Pinhas P. Schachter

Correct preoperative localization: Does it permit a change in operative strategy for primary hyperparathyroidism?

BACKGROUND A meticulous bilateral neck exploration by an experienced endocrine surgeon offers a high cure rate with low morbidity for patients with primary hyperparathyroidism. The advent of localizing studies raises the possibility of unilateral neck exploration. The cost-effectiveness of preoperative localizing studies and unilateral neck exploration in primary hyperparathyroidism are controversial issues. This study was designed to determine the risks of missing a contralateral pathologic parathyroid gland in patients with preoperative localization that was confirmed at neck exploration. METHODS Preoperative studies (ultrasonography, nuclear radioactive imaging scan, or both) were performed in 79 patients with primary hyperparathyroidism. In 58 patients a definite localization of an enlarged parathyroid gland was confirmed at operation. All patients underwent a meticulous bilateral neck exploration. RESULTS Unilateral neck exploration was feasible only in 73.4% of the patients, according to our localizing modalities, and an additional enlarged parathyroid gland on the contralateral side, not detected before operation, was revealed in five patients (8.6%). False-positive rates were 1.7% for ultrasonography and 13% for scan. CONCLUSIONS These results indicate an unacceptably high surgical failure rate for unilateral neck exploration guided by preoperative localizing studies compared with a bilateral neck exploration by an experienced endocrine surgeon, questioning the cost-effectiveness of preoperative localizing studies.

The Use of 99mTc-Recombinant Human Annexin V Imaging for Differential Diagnosis of Aseptic Loosening and Low-Grade Infection in Hip and Knee Prostheses

The aim of this study was to assess the pattern of annexin V uptake in hip and knee prostheses suspected of being infected. Methods: A total of 7 patients undergoing revision surgery for hip or knee prostheses were studied; 5 patients had total hip replacements, and 2 had total knee replacements. Infection was confirmed by pathology, culture results, laboratory evaluation, and clinical follow-up. All patients also underwent a bone scan before surgery. Results: Annexin V scan findings were positive in 5 patients and negative in 2. Annexin V uptake was either focal (n = 4) or linear (n = 1). There were 4 true-positive, 2 true-negative, 1 false-positive, and no false-negative annexin V studies. Annexin V uptake was either more extensive or less extensive than, and usually was incongruent with, 99mTc-methylene diphosphonate uptake. Conclusion: Our findings suggest that annexin V imaging shows greater uptake with infection than with aseptic loosening and has a high negative predictive value for prosthetic infection.

Combined Systemic Chronotherapy and Hepatic Artery Infusion for the Treatment of Metastatic Colorectal Cancer Confined to the Liver

Background: The optimal treatment of patients with metastatic colorectal cancer is still a clinical challenge. We describe the use of combined hepatic arterial infusion (HAI) of irinotecan (CPT-11) in conjunction with systemic chronotherapy infusion of 5-fluorouracil (5FU), folinic acid and carboplatin in patients with colorectal liver metastases. Methods: Twenty-three patients with colorectal cancer and isolated liver metastases were enrolled in this trial. Intraoperative insertion of an intra-arterial catheter into the hepatic artery was accomplished during the colon operation (in cases of synchronous tumor) or as a separate procedure in colorectal cancer patients with newly diagnosed liver metastases. A systemic double-lumen double-chamber port was inserted via the subclavian vein as a separate procedure. The treatment plan included irinotecan given by intra-arterial infusion at 150 mg/m2 for 1 h. After 2 weeks of rest chronomodulated 5FU (700 mg/m2; peak delivery rate at 04:00 h), leucovorin (175 mg/m2; peak delivery rate at 04:00 h) and carboplatin (40 mg/m2; peak delivery rate at 16:00 h) for 4 days was followed by 10 days’ rest and then given again. After 10 days’ rest another HAI was introduced using the same method. Each cycle of therapy included 2 HAI courses and 2 chronotherapy courses in between. After 2 complete cycles, patients were evaluated for their response with weekly accessed toxicity recording. Results: Seven women, 8 men, median age 61 years (range 46–72). Eight patients had synchronous colon and hepatic disease and 7 patients had metachronous disease. Ten patients had previously been treated with 5FU and leucovorin while 5 patients were chemonaive. The mean number of cycles were 11.6 per patient (range 8–19). Partial response was achieved in 6 patients (40%) and was followed by laparoscopic radiofrequency ablation in 5 patients (33%). Disease stabilization was observed in 2 patients (13%) and disease progression in 7 patients (47%) mainly after previous chemotherapy failure. Side effects were infrequent and mild including grade 2 GIT complaints (5 patients), RUQ pain during HAI (9 patients) and grade 2 hematological complaints in 2 patients. Conclusion: A combined chemotherapy protocol (HAI and chronotherapy) with irinotecan (CPT-11) together with chronomodulated infusion of 5FU, folinic acid and carboplatin can be used in metastatic colorectal patients with a high efficacy rate and minor side effects especially in pretreated patients.

