A 15-year experience: intraoperative parathyroid hormone assay for the management of primary hyperparathyroidism in a UK endocrine surgical unit.

PURPOSE: This study aims to evaluate the outcomes of first-time parathyroidectomy for primary hyperparathyroidism using intraoperative PTH (IOPTH) assay in the light of the UK National Institute for Health and Care Excellence (NICE) guidelines for the management of primary hyperparathyroidism. METHOD: This is a retrospective cohort analysis of a prospectively maintained database of endocrine surgery in a tertiary centre. Preoperative radiological localisation (concordance and accuracy), intraoperative PTH parameters and adjusted serum calcium at minimum 6-month follow-up were analysed. The accuracy of IOPTH to predict post-operative normocalcaemia and the number needed to treat (NNT) within the cohort when IOPTH was utilised were determined. Differences between groups were evaluated with Chi-squared and Fisher's exact test. RESULTS: Between January 2004 and September 2018, 849 patients (75.4% women), median age 64 years (IQR 54-72), were analysed. The median preoperative adjusted serum calcium was 2.80mmol/l (IQR 2.78-2.90), and the median preoperative PTH was 14.20pmol/l (IQR 10.70-20.25). The overall first-time cure (normocalcaemia) rate was 96.4%. The sensitivity, specificity, positive predictive value and negative predictive values of IOPTH were 96.8%, 83.2%, 97.6% and 78.8%, respectively, with an accuracy of 95.1%. For patients with concordant scans (48.3%), a targeted approach without IOPTH would have achieved a cure rate of 94.1% compared with 98.0% using IOPTH (p<0.01) CONCLUSION: The use of IOPTH assay significantly improved the rate of normocalcaemia at 6 months. The low NNT to benefit from IOPTH, particularly those patients with a single positive scan, and the inevitable reduction in the potential costs incurred from failure and reoperation justify its utilisation.

Outcomes of surgery for benign and malignant adrenal disease from the British Association of Endocrine and Thyroid Surgeons' national registry.

BACKGROUND: This study investigated the indications, procedures and outcomes for adrenal surgery from the UK Registry of Endocrine and Thyroid Surgery database from 2005 to 2017, and compared outcomes between benign and malignant disease. METHODS: Data on adrenalectomies were extracted from a national surgeon-reported registry. Preoperative diagnosis, surgical technique, length of hospital stay, morbidity and in-hospital mortality were examined. RESULTS: Some 3994 adrenalectomies were registered among patients with a median age of 54 (i.q.r. 43-65) years (55·9 per cent female). Surgery was performed for benign disease in 81·5 per cent. Tumour size was significantly greater in malignant disease: 60 (i.q.r. 34-100) versus 40 (24-55) mm (P < 0·001). A minimally invasive approach was employed in 90·2 per cent of operations for benign disease and 48·2 per cent for cancer (P < 0·001). The conversion rate was 3·5-fold higher in malignant disease (17·3 versus 4·7 per cent; P < 0·001). The length of hospital stay was 3 (i.q.r. 2-5) days for benign disease and 5 (3-8) days for malignant disease (P < 0·050). In multivariable analysis, risk factors for morbidity were malignant disease (odds ratio (OR) 1·69, 1·22 to 2·36; P = 0·002), tumour size larger than 60 mm (OR 1·43, 1·04 to 1·98; P = 0·028) and conversion to open surgery (OR 3·48, 2·16 to 5·61; P < 0·001). The in-hospital mortality rate was below 0·5 per cent overall, but significantly higher in the setting of malignant disease (1·2 versus 0·2 per cent; P < 0·001). Malignant disease (OR 4·88, 1·17 to 20·34; P = 0·029) and tumour size (OR 7·47, 1·52 to 39·61; P = 0·014) were independently associated with mortality in multivariable analysis. CONCLUSION: Adrenalectomy is a safe procedure but the higher incidence of open surgery for malignant disease appears to influence postoperative outcomes.

