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Biomedical subjects

Marisa Halpern

Publications and source records attributed to Marisa Halpern.

13 recordsLinked to original sources

Transthoracic needle biopsy in the diagnosis of large-cell neuroendocrine carcinoma of the lung.

To determine the effect of cytological diagnosis, fine-needle aspiration and brush cytology on lung tumors and core-needle biopsy, we retrospectively reviewed 11 cases of large-cell neuroendocrine carcinoma (LCNEC) found in our archives between the years 1997 and 2004. The preoperative cytological diagnosis of LCNEC is challenging because of the broad histologic similarity to other neuroendocrine tumors of the lung. The original cytologic diagnosis was LCNEC in nine of the cases while the remaining two were misdiagnosed as small-cell lung carcinoma. Smears were composed of clusters of intermediate-size cells with amphophylic cytoplasm, some with large nuclei and prominent nucleoli. In two of the cases there was discordance between the cytological findings and the immunohistochemical results. The cytological findings were correlated with histopathological observations.

Adult↗

An improved technique for mitosis counting.

Mitosis counting remains one of the most valuable prognostic indicators in tumor pathology; however, as currently carried out it is time consuming and not reproducible. In this study, 6 different pathologists, using different microscopes, arrived at widely different mitotic counts on the same slide, ranging from 4 to 16. These differences were mainly due to the different field areas of the various microscopes used and the method used for counting and recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19. Instead, when an average of 40 fields was recorded, the range was 4-11. Using the mitosis/volume index, which expresses the number of mitotic figures per mm2 of viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this method is complicated and not "user-friendly.'' We suggest a variation of the technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under the microscope, centered on the most mitotically active area of the tumor. The mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is estimated under low magnification. The number of mitoses per mm2 of viable tumor (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this modified method, the range of mitoses counted by the different observers was very narrow (9 to 11), and the time required for the counting was only 5-10 minutes.

Female↗

Expression of the intestinal marker Cdx2 in secondary adenocarcinomas of the colorectum.

CONTEXT: Secondary adenocarcinomas of the large bowel can closely mimic primary tumors. The differentiation of secondary from primary adenocarcinomas of the colorectum, however, is important because their clinical management and prognosis are different. Immunostaining with the nuclear transcription factor Cdx2, expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be of potential diagnostic use. OBJECTIVE: To investigate the diagnostic value of Cdx2 immunoexpression in distinguishing primary from common forms of secondary colorectal adenocarcinomas. DESIGN: Cdx2 immunoexpression was analyzed in 20 primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas and their corresponding primary tumors. All secondary tumors were diagnosed through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2 mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3 of prostatic, 3 of colorectal, and 2 of endometrial origin. RESULTS: Cdx2 was expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4) origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and endometrial origin. CONCLUSION: Cdx2 immunostaining may be useful in discriminating primary colorectal carcinomas from frequent types of secondary colorectal adenocarcinomas of nongastrointestinal origin. We suggest including Cdx2 in any antibody panel put together to distinguish between primary and secondary epithelial colorectal malignancies.

Adenocarcinoma↗

Diagnostic value of galectin-3 as a marker for malignancy in follicular patterned thyroid lesions.

BACKGROUND: The determination of malignancy in follicular patterned thyroid lesions is based on postoperative histologic findings. Therefore, affected patients are referred for surgery, although only 20% will have a final diagnosis of malignancy. The aim of this study was to investigate the potential of galectin-3 as a marker of malignancy in these lesions. METHODS: Fifty-four tissue specimens of follicular patterned thyroid lesions were immunohistochemically stained for galectin-3. Area and intensity scores were recorded. RESULTS: Significant differences were found between the benign and malignant lesions. The sensitivity, specificity, positive predictive values, and negative predictive values of galectin-3 staining were 82%, 68%, 75%, and 77%, respectively (p=.0002). Significant differences were also found between the subgroups of benign and malignant lesions (p < or =.05). CONCLUSIONS: Galectin-3 staining is highly sensitive for malignancy in follicular patterned thyroid lesions. Diagnostic problems may arise in the presence of Hurthle cell proliferation or minimally invasive follicular carcinoma.

