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Biomedical subjects

Aviram Nissan

Publications and source records attributed to Aviram Nissan.

At least 19 recordsLinked to original sources

Predictors of recurrence in patients with T2 and early T3, N0 adenocarcinoma of the rectum treated by surgery alone.

PURPOSE: Treatment of rectal cancer with neoadjuvant radiotherapy has been shown to reduce local recurrence and improve overall survival. The role of chemoradiotherapy in patients with T2, N0 and early T3, N0 rectal cancer, treated by radical surgery with total mesorectal excision, remains controversial. The aim of this study was to identify predictors of recurrence in this group of patients to enhance treatment selection. PATIENTS AND METHODS: One hundred patients with primary T2-3, N0 adenocarcinoma of the rectum, uniformly treated by surgery alone, were studied. The pathology slides available for 97 patients were rereviewed. Three patients with incomplete data sets were excluded. Clinical and survival data were obtained from a prospective computerized database and updated from hospital and office charts. The study end points were disease-free survival, disease-specific survival (DSS), time to pelvic recurrence (PR), and distant recurrence. RESULTS: Complete follow-up was available for all study patients. Median follow-up was 79.5 months (range, 57.7 to 105.9 months). During this time period 30 patients (31.9%) died as a result of disease and 64 patients (68.1%) remained alive and disease free. Five-year DSS was 73%. The cumulative risk for PR was 8% at 5 years and 10% at 8 years. Lymphovascular invasion, preoperative serum carcinoembryonic antigen (CEA > 5 ng/mL) level, and age older than 70 years were all associated with adverse outcome. CONCLUSION Patients with T2-3, N0 rectal cancers and either lymphovascular invasion or elevated CEA levels have reduced survival and a higher incidence of PR, and should be considered for future randomized trials.

Adenocarcinoma↗

Crosslinked chitosan implants as potential degradable devices for brachytherapy: in vitro and in vivo analysis.

Compared with conventional external beam radiation, brachytherapy offers a superior therapeutic regimen. However, some major constraints are associated with its implementation, including the need of complicated procedures for device placement and removal. The purpose of this study was to examine whether crosslinked chitosan (Ct) implants could serve as potential biodegradable devices for brachytherapy. Ct was reacted with increasing amounts of glutaraldehyde to obtain hydrogels with different crosslinking densities, which were characterized chemically, thermally and mechanically. The effect of the dialysis medium conditions (ionic strength, osmolarity and pH) on the gel hydration and in vivo degradation was assessed. Two types of implants, slow and fast degrading gel (SDG and FDG, respectively), were prepared and implanted with or without Sudan Black (SB) in the rat. While SDG withstood for over a month, the FDG degraded within two weeks after implantation. The release kinetics of SB from the hydrogels verified their in vivo degradation properties. The incorporation of the radioactive compound (131)I-norcholesterol ((131)I-NC) into the SDG altered the degradation kinetics of the gel as reflected by the release kinetics of the radioactive marker. Eighty percent of (131)I-NC was released within a month after implantation, after which time, radioactivity was detected in the regional lymph nodes. Histological examination of the tissues surrounding the implants demonstrated negligible tissue response to the implants, when compared to biodegradable surgical sutures. It is concluded that hydrogels made of crosslinked Ct are potential novel, safe, degradable devices for brachytherapy.

19-Iodocholesterol↗

[The prognostic value of CA 19-9 in the preoperative work-up of pancreatic cancer patients].

Carbohydrate antigen (CA) 19-9 is produced by adenocarcinomas of the pancreas, stomach, gall bladder, colon, ovary and lung. Serum CA 19-9 is considered the most sensitive marker for pancreatic cancer, being elevated in 75% or more of patients with pancreatic cancer. In all three cases of pancreatic cancer presented, patients died of their disease quite shortly after diagnosis. Preoperative imaging was unsuccessful in exposing the actual advanced state extent of the disease and even during surgery its real extent was underestimated. The only prognostic indicator of the observed rapid disease progression was a very significant elevation of preoperative serum CA 19-9.