ANTECEDENTES: Este estudio investigó las indicaciones, procedimientos y resultados de la cirugía de la glándula suprarrenal a partir de la base de datos de la UKRETS desde 2005-2017 y comparó los resultados entre enfermedad benigna y maligna. MÉTODOS: Se examinó un registro nacional con datos notificados por cirujanos que incluye 3.994 suprarrenalectomías; 57% mujeres, mediana de edad 53 (8-88 años). Se evaluaron el diagnóstico preoperatorio, la técnica quirúrgica, la duración de la estancia hospitalaria, la morbilidad y la mortalidad hospitalaria. RESULTADOS: En el 82% de los casos la cirugía se realizó por enfermedad benigna. El tamaño del tumor fue significativamente mayor en la enfermedad maligna: 60 mm (34-100 mm) versus 40 mm (24-55 mm), P < 0,001. Se utilizó un abordaje mínimamente invasivo en el 90% de los casos de enfermedad benigna y en el 48% de las operaciones por cáncer (P < 0,001). La tasa de conversión fue 3,5 veces más alta en la enfermedad maligna (17% versus 4,9%, P < 0,001). La duración de la estancia fue 3 días (rango intercuartílico, interquartile range, IQR 2-5) para la enfermedad benigna y 5 (IQR 3-8) días para la enfermedad maligna (P < 0,05). En el análisis multivariable, los factores de riesgo para la morbilidad fueron: enfermedad maligna (razón de oportunidades, odds ratio, OR 1,64, 1,217-2,359; P = 0,002), tamaño del tumor (OR 1,433, 1.040-1,967; P = 0,028) y conversión a cirugía abierta (OR 3,483, 2,160-5,612; P < 0,0001). La mortalidad hospitalaria global fue baja (< 0,5%) pero significativamente mayor en el escenario de la enfermedad maligna (1,2% versus 0,2%, P < 0,001). La enfermedad maligna (OR 4,881, 1,171-20,343; P = 0,029) y el tamaño del tumor (OR 7,474, 1,515-39,610; P = 0,014) se asociaron de forma independiente con la mortalidad en el análisis multivariable. CONCLUSIÓN: La suprarrenalectomía es un procedimiento seguro, pero la mayor incidencia de cirugía abierta para la enfermedad maligna parece tener un impacto sobre los resultados postoperatorios.

Intraoperative Parathyroid Hormone Assay Remains Predictive of Cure in Renal Impairment in Patients with Single Parathyroid Adenomas.

BACKGROUND: Parathyroid hormone (PTH) has a short half-life and is cleared by the liver and kidneys. This study examined whether declining estimated glomerular filtration rate (eGFR) affects application of the Miami criterion for intraoperative PTH (ioPTH) decline during parathyroidectomy for primary hyperparathyroidism (pHPT). METHODS: A retrospective review of consecutive patients undergoes parathyroidectomy for pHPT. Patients with multi-gland disease, without ioPTH, failure-to-cure and those <18 years were excluded. Baseline demographics, pre-operative PTH, ioPTH and 6-month follow-up data were available. Patients were categorised into normal or chronic kidney disease (CKD stage 2-5) based on pre-operative eGFR. Nonparametric data were compared using Mann-Whitney U test/Kruskal-Wallis test. The primary outcome measure was to assess whether CKD-affected ioPTH decline in parathyroidectomy for pHPT. RESULTS: A total of 476 patients were included [75.4% women; median age 63.8 years (18-92)]. CKD was present in 362 (76%) (CKD2:289; CKD3:66; CKD4/5:7). Increasing CKD stage was associated with advancing age [normal 53 years (41-61); CKD2 65 (57-73); CKD3 73.5 (66-78); CKD4/5 74(63-81); p < 0.001] and higher pre-operative PTH [16.6 pmol/L (11.1-22.9); 13.1 (10.4-17.7); 22.6 (13.8-33.7); 33.8(12.4-41.7); p < 0.001]. Baseline and post-excision ioPTH were significantly higher in those with CKD4/5 (p < 0.05). The Miami criterion was met in all patients, but median fall in ioPTH at 10-min varied between groups [normal:0.78 (0.71-0.82); CKD2:0.76 (0.69-0.83); CKD3:0.75 (0.69-0.82); CKD4/5:0.69 (0.61-0.70); p = 0.048)]. It was significantly lower in those with CKD4/5 compared with the remainder of patients [0.69 (0.61-0.70) vs. 0.76 (0.70-0.82); p = 0.008]. CONCLUSIONS: Although the reduction in ioPTH after successful parathyroidectomy is lower in severe CKD, the Miami criterion remains predictive of cure. Differences in absolute levels of PTH and tumour weight suggest that renal HPT may be a confounding factor.

