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Biomedical subjects

Gerard M Doherty

Publications and source records attributed to Gerard M Doherty.

At least 19 recordsLinked to original sources
PubMed2006

Gardner's syndrome in a 40-year-old woman: successful treatment of locally aggressive desmoid tumors with cytotoxic chemotherapy.

BACKGROUND: Desmoid tumors that present as a part of Gardener's syndrome can present very difficult management problems. CASE PRESENTATION: We report a case of intra-abdominal desmoid tumor causing distal small bowel obstruction that complicated the management of a more proximal enterocutaneous fistula from the jejunum. After failure of more conventional management options including imatinib, the patient's disease responded to doxorubicin and ifosfamide. The response resolved the bowel obstruction and allowed small intestinal resection to resolve the enterocutaneous fistula. CONCLUSION: Systemic cytotoxic therapy with doxorubicin and ifosfamide can be useful for patients with complications from intra-abdominal desmoid tumor.

Journal Article↗
PubMed2006

Interpretation of intraoperative parathyroid hormone monitoring in patients with baseline parathyroid hormone levels of <100 pg/mL.

BACKGROUND: Common guidelines for intraoperative parathyroid hormone (IOPTH) interpretation are based on clearly elevated baseline parathyroid hormone (PTH) values. We hypothesize that patients with low-baseline levels (<100 pg/mL) have a higher incidence of multigland disease (MGD) and display differences in PTH kinetics compared with patients with high-baseline levels. METHODS: We retrospectively reviewed the cases of 1151 patients with primary hyperparathyroidism who underwent parathyroidectomy with IOPTH monitoring. Of these, 141 patients had low-baseline values. Multiple comparisons were made between the low-baseline and high-baseline groups. RESULTS: Twenty-six percent of the low-baseline patients had MGD versus 15% of the high-baseline patients (P = .002). The PTH kinetics differed between groups after gland excision at both 5 and 10 minutes. Adherence solely to the "50% rule" during minimally invasive parathyroidectomy potentially would have missed 25% of patients with MGD in the low-baseline group versus 10% in the high-baseline group; 5.7% of the low-baseline patients had persistent or recurrent hypercalcemia versus 2.9% of the high-baseline patients. CONCLUSION: MGD is significantly more prevalent among low-baseline patients, and PTH kinetics are somewhat different between groups. The current guidelines that are used for IOPTH monitoring may not be ideal for use in this low-baseline group and will likely need to be revised after further study of this group of patients.

Diagnosis, Differential↗
PubMed2006

Laparoscopic skills are improved with LapMentor training: results of a randomized, double-blinded study.

OBJECTIVE: To determine if prior training on the LapMentor laparoscopic simulator leads to improved performance of basic laparoscopic skills in the animate operating room environment. SUMMARY BACKGROUND DATA: Numerous influences have led to the development of computer-aided laparoscopic simulators: a need for greater efficiency in training, the unique and complex nature of laparoscopic surgery, and the increasing demand that surgeons demonstrate competence before proceeding to the operating room. The LapMentor simulator is expensive, however, and its use must be validated and justified prior to implementation into surgical training programs. METHODS: Nineteen surgical interns were randomized to training on the LapMentor laparoscopic simulator (n = 10) or to a control group (no simulator training, n = 9). Subjects randomized to the LapMentor trained to expert criterion levels 2 consecutive times on 6 designated basic skills modules. All subjects then completed a series of laparoscopic exercises in a live porcine model, and performance was assessed independently by 2 blinded reviewers. Time, accuracy rates, and global assessments of performance were recorded with an interrater reliability between reviewers of 0.99. RESULTS: LapMentor trained interns completed the 30 degrees camera navigation exercise in significantly less time than control interns (166 +/- 52 vs. 220 +/- 39 seconds, P < 0.05); they also achieved higher accuracy rates in identifying the required objects with the laparoscope (96% +/- 8% vs. 82% +/- 15%, P < 0.05). Similarly, on the two-handed object transfer exercise, task completion time for LapMentor trained versus control interns was 130 +/- 23 versus 184 +/- 43 seconds (P < 0.01) with an accuracy rate of 98% +/- 5% versus 80% +/- 13% (P < 0.001). Additionally, LapMentor trained interns outperformed control subjects with regard to camera navigation skills, efficiency of motion, optimal instrument handling, perceptual ability, and performance of safe electrocautery. CONCLUSIONS: This study demonstrates that prior training on the LapMentor laparoscopic simulator leads to improved resident performance of basic skills in the animate operating room environment. This work marks the first prospective, randomized evaluation of the LapMentor simulator, and provides evidence that LapMentor training may lead to improved operating room performance.