Adult↗

Electrical impedance scanning for the early detection of breast cancer in young women: preliminary results of a multicenter prospective clinical trial.

PURPOSE: To evaluate the feasibility and patient satisfaction with electrical impedance scanning (EIS) for early detection of breast cancer in young women. METHODS: Women undergoing screening clinical breast examination, imaging, or biopsy were eligible for EIS examination with T-Scan 2000ED (Mirabel Medical Systems, Austin, TX). Multiple logistic regression analysis evaluated the association between clinical variables and EIS performance. Patients completed a screening EIS satisfaction questionnaire (1 = least satisfied to 5 = most satisfied). RESULTS: Twenty-nine cancers were identified among 1,103 women. Sixty-six percent (19 of 29) of cancers were nonpalpable and 55% (16 of 29) were in women age < or = 50 years. EIS sensitivity and specificity in women younger than 40 years was 50% and 90%, respectively. Exogenous estrogen use (P < .001) and menopausal status (P = .007) correlated significantly with EIS performance. False-positive rates were increased in postmenopausal women and those taking exogenous hormones. No correlation was evident between EIS performance and family history, prior breast cancer, breast density, or palpability. EIS-positive women younger than age 40 were 4.5 times more likely to have breast carcinoma than were women randomly selected from the general population. Patients were highly satisfied with the comfort, speed, and reporting of EIS screening (mean score, 4.8). CONCLUSION: EIS seems promising for early detection of breast cancer, and identification of young women at increased risk for having the disease at time of screening. Positive EIS-associated breast cancer risk compares favorably with relative risks of conditions commonly used to justify early breast cancer screening. Patients are satisfied with a screening paradigm involving breast EIS.

Adult↗

Electrical impedance scanning of thyroid nodules before thyroid surgery: a prospective study.

BACKGROUND: Electrical impedance scanning (EIS) is a novel imaging technique based on differential electrical conductivity and capacitance of malignant and normal human tissues. The aim of this study was to evaluate the accuracy of EIS in the detection of thyroid malignancies. METHODS: Patients with thyroid nodules scheduled for thyroid surgery were eligible for the study. Enrolled patients underwent EIS with a T-Scan 2000ED. Nodule location, size, and type (cystic vs. solid) measured by ultrasound, cytology results, thyroid conductivity, and capacitance calculated by EIS were recorded. EIS results were interpreted as positive or negative for malignancy and compared with final histopathology results. Study end points included EIS accuracy, sensitivity, specificity, negative and positive predictive values, and false-positive and false-negative rates. RESULTS: Sixty-four patients were enrolled onto the study, and all underwent either lobectomy-isthmusectomy (20%) or total thyroidectomy (80%). The mean tumor diameter was 2.64 +/- 14.8 mm. Thyroid cancers were identified by histology in 30 patients (46.9%). There were 11 false-positive and four false-negative cases. The overall diagnostic accuracy of EIS was 76.6% (49 of 64 correct diagnoses). The sensitivity and specificity of EIS were 86.7% (26 of 30 true positive) and 67.6% (23 of 34 true negative), respectively. The corresponding positive and negative predictive values were 70.3% and 85.2%. CONCLUSIONS: EIS is a potentially useful imaging modality for differentiating thyroid neoplasms. If these results are confirmed in large-scale trials, EIS may be an important part of the evaluation of thyroid nodules.

Adolescent↗

Technical complications and durability of hepatic artery infusion pumps for unresectable colorectal liver metastases: an institutional experience of 544 consecutive cases.