Is Unilateral Neck Surgery Feasible in Patients with Sporadic Primary Hyperparathyroidism and Double Negative Localisation?

INTRODUCTION: Ultrasound and Tc99mMIBI scans are used to localise parathyroid tumours in sporadic primary hyperparathyroidism (pHPT). Intra-operative PTH (ioPTH) assay facilitates unilateral neck exploration (UNE). When both ultrasound and MIBI are negative, it is our policy to explore the left side of the neck and only proceed to bilateral neck exploration (BNE) when either a tumour is not found or when ioPTH does not fall to >50% of the highest pre-excision value. The aim of this study was to investigate the outcome of our approach to 'double negative' patients. METHODS: A retrospective analysis of patients undergoing primary parathyroidectomy for pHPT. Data were obtained from a prospective surgical database and the hospital electronic patient record. RESULTS: Between January 2004 and November 2014, 746 patients underwent a parathyroidectomy for pHPT. Those who did not have both pre-operative scans, ioPTH or a minimum of 6-month follow-up were excluded. Of 552 patients, 111 (20%) had double negative scans (group A), and in 441, either one or both scans were positive (group B). Median age was 61.5 years (range 10-88). Pre-operative PTH level was significantly lower in group A: 11.8 pmol/l (range 3.1-38.8) versus 14.9 pmol/l (range 2.8-101.6; P < 0.01). Median tumour weight was significantly lower in group A: 280 mg (range 50-3710) versus 573 mg (range 10-12,000; P < 0.01). Overall rate of multiple gland disease (MGD) was 11%; 24% in group A and 7% in group B (P < 0.01). Overall rate of UNE in Group A was 28% and converse to the rate in Group B (76%; P < 0.01). Sensitivity and specificity of ioPTH to detect MGD were 98 and 98% in Group A versus 98 and 100% in Group B. First-time cure rate was 92.7% in group A and 96.8% in group B (P < 0.05). CONCLUSION: A double negative scan is associated with small tumours and higher rates of MGD. Despite these challenges, surgery is successful in this group of patients reinforcing the message that negative localisation is not a contraindication for parathyroidectomy. We demonstrated that it is feasible to offer unilateral neck surgery to 28% of patients with double negative scans. A randomised trial is needed to compare BNE with ioPTH/UNE in this select population.

A decade of change in the uptake of parathyroidectomy in England and Wales.

INTRODUCTION: Since the late 1990s, a number of factors have reduced the threshold for parathyroidectomy in patients with primary hyperparathyroidism. This study examined whether this has translated into increased numbers of parathyroid operations over the last decade. METHODS: A retrospective analysis was performed of the Patient Episode Database for Wales and English Hospital Episode Statistics annual data from 2000 to 2010 for parathyroidectomy admissions per 100,000 population. Statistical analysis was by linear regression. RESULTS: Between 2000 and 2010 there were 24,247 parathyroid operations in England and Wales (0.005% of the population), with 3 times as many women treated as men. Overall, incidence of parathyroidectomy rose from 3.3/100,000 population in 2000 to 5.8/100,000 in 2010 (p<0.0001). In England, it increased from 3.3/100,000 population to 5.8/100,000 and in Wales, it increased from 2.4/100,000 population to 4.6/100,000. Despite similar population demographics, the difference in the rate of change between England and Wales was significant (p<0.05). Uptake also varied according to age; in those aged 0-14 years, incidence of parathyroidectomy remained static whereas in all other age groups, uptake of parathyroidectomy increased significantly from 2000 to 2010. Most notably, surgical intervention in those aged 60-74 and >75 years nearly doubled over the decade (p<0.0001). CONCLUSIONS: The incidence of parathyroidectomy in adults has increased significantly in the last decade in England and Wales. This likely reflects changes in population demography, available guidelines, lower threshold for referral, changing surgical approach and the realisation that surgical morbidity is now infrequent.

