaliplatin exerts its antineoplastic activity through the formation of platinum-DNA adducts. Resistance to oxaliplatin is through repair of these adducts, which is inhibited by irinotecan. PATIENTS AND METHODS: Oxaliplatin and irinotecan were administered weekly for 4 weeks followed by a 2-week rest period. The dose of oxaliplatin was escalated first, starting at 30 mg/m(2). Once a dose of 60 mg/m(2) was attained, the weekly dose of irinotecan was escalated, from 40 mg/m(2) to 85 mg/m(2). A total of 49 previously treated patients with metastatic colorectal cancer were entered in order to establish the maximum tolerated dose. Pharmacokinetics of oxaliplatin and irinotecan were analyzed. RESULTS: Forty-nine patients were evaluable for toxicity. The recommended phase II doses for this combination are oxaliplatin 60 mg/m(2) and irinotecan 50 mg/m(2), weekly x 4 q 6 weeks. Diarrhea was the most common dose-limiting toxicity. No pharmacological interactions were noted between oxaliplatin and irinotecan. Twelve of the 47 evaluable patients (26%) achieved a partial response. CONCLUSION: Weekly combination of oxaliplatin and irinotecan appears to be a well tolerated and active regimen in patients previously treated for metastatic colorectal cancer. Further investigations of this regimen are warranted.

Adult↗

PubMed2002

Qualitative and quantitative comparison between images obtained with filtered back projection and iterative reconstruction in prostate cancer lesions of (18)F-FDG PET.

BACKGROUND: Recently, iterative reconstruction with segmented attenuation corrections (IRSAC) has been introduced for reconstruction of (18)F-FDG PET images. IRSAC produces images that are more pleasing to the eye, but qualitative and quantitative comparisons between IRSAC and filtered back projection (FBP) have not been reported for metastatic cancer. Since quantitative data has been widely used as an adjunct to interpretation of PET scans, comparison between IRSAC and FBP is needed. The purpose of this study was to compare image quality and the maximum standardized uptake value (SUVmax) obtained with FBP and with IRSAC in metastatic lesions from prostate cancer. METHODS: Twenty (18)F-FDG PET scans (10 baseline and 10 follow-up) were performed in 10 patients with prostate cancer (ages 66-85 yrs, mean 73.6 yrs). Acquisition began 45 min after injection of 370 MBq of (18)F-FDG. Images were reconstructed using FBP and IRSAC, and submitted to visual and quantitative analysis. SUVmax was obtained for all metastases, on FBP and IRSAC. A Jaszczak phantom study was also performed. RESULTS: IRSAC images showed better image quality than FBP especially in regions of high activity concentrations. IRSAC detected 106 lesions on both baseline and follow-up scans, while FBP detected 100 and 95 lesions on baseline and follow-up scans, respectively. Therefore, 17 more lesions were seen on IRSAC. The mean SUVmax values on baseline scans for FBP and IRSAC were systematically different, at 4.46+/-1.99 and 5.13+/-2.67, respectively. On follow-up scans values were 3.89+/-1.72 for FBP and 4.29+/-1.93 for IRSAC. Comparison of FBP with IRSAC on baseline and follow-up scans were statistically significant (baseline: paired "t"-test p=0.0017; follow-up: paired "t"-test p=0.0008). Phantom studies reveal that these differences can be explained by the type of reconstruction filters used, and IRSAC was more accurate than FBP. CONCLUSIONS: IRSAC detects smaller volumes in phantoms, patient images are easier to interpret and more metastatic lesions were detected. In addition, IRSAC provides reproducible quantitative data, comparable to data provided by FBP. IRSAC SUV and FBP SUV are in close agreement but there was a statistically significant difference between the two, and therefore threshold values of SUV will probably need to be re-determined with IRSAC, and are likely to be 10 to 19% higher than currently reported.

