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Biomedical subjects

K T Robbins

Publications and source records attributed to K T Robbins.

At least 55 records · Page 3Linked to original sources
PubMed1995

Selective intra-arterial infusion of high-dose cisplatin in patients with advanced head and neck cancer results in high tumor platinum concentrations and cisplatin-DNA adduct formation.

A group of 23 patients with advanced head and neck cancer were treated with highly selective intra-arterial (IA) cisplatin 150 mg/m2 delivered rapidly through microcatheters. The systemic effects of cisplatin were neutralized by concurrent administration of sodium thiosulfate. Two-to-threefold higher tumor platinum contents were detected in tumor biopsies after selective IA cisplatin administration compared to historical controls (treated with 100 mg/m2 IA). Cisplatin-induced DNA modification in human tumor biopsies was quantitated using the antiserum NKI-A59. High levels of cisplatin DNA adducts were detected which correlated linearly with the tumor platinum content (r2 = 0.62). The addition of radiotherapy to this high dose intensity cisplatin treatment resulted in a 92% complete response (CR) rate (12 of 13 patients achieved a CR). Since no difference in tumor platinum content was detected between patients receiving or not receiving radiotherapy (13 and 10 patients, respectively), but the response rate was substantially different (12 CR and 1 partial response with radiotherapy versus 6 partial and 4 non-responders without radiotherapy), these data suggest that the high platinum levels achieved by selective IA infusion were sufficient to produce enough interaction with radiotherapy to cause a 92% CR rate. Whether this interaction is additive or synergistic is as yet unclear.

Antineoplastic Agents↗
PubMed1994

Sponge-gel-supported histoculture drug-response assay for head and neck cancer. Correlations with clinical response to cisplatin.

OBJECTIVE: Sponge-gel-supported histoculture drug-response assay (SSHDRA) represents a promising method to determine chemosensitivity of solid tumors. To determine whether the assay correlates clinically, we compared the in vivo and in vitro effects of cisplatin in 23 of 26 patients with head and neck cancers. DESIGN: The criterion for in vitro sensitivity to cisplatin was an 84% or greater inhibition by cisplatin of the number of tritiated thymidine-incorporating cells of the histocultured tumors compared with untreated control culture preparations, as measured by means of histologic autoradiography. Comparisons were made with clinical responses, ie, complete response, partial response, or no response. PATIENTS: The study was carried out in patients with head and neck cancers and comprised 21 patients with squamous-cell carcinoma, three patients with other carcinomas, and two patients with sarcoma. RESULTS: Ten of 12 patients with in vitro-sensitive tumors had either complete or partial response clinically. The overall accuracy of the SSHDRA was 74% in this correlative clinical trial; the predictive-positive value was 83%, the sensitivity was 71%, and the specificity was 78%. Seven of 11 patients with in vitro-resistant tumors demonstrated no response for a predictive-negative value of 64%. CONCLUSIONS: We conclude that the SSHDRA shows a high correlation for tumors that demonstrate both in vivo drug resistance and sensitivity. The in vitro-like maintenance of three-dimensional tissue architecture of the tumors in histoculture probably contributes to high clinical predictivity of drug response of the SSHDRA. The data support further comparisons to determine the clinical usefulness of the SSHDRA for identifying complete and partial responders to chemotherapy.

Adenocarcinoma↗
PubMed1994

Diagnostic localization studies for primary hyperparathyroidism. A suggested algorithm.

OBJECTIVE: To assess the accuracy of preoperative imaging studies in primary hyperparathyroidism. DESIGN: Retrospective review of all patients treated surgically for primary hyperparathyroidism at The University of California-San Diego Medical Center between January 1990 and May 1992. Results of preoperative imaging studies were compared with surgical and pathologic findings. SETTING: The University of California-San Diego Medical Center, a primary care and referral center. PARTICIPANTS: Twenty-eight patients were included in the study, and a total of 41 imaging studies were obtained. OUTCOME MEASURES: The accuracy of preoperative imaging studies in correctly localizing the site of a parathyroid adenoma. RESULTS: Ultrasound correctly identified the site of a solitary parathyroid adenoma in 82% of cases, and magnetic resonance imaging in 80% of cases. The adenomas that were not localized by ultrasound were correctly localized by magnetic resonance imaging. These findings are discussed within the context of recent trends in parathyroid surgery. CONCLUSIONS: Based on the results and a review of the literature, a simple algorithm for the use of these imaging studies is proposed. Use of this algorithm will improve preoperative planning, and potentially reduce operative time and morbidity.