Clinical Competence↗
PubMed2006

The so-called stunning of thyroid tissue.

UNLABELLED: When thyroid tissues exhibited concentrations of therapeutic (131)I that appeared to be less than that predicted by data from the preceding diagnostic (131)I, the phenomenon was called stunning. We hypothesized that stunning arose from the early effects of the therapeutic dose of (131)I and that the initial uptake of (131)I, observed within the first day, was not impaired by the diagnostic dose. METHODS: The hypothesis was tested by 2 types of studies. In each type, the fractional concentrations of (131)I in residual neck thyroid tissues of patients with papillary thyroid carcinoma were quantified. In the first study, fractional concentrations of diagnostic and therapeutic (131)I were measured at 2 d, a time when stunning has been observed, and expressed as ratios of radioactivity: therapeutic/diagnostic (Rx/Dx). Three different doses of diagnostic (131)I were prescribed to assess a dose response. In the second study, patients were prospectively recruited and tested to record disappearances of radioactivity from thyroid tissues. Diagnostic doses were 1.0 mCi (37 MBq) in all; therapeutic doses were 150 and 30 mCi (5,550 and 1,110 MBq), each to half of the patients. The disappearance curves were extrapolated to the period between 0 and 1 d, an interval when maximum uptake of ingested (131)I would be expected. The fractional concentrations of (131)I at 2 d and at 0-1 d were compared in terms of Rx/Dx ratios to assess changes at each time point. RESULTS: In the first study, after diagnostic doses of 2, 1, and 0.5 mCi (74, 37, and 18.5 MBq), mean 2-d Rx/Dx values in 24, 29, and 17 patients were 0.35, 0.50, and 0.46 (P = 0.087). Of all patients, 74% exhibited Rx/Dx <0.6. In the second study, 6 of 10 patients exhibited disappearance curves of (131)I in which Rx/Dx was <0.6 at 2 d; 5 of the 6 had Rx/Dx values >0.97 at the 0- to 1-d point. In 1 patient the Rx/Dx was 0.54 at 2 d and 0.66 at the earlier time point. The other 4 patients had disappearance curves in which Rx/Dx values were >1.0 throughout or were above 0.6 and did not greatly change. CONCLUSION: Two days after the administration of (131)I, the mean fractional concentration of radioactivity in thyroid tissues after a therapeutic dose is <60% of the diagnostic dose in most patients, but no correlation of Rx/Dx with the mCi in the diagnostic dose was seen. In 5 of 6 patients in whom the Rx/Dx at 2 d was <0.6, the maximum fractional concentrations of therapeutic and diagnostic (131)I (i.e., the tissue uptakes during the first day) were similar; this pattern was most apparent after therapies with 150 mCi. These results support the hypothesis that "stunning" of thyroid tissues, often observable by 2 d, is primarily the consequence of early destructive effects from therapeutic (131)I.

Adolescent↗
PubMed2005

Multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia-1 (MEN-1) is an autosomal dominant inherited syndrome that occurs due to inactivating mutations of the MEN1 gene locus, coding for a tumor-suppressor protein, menin. The components of MEN-1 are hyperparathyroidism due to multiple parathyroid adenomas, pancreatic neuroendocrine tumors, and pituitary adenomas, in addition to some less common neoplastic manifestations. Care of people with MEN-1 requires knowledge of the problems that may arise, and the best approaches to detect and care for the manifestations of this incurable, but manageable, disease.

Adenoma↗
PubMed2005

Rare endocrine tumours of the GI tract.