Adenocarcinoma, Follicular↗

Closure of skin incisions in rabbits by laser soldering II: Tensile strength.

BACKGROUND AND OBJECTIVES: The basic characteristic property of wound closure is the immediate and long-term tensile strength (LTS). The objective of the current study was to compare tissue laser soldering to other available methods (i.e., cyanoacrylate glues and sutures) in the performance and outcome of wound closure and reparative healing process, with an emphasis on the immediate and LTS. STUDY DESIGN/MATERIALS AND METHODS: The animals were divided into three groups according to the type and details of the closure procedure. Group A: laser treatments at different temperatures were compared to sutured incisions, emphasizing the LTS after 10 days. Group B: laser soldering at 65 +/- 5 degrees C was compared to chemical glues (i.e., Histoacryl and Dermabond), emphasizing the immediate tensile strength (ITS). Group C: LTS of laser soldered incisions was compared to that of sutured incisions at various time intervals emphasizing LTS (3, 7, 14, 28 days). RESULTS: Group A: LTS at 60 degrees C exhibited the highest values (0.48 MPa). Group B: no ITS difference was detected between laser soldering and chemical glues. Group C: soldered incisions at 65 degrees C exhibited higher LTS (1.81 MPa) than that of sutured incisions (1.08 MPa) (P < 0.043). CONCLUSIONS: Temperature-controlled laser soldering at 65 degrees C provided sufficient ITS and higher bonding LTS values compared with sutures, resulting in better wound healing characteristics. The laser soldering system presented here should be tested on larger animal models before adopting it for clinical usage.

Animals↗

Closure of skin incisions in rabbits by laser soldering: I: Wound healing pattern.

BACKGROUND AND OBJECTIVES: Temperature-controlled tissue laser soldering is an innovative sutureless technique awaiting only solid experimental data to become the gold-standard surgical procedure for incision closure. The goals of the current study were: (1) to define the optimal laser soldering conditions, (2) to explore the immediate skin reparative healing events after sealing the wound, and (3) to determine the long-term trajectory of skin wound healing. STUDY DESIGN/MATERIALS AND METHODS: Skin incisions were generated over rabbit dorsa and were closed using different wound-closure interventions, in three groups: (a) closure, using a temperature-controlled infrared fiberoptic CO2 laser system, employing 47% bovine serum albumin as a solder; (b) wound closure by cyanoacrylate glues; and (c) wound closure by sutures. The reparative outcomes were evaluated macroscopically and microscopically, employing semi-quantitative grading indices. RESULTS: Laser soldering of incisions at T = 65 degrees C emerged as the optimal method achieving immediate wound sealing. This in turn induced accelerated reparative events characterized by a reduced inflammatory reaction, followed by minimal scarring and leading to a fine quality healing. CONCLUSIONS: Temperature-controlled laser soldering offers an accelerated wound reparative process with numerous advantages over the conventional methods. Further investigations may reveal additional benefits in the spectrum of advantages that this innovative surgical technology has to offer. This can introduce new scientific insight that will pave the way for clinical use.

Animals↗

Laparoscopic laser soldering for repair of ureteropelvic junction obstruction in the porcine model.

BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty is used for the repair of ureteropelvic junction (UPJ) obstruction. Our objective was to introduce laser soldering to this procedure. MATERIALS AND METHODS: We developed a system based on a CO2 laser, an infrared detector, and two infrared transmitting optical fibers to obtain temperature-controlled laser soldering of cuts in tissues. The system was used for laparoscopic soldering of incisions in the kidneys of pigs. RESULTS: We carried out laparoscopic pyeloplasty successfully in a porcine model using fiberoptic laser soldering. Laparoscopic laser soldering was found to be faster than suturing. It was easier to use and provided watertight bonding. CONCLUSIONS: This technique will be useful in pyeloplasty as well as other laparoscopic surgical procedures.

Animals↗

Lactobacillus GG bacteria ameliorate arthritis in Lewis rats.