BACKGROUND: Hepatic arterial infusion pump chemotherapy is an important component in the treatment of patients with hepatic metastases. Successful use of a hepatic arterial infusion pump requires a low technical complication rate. We evaluated the complications and longterm durability of these devices at our institution. STUDY DESIGN: Between April 1986 and March 2001, 544 patients underwent hepatic arterial infusion pump placement for treatment of unresectable colorectal liver metastases. Patient- and pump-related data were collected by chart review. Pump-related complications, duration of pump function, and overall patient survival were recorded. RESULTS: Median patient survival was 24 months after pump placement. The incidences of pump failure were 9% at 1 year and 16% at 2 years. Pump complications occurred in 120 (22%) of the patients. Complications that occurred early after operation (< 30 days) were more likely to be salvaged than those occurring late (70% versus 30%, p < 0.001). Increased pump complication rates occurred in the setting of variant arterial anatomy (28% versus 19%, p = 0.02), when the catheter was inserted into a vessel other than the gastroduodenal artery (42% versus 21%, p = 0.004), if the pump was placed during the first half of the study period (1986 to 1993, 25% versus 1994 to 2001, 18%; p = 0.05), and if the surgeon had performed fewer than 25 earlier procedures (< 25, 31% versus > or = 25, 19%; p < 0.002). CONCLUSIONS: In this large single institution experience, pump-related complications were low, the majority of early pump complications were salvaged, and pump complication rates improved as institutional experience accumulated. Longterm durability of pump function was excellent.

Catheterization↗

Does any lower gastrointestinal bleeding in patients suffering from hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu) necessitate a full colonic visualization?

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) (the Osler-Weber-Rendu syndrome) is a rare autosomal dominant disease characterized by telangiectasias and arteriovenous malformations of the upper and lower respiratory tract, gastrointestinal tract, skin and central nervous system. Several previous reports have documented the appearance of a concomitant neoplasm in patients with this syndrome. AIMS: To study the occurrence and the clinical characterization of colonic neoplasm in patients with HHT. METHODS: We retrospectively reviewed the computerized database of the Hadassah University Hospitals (Jerusalem, Israel) for all patients with the diagnosis of HHT between January 1st, 1980 and July 30th, 2002. Cases of neoplasm were documented by review of medical charts and pathology reports. RESULTS: Six of the 24 patients developed malignancy. Three of the cases had extra colonic malignancy (melanoma in two patients and adenocarcinoma of urinary bladder in one patient) and three patients had adenocarcinoma of the colon. An additional three patients developed multiple colonic polyps (one patient had melanoma and one patient had adenocarcinoma of urinary bladder). CONCLUSIONS: HHT may be associated with the development of colonic adenocarcinoma and polyps. Therefore, in patients with HHT who present with new-onset anemia or gastrointestinal bleeding a lower gastrointestinal tract evaluation should be performed, even if their blood loss is suspected to be a manifestation of gastrointestinal HHT.

Adenocarcinoma↗

Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients.

BACKGROUND: Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD. AIM: As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls. METHODS: Appendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area. RESULTS: Ganglionic density was 10.13 per mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was 70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The other parameters were not different between the two groups. CONCLUSION: Densities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.

Adolescent↗

Clinical profile of breast cancer in Arab and Jewish women in the Jerusalem area.

BACKGROUND: The clinical profile of breast cancer may vary among different ethnic groups living in the same country and therefore affect the yield of a breast cancer screening program. The present study attempts to better characterize the breast cancer clinical profile of Arab women compared with Jewish women in the greater Jerusalem area with a future aim of establishing a comprehensive and effective screening program for this population. METHODS: Retrospective chart review was conducted and the following covariates were correlated with survival: ethnicity, age at diagnosis, and American Joint Committee on Cancer (TNM) stage at diagnosis. RESULTS: A total of 312 women were operated on for breast cancer between 1994 and 1999; 51% were Ashkenazi Jews (AJ), 26% were Sephardic Jews (SJ), 21% were Palestinian Arabs (PA), and 2% patients did not fit into those ethnic groups. The mean age at diagnosis was 51.5 years for the PA group, 53.4 +/- 1.5 for the SJ group, and 55.9 years for the AJ group (P <0.03 PA versus AJ). The tumor size (mean +/- SEM) was 38.8 +/- 3.7 mm, 31.1 +/- 2.4 mm, and 24.5 +/- 1.6 mm for the PA, SJ, and AJ groups, respectively (P = 0.03 for PA versus SJ and P <0.001 for PA versus AJ). Five-year overall survival was 77 %, 72%, and 58% for the AJ, SJ, and PA groups, respectively (P = 0.02); and 5-year disease-free survival was 72%, 51%, and 50% for the AJ, SJ, and PA groups, respectively (P = 0.03, AJ versus SJ). CONCLUSIONS: Our data demonstrate younger age and larger primary tumor size for the Arab patients compared with the Jewish patients. These findings were associated with lower 5-year survival and disease-free survival of the Arab patients.