Functional pancreatic endocrine tumors other than gastrinoma and insulinoma are quite rare. The principles of management include the diagnosis and management of the functional hormonal syndrome, and management of the potentially malignant tumor. Optimally, control of the hormonal syndrome is achieved preoperatively to stabilize the patient status for the operation, however, resection may be an important part of the control of the hormonal syndrome. Ultimately, the only curative treatment for these neoplasms is complete tumour resection, when feasible.

Adult↗
PubMed2005

Revisiting lithium-associated hyperparathyroidism in the era of intraoperative parathyroid hormone monitoring.

BACKGROUND: Chronic lithium therapy may cause hyperparathyroidism (HPT). The utility of intraoperative parathyroid hormone monitoring (IOPTH) in these patients is unknown. The authors' hypothesis was that multiglandular disease is more common in these patients, and the ability of IOPTH to predict cure may be limited. METHODS: Twelve patients had HPT during chronic lithium therapy and underwent parathyroidectomy with IOPTH. Criteria for curative resection were a decrease > or =50% from baseline and into the normal range. Calcium and PTH levels were measured during follow-up. RESULTS: Preoperatively, mean calcium was 11.0 +/- 0.1 mg/dL, and PTH was 116 +/- 14 pg/mL. Fifty percent of patients had multiglandular disease confirmed by IOPTH levels. Mean IOPTH decrease from baseline was 74 +/- 4%. Although 10 of 12 patients met criteria for curative resection, only 8 remain normocalcemic. The 2 patients who did not meet criteria remain normocalcemic. Mean postoperative calcium for all patients was 9.5 +/- 0.2 mg/dL. Of the 10 normocalcemic patients, 4 also have hyperparathormonemia (mean PTH, 119 +/- 19 pg/mL). CONCLUSIONS: The incidence of multiglandular disease in HPT after chronic lithium exposure is higher than standard HPT. The ability of IOPTH to predict durable normocalcemia is limited. Bilateral neck exploration should be considered for these patients regardless of whether IOPTH monitoring is used.

Adult↗
PubMed2005

Long-term functionality of cryopreserved parathyroid autografts: a 13-year prospective analysis.

BACKGROUND: The functional results of cryopreserved heterotopic parathyroid autotransplantation (CHPA) are not well defined. The authors evaluated the outcomes of delayed CHPA for the treatment of surgically induced hypoparathyroidism. METHODS: Since November 1991, 448 parathyroid samples from 436 patients were cryopreserved at our institution. Of these, 29 patients underwent 34 CHPA procedures, with placement of 20 to 25 pieces of parathyroid tissue (approximately 50 to 75 mg) into the forearm. Outcomes were determined based on peripheral parathyroid hormone (PTH) levels and, where available, PTH gradients between grafted and nongrafted arms. Graft function results were defined as completely functional (patients with normal PTH and calcium levels off all calcium/vitamin D supplementation), partially functional (normal PTH levels and mild hypocalcemia on calcium supplementation), or nonfunctional (low PTH levels and dependent on calcium/vitamin D supplementation). RESULTS: Of the 29 patients with CHPA, prospective data were available for 26 patients undergoing 30 CHPA procedures (9 patients with MEN 1, 4 with MEN 2A, 1 with MEN 2B, and 12 with sporadic hyperparathyroidism). The mean follow-up interval was 2 years. Twelve of 26 patients (46%) had completely functional grafts, 6 patients (23%) had partially functional grafts, and the remaining 8 patients (31%) had nonfunctional grafts. No patient with CHPA had graft-dependent recurrent hyperparathyroidism. Of the 14 patients (15 autografts) with MEN, 7 patients (50%) had fully functional grafts, and 2 patients (14%) had partially functional grafts. The mean cryopreservation period was 7.9 months (range, 1 week to 22 months) for functional autografts and 15.3 months (range, 2 weeks to 106 months) for nonfunctional autografts (P < .01). CONCLUSIONS: Based on these data and those in previous studies, approximately 60% of delayed, cryopreserved parathyroid autografts are functional. In this study 40% autografts (46% of patients) achieved full competency off supplements. Some patients have evidence of graft function with normal PTH levels but are not normocalcemic. Results were similar for patients with MEN and nonhereditary hyperparathyroidism. The duration of cryopreservation was a significant indicator of graft failure, and no functional autograft was observed beyond 22 months of preservation. CHPA is a useful treatment modality for patients with postoperative hypocalcemia after thyroid or parathyroid surgery, who do not respond to immediate parathyroid autotransplantation.

