18F-fluorocholine PET/MRI versus ultrasound and sestamibi for the localization of parathyroid adenomas.

PURPOSE: Accurate preoperative localization is imperative to facilitate a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). This study aims to compare the diagnostic value of standard-of-care localization techniques (ultrasound [US] and 99mTechnetium (99mTc) -sestamibi scintigraphy) to [F-18]-fluorocholine positron emission tomography/magnetic resonance imaging (FCH-PET/MRI) to determine the additional clinical usefulness of PET/MRI in a Canadian cohort. METHODS: We conducted a prospective, appropriately powered, study to compare the diagnostic value of -FCH PET/MRI to that of the US and 99mTc-sestamibi scintigraphy for localization of parathyroid adenomas in a patient with pHPT. The primary outcome was the per-lesion sensitivity and positive predictive value (PPV) of FCH-PET/MRI, US, and 99mTc-sestamibi scintigraphy. Intraoperative surgeon localization, parathormone levels, and histopathological findings were used as reference standards. RESULTS: Forty-one patients underwent FCH-PET/MRI of which 36 patients had parathyroidectomy. In these 36 patients, 41 parathyroid lesions were histologically confirmed as adenomas or hyperplastic glands. Per-lesion sensitivity of FCH-PET/MRI was 82.9% and of US and 99mTc-sestamibi scintigraphy combined at 50.0%, respectively. The sensitivity of FCH-PET/MRI was superior to that of US and 99mTc-sestamibi scintigraphy (p = 0.002). In the 19 patients in whom both US and 99mTc-sestamibi scintigraphy were negative, PET/MRI correctly identified the parathyroid adenoma in 13 patients (68%). CONCLUSIONS: FCH-PET/MRI is a highly accurate imaging modality for localization of parathyroid adenomas in a tertiary center in North America. It is a superior functional imaging modality to 99mTc-sestamibi scintigraphy alone and more sensitive for localization of parathyroid lesions than US and 99mTc-sestamibi scintigraphy combined. This imaging modality could become the most valuable preoperative localization study given its superior performance in localizing parathyroid adenomas.

Understanding and reducing work-related psychological distress in interns: a systematic review.

The aim of this study was to collate and evaluate studies investigating either the factors influencing work-related psychological distress in postgraduate year one (PGY1) doctors or the strategies designed to reduce it. This is a systematic review conducted in May 2014. The data sources were key databases (MEDLINE, PsycINFO and Embase) and manual searches of reference lists for relevant studies published in the last 15 years. This study is an empirical research designed either to elucidate the factors influencing work-related psychological distress in PGY1 doctors, or examine the effects of an intervention designed to reduce it. Key information was extracted into an electronic data extraction form, which incorporated elements of Murphy's model of work stress factors. A total of 21 studies was included in the review; 16 studies had examined the factors influencing work-related psychological distress, four studies had investigated strategies to reduce it, and a single study addressed both. Analysis of the findings of each individual study through the conceptual framework provided by Murphy's model revealed a discrepancy between the factors influencing work-related psychological distress and the focus of strategies designed to reduce it. Factors such as career progression and a PGY1 doctor's role within the organisation were not addressed in the interventions identified. Significant sources of psychological distress in PGY1 doctors remain overlooked by current interventions. Strategies designed to prevent or reduce psychological distress should be broad-based and grounded in both the literature exploring salient factors and existing theories of work-related stress.

Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study.

PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.

Australian resident doctors want more palliative medicine education: a survey of attitudes and perceived needs.

Most expected deaths occur in acute hospitals, and medical staff providing end-of-life care are generally not palliative medicine specialists. Through a voluntary self-administered survey, this study explored resident doctors' attitudes to palliative medicine and their perceived educational needs. Fifty-two resident doctors participated (response rate 39%), mostly acknowledging the importance of palliative medicine to their practice and emphasising that further postgraduate education is necessary.

How can we meet the information needs of patients with early stage papillary thyroid cancer considering radioactive iodine remnant ablation?

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer.

Cellular transplantation in the treatment of experimental hepatic failure.

The survival of Lewis rats with D-galactosamine-induced fulminant hepatic failure was prolonged if they were given intraperitoneal injections of single-cell suspensions of liver or bone marrow cells from normal rats. Suspensions of liver cells were also effective in prolonging the survival of rats with ischemia-induced hepatic necrosis. The liver cells did not act by repopulating the recipient liver.

Thyroiditis as the presenting manifestation of disseminated extrapulmonary Pneumocystis carinii infection.