Recurrent urolithiasis following parathyroidectomy for primary hyperparathyroidism.

INTRODUCTION: The effect of parathyroidectomy on the incidence of recurrent stone formation is uncertain. We aimed to compare the biochemistry and recurrence rate of urolithiasis in patients with primary hyperparathyroidism (pHPT) and stone formation (SF) and non-stone formation (NSF) with idiopathic stone formers (ISF). METHODS: Patients with pHPT and SF (Group 1) were identified from a prospective database. pHPT patients and NSF (Group 2) and ISFs (Group 3) were randomly selected from respective databases to form three equal groups. Preoperative and postoperative biochemical data were analysed and recurrent urolithiasis diagnosed if present on follow-up radiology. Out-of-area patients were asked about recurrence via telephone. RESULTS: From July 2002 to October 2011, 640 patients had parathyroidectomy for pHPT. Of these, 66 (10.3%) had a history of renal colic; one was lost to follow-up. Patient demographics were similar across all three groups. Three months post-parathyroidectomy, Groups 1 and 2 had significantly reduced serum calcium concentrations (p<0.01). Group 1 had lower urinary calcium excretion after parathyroidectomy (p<0.01), but estimated glomerular filtration rate did not change following surgery. During median follow-up of 4.33 years (0.25-9 years) in Groups 1 and 2 and 5.08 years (0.810-8 years) in Group 3, one patient (1.5%) in Group 1 and 16 patients (25%) in Group 3 had recurrent urolithiasis (p<0.01). No Group 2 patients developed stones. CONCLUSION: Curative parathyroidectomy confers a low recurrence rate for urolithiasis, but does not prevent recurrence in all patients. Further research should aim to identify the risk factors for continued SF in these patients.

Hypocalcaemia following thyroidectomy for treatment of Graves' disease: implications for patient management and cost-effectiveness.

BACKGROUND: No consensus exists on optimal treatment for Graves' disease once anti-thyroid medication fails to induce remission. Total thyroidectomy is a more cost-effective treatment than radioactive iodine or life-long anti-thyroid medication, but hypocalcaemia is an important complication, leading to longer hospital admissions and increased prescription costs. This study aimed to compare the relative risk of hypocalcaemia requiring medical treatment for patients with Graves' disease. METHODS: Prospective cohort study of patients undergoing total thyroidectomy for Graves' disease and for multinodular goitre, calculating serum calcium levels 24-hours post-operatively and prescription rates. RESULTS: Mean corrected calcium concentrations 24 hours post-operatively were 2.05 mmol/l for Graves' disease patients and 2.14 mmol/l for multinodular goitre patients (p = 0.003). Biochemical hypocalcaemia developed in 92 per cent (n = 34) of Graves' disease patients and 71 per cent (n = 43) of multinodular goitre patients (p = 0.012). Graves' disease patients were more likely to be prescribed calcium supplementation pre-discharge (p = 0.037). CONCLUSION: Total thyroidectomy for Graves' disease carries an increased risk of hypocalcaemia at 24 hours, and of calcium supplementation pre-discharge. Graves' disease patients should be informed of the increased risk of hypocalcaemia associated with total thyroidectomy, and this risk must be factored into future cost-effectiveness analysis.

Abdominal complications from crack cocaine.

Not only is cocaine a powerfully addictive and dangerous drug of abuse, the use of the purified cocaine derivative crack has also reached epidemic proportions. Apart from causing fatal cardiorespiratory complications, crack cocaine is capable of producing surgical emergencies, which may or may not be associated with the pharmacology of cocaine itself. This is a report of crack-induced pneumoperitoneum, the mechanism of which seemed to be related to the prolonged Valsalva manoeuvre during crack smoking. Other differential diagnoses of crack related pneumoperitoneum are also discussed.

The role of fibrinolytic system proteins in cholesterol gallstone formation.

