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Biomedical subjects

M R Schwartz

Publications and source records attributed to M R Schwartz.

At least 37 records · Page 2Linked to original sources

A new immunocompetent murine model for oral cancer.

OBJECTIVE: To develop and characterize a new immunocompetent murine model that attempts to parallel the clinical and biological nature of head and neck cancer. DESIGN: The growth rate and histologic characteristics of the SCC VII/SF cell line were initially determined in tissue culture experiments. Animal experiments were subsequently performed on C3H/HeJ mice. Using direct injection, 5 x 10(5) SCC VII/SF cells were delivered to the floor of the mouth of each animal. Animals were killed after 1, 2, and 3 weeks, and tumor growth, invasion, and regional and distant metastases were evaluated. RESULTS: Squamous cell carcinomas that could be palpated and measured externally were identified in the floor of the mouth of C3H/HeJ mice after 5 to 7 days. Local invasion into the mylohyoid musculature and mandible was present. Cervical lymph node and pulmonary metastases were identified between 2 and 3 weeks. CONCLUSIONS: This study introduces a new oral cancer animal model that shows initial locoregional tumor invasion, direct extension into the neck, early cervical metastases, and pulmonary metastases. These clinical and histopathologic attributes reflect the biological behavior and tumor progression seen in human oral cancer and therefore provide a model for clinically applicable research for primary and metastatic head and neck cancer.

Animals↗

Optimizing suicide gene therapy for head and neck cancer.

An effective "suicide gene" therapy strategy in experimental studies has been the use of the herpes simplex virus thymidine kinase gene (HSV-tk) to sensitize tumors to the cytotoxic effects of ganciclovir administration. Previous studies using this model have focused on utilizing maximal viral titers and high levels of ganciclovir that are not compatible with human dosing. Because of the high ganciclovir doses and the maximal viral titers, this strategy has limited application to actual clinical scenarios. In the following studies the authors investigate tumor regression in an oral squamous cell carcinoma animal model as a function of variable adenoviral titers and more physiologic ganciclovir dosing. Using adenoviral titers ranging from 1 x 10(8) to 2 x 10(9) plaque forming units (pfu) to treat oral tumors, they found no statistical difference in tumor regression among the different viral doses, despite differences in mitotic activity. Each treatment group, however, demonstrated a significant effect on tumor regression when compared with controls. Furthermore, the authors were able to reduce the level of ganciclovir administration to 10 mg/kg twice daily from established levels of 100 to 150 mg/kg twice daily while maintaining significant tumor responses to the HSV-tk therapy. Mean survival of animals treated with this lower ganciclovir dose was significantly higher than in controls and was equal to established means based on previous studies using higher ganciclovir doses. The optimization of this suicide gene therapy strategy is imperative in order to minimize theoretical and known viral and ganciclovir toxicities while establishing a foundation upon which to design appropriate and effective clinical trials.

Animals↗

Stereotactic core breast biopsy of a minimal carcinoma complicated by a large hematoma: a management dilemma.

Stereotactic core biopsy of a 4-5-mm, suspicious mammographic lesion was complicated by substantial hematoma formation in a patient with subsequently diagnosed factor XI deficiency. As a result, the small infiltrating ductal carcinoma could no longer be identified at mammography to allow accurate needle localization for lumpectomy. Sufficient resorption of the hematoma at 3 months permitted successful needle localization and lumpectomy. In these cases, expectant management may obviate extensive surgery.

Biopsy↗

Localized thymic Langerhans' cell histiocytosis and its relationship with myasthenia gravis. Immunohistochemical, ultrastructural, and cytometric studies.

OBJECTIVE: It has been suggested that localized Langerhans cell histiocytosis may represent an exaggerated form of a proliferative process that has been reported in a few patients with myasthenia gravis. To evaluate the relationship between thymic Langerhans' cell proliferation and myasthenia gravis, we analyzed a rare case of localized thymic Langerhans' cell histiocytosis and examined thymic Langerhans' cell distribution in myasthenic and control patients. DESIGN: Immunohistochemical, ultrastructural, and image cytometric DNA analyses were performed on the index case. Immunostaining for S100 was performed on 20 additional thymuses, 10 from patients with myasthenia gravis and 10 from control patients. RESULTS: Immunohistochemical studies revealed no increase in Langerhans' cells in the surrounding thymic tissue of the index case. No difference was found between the number of Langerhans' cells in the remaining thymuses of myasthenia patients compared with the control group, and no micronodular proliferations were identified in either group. CONCLUSIONS: Localized thymic Langerhans' cell histiocytosis is an unusual lesion that is associated with myasthenia gravis in some patients. In the few cases reported at present, however, the lesion does not appear to be related pathogenetically to myasthenia gravis.

Adult↗

Adenovirus-mediated gene therapy for human head and neck squamous cell cancer in a nude mouse model.

Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir administration was used to treat human head and neck cancer in nude mice. Tumors were generated by transcutaneous needle injection of 6 x 10(6) human squamous carcinoma cells into the floor of the mouth. After 14 days, 10(10) particles of a replication-defective recombinant adenovirus containing the herpes simplex virus thymidine kinase gene (ADV/RSV-tk) were injected directly into the tumors. The mice subsequently received ganciclovir injections for six consecutive days and were sacrificed at 21 days post tumor cell implantation. Clinical response to the treatment was assessed by computer-imaged morphometric analysis of cross sectional area of nonnecrotic tumor and mitotic activity, which were used for the calculation of a tumor index. The median tumor index value of the treatment group was 280- to 2400-fold smaller than controls which did not receive the therapeutic gene (P < 0.001-0.016), and three-quarters of the treatment group had tumor index values that were indicative of near total tumor regression. Survival studies show that 50% of the ADV/RSV-tk-treated mice are free of tumor at 160 days post adenovirus injection, while all controls died or required sacrifice within 43 days. These results demonstrate that clinically effective in vivo treatment of human squamous cell cancer can be achieved using adenovirus-mediated gene therapy.

Adenoviridae↗

Alpha 1-antitrypsin deficiency and chronic pancreatitis.

Alpha 1-antitrypsin deficiency is a genetic disorder commonly associated with pulmonary and hepatic injury. Low serum levels of this glycoprotein result in an imbalance between circulating protease and protease inhibitors, which is thought to play a role in the development of emphysema. In recent studies, a protease-to-protease inhibitor imbalance in patients with alpha 1-antitrypsin deficiency was thought to be a mechanism contributing to the development of chronic pancreatitis. The heterozygous phenotype and low levels of this glycoprotein have been reported to occur more frequently in patients with chronic pancreatitis than in healthy controls. We report a patient with Pi-SS phenotype alpha 1-antitrypsin deficiency and chronic pancreatitis complicated by recurrent pancreatic pseudocysts and chronic abdominal pain. Our case supports the association between chronic pancreatitis and alpha 1-antitrypsin deficiency. Furthermore, this case provides support for the use of pancreatic stent drainage in the management of intractable abdominal pain in patients with chronic pancreatitis and a dominant stricture.

Abdominal Pain↗

Neuroendocrine neoplasms of the larynx.

Neuroendocrine neoplasms of the larynx are a rare group of tumors that include carcinoid tumor, atypical carcinoid tumor, and small cell carcinoma. These neoplasms pose interesting diagnostic, prognostic, and therapeutic dilemmas, and they are, as a whole, aggressive tumors with a tendency for local and distant spread. The authors of this study examined six new cases of laryngeal neuroendocrine neoplasms. One case manifested itself as a primary atypical carcinoid tumor and caused a "carcinoid syndrome." The remaining five cases were small cell carcinomas of the larynx. Histologic, immunocytochemical, DNA flow cytometric, and p53 studies were performed on all cases. The expression of neuron-specific enolase and chromogranin were the most useful markers in this group of tumors. Overexpression of p53 protein was present in the majority of cases, including the atypical carcinoid tumor. The implications of these studies for diagnosis, classification, and treatment are discussed.

Adult↗

Atypical and malignant lipomatous lesions of the head and neck.

Although liposarcoma is the second most common soft-tissue sarcoma in adults, the incidence of liposarcoma of the head and neck is low. There are only 83 reported cases of head and neck liposarcoma. We report four cases of atypical and malignant lipomatous lesions of the head and neck and discuss their histologic classification and treatment implications. The histologic nature of liposarcoma is correlated clinically with treatment outcome. Recently, many authors have adopted the term atypical lipoma to describe well-differentiated lipomatous lesions in superficial extremity locations because of their tendency toward local recurrence only, without metastases or patient mortality. Although we accept the classification atypical lipoma for superficial, well-differentiated lesions, we believe that histologically similar lesions in nonsuperficial locations in the head and neck are best designated "well-differentiated liposarcoma."

Adult↗

Non-specific fluorescent whitener stains in the rapid recognition of pulmonary dirofilariasis: a report of 20 cases.

BACKGROUND: Solitary lung nodules in humans caused by the dog parasite Dirofilaria immitis are steadily increasing in number. The organisms can be easily missed in haematoxylin and eosin stained tissue when they are degenerated and pale staining. METHODS: The value of Tinopal CBS-X (TCBS-X) and Calcofluor white (CFW), two rapid, inexpensive, simple non-specific fluorescent whitening stains, were assessed in the identification of these worms. Deparaffinised rehydrated tissue slides prepared from the pulmonary nodules were stained for one minute in 1% w/v aqueous solutions of TCBS-X or CFW, counterstained, coverslipped, and viewed with a fluorescent microscope. RESULTS: The stains demonstrated the intact worm and worm fragments in 20 cases of pulmonary dirofilariasis collected from hospitals in Houston. The filariae and fragments of filariae stained bright green while the background tissue stained red, delineating the internal structures of the worm. CONCLUSIONS: Dirofilariasis should be included in the differential diagnosis of subpleural masses, and non-specific fluorescent whitening stains can help in the rapid recognition of the fragmented organism in cytological or surgical material.