Adolescent↗
PubMed2005

Interferon regulatory factor 1 (IRF-1) and IRF-2 expression in breast cancer tissue microarrays.

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine with potent antitumor effects, both in vitro and in vivo. The antitumor activity of IFN-gamma is mediated in part through IFN regulatory factor-1 (IRF-1) and may be blocked by IRF-2. To test our hypothesis that some tumors escape the antitumor effects of IFN-gamma by cellular changes reflected in IRF-1 and IRF-2 expression, we examined IRF-1 and IRF-2 expression in tissue microarrays (TMA) containing 187 specimens of clinically defined invasive breast carcinoma. TMAs (Cooperative Breast Cancer Tissue Resource [CBCTR], National Cancer Institute [NCI]) were stained and then scored by three evaluators blinded to the patients' clinical status. After final scoring, the CBCTR provided the available clinical data for each patient. Whether sorted by carcinoma type or for all data together, statistical analysis showed a significant positive correlation between IRF-1 and IRF-2 expression (p = 0.01) and a negative correlation between IRF-1 expression and tumor grade (p = 0.005). IRF-1 expression is consistent with its role as a tumor suppressor; high-grade breast carcinomas were less likely to maintain expression of IRF-1, a finding consistent with a role for IRF-1 as a tumor suppressor. Further, tumors maintained expression of IRF-2 if there was coincident expression of IRF-1. These data support a model in which alterations of the expression of intracellular effectors of IFN-gamma signaling may diminish the immune-mediated tumor control mechanisms of IFN-gamma.

Breast Neoplasms↗
PubMed2004

IFNgamma sensitization to TRAIL-induced apoptosis in human thyroid carcinoma cells by upregulating Bak expression.

TRAIL preferentially induces apoptosis in tumor cells and virus-infected cells. Unlike other tumor necrosis factor family members, TRAIL does not kill cells from most normal tissues and has thus been proposed as a promising new cancer treatment. Our study demonstrated that IFNgamma combined with TRAIL can trigger apoptosis in vitro in several resistant thyroid tumor cell lines, such as thyroid anaplastic carcinoma cells (ARO cells), while either agent alone exerts only a minimal effect. We further tested this effect on a mouse thyroid tumor model, when in vivo tumor growth was also significantly inhibited by this combination. The mechanism of how IFNgamma sensitized thyroid carcinoma cells to TRAIL-induced apoptosis was investigated by screening global gene alterations in ARO cells treated with IFNgamma. Microarray data revealed that a proapoptotic gene, Bak, is markedly upregulated by IFNgamma, and this was confirmed by RNase protection assay. Western blot analysis also showed a significant increase in Bak at the protein level. Upregulation of Bak and sensitization for apoptosis by IFNgamma was blocked by overexpression of antisense Bak in ARO cells. Furthermore, overexpression of Bak sensitized ARO cell to TRAIL-induced apoptosis without the need for IFNgamma pretreatment. This suggests that Bak is a regulatory molecule involved in IFNgamma-facilitated TRAIL-mediated apoptosis in thyroid cancer cells.

Animals↗
PubMed2004

Impact of intraoperative parathyroid hormone monitoring on the prediction of multiglandular parathyroid disease.