Probiotic bacteria have beneficial effects in infectious and inflammatory diseases, principally in bowel disorders. In the case of chronic progressive autoimmune arthritides, a major goal of treatment is to reduce inflammation. We hypothesized that probiotic bacteria would ameliorate inflammation found in arthritis models. To assess this effect, Lewis rats were injected with 50 microg bovine alpha-tropomyosin (TRM) or complete Freund's adjuvant (CFA) to induce tropomyosin arthritis (TA) or adjuvant arthritis (AA), respectively. In both models, the rats were divided into 6 groups and fed 0.5 mL/d of the following suspensions: 1) heat-killed Lactobacillus GG (LGG) bacteria; 2) live LGG, both 10(11) colony-forming units (cfu)/L; 3) sterilized milk; 4) plain yogurt; 5) yogurt containing 10(11) cfu/L LGG; or 6) sterilized water. In the disease-prevention experiments, feeding started 1 wk before or after disease induction. In the therapeutic experiments, feeding was initiated at the onset of clinical arthritis. In all experiments, there were significant interactions between time and treatment (P < 0.001), except for milk, which had no effect in the therapeutic experiment. Histologically, rats fed yogurt containing LGG had a milder inflammation in all experiments (P < 0.05), whereas rats fed plain yogurt exhibited a moderate inflammatory score only in the prevention experiments. Anti-TRM antibody titers were not affected by any of the treatments in any of the experiments. Ingestion of live or heat-killed human LGG had a clinically beneficial effect on experimental arthritis. Our observation of the remarkable preventive and curative effect on arthritis using commercial yogurts containing lactobacilli, especially LGG, suggests the need for investigation of these agents in arthritic patients.

Administration, Oral↗

c-kit expression in primary and metastatic merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin that is associated with a high incidence of recurrence and metastasis. The therapeutic arsenal for this malignancy is limited and once it spreads, there is no effective treatment. c-kit expression has been demonstrated previously in primary MCCs thus raising the possibility of treating MCCs with imatinib mesylate, the tyrosine kinase inhibitor that has shown promise in the management of c-kit expressing tumors. In this study we examine 25 additional primary MCCs and also 6 of their lymph node metastases. Formalin-fixed, paraffin-embedded tissues were stained immunohistochemically with an antibody directed against the KIT receptor. Percentage and intensity of staining were analyzed semiquantitatively using a three-tiered system. Twenty-one of the 25 (84%) primary tumors stained positively for KIT, of which 14 (67%) showed widespread positivity. Five of the 6 lymph nodes (83%) were similarly positive. High mitotic rate and vascular invasion in the primary tumors tended to be associated with prominent staining in the lymph node metastases. No association was found between c-kit expression and outcome. We confirm that the majority of primary MCCs express c-kit and further find that metastases are positive for the KIT receptor as well. Thus, c-kit expression may be an early event in the transformation of MCC, but not a marker for tumor progression.

Aged↗

Placental immunomodulator ferritin, a novel immunoregulator, suppresses experimental arthritis.

OBJECTIVE: To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats. METHODS: The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats. C48 was injected intraperitoneally daily from day 3 to day 9 or from day 7 to day 13 after induction of synovitis by zymosan, and every other day from day 2 to day 14 after induction of AIA. Swelling of the joints and histologic features of the synovium were assessed. Th1 and Th2 cytokines were quantified by enzyme-linked immunosorbent assay. RESULTS: Both PLIF and C48 significantly inhibited the in vitro immunoreactivity of mouse splenocytes in MLCs. Treatment of ZIA mice and AIA rats with C48 effectively reduced joint swelling. C48 treatment reduced synovial lining thickening, numbers of mononuclear cells and histiocytes, as well as cartilage destruction and bone erosions. In vitro, activated splenocytes from C48-treated ZIA and AIA animals produced significantly higher levels of interleukin-10 (IL-10). In animals with ZIA, this was accompanied by lower levels of tumor necrosis factor and IL-2. CONCLUSION: Human PLIF and C48 were shown to exert cross-species immunosuppressive activity in vitro. The in vivo suppression of articular inflammation in the experimental models of ZIA and AIA was the result of treatment with the antiinflammatory human C48. These results suggest that treatment with C48 may offer an effective immunotherapeutic means of controlling inflammatory polyarthritis.