Adenocarcinoma↗

PubMed2001

Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of concurrent systemic irinotecan and hepatic arterial infusion (HAI) of floxuridine (FUDR) and dexamethasone in patients with unresectable hepatic metastases from colorectal cancer, to determine the safety of this combination in patients who have undergone cryosurgery, and to evaluate the pharmacokinetic effects of HAI FUDR on the metabolism of irinotecan. PATIENTS AND METHODS: Forty-six previously treated patients with unresectable liver metastases and no known extrahepatic disease were treated concurrently with intravenous irinotecan weekly for 3 weeks and with HAI of FUDR and dexamethasone for 14 days (both were recycled in 28 days). Parallel cohorts of patients treated with or without cryosurgery were entered at escalating dose levels. RESULTS: The MTD for patients who did not undergo cryosurgery was 100 mg/m2 of irinotecan weekly for 3 weeks every 4 weeks with concurrent HAI FUDR (0.16 mg/kg/d x pump volume/flow rate) plus dexamethasone for 14 days of a 28-day cycle. The dose-limiting toxicities were diarrhea and neutropenia. The response rate (complete and partial) among all patients who did not undergo cryosurgery was 74%. All patients in the cryosurgery group responded, and seven of the eight cryosurgery patients developed normal positron emission tomography scans after chemotherapy. HAI FUDR had no effect on the metabolism of irinotecan. CONCLUSION: Combination therapy with HAI FUDR and dexamethasone plus systemic irinotecan may be safely administered to patients with unresectable hepatic metastases from colorectal cancer. The MTD has been reached for patients with unresectable disease, and we continue to investigate the MTD for patients who have undergone cryosurgery. Although the main objective of this study was to evaluate the toxicity of the combined regimen, a high response rate (74%) was observed.

Adult↗

PubMed2001

FDG-PET standardized uptake values in normal anatomical structures using iterative reconstruction segmented attenuation correction and filtered back-projection.

Filtered back-projection (FBP) is the most commonly used reconstruction method for PET images, which are usually noisy. The iterative reconstruction segmented attenuation correction (IRSAC) algorithm improves image quality without reducing image resolution. The standardized uptake value (SUV) is the most clinically utilized quantitative parameter of [fluorine-18]fluoro-2-deoxy-D-glucose (FDG) accumulation. The objective of this study was to obtain a table of SUVs for several normal anatomical structures from both routinely used FBP and IRSAC reconstructed images and to compare the data obtained with both methods. Twenty whole-body PET scans performed in consecutive patients with proven or suspected non-small cell lung cancer were retrospectively analyzed. Images were processed using both IRSAC and FBP algorithms. Nonquantitative or gaussian filters were used to smooth the transmission scan when using FBP or IRSAC algorithms, respectively. A phantom study was performed to evaluate the effect of different filters on SUV. Maximum and average SUVs (SUVmax and SUVavg) were calculated in 28 normal anatomical structures and in one pathological site. The phantom study showed that the use of a nonquantitative smoothing filter in the transmission scan results in a less accurate quantification and in a 20% underestimation of the actual measurement. Most anatomical structures were identified in all patients using the IRSAC images. On average, SUVavg and SUVmax measured on IRSAC images using a gaussian filter in the transmission scan were respectively 20% and 8% higher than the SUVs calculated from conventional FBP images. Scatterplots of the data values showed an overall strong relationship between IRSAC and FBP SUVs. Individual scatterplots of each site demonstrated a weaker relationship for lower SUVs and for SUVmax than for higher SUVs and SUVavg. A set of reference values was obtained for SUVmax and SUVavg of normal anatomical structures, calculated with both IRSAC and FBP image reconstruction algorithms. The use of IRSAC and a gaussian filter for the transmission scan seems to give more accurate SUVs than are obtained from conventional FBP images using a nonquantitative filter for the transmission scan.

Aged↗

PubMed2001

Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma.