Adult↗

Prognostic indicators of outcomes in patients with distant metastases from differentiated thyroid carcinoma.

BACKGROUND: Distant metastasis is uncommon in differentiated thyroid cancer and the prognosis is unclear. This study aims to evaluate outcomes and to define independent variables that are associated with tumor-related mortality in patients with distant metastasis from thyroid carcinoma. STUDY DESIGN: A retrospective review of the thyroid cancer research database identified 336 patients with distant metastasis from differentiated thyroid carcinoma treated at a single institution between 1941 and 2000. After excluding patients with local or regional recurrence, distant disease was either the first site of recurrence or was detected at the time of diagnosis of the primary tumor in 242 patients (72%). Patient, tumor, and treatment-related factors were analyzed for their relation to disease-specific survival (DSS) using multivariate Cox regression and the log-rank test. RESULTS: Median survival was 4.1 years and 10-year DSS was 26%. Distant disease was synchronous with the primary diagnosis in 97 of 242 (40%) patients. The site of metastasis was lung only in 103 (43%) patients, bone only in 80 (33%), other sites in 14 (6%), and more than one organ system in 45 (19%). Multivariate analysis identified age 45 years or more, symptoms, site other than lung only or bone only, and no radioactive iodine treatment for the metastasis as predictors of poor outcome with 13%, 11%, 16%, and 12% 10-year DSS, respectively. This compares with age less than 45 years, asymptomatic presentation, metastasis only in the lung or bone, and radioactive iodine treatment with 10-year DSS rates of 58%, 45%, 32%, and 33%, respectively (all p < 0.0001). Radioactive iodine treatment was more often given in patients who were less than 45 years of age, asymptomatic, and with metastasis only in the lung or bone only (p = 0.03, 0.11, 0.01). CONCLUSIONS: Longterm survival is possible in patients with distant metastasis from differentiated thyroid cancer. This retrospective study found that age of 45 years or more, site other than lung only or bone only, and symptoms at the time of diagnosis are associated with poorer outcomes.

Adenocarcinoma, Follicular↗

Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis.

We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck. Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness. Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome. Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.

Adenoma↗

Adrenocortical adenoma and carcinoma: histopathological and molecular comparative analysis.

We compared histomorphological features and molecular expression profiles of adrenocortical adenomas (ACAd) and carcinomas (ACCa). A critical histopathological review (mean, 11 slides per patient) was conducted of 37 ACAd and 67 ACCa. Paraffin-embedded tissue cores of ACAd (n = 33) and ACCa (n = 38) were arrayed in triplicate on tissue microarrays. Expression profiles of p53, mdm-2, p21, Bcl-2, cyclin D1, p27, and Ki-67 were investigated by immunohistochemistry and correlated with histopathology and patient outcome using standard statistical methodology. Median follow-up period was 5 years. Tumor necrosis, atypical mitoses, and >1 mitosis per 50 high-power fields were factors that were highly specific for ACCa (P <.001). Number (0 to 4) of unfavorable markers [Ki-67 (+), p21 (+), p27 (+), mdm-2(-)] expressed was significantly associated with mitotic activity and morphologic index (i.e., number of adverse morphologic features) and highly predictive of malignancy (P <.001). Ki-67 overexpression occurred in 0 ACAd and 36% ACCa (P <.001) and was significantly associated with mitotic rate and unfavorable morphologic index (P <.001). Tumor necrosis, atypical mitoses, >5 mitoses per 50 high-power fields, sinusoidal invasion, histologic index of >5, and presence of more than two unfavorable molecular markers were associated significantly with metastasis in ACCa. Well-established histopathologic criteria and Ki-67 can specifically distinguish ACCAd from ACCa. Tumor cell proliferation (Ki-67) correlates with mitotic activity and morphologic index. Tumor morphology is a better predictor of metastatic risk in ACCa than current immunohistochemistry-detected cell cycle regulatory and proliferation-associated proteins.