Adenoma↗
PubMed1994

Growth effects of tamoxifen and estradiol on laryngeal carcinoma cell lines.

OBJECTIVES: We tested the in vitro and in vivo growth effects of estradiol and tamoxifen citrate to determine whether patients with laryngeal carcinoma could benefit from antiestrogen therapy as demonstrated for cancers of other estrogen-responsive organs. DESIGN: A comparison of growth effects of the hormones relative to controls by using a tetrazolium dye reduction assay and nude mice. MATERIALS: Two estrogen-positive laryngeal carcinoma cell lines (UMSCC5 and UMSCC11B) and athymic mice were used. RESULTS: There were marked growth inhibitory effects of tamoxifen alone in concentrations of 3 to 8 mumol/L on both cell lines. There were no in vitro growth effects of estradiol-17 beta alone in concentrations of 0.1 to 9.6 mumol/L, but there was antagonism of the estradiol to the growth inhibitory effects of tamoxifen. In athymic mice, estradiol markedly stimulated the growth of UMSCC5, whereas tamoxifen inhibited growth. CONCLUSIONS: These results support the concept of chemotherapeutic growth inhibition of estrogen receptor-positive laryngeal cancer with antiestrogens.

Animals↗
PubMed1994

A targeted supradose cisplatin chemoradiation protocol for advanced head and neck cancer.

BACKGROUND: Hypothesizing that cisplatin (DDP) drug resistance is dose dependent and the radiosensitizing effect of DDP is clinically beneficial, we conducted a chemoradiation protocol using extremely high doses of DDP delivered intra-arterially (IA) to locally advanced head and neck tumors. PATIENTS AND METHODS: Twenty-nine patients with untreated stage IV disease received 4 weekly infusions of 150 mg/m2, simultaneous systemic DDP neutralization with intravenous (IV) bolus sodium thiosulfate, and concomitant radiotherapy (180 to 200 cGy/day x 35 fractions). RESULTS: The complete response rate of the 24 evaluable patients as determined with repeat biopsies was 23/24 (96%). Of the 29 patients evaluable for toxicity, central nervous system complications related to the infusion technique occurred with 2/110 infusions, both of which were reversible. The rate of grade III to IV chemotoxicity was 13%. The median length of follow-up was 22 months. There have been 6 recurrences: 1 local; 3 regional; and 2 at distant sites. The projected overall and disease-free 3-year survival was 88% and 53%, respectively. CONCLUSION: We conclude that the combination of rapid selective delivery of supradose DDP/IV thiosulfate neutralization and concomitant radiotherapy can be safely and effectively applied to patients with advanced head and neck cancer. Preliminary survival analysis indicates that this approach may improve the prognosis for patients with an otherwise devastating disease.

Adult↗
PubMed1994

Highly selective infusions of supradose Cisplatin for cranial base malignancies.

Treatment results for malignant skull base lesions may be improved with combined modality therapy. Using a novel drug infusion technique that capitalizes on the pharmacodynamic cisplatin-neutralizing properties of thiosulfate, 14 patients (6 untreated, 8 recurrent) received cisplatin (120 to 200 mg/m(2) for 1 to 4 weeks x 2-4 cycles) as part of a multimodality treatment program. Histology included squamous cell carcinoma, 11 patients (8 upper aerodigestive tract, 3 cutaneous); sarcoma, 2 patients (malignant fibrous histiocytoma, synovial cell sarcoma); and salivary gland cancer, 1 patient. The lesions involved the lateral skull base (12 patients) and the anterior (2 patients).Dose intensities for cisplatin were between 33.3 and 200 mg/m(2)/wk. Major responses occurred in 9/14 patients (64.3%), 3 of whom had complete responses. Drug toxicity, occurring in 11 patients, was mild and there were no significant complications as a result of the infusions. Eleven patients subsequently underwent surgical resections. The mean survival time is 23.3 months. Eight patients are alive without disease, 2 alive with disease, and 4 are dead of disease.The effectiveness of this highly selective supradose cisplatin infusion technique and its low morbidity support continued investigations of its application to patients with cranial base malignancies.