BACKGROUND: Accelerated nucleation, supersaturation of bile, and biliary stasis are known to be key factors in cholesterol gallstone formation. The mechanisms through which these factors interact to form stones are still incompletely understood. Among the proteins now known to be present in bile are several components of the fibrinolytic system: tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors 1 and 2. The concentrations of plasminogen activator inhibitors 1 and 2 in gallbladder bile are increased in patients with gallstones. The aim of this study was to determine whether these fibrinolytic system proteins act as pro-nucleating agents for cholesterol gallstone formation. METHODS: Nucleation assays were done on gallbladder bile from eight cholesterol stone patients and eight control patients. The effects of tissue plasminogen activator, urokinase-like plasminogen activator, and plasminogen activator inhibitors I and 2 on cholesterol crystal appearance time (CCAT) were tested, by direct observation using polarizing microscopy, after measurement of biliary lipids and calculation of cholesterol saturation indices. RESULTS: There was no significant difference in cholesterol saturation indices between bile that nucleated and bile that did not (mean, 2.0 +/- 1.5 versus 1.8 +/- 0.5). When all samples in which nucleation occurred were compared, tissue plasminogen activator significantly shortened CCAT median from 4.75 days (range, 2-21) to 3.5 days (2.5-18) (P < 0.05). This was similar to the effect of fibronectin (3.75 days; range, 2-20), a known pro-nucleator used as a nucleation accelerating control (P < 0.05). None of the other fibrinolytic system proteins significantly accelerated CCAT. CONCLUSIONS: The results of this study suggest that tissue plasminogen activator may act as a pro-nucleating agent for cholesterol gallstone formation in gallbladder bile.

Comparison of immunologic and physiologic effects of CO2 pneumoperitoneum at room and body temperatures.

BACKGROUND: Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas. The aim of this study was to compare the effects of a conventional room temperature carbon dioxide (CO2) pneumoperitoneum with those of a body temperature pneumoperitoneum. METHODS: Patients were randomized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature (n = 15) or room temperature (n = 15). The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures, peritoneal fluid cytokine concentrations, and postoperative pain. RESULTS: The mean duration of surgery was 32 min in both groups. Core temperature was reduced in the room temperature group (mean, 0.42 degrees C; p < 0.05). No reduction in temperature occurred when the gas was warmed. Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha (TNF-alpha): mean, 10.9 pg/ml vs. 0.42, p < 0.05; interleukin 1 beta (IL-1beta): mean, 44.8 pg/ml vs. 15.5, p < 0.05; and IL-6: mean, 60.4 ng/ml vs. 47.2. There was no difference in postoperative pain scores or analgesia consumption between the two groups. CONCLUSIONS: The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas, even in short laparoscopic procedures. In addition, warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response.

Fibrinolysis and the biliary tree.

AIMS: To investigate the fibrinolytic activity of normal and calculous human bile. METHODS: Fibrinolytic properties of the biliary tract were studied in patients with gall bladder stones (n = 7) compared with acalculous gall bladders (n = 8). RESULTS: Bile plasminogen activating activity was detected in a wide range in both groups (calculous bile median 0.35 IU/ml; range: 0.06-6.59, versus normal bile 0.70 IU/ml; 0.19-3.56). There was no difference in the bile concentration of tissue plasminogen activator between the two groups (calculous bile median 21.5 ng/ml versus normal bile 9.5 ng/ml), which was present in much greater concentrations than urokinase (calculous bile median 0.10 ng/ml versus normal bile 0.36 ng/ml). Both plasminogen activators were detected in low concentrations in gall bladder mucosa. Plasminogen activator inhibitors-1 and 2 were detected in bile in significantly greater concentrations in patients with gall bladder stones (plasminogen activator inhibitor-1: calculous bile median 15 ng/ml versus normal bile < 2 ng/ml, plasminogen activator inhibitor-2: 157 ng/ml versus < 6 ng/ml, p < 0.05). CONCLUSIONS: Human bile possesses fibrinolytic activity and the principal plasminogen activator in bile seems to be tissue plasminogen activator. Plasminogen activator inhibitors were present in greater concentrations in stone bile and may be a factor in the pathogenesis of gall stone formation.