A 38-yr-old male with acquired immunodeficiency syndrome developed neck pain in association with mild hyperthyroidism and a diffusely enlarged thyroid gland. Radioactive iodine scanning was consistent with thyroiditis, and biopsy of the thyroid demonstrated the presence of pneumocystis carinii in thyroid tissue. Treatment with pentamidine followed by trimethoprim sulfamethoxazole led to rapid normalization of thyroid size in association with the development of hypothyroidism. This case illustrates the natural history of pneumocystis carinii thyroiditis and suggests that thyroid disease be added to the spectrum of human immunodeficiency virus-associated endocrine dysfunction.

Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression.

Recent investigation of a biologically active synthetic polymer, NED 137, has demonstrated its ability to induce a B cell differentiation response to certain antigens, even in the presence of T cell depletion. In this report, the effect of T cell depletion combined with NED 137, on skin allografting, is explored in the Lewis strain rat. Animals were T cell-depleted by thymectomy, total body irradiation, and syngeneic marrow repopulation. They were then challenged with skin allografts +/- NED 137 treatment. Graft survival was significantly prolonged in the T-depleted rats regardless of treatment with NED 137. The drug did not increase the immune response to donor antigen as measured by in vivo lysis of 51Cr-labeled cells. Immunization with heterologous erythrocytes produced a low level of differentiation of IgM-producing cells in the T cell-depleted skin allografted group, but in contrast the T-depleted NED 137-treated rats had a normal response to immunization. These data suggest that selective stimulation of the humoral component of the immune response is feasible at a time when T cell-mediated function has been radically suppressed, without producing adverse effects on allograft survival.

Allogeneic and xenogeneic hepatocyte transplantation in experimental hepatic failure.

Previous studies have demonstrated the efficacy of syngeneic hepatocyte transplantation in the treatment of D-galactosamine-induced acute hepatic failure in Lewis strain rats. This report describes the efficacy and immunological consequences of allogeneic and xenogeneic hepatocyte transplantation in the same model. The i.p. administration of allogeneic (minor and major histoincompatibility) hepatocytes or xenogeneic (rabbit or porcine) hepatocytes at a dose of 4 x 10(7) cells/rat given at 48 hr after toxin all resulted in significant improvement in survival compared to that of controls, and also comparable to the results obtained with syngeneic hepatocyte transplantation. Sensitization to i.p. allogeneic (WF) hepatocyte administration was demonstrated by in vivo 51Cr release, indirect immunofluorescent technique, and accelerated skin allograft rejection. Similarly, the in vivo 51Cr release assay was able to detect sensitization to porcine hepatocytes. Despite evidence of immunogenicity, redosing with either WF or porcine hepatocytes resulted in no overt toxicity. Furthermore, presensitization by either WF hepatocytes or skin allografts did not adversely affect survival after WF hepatocyte treatment in D-galactosamine-induced hepatic failure in Lewis strain rats. These data demonstrate that histocompatibility is not a constraint to successful hepatocyte transplantation and that repeated treatments are potentially safe and efficacious despite sensitization.

Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.

We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.

Comparison of the antitumor effects of a synthetic biopolymer and standard adjuvants.

The synthetic biopolymer NED 137 is capable of stimulating an immune response to tumor antigen. This article compares the efficacy of NED 137 to bacille Calmette-Guerin, Corynebacterium parvum, pyran, levamisole, and Freund's complete adjuvant in a rat tumor model where adjuvant treatment is administered after excision of subcutaneous tumor implants. A single intraperitoneal injection of NED 137 at 30 mg/kg body weight prolonged survival beyond 60 days with no evidence of recurrent or metastatic disease, whereas with the other adjuvants, animals survived a mean of 30 to 40 days with 100% local recurrence and a 60% to 90% incidence of pulmonary metastases. Use of NED 137 resulted in a greater lysis of tumor cells compared to other adjuvants when assessed in an in vivo 51Cr release assay. A phase I clinical study of high-risk gastrointestinal cancer patients treated with NED 137 is reported at a median survival time of 23 weeks (103 patients). This group is compared to a historical control group from the same institution. No NED 137-related toxicity has been noted to date.

Lithiumogenic disorders of the thyroid and parathyroid glands as surgical disease.