Journal Article↗
PubMed1994

Phase I study of highly selective supradose cisplatin infusions for advanced head and neck cancer.

PURPOSE: To determine the maximum dose-intensity of cisplatin (DDP) that could be administered by selective intraarterial (IA) infusion in combination with systemic sodium thiosulfate neutralization to patients with head and neck carcinoma. PATIENTS AND METHODS: Forty-two patients (23 untreated stage III/IV, 19 recurrent) received highly selective IA DDP, rapidly delivered through microcatheters placed angiographically, to a maximum dose-intensity of 200 mg/m2/wk. Concurrently, the systemic effects of DDP were neutralized by intravenous (IV) bolus sodium thiosulfate. RESULTS: Problems related to the infusion technique occurred in eight of 140 courses, all of which were inconsequential. The rates of reversible grade I/II and grade III/IV toxicity were 14.8% and 1.1%, respectively. Dose-limiting toxicity, which consisted of severe electrolyte loss, occurred at a dose of 200 mg/m2/wk. The maximum-tolerated dose of DDP was 150 mg/m2 administered weekly for four doses. The overall and complete response rates in 38 assessable patients were 19 of 22 (86%) and nine of 22 (41%) for stage III/IV untreated tumors and 10 of 16 (62%) and four of 16 (25%) for patients with recurrent disease, respectively. CONCLUSION: This pharmacologic strategy permits the selective and rapid delivery of extremely high doses of DDP to head and neck carcinomas with minimal procedural complications, low systemic toxicity, and high tumor response rates.

Adult↗
PubMed1992

Oronasal reconstruction with local mucoperiosteal and free latissimus dorsi flaps.

We describe the use of maxillary sinus mucoperiosteum as a pedicled flap to reconstruct the floor of the nose following resection of cancer involving the palate, buccal mucosa, and mandible. Complete inferior turbinectomy allows access to the roof of the maxillary sinus to harvest the mucoperiosteum as a vascularized flap pedicled under the remaining middle turbinate. A free latissimus dorsi myocutaneous flap suspended from the floor of the orbit and nasal septum is then used to obliterate the maxillary sinus, reconstruct the palate, and support the floor of the nose. A reconstruction employing this combination of flaps is presented, including postoperative endoscopic intranasal photography and magnetic resonance imaging. Despite the elevated level of the floor of the nose and the absence of the inferior turbinates, rhinomanometry performed 3 months postoperatively demonstrates adequate nasal airflow with normal responses to nasal decongestants.

Aged↗
PubMed1992

Multidimensional scaling of head and neck metastases.

A mathematical analysis, called multidimensional scaling, was applied to two sets of data on metastases from head and neck cancers. The analysis places lymph nodes in an imaginary space (here termed a 'nodalgram') such that distances between nodal clusters are proportional to differences in the occurrence of tumor metastases. Two-dimensional scaling explains 93% of the variance in clinical data from 1008 patients and 91% of the variance in pathological data from a different set of 415 patients. These independent results are closely correlated, and both explain vastly more of the data than expected by chance. The dimensions of the nodalgram are not related to anatomical coordinates of the nodes, suggesting that a representation of these structures in an abstract space explains the spread of cancers better than an analysis of spread in real space. Surprisingly, a plot of the extent to which metastases from different primary sites spread along the nodalgram dimensions is closely related to the normal anatomical locations of the primaries. This shows that although the nodalgram may be difficult to interpret, it must have some biological significance. In conclusion, multidimensional scaling successfully quantifies a pattern in the spread of head and neck cancers.