Adolescent↗

[Surgery for quality of life improvement in Crohn's disease: long-term follow-up].

Crohn's disease is an inflammatory disorder that affects various parts of the gastrointestinal tract. The management of Crohn's disease involves various anti-inflammatory and antibiotic agents while the role of surgery is limited to the treatment of disease associated complications. During recent years surgical therapy was also advocated for the improvement of the quality of life in patients with incapacitating Crohn's disease. In a previous study we demonstrated both the safety and efficacy of bowel-preserving surgery in a group of patients with Crohn's disease with no absolute indication for surgery, but with severe impediment of their quality of life due to severe disease activity and its therapy. The present study was undertaken to evaluate the long-term outcome of this group of patients. Fifteen Crohn's disease patients operated on for the improvement of the quality of life were followed for a median of 106 (range 82-132) months. During this time only 27% of the patients required reoperation for the treatment of recurrent Crohn's disease. The median surgery-free interval was 92.6 months and the 10-year surgery-free survival was 72%. Based on our results in this small group of patients, we suggest that there is a long-term benefit of surgical therapy for patients with Crohn's disease operated on in an attempt to improve their quality of life.

Adult↗

[Screening mammography for early diagnosis of breast cancer: facts, controversies, and the implementation in Israel].

BACKGROUND: Breast cancer is the leading cancer among Israeli women. Mammography is the most widely used tool for early diagnosis of breast cancer. Eight published randomized controlled trials followed nearly 500,000 women over 7 to 18 years. Most trials found that screening mammography decreases breast cancer mortality by 20 to 40%. A recent study examined the methodology of the randomized clinical trials and found that most trials were flawed in the methodology of data collection and analysis in a way that might have influenced the results of those trials. PURPOSE: To review the studies, clarify the issues, and reach a conclusion regarding the utility of screening mammography in reducing breast cancer-related mortality in Israel. METHODS: A review of the world literature, and analyses of the Israeli data. RESULTS: Seven out of eight published randomized controlled trials found a significant decrease in breast cancer mortality among women who underwent screening mammography. A meta-analysis of the trials also supports the utility of screening mammography in decreasing breast cancer mortality. The criticism over the methodology of these trials does not necessarily invalidate their conclusions. CONCLUSIONS: The data indicate that screening mammography does indeed assist in early diagnosis, and most published studies show a significant reduction in breast cancer-related mortality in the screened population. Due to the high incidence of breast cancer in the Israel, especially among young women, the national screening program should continue. Moreover, consideration should be given to expanding it to women starting at age 45, instead of 50, as is practiced today.

Adult↗

Comparison of bursting pressure of abdominal wall defects repaired by three conventional techniques.

Still debated are the appropriate techniques for the repair of abdominal wall defects and the methods used to measure their strength. Although tension has been used in many studies to test wound strength, bursting pressure reflects more accurately the pathophysiology of wound dehiscence. The aim of the current study was to evaluate three different techniques for closure of abdominal wall defects using a new and more accurate device for bursting pressure measurements. Full thickness abdominal wall defects measuring 2 cm2 were created in 43 anesthetized rats randomly assigned to three groups: simple primary closure (n = 15), Mayo repair (n = 14), and primary closure reinforced with a mesh (n = 14). Thirty days after surgery, the rats were sacrificed. The abdominal wall was fully excised and placed over a bursting chamber made of a metal cylinder connected to a carbon dioxide source with a control valve and a manometer. Gas was gradually released while the pressure was recorded until bursting occurred. Disruption of all closures occurred at the point where the suture itself penetrated the tissue. The average bursting pressure was 1383 +/- 299 mm Hg for the primary closure group, 1200 +/- 409 mm Hg for the mesh reinforcement group, and 1607 +/- 337 mm Hg for the imbrication repair (Mayo) group (P < 0.03). The data suggests an advantage for the Mayo repair over the other two repairs. The bursting chamber tested is a new and more reliable method to study techniques and conditions influencing the strength of abdominal wall closure.

Abdominal Wall↗

Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

Adolescent↗