Little notice has been paid in the surgical literature to problems with psychoeffective lithium, which by interfering with adenylate cyclase affects thyroid and parathyroid function, causing hypercalcemia, hyperparathyroidism, and hypothyroidism. Seven patients with lithiumogenic hyperparathyroidism occurring after years of lithium therapy underwent treatment and manifested osteoporosis (n = 2), hypertension (n = 2), nephrolithiasis (n = 1), coma (n = 1), rising hypercalcemia (n = 1), goitrous myxedema (n = 4), nephrogenic diabetes insipidus (n = 2), renal failure (n = 2), and hyperlipidemia (n = 1). Disease-directed parathyroidectomy (without morbidity) was curative. Unique laboratory findings included normal serum phosphorus and reduced urinary calcium and cyclic adenosine monophosphate values. Three separate cases of thyroid carcinoma after long-term lithium therapy were also treated, being preceded by myxedema (n = 2) and concurrent with hyperparathyroidism (n = 1). There has been only one previous report of lithium-associated thyroid carcinoma. All patients taking lithium should undergo surveillance for thyroid and parathyroid dysfunction and neoplasia, and appropriate surgical and medical treatment should be considered in each situation. Although hyperparathyroidism may be reversible with lithium discontinuance, such therapy may be obligatory for patient well-being, thus dictating parathyroidectomy.

Effect of radiofrequency hyperthermia and chemotherapy on primary and secondary hepatic malignancies when used with metronidazole.

Hyperthermia is selectively toxic to neoplastic tissue. Since August 1981, 357 patients with incurable tumors in various body areas have been treated with chemotherapy and radiofrequency hyperthermia (RFHT) with adjuvant metronidazole at this center. Of this group, the cases of 102 patients with hepatic tumors are reported here. Patients received one to ten treatment courses, each course consisting of two to five daily RFHT sessions. Systemic temperature rose 0.6 +/- 0.3 degrees C during treatment, and tumor core temperature (measured by percutaneous transhepatic thermistor) reached 39.5 +/- 1.2 degrees C in 38 monitored patients. Results have been encouraging; in particular, among 15 patients with newly diagnosed colorectal metastases limited to the liver (and as yet untreated for their secondary disease), there has been objective partial tumor regression in 66.7%. Side effects have been few. Skin burns and subcutaneous fat necrosis were seen in 3.9% and 13.7% of patients, respectively. Tumor temperature is difficult to measure reliably and does not correlate with machine power or tumor response. A phase III trial is currently underway to determine the efficacy of RFHT and chemotherapy for patients with hepatic metastases from colorectal adenocarcinoma.

Reversal of toxic and anoxic induced hepatic failure by syngeneic, allogeneic, and xenogeneic hepatocyte transplantation.

This report describes the efficacy of syngeneic hepatocyte transplantation in an anoxic model and of xenogeneic (rabbit and porcine) hepatocyte transplantation in a toxic model of fulminant hepatic failure in the rat. Lewis strain rats that received 4 X 10(7) hepatocytes intraperitoneally at 48 hours after hepatic artery ligation had a significantly improved survival rate (79%, n = 14) when compared with control animals (38%, n = 21, P less than 0.05). Xenogeneic hepatocytes (4 X 10(7) cells/rat) given intraperitoneally to D-galactosamine-poisoned Lewis rats at 48 hours after toxin administration were able to significantly improve survival rate as compared with controls (71% versus 14%, n = 14, P less than 0.01 for rabbit; and 75%, n = 14 versus 12.5%, n = 16, P less than 0.001 for porcine). Although an increase in in vivo cytotoxicity could be demonstrated after procine hepatocyte transplantation, no adverse clinical effects were observed. The methodology for the harvest and storage of large numbers of hepatocytes from a large animal liver has been developed, and it is now feasible to proceed to the clinical application of hepatocyte transplantation for human fulminant hepatic failure.

Do we really need another localizing technique for parathyroid glands?

To evaluate magnetic resonance imaging (MRI) in the preoperative localization of abnormal parathyroid glands, we examined 16 patients with primary hyperparathyroidism at initial presentation with MRI and ultrasound of the neck. These studies were analyzed prospectively and compared with the findings at bilateral neck exploration. The surgeon was intentionally blinded to the imaging studies. MRI was accurate in the lateralizing of an abnormal gland in 21 of 32 sides (66 percent). Sensitivity was 65 percent and specificity was 66 percent. Ultrasound was accurate in 19 of 32 sides (59 percent). Sensitivity was 50 percent and specificity was 75 percent. The difference was not statistically significant. We do not believe that MRI is indicated prior to initial exploration in patients with primary hyperparathyroidism.

The iliac crest and the radial forearm flap in vascularized oromandibular reconstruction.