Optimal interpretation of the results of intraoperative parathyroid hormone (IOPTH) monitoring during neck exploration for primary hyperparathyroidism (pHPT) is still controversial. The reliability of the "50% rule" in multiglandular disease (MGD) is often disputed, mostly because of competing pathophysiologic paradigms. The aim of this study was to ascertain and corroborate the ability of IOPTH monitoring to detect MGD in a practice, combining conventional and alternative parathyroidectomy techniques. This is a retrospective single institution analysis of 69 consecutive patients undergoing cervical exploration for pHPT by various approaches. The IOPTH measurements were performed after induction of anesthesia but prior to skin incision and 10 minutes after excision of the first visualized enlarged parathyroid gland. In this series, 55 patients (80%) had single adenomas, and 14 patients (20%) had MGD. In 8 of the 14 patients with MGD, IOPTH levels were obtained sequentially after removal of every enlarged gland. Of these 8 patients, 6 (75%) had a false-positive decrease (decrease below 50% of baseline value in presence of another enlarged gland) failing to predict the presence of a second enlarged gland. In 2 cases IOPTH monitoring provided a true-negative result, correctly predicting MGD. If MGD is defined by gross morphologic criteria, IOPTH monitoring fails to predict the presence of MGD reliably. However, if MGD is defined by functional criteria, the course of these patients does not seem significantly affected. The importance of these findings must be further investigated, especially with regard to the outcome of minimally invasive parathyroid procedures.

Adenoma↗
PubMed2004

An alternative analysis of intraoperative parathyroid hormone data may improve the ability to detect multiglandular disease.

HYPOTHESIS: A nomogram based on regression analysis of intraoperative parathyroid hormone level decay discriminates single gland disease from multiglandular (MG) disease more accurately than the currently used 50% rule. DESIGN: Retrospective case series. SETTING: Academic health center. PATIENTS: Two hundred thirty-five patients (222 patients with single gland disease and 13 patients with MG disease) who underwent parathyroidectomy. INTERVENTIONS: Intraoperative parathyroid hormone level analysis at baseline, time 1 (about 5 minutes), and time 2 (about 10 minutes) after excision of the first gland. MAIN OUTCOME MEASURES: The mean slope was calculated at time 1 and time 2 and analyzed using one-way analysis of variance and the Fisher least significance difference post hoc tests using data normalized to baseline intraoperative parathyroid hormone levels to compare patients with single gland disease with patients with MG disease. A regression-based nomogram was created to analyze individual kinetic decay data. RESULTS: The mean (SEM) single gland disease slope was significantly steeper than the MG disease slope at both time 1 (-0.91 [0.02] vs -0.66 [0.05]; P<.01) and time 2 (-0.77 [0.01] vs -0.56 [0.05]; P<.01). When the standard threshold rule of a 50% decrease from baseline was used, only 23% of the patients with MG disease were correctly predicted by intraoperative parathyroid hormone values (77% false-positive result rate) at time 1. However, the nomogram correctly predicted 54% of the patients with MG disease at time 1 (46% false-positive result rate). At time 2, the standard threshold 50%-rule method correctly predicted 38% of the patients with MG disease (62% false-positive result rate), while the nomogram still correctly classified 54% of the patients with MG disease (46% false-positive result rate). CONCLUSIONS: A regression-based nomogram incrementally improves prediction of MG disease compared with the standard 50%-rule method and accounts for variability in the exact timing of samples. Slope analysis suggests that the earliest time point best isolates the kinetics of the excised gland. The nomogram will need to be validated prospectively.

Academic Medical Centers↗
PubMed2004

Multiple endocrine neoplasia type 1 parathyroid adenoma development over time.

Multiple gland parathyroid disease is one of the hallmarks of multiple endocrine neoplasia (MEN) type 1. Often mislabeled parathyroid hyperplasia, the process is actually the development of multiple adenomas. Some clinicians have reported results of selective parathyroidectomy in this group, removing only grossly enlarged glands. We argue that all the glands are at risk and should be addressed at any planned parathyroid intervention. Our hypothesis is that, given sufficient time, patients would all develop adenomas in each of the parathyroid glands. Our available data to address this issue are the parathyroidectomy results from a single institution series. Patients who had initial parathyroid exploration for hyperparathyroidism in the setting of MEN-1 were reviewed. This study includes those patients who had the weights of the resected glands documented; 23 men and 21 women met the criteria. The total weight of the parathyroid glands did not vary with the age of the patient at operation. However, the number of normal glands identified did vary significantly with age (p < 0.02), with older patients being less likely to have any normal parathyroid glands. Although total parathyroid weight may correlate with development of hypercalcemia and indications for operation, the involvement of multiple parathyroid glands in MEN-1 is a function of time, as independent events in each gland must occur. Given time, MEN-1 patients all develop multiple gland disease, and this reality must be used in planning operative management for patients with this syndrome.