OBJECTIVE: To analyze resectability and survival in patients with hilar cholangiocarcinoma according to a proposed preoperative staging scheme that fully integrates local, tumor-related factors. SUMMARY BACKGROUND DATA: In patients with hilar cholangiocarcinoma, long-term survival depends critically on complete tumor resection. The current staging systems ignore factors related to local tumor extent, preclude accurate preoperative disease assessment, and correlate poorly with resectability and survival. METHODS: Demographics, results of imaging studies, surgical findings, pathology, and survival were analyzed prospectively in consecutive patients. Using data from imaging studies, all patients were placed into one of three stages based on the extent of ductal involvement by tumor, the presence or absence of portal vein compromise, and the presence or absence of hepatic lobar atrophy. RESULTS: From March 1991 through December 2000, 225 patients were evaluated, 77% of whom were seen and treated within the last 6 years. Sixty-five patients had unresectable disease; 160 patients underwent exploration with curative intent. Eighty patients underwent resection: 62 (78%) had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative histologic margins). Negative histologic margins, concomitant partial hepatectomy, and well-differentiated tumor histology were associated with improved outcome after all resections. However, in patients who underwent an R0 resection, concomitant partial hepatectomy was the only independent predictor of long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a concomitant hepatic resection and none had tumor-involved margins; 3 of these 9 patients remained free of disease at a median follow-up of 88 months. The rates of complications and death after resection were 64% and 10%, respectively. In the 219 patients whose disease could be staged, the proposed system predicted resectability and the likelihood of an R0 resection and correlated with metastatic disease and survival. CONCLUSION: By taking full account of local tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately predicts resectability, the likelihood of metastatic disease, and survival. Complete resection remains the only therapy that offers the possibility of long-term survival, and hepatic resection is a critical component of the surgical approach.

Adult↗

PubMed2001

Complications of type I thyroplasty and arytenoid adduction.

OBJECTIVES/HYPOTHESIS: Unilateral vocal fold paralysis resulting in glottal incompetence can cause significant morbidity attributable to impaired speech, swallowing, and ability to protect the airway. Type I thyroplasty in combination with arytenoid adduction is a proven technique for medialization of the paralyzed vocal fold but must be evaluated in light of potential complications following laryngeal framework surgery. STUDY DESIGN AND METHODS: The charts of 237 patients who underwent unilateral vocal fold medialization surgery between July 1, 1991, and August 30, 1999, at a tertiary care cancer referral center were retrospectively reviewed. RESULTS: There were 98 cases of type I thyroplasty alone and 96 cases of type I thyroplasty with arytenoid adduction. The two groups had similar patient characteristics. Mean time of surgery (45 vs. 73 min, P <.0001) and length of hospital stay (1.1 vs. 1.8 d, P <.0001) were increased when arytenoid adduction was performed. Overall improvement of symptoms was similar in both groups (93%-94%), but posterior glottic closure appeared subjectively improved when arytenoid adduction was used (P =.0054). Overall complication rates were slightly higher in the arytenoid adduction group (14% vs. 19%), primarily because of transient vocal fold edema and wound complications (9 vs. 19 cases), but the increase was not statistically significant (P =.1401). Complications warranting medical or surgical intervention occurred in 8% of cases. Two patients who underwent type I thyroplasty with arytenoid adduction required tracheotomy as a consequence of postoperative complications. The three patients who had extrusion of the implant underwent type I thyroplasty alone. CONCLUSION: Using the appropriate technique, the potential benefits of improved glottic function following type I thyroplasty with arytenoid adduction outweigh the small risk of significant complications observed.

Adult↗

PubMed2001

Lymphoscintigraphy and sentinel node localization in breast cancer patients: a comparison between 1-day and 2-day protocols.

UNLABELLED: The purpose of this study was to compare the results of isotope injection the morning of surgery (1-d protocol) with isotope injection the day before surgery (2-d protocol) in patients having sentinel lymph node (SLN) biopsy for breast cancer. METHODS: The 1-d (protocol 1) and 2-d (protocol 2) protocols included 514 and 152 patients, respectively, treated contemporaneously by surgeons experienced with the SLN biopsy technique. All had preoperative lymphoscintigraphy (LSG) and SLN biopsy using both blue dye and (99m)Tc-sulfur colloid. All patients had a single-site intradermal injection of unfiltered (99m)Tc-sulfur colloid in 0.05 mL normal saline: 3.7 MBq (0.1 mCi) on the morning of surgery for protocol 1 and 18.5 MBq (0.5 mCi) on the afternoon before surgery for protocol 2. RESULTS: The patients in protocols 1 and 2 were comparable in terms of age, tumor size, tumor location, histologic type, node positivity, and frequency of a previous surgical biopsy. Comparing protocols 1 and 2, early (30 min) LSG images found the SLN equally often (69% vs. 68%). Isotope identified the SLN equally often at surgery (93% vs. 97%) as did isotope plus dye (98% vs. 99%). A comparable number of SLNs was found (2.5 vs. 2.8 per axilla), and the concordance between isotope and dye in the SLN was also comparable (97% vs. 95%). Late LSG images (at 2 h, possible only for protocol 2) identified the SLN in significantly more patients compared with early images (86% vs. 68%). CONCLUSION: With unfiltered (99m)Tc-sulfur colloid injected intradermally, the results of SLN biopsy under the 1-d and 2-d protocols are virtually identical. A 2-d protocol allows increased efficiency in scheduling, both for nuclear medicine physicians and for the operating room, with no compromise in the effectiveness of SLN mapping.