Sixty cases (59 patients) of oromandibular reconstruction using vascularized iliac crests were compared with 13 in which radial osteocutaneous flaps were used. These patients were reviewed from the standpoint of cosmetic results and function as well as their operative and postoperative courses. In both groups, the results were generally good. However, revisionary surgery was more frequent in those receiving the iliac crest. This group also had a higher incidence of intraoral wound breakdown and bone exposure. Nevertheless, the sheer size of the iliac crest made it ideal for massive oromandibular defects, just as its natural curvature lent itself to precise replication of the mandible in bone-only reconstructions. Its bulk proved a major obstacle in small composite defects. The radial forearm flap carried thin, pliable, well-vascularized skin that was superior to groin skin for oral lining. Bone gaps of up to 9 cm could be handled with ease, thus making it complementary to the iliac crest over the wide spectrum of mandibular reconstruction.

Defining the needs for adjuvant therapy of rectal and colonic cancer.

Current trials concerned with the adjuvant therapy for large bowel cancer demonstrate for the first time that improvements in survival through the use of adjuvant therapy may be possible in rectal cancer. Similar results in well-designed studies are not evident for colonic cancer. These trials deserve confirmation. In addition, they demonstrate the biologic difference in the behavior of colonic and rectal cancer despite similar requirements in defining curative surgical resection. A comparison of trials unique to individual institutions suggests that the lenient criteria for patient selection and the use of historical control groups make the data from these studies impossible to interpret for extrapolation to wide clinical use. The variations in the survival rates of historical groups, both among different studies and within the same study, suggest that the design of adjuvant therapy programs without concurrent surgically treated control groups will predictably produce a study of limited value, but one that is guaranteed to generate continued controversy. Uniformity of language, staging, and method of reporting is invaluable if individual trials of adjuvant therapy are to become comparable. The development and widespread use of an agreed-upon staging method is an important step in the preparation for further adjuvant trials. The definition of additional prognostic factors (beyond mural penetration and nodal involvement) in rectal cancer and stratification for these additional factors in the design of studies concerning adjuvant therapy in rectal cancer seems to be a target of importance for future studies of adjuvant therapy. Focusing attention on which patients with rectal cancer actually derived a benefit from treatment may assist in the development of a pattern in which surgical goals and radiation goals can achieve better definition in clinical use.

A retrospective comparison of the morbidity and cost of different reconstructive strategies in oral and oropharyngeal carcinoma.

PURPOSE: Evaluate and compare the morbidity and costs of different reconstructive strategies in oral and oropharyngeal carcinoma. STUDY DESIGN: Retrospective cross-sectional. PATIENTS AND METHODS: One hundred twenty-seven consecutive patients treated surgically for oral and oropharyngeal carcinoma between 1990 and 1996 were evaluated. Sixty-three patients had segmental mandibulectomies with 30 plate-soft tissue reconstructions and 33 bone-soft tissue flaps. Sixty-four patients had soft-tissue-only reconstructions. The following outcome parameters were analyzed: operative time, intraoperative blood loss, postoperative admission length, ICU and coronary care unit admission length, surgical interventions for complications, re-admissions, and prolonged (>6 mo) gastrostomy tube feeding, and all costs within the disease-free interval. Means and standard deviations were calculated for continuous parameters. Differences among the three groups were analyzed using one-way analysis of variance. For discontinuous parameters, the chi-square test was applied. RESULTS: Longer operative time (1.8 h) and more blood loss (150 mL) for bone-soft tissue flaps were the only statistically significant findings (P<.05) between the three groups. CONCLUSION: There is no rationale for allowing presumed factors of morbidity or cost select for type of reconstruction in patients with oral and oropharyngeal carcinoma.

Accuracy of pathologic diagnosis in thyroid lesions.

Although there is much literature devoted to the role that fine-needle biopsy plays in the management of the thyroid mass, only a handful of studies deal with the diagnostic accuracy of the frozen section and final paraffin section of thyroid lesions. Fine-needle biopsy results, frozen-section diagnoses, final paraffin-section diagnoses, and panel review diagnoses were recorded for 137 consecutive patients who underwent thyroidectomy procedures. The overall accuracy of fine-needle biopsy, frozen-section, and paraffin-section diagnoses was 81%, 87%, and 94%, respectively. The high positive predictive value and specificity of both the fine-needle and frozen-section modalities suggests that intraoperative pathology consultation, given that the preoperative needle aspirate is positive for malignant neoplasia, can offer little further in the treatment of the patient. Statistical analysis of the accuracy of the three modalities suggests strategies for accurate treatment of the thyroid nodule.