Adjuvants, Immunologic↗

Small nonpolypoid colorectal carcinoma.

The objective of this study was to characterize and assess the presence and frequency of small nonpolypoid colorectal adenocarcinomas among patients with colorectal cancer referred for surgery. The medical, endoscopic, and surgical reports and the histopathologic slides of all patients operated on for colorectal cancer were retrospectively reviewed. Small nonpolypoid colorectal cancer (SNPCC) was defined as a malignant, nonpolypoid lesion smaller than 15 mm. SNPCC was classified according to the Japanese macroscopic classification of colorectal carcinoma. The frequency of SNPCC among patients referred for operation was 1.8%. Most of these patients were asymptomatic and were diagnosed by the same endoscopist using a high-resolution video-endoscope without the assistance of enhancement techniques. These lesions had a mean size of 10.8 mm, were mainly of the flat or flat elevated type, and were located in the distal colon. Among patients with colorectal cancer referred for surgery, 1.8% had SNPCC. These lesions can be detected using high-resolution video-endoscopy equipment without the need for enhancement techniques, as reported in Japanese series. Increased awareness of the existence of such SNPCC lesions may help the average endoscopist detect such lesions. As SNPCC represents colorectal cancer, all the cases in our series were treated by typical oncologic surgical resection.

Adenocarcinoma↗

The great auricular nerve; does it penetrate the parotid gland? An anatomical and microscopical study.

UNLABELLED: Conflicting opinions exist in the literature regarding the exact anatomical course of the great auricular nerve. The aim of this work was to study the pathway of its anterior branch and endings in relation to the parotid gland. MATERIAL AND METHODS: Thirty-seven specimens were dissected from 19 fresh adult cadavers and studied including the parotid gland at the region of the termination of the anterior branch of the nerve. The causes of death were not due to pathology in the parotid region. All the specimens were fixed in formaldehyde, serially cut, stained by haematoxylin and eosin, and examined by light microscope. RESULTS: In most of the glands (21/37 = 57%), there was no evidence of well-organized nerve fibres of the great auricular nerve inside the parotid gland. In a few (5/37 = 13%), nerve fibers were seen to penetrate the interlobular septa and in 30% of the cases (11/37) nerve bundles were found deep in the gland along side small ducts and close to thin-walled blood vessels. CONCLUSION: These findings prove that there are anatomical variations of the endings of the anterior branch of the great auricular nerve. The significance of nerve bundles deep in the gland along ducts and near vessels remains to be explored.

Adult↗

A new scoring system using multiple immunohistochemical markers for diagnosis of uterine smooth muscle tumors.

The diagnosis of uterine smooth muscle neoplasms by light microscopy is difficult. Multiple classification schemes have been proposed based on mitotic rate, nuclear atypia, and the presence or absence of necrosis. None of these classification systems has been entirely successful. This study was undertaken to evaluate the use of selected immunohistochemical and histochemical markers in differentiating these tumors, in addition to accepted morphologic criteria. Ten cases of each of the following: leiomyosarcomas (LMS), atypical leiomyomas (AL), cellular leiomyomas (CL) and usual leiomyomas (UL), were classically evaluated for histological diagnosis and were stained for Ki-67 (MIB-1), bcl- 2 and p53 using monoclonal antibodies and the avidin-biotin peroxidase method, and argyrophilic nucleolar organizer region (AgNORs). The number of stained cells was counted in the most positively stained region in a 4 mm2 square cover glass mounted on each slide. The mean value was calculated for each group of tumors. The data for Ki-67 (MIB- 1), bcl-2, p53 and AgNOR staining respectively, were significantly higher in LMS by comparison to UL, CL or AL. Because many singular cases had superimposed data being difficult to diagnose, a new scoring system for pathological evaluation was created. The results obtained by this scoring system suggest that immunohistochemical markers Ki-67 (MIB-1), bcl-2, p53 together with the AgNOR staining could be useful, by the scoring system, as an adjunct to the current accepted morphologic criteria in differentiating smooth muscle tumors of the uterus.

Antigens, Nuclear↗