Adult↗

PubMed2001

Augmentation of apoptosis and tumor regression by flavopiridol in the presence of CPT-11 in Hct116 colon cancer monolayers and xenografts.

CPT-11, a DNA topoisomerase I inhibitor, has demonstrated clinical activity in colorectal cancer. Flavopiridol, a cyclin-dependent kinase inhibitor, is rapidly emerging as a chemotherapy modulator. To enhance the therapeutic index of CPT-11 in colon cancer, we studied the combination of these two drugs in relatively resistant human colon cancer cells, Hct116. Exposure of parental Hct116 cells to clinically achievable concentrations of SN-38 (the active metabolite of CPT-11) induces p21 and a G(2) arrest. However, these conditions fail to induce apoptosis. In contrast, Hct116 cells that are p21 deficient (p21-/- Hct116) readily undergo apoptosis after treatment with SN-38. In this study we show that the parental Hct116 cells can be sensitized to undergo apoptosis by the addition of flavopiridol after SN-38 treatment. The induction of apoptosis was greatest with sequential therapy consisting of SN-38 followed by flavopiridol. Clonogenic assays also showed greatest inhibition with this sequence. Sequential treatment with SN-38 followed by flavopiridol was associated with higher activation of caspase-3 and greater cleavage of both p21 and XIAP, an inhibitor of apoptosis, compared with other treatment schedules. CPT-11 induced some tumor regressions but no complete responses in the p21-intact Hct116 xenografts. CPT-11 with flavopiridol more than doubled tumor regression, compared with CPT-11 alone, and produced a 30% complete response rate. Our studies indicate that CPT-11 induces cell cycle arrest rather than cell death and that flavopiridol, by activating the caspase cascade, cleaves the inhibitors of apoptosis and sensitizes the cells to undergo cell death. Thus, flavopiridol combined with CPT-11 may provide a completely new therapeutic approach in the treatment of colon cancer.

Animals↗

PubMed2001

Local detection of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose: comparison of filtered back projection and iterative reconstruction with segmented attenuation correction.

BACKGROUND: To compare filtered back projection (FBP) and iterative reconstruction with segmented attenuation correction (IRSAC) in the local imaging of prostate cancer by positron emission tomography with 2-fluorodeoxyglucose (FDG-PET). METHODS: We retrospectively identified 13 patients with primary (n=7) or recurrent (n=6) prostate cancer who had increased uptake in the prostate on FDG-PET performed without urinary catheterization, contemporaneous biopsy confirming the presence of active tumor in the prostate, and correlative cross-sectional imaging by MRI (n=8) or CT (n=5). FDG-PET images were reconstructed by FBP and IRSAC. Two independent nuclear medicine physicians separately rated FBP and IRSAC images for visualization of prostatic activity on a 4-point scale. Results were compared using biopsy and cross-sectional imaging findings as the standard of reference. RESULTS: IRSAC images were significantly better that FBP in terms of visualization of prostatic activity in 12 of 13 patients, and were equivalent in 1 patient (p<0.001, Wilcoxon signed ranks test). In particular, 2 foci of tumor activity in 2 different patients seen on IRSAC images were not visible on FBP images. In 11 patients who had a gross tumor mass evident on cross-sectional imaging, there was good agreement between PET and cross-sectional anatomic imaging with respect to tumor localization. CONCLUSIONS: In selected patients, cancer can be imaged within the prostate using FDG-PET, and IRSAC is superior to FBP in image reconstruction for local tumor visualization.

Aged↗