Algorithms↗
PubMed1992

Surgical management of the thyroid nodule: patient selection based on the results of fine-needle aspiration cytology.

To determine whether the routine use of fine-needle aspiration (FNA) cytology reduces the rate of unnecessary surgery, the surgical pathology of 54 thyroidectomy patients who had preoperative FNA was compared to the results obtained with 24 thyroidectomy patients who did not have preoperative FNA. Twenty-nine (85.3%) of the 34 patients who had a positive FNA were confirmed by histology to have a thyroid neoplasm; in 24 patients, the neoplasm was malignant. Two of the 17 patients who had a negative FNA but underwent thyroidectomy based on other factors were found to have thyroid cancer. Only 8 (33.3%) of the 24 surgical specimens of patients who did not have an FNA were found to be malignant. FNA had a sensitivity of 93.5% and a specificity of 75.0%. The results indicate that the routine use of FNA for patients with thyroid nodules reduces the incidence of unnecessary surgery. Furthermore, FNA alone is sufficient to identify most patients at risk and is, therefore, cost-effective. However, the presence of other findings suspicious of malignancy should preclude clinical decision making based on FNA alone.

Adolescent↗
PubMed1991

Drug response of head and neck tumors in native-state histoculture.

We describe a chemosensitivity testing of head and neck tumors, in which a native-state histoculture, ie, a three-dimensional culture system that maintains important in vivo properties, including tissue architecture, was used. Fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL; fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and combinations of cisplatin and fluorouracil in corresponding doses. Growth and measurement of drug responses were successfully completed in 10 specimens (five others were contaminated, four of them prior to instituting rigorous antibiotic washes). The results indicated cisplatin sensitivity in five of 10 patients; fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin sensitivity in seven of eight patients. Our preliminary results indicate that the native-state histoculture technique is feasible to test chemosensitivity of head and neck tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Standardizing neck dissection terminology. Official report of the Academy's Committee for Head and Neck Surgery and Oncology.

The emergence of the multitude of modified techniques for neck dissection procedure has resulted in a nomenclature system that is nonuniform. To eliminate potential misinterpretation, overlap, and lack of standardization, the Academy's Committee for Head and Neck Surgery and Oncology, with input from the Education Committee of the American Society of Head and Neck Surgery, has developed a classification system for these procedures. This has now been adopted by the American Academy of Otolaryngology-Head and Neck Surgery. The classification is based on the following concepts: (1) radical neck dissection is the fundamental procedure with which all other neck dissections are compared, (2) modified radical neck dissection denotes preservation of one or more nonlymphatic structure(s), (3) selective neck dissection denotes preservation of one or more group(s) of lymph nodes, and (4) extended radical neck dissection denotes removal of one or more additional lymphatic and/or nonlymphatic structure(s). Adherence to the principles of this classification system to describe neck dissection techniques should provide an improved method of communication. Furthermore, the system provides a rational framework on which subsequent terminology can be added.

Head and Neck Neoplasms↗
PubMed1991

Mandible reconstruction with vascularized bone grafts. A histologic evaluation.

To our knowledge, a histologic evaluation of bone healing after mandible reconstruction with vascularized human bone grafts has not been previously reported. Serial sections through both the decalcified graft and the junction between mandible and graft were evaluated in four patients who required surgical removal of their reconstructed mandibles. A failed scapular bone graft that had been wrapped within a pectoralis major myocutaneous flap for salvage following pedicle thrombosis showed markedly resorbed but viable bone with a fibrous union to the native mandible. Viable vascularized grafts without evidence of ongoing resorption characterized an iliac osteocutaneous bone graft and two scapula osteocutaneous grafts that healed with continuity of healthy bone between graft and mandible. Observations from the evaluation of these specimens are made regarding bone circulation, bone union, and bone graft survival as they occur clinically. Implications regarding the techniques of bone plating and indications for use of vascularized bone in mandible reconstruction are discussed.

Bone Transplantation↗