Differential expression of kinase genes in primary hyperparathyroidism: adenoma versus normal and hyperplastic parathyroid tissue.

CONTEXT Differentiation between adenoma and hyperplasia or even normal parathyroid tissue is difficult and based mainly on the surgeons skill. Exploration of genes that express differentially in these various tissues using microarrays and other sophisticated research tools will enable identification and perhaps development of new methods of perioperative diagnosis. OBJECTIVE To assemble a panel of kinase genes to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue. DESIGN RNA was extracted from adenoma, hyperplasia, and normal parathyroid tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes. Signals of exposure were scanned and quantified with software for digital image analysis. Semiquantitative reverse transcriptase polymerase chain reaction analysis of sample genes was performed, up-regulated or down-regulated, to validate the microarray results. RESULTS The ratio values considered significant (<0.5 or >1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for blood vessel angiogenesis and genes belonging to the cyclin-dependent kinase inhibitor groups. Genes down-regulated in parathyroid adenoma are related to cellular growth and apoptosis--genes from the mitogen-activated protein kinase group and DNA-dependent protein kinase group. An interesting gene down-regulated in the parathyroid adenoma samples is related to the serine/threonine protein kinases that exert a key function in calcium handling. A panel of 5 genes was defined: p19, p21 and the gene for vascular endothelial growth factor from the up-regulated group, and the gene for protein kinase C and SGK from the down-regulated group. Reverse transcriptase polymerase chain reaction confirmed the microarray results for these genes. CONCLUSIONS The kinase genes panel presented can be used to differentiate parathyroid adenoma from normal and hyperplastic parathyroid tissue in particular when histopathology fails to provide a decisive diagnosis.

Residual curarization and postoperative respiratory complications following laparoscopic sleeve gastrectomy. The effect of reversal agents: sugammadex vs. neostigmine

Abstract Background: Incomplete muscle relaxant reversal or re-curarization may be associated with postoperative respiratory complications. In this retrospective study we compared the incidence of postoperative residual curarization and respiratory complications in association with the type of muscle relaxant reversal agent, sugammadex or neostigmine, in patients undergoing laparoscopic sleeve gastrectomy. Material and methods: We reviewed the charts of all patients (179) undergoing laparoscopic sleeve gastrectomy from July 2012 to July 2013 at Wolfson Medical Center. Sugammadex 1.5-2 mg/kg (112 patients) or neostigmine 2.5 mg (67 patients) were used as reversal agents. Results were compared by the type of reversal agent employed. Compared parameters included demographic and anaesthetic data, residual curarization, oxyhemoglobin saturation (SpO2) in the recovery room (PACU), episodes of SpO2 lower than 90% in PACU, unexpected intensive care (ICU) admissions, incidence of atelectasis and pneumonia, re-intubation and duration of hospitalization. Results: Obstructive sleep apnea syndrome (OSAS) was more frequent in the sugammadex group (19% vs. 8%; p = 0.026). Total intravenous anesthesia (TIVA) was more frequently associated with sugammadex (33% vs. 16%; p = 0.007). There were no differences in postoperative residual curarization, SpO2 < 90% episodes, reintubation, ICU admissions, pulmonary complications and duration of hospitalization. Conclusion: With the inherent limitations of a retrospective study, the use of sugammadex following laparoscopic sleeve gastrectomy showed no advantage over neostigmine in terms of residual curarization and respiratory complications.

Non‐autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism

A patient with acute primary hyperparathyroidism treated with mithramycin preoperatively, underwent neck exploration and two enlarged parathyroid glands were excised: one huge adenoma (6g) and another smaller gland. Mithramycin was administered preoperatively to lower life‐threatening hypercalcaemia, and parathyroid slices from the huge adenoma removed at surgery were submitted in vitro to various calcium concentrations in the media to determine the influence of calcium on parathyroid adenoma secretory pattern in acute primary hyperparathyroidism. Mithramycin induced a significant decline in calcium levels and significant elevations of calciotrophic hormones (intact PTH, mid‐region specific PTH, calcitonin and calcitriol). Significant suppression in PTH output in vitro was achieved by increasing calcium levels in the media. These results exclude autonomous PTH secretion (non‐calcium dependent) as a possible aetiology of acute primary hyperparathyroidism. We suggest that a sudden increase in the set‐point of the diseased parathyroid cells in the presence of a huge cell mass accounts, in large part, for both the marked hypercalcaemia and elevated PTH levels in this patient.