Surgical management of gastrointestinal endocrine tumours.

The surgical management of gastrointestinal endocrine tumours must involve a multidisciplinary approach. The importance of accurate diagnosis, rendering the patient safe, and, in our opinion, localizing the tumour(s) before embarking on surgery cannot be overemphasized. Surgery is the only available treatment for cure. Occult primary tumours are now rarely a problem with novel imaging techniques, which can also improve detection and hence clearance of local spread. Surgical management in extensive metastatic or multicentric disease is less rigidly defined, and is dependent on the endocrine syndrome. A better understanding of tumour pathology, for example in MEN 1, has not always simplified matters. An appreciation of the benefit of chemotherapy, use of somatostatin analogues and hepatic artery embolization are vital to target appropriate palliative surgery. Hepatic transplantation may have an increasing role in the future. Surgical strategies must adapt to new medical treatments. If therapeutically relevant, advances in tumour biology (for example somatostatin receptor subtypes and growth factors) will influence surgical strategies in the future.

The operative peritoneal fibrinolytic response to abdominal operation.

OBJECTIVE: To measure changes in the fibrinolytic properties of human peritoneum during operation. DESIGN: Open study. SETTING: University hospital, UK. SUBJECTS: 20 patients undergoing elective operations for non-inflammatory disease. INTERVENTIONS: Peritoneum was biopsied at the beginning and end of operation. MAIN OUTCOME MEASURES: Peritoneal plasminogen activating activity (PAA) and the concentrations of tissue plasminogen activator (t-PA), urokinase, and plasminogen activator inhibitors 1 and 2 were measured at both time points. RESULTS: Peritoneal PAA was reduced over the time of the operation (p < 0.05) as was the concentration of t-PA (p < 0.05). The urokinase concentration rose significantly (p < 0.05), but plasminogen activator inhibitors 1 and 2 were not detected. CONCLUSIONS: Elective abdominal operation caused an immediate reduction in peritoneal PAA which seemed to be secondary to a reduced concentration of t-PA. Such a reduction in peritoneal fibrinolytic activity allows the early deposition of fibrinous deposits within the peritoneal cavity.

Experimental adhesion prophylaxis with recombinant tissue plasminogen activator.

The deposition of fibrin in the peritoneal cavity leads to fibrous adhesion formation. Recombinant tissue plasminogen activator (rtPA), delivered locally, was investigated as a method of preventing adhesion formation. Six standardised areas of peritoneal ischaemia were formed in each of 36 male Wistar rats randomised to three intraperitoneal treatments: (A) no treatment control; (B) carboxymethylcellulose gel; (C) rtPA-carboxymethylcellulose gel combination. At 1 week all animals underwent relaparotomy and the number of ischaemic sites with an adhesion counted by an independent observer. rtPA-treated animals formed fewer adhesions compared with gel alone or controls (median number of adhesions 1.5 versus 2.5 versus 5, P < 0.001, ANOVA). Intraperitoneal rtPA in a slow-release formulation is able to reduce adhesion formation significantly in an animal model and may prove to have clinical benefit.

Surgical treatment of primary duodenal carcinoma: a personal series.

In a personal series, 22 patients (11 men, 11 women) of median age 60 (range 25-81) years with primary duodenal adenocarcinoma underwent operation between 1979 and 1993. Tumours arising from bile duct, ampullary or pancreatic tissue were excluded. Principal presenting symptoms were jaundice (12 patients), pain (seven), anaemia (six) and vomiting (six). A pre-existing villous adenoma was seen in 11 patients and adjacent duodenal dysplasia in 13. Sites of origin were mostly the second part of the duodenum (18 patients) but also the third and fourth parts (two each). Seventeen patients underwent 'curative' resection with one hospital death at 25 days; the 5-year survival rate thereafter was 40 per cent. Five patients who received palliative surgery survived for a median of 7 months. Primary duodenal carcinoma is a distinct entity with a better prognosis than pancreatic cancer after radical resection. It favours the descending duodenum and is closely linked with villous adenoma and epithelial dysplasia.