Adult↗

Life-threatening presentations of fibrovascular esophageal and hypopharyngeal polyps.

Giant fibrovascular polyps of the esophagus and hypopharynx are benign tumors of the upper digestive tract. Although a rare cause of asphyxiation, laryngeal impaction by a regurgitated polyp of the esophagus may be the initial symptom that brings the patient to request medical attention. Two new cases of giant fibrovascular polyps with dramatic and potentially life-threatening presentations illustrate the unpredictable behavior of these unusual tumors. Both patients presented to the emergency center with a history of coughing and eructation followed by temporary airway obstruction that was relieved by clenching a regurgitated fleshy mass between the teeth. Diagnostic and therapeutic intervention requires aggressive airway management, radiographic and endoscopic evaluation, and definitive surgical treatment. Tracheotomy was required in one patient, and successful endotracheal intubation provided satisfactory airway control in the second. Esophagoscopy revealed the origin of both tumors to be near the cricopharyngeal muscle. Complete surgical excision was curative in both cases.

Aged↗

Refining the indications for arteriography in penetrating extremity trauma: a prospective analysis.

PURPOSE: Five hundred fourteen consecutive patients with an isolated upper or lower extremity penetrating injury were entered into a prospective study designed to refine the indications for diagnostic arteriography. METHODS: Twenty-two (4%) patients with limb-threatening ischemia who required immediate operation and 23 (4%) who refused arteriography were excluded from subsequent analyses. The remaining 469 patients were classified as being at high, intermediate, or low risk for an arterial injury. RESULTS: Two hundred thirteen patients who were at low risk were observed for 24 hours, discharged, and monitored as outpatients. No delayed complications of an arterial injury developed in any patient in this group. The intermediate-risk group of 151 patients and the high-risk group of 105 patients underwent arteriography. Seventy-seven injuries were identified; 24 were major (limb-threatening) and 53 were minor. Fourteen major injuries required operative repair or transcatheter embolization; the remaining 10 nonocclusive major injuries were observed without sequelae. CONCLUSIONS: By step-down logistic regression only pulse deficit (p < 0.01) and an ankle/brachial or wrist/brachial index less than 1.00 in the injured extremity (p < 0.03) were found to be significant predictors of an arterial injury. The presence of either of these two clinical variables successfully predicted all major arterial injuries. This prospective study supports the proposition that arteriography that is limited only to those patients who have either a pulse deficit or minimum ankle/brachial or wrist/brachial index less than 1.00 successfully detects all significant arterial injuries.

Adolescent↗

Carcinoma of the gallbladder found during laparoscopic cholecystectomy: a case report and review of the literature.

Laparoscopic cholecystectomy has become an accepted appropriate method for removal of the diseased gallbladder. With cancer of the gallbladder to be expected in 1-2% of all biliary tract operations, it is likely that surgeons may be confronted with the unsuspected finding of gallbladder carcinoma during the course of laparoscopic cholecystectomy. We present here a case of gallbladder carcinoma found at laparoscopic cholecystectomy, and discuss the interesting clinical findings associated with this entity, including the preoperative suggestion of Trousseau's syndrome. A review of the pertinent literature is included.

Adenocarcinoma↗

Estrogen and progesterone receptors in bronchogenic carcinoma.

Although the lung is not usually considered a major target organ of sex hormones, epidemiological observations, studies of pulmonary neoplasms in laboratory animals, and investigations of carcinomas derived from other "nontarget" organs suggest that sex hormones may have a role in the pathogenesis of bronchogenic carcinoma. To confirm that estrogen (ER) and progesterone receptors are present in human lung cancers, 19 resected lung cancers were examined for receptors using a prelabeled sucrose gradient method. Three squamous cell carcinomas were positive for ER (greater than 6.9 fmol/mg cytosol protein). Three squamous cell carcinomas, two adenocarcinomas, and one small cell carcinoma were positive for progesterone receptors (greater than 6.9 fmol/mg cytosol protein). One tumor, a squamous cell carcinoma arising in a woman who smoked, had an ER level of 301 fmol/mg, a highly positive level even for breast cancers. These observations may provide a basis for adjuvant hormonal therapy in selected lung cancer patients.

Aged↗

Serous surface carcinoma of the peritoneum: a clinicopathologic study of 22 cases.

Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesothelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (100%), Leu-M1 (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease.

Adult↗

Thymic carcinoma. A clinicopathologic study of 13 cases.

Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas or thymic cysts, we conclude that TCA is derived from thymic epithelium.

Adenocarcinoma↗