Adenoma↗
PubMed2004

Trends in utilization of adrenalectomy in the United States: have indications changed?

Minimally invasive approaches have dramatically reduced morbidity associated with adrenalectomy. There has been concern that an increased frequency of adrenal imaging along with the advantages of less morbidity could influence the indications for adrenalectomy. We tested the hypothesis that adrenalectomy has become more common over time and that benign diseases have been increasingly represented among procedural indications. The Nationwide Inpatient Sample (NIS) database was utilized to determine the incidence of adrenalectomy and the associated surgical indications in the United States between 1988 and 2000. All discharged patients were identified whose primary ICD-9-CM procedure code was for adrenalectomy, regardless of the specific surgical approach (laparoscopic adrenalectomy was not reliably coded). This subset was then queried for associated ICD-9-CM diagnostic codes. Linear regression and t-tests were utilized to determine the significance of trends. The total number of adrenalectomies increased significantly, from 12.9 per 100,000 discharges in 1988 to 18.5 per 100,000 discharges in 2000 (p = 0.000003). The total number of adrenalectomies with a primary ICD-9-CM code for malignant adrenal neoplasm did not increase significantly: from 1.2 per 100,000 discharges in 1988 to 1.6 per 100,000 discharges in 2000 (p = 0.47). The total number of adrenalectomies with a primary ICD-9-CM diagnostic code for benign adrenal neoplasm increased significantly, from 2.8 per 100,000 discharges in 1988 to 4.8 per 100,000 discharges in 2000 (p = 0.00002). The average percentage of adrenalectomies performed for malignant neoplasm was significantly higher during the period 1988--1993 when compared to 1994--2000 (11% vs. 9%; p = 0.002). The average percentage of adrenalectomies performed for benign neoplasm was significantly lower during 1988--1993 when compared to 1994--2000 (25% vs. 28%; p = 0.015). Adrenalectomy is being performed with increasing frequency. This is associated with an increase in the proportion of adrenalectomies performed for benign neoplasms. Assuming no significant change in disease prevalence during the study period, these data suggest that indications for adrenalectomy may have changed somewhat over that period.

Adrenal Gland Diseases↗
PubMed2004

The influence of sample site on intraoperative PTH monitoring during parathyroidectomy.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) monitoring is common during parathyroidectomy. We hypothesized that sample site (peripheral vs central vein) may impact IOPTH interpretation. METHODS: Two hundred and one patients underwent curative parathyroidectomy for single-gland disease. IOPTH was drawn peripherally (PV) in 114 patients and centrally (CV, jugular vein) in 87 patients. Decrease from baseline IOPTH and the presence of a normal value at 10 and 15 minutes were determined. The slope of IOPTH decay was calculated. These data were compared between sample sites. RESULTS: Median baseline IOPTH was 268 pg/mL (CV) and 191 pg/mL (PV, P = .003). The mean IOPTH decay slopes were -0.75 (PV) and -0.76 (CV, P = NS), and the mean percent IOPTH decrease at 10 minutes was 79% PV and 80% CV (P = NS). At 10 minutes, a > or =50% drop from baseline was seen in 94% (CV) versus 97% (PV) of patients ( P = NS), resulting in a median IOPTH of 40 pg/mL (CV) versus 34 pg/mL (PV, P = .09). By 15 minutes, the central IOPTH had decreased by > or =50% of baseline in 98% of patients ( P = NS when compared to the 10-minute PV site). CONCLUSIONS: IOPTH kinetics are largely the same for PV and CV sample sites, but baseline values are higher with central sampling. Consequently, CV IOPTH levels are generally higher at 10 minutes, but this discrepancy resolves by 15 minutes. The surgeon utilizing CV samples may need to extend the sampling period.

Blood Specimen Collection↗