bluuebunny/crossref_metadata_2025 huggingface dataset:
Elective total hip replacement surgery may be a poor model of the inflammatory response to trauma
Authors: Foëx B A , Lamb W R , Roberts T E , Hodgkinson J P , Brenchley P E C
Published: March 2003

Background

One of the many problems associated with studying the inflammatory response to major trauma is the variability of injuries and their severity. To overcome this problem, an assessment was made of whether elective total hip replacement (THR) surgery, which includes skeletal and muscle trauma, might provide a reliable model of the inflammatory response to trauma.

Methods

Serial venous blood samples were taken from ten patients before, during and for 24 h after THR. Sandwich immunoassays were performed to detect free and receptor-bound interleukin (IL) 6 and tumour necrosis factor (TNF) α. Whole blood was also taken from nine of the patients for in vitro incubation with endotoxin to assess white cell responsiveness.

Results

None of the patients had a measurable TNF-α response during or after surgery. Only two patients had raised IL-6 during and after surgery (maximum 145 pg ml−1). Incubation of preoperative blood samples with endotoxin resulted in TNF-α and IL-6 production. The median for TNF-α was 710 (range 416–2800) pg ml−1 and that for IL-6 was 1050 (range 121–2350) pg ml−1. Some 24 h after surgery the median for TNF-α was only 450 (range 75–1760) pg ml−1. The median IL-6 production was 950 (range 124–1840) pg ml−1. There was a reduction in in vitro TNF-α production in all nine patients (mean reduction 57 per cent; P < 0·05) at 24 h. There was no significant change in in vitro IL-6 production before and after surgery. The reduction in TNF-α response indicated downregulation, which was not apparent for IL-6.

Conclusion

In this study THR did not produce the typical inflammatory response described for other forms of elective surgery. THR may not be a reliable model for studying the inflammatory response to trauma. The cement used to secure the prosthesis may have an effect on the inflammatory response.
Fluid shifts during cardiopulmonary bypass with special reference to the effects of hypothermia
Authors: Heltne J K , Koller M E , Rynning S T , Farstad M , Lurid T , Husby P
Published: March 2003

Background

Generalized overhydration, oedema and organ dysfunction occurs in patients undergoing open heart surgery using cardiopulmonary bypass (CPB) and hypothermia. Inflammatory reactions induced by contact between blood and the foreign surfaces of the extracorporeal circuit are commonly held responsible for the disturbances in fluid balance (‘capillary leak syndrome’). Using the CPB circuit reservoir as a fluid gauge (measuring continuous extracorporeal blood volume), fluid shifts between the intravascular and the extravascular space, and differences between normothermic and moderately hypothermic CPB, were examined.

Methods

Piglets were placed on CPB (thoracotomy) under general anaesthesia. In the normothermic group (n = 7) the core temperature was kept at 38°C before and during 2 h on CPB, whereas in the hypothermic group (n = 7) the temperature was lowered to 29°C during bypass. In addition to accurate recording of fluid during operation, the extracorporeal blood volume was kept constant by maintaining a certain blood level in the CPB circuit's reservoir. Acetated Ringer was used as priming solution in the CPB, as maintenance fluid and for adding fluid to the reservoir if necessary.

Results

Cardiac output, serum electrolytes and arterial blood gases were all similar in the two groups. Haematocrit fell significantly following the start of CPB in both groups. The reservoir fluid level fell markedly in both groups necessitating fluid supplementation. This extra fluid requirement was transient in the normothermic group, but persisted in hypothermic animals. At the end of 2 h of CPB the hypothermic animals had received seven times more extra fluid than the normothermic pigs.

Conclusion

There were strong indications of a greater fluid extravasation induced by hypothermia. The model described, using the PBC circuit reservoir as a fluid gauge, provides the opportunity for further study of fluid volume shifts, their causes and potential ways to manipulate fluid pathophysiology related to hypothermia and to PBC.
Shape and propagation of systemic pulsatile blood pressure during the evolution of porcine haemorrhagic shock
Authors: Dark P , Purdy J , Atherton J , Dodds D , Little R
Published: March 2003

Background

The shape and propagation of systemic pulsatile blood pressure was evaluated during the evolution of haemorrhagic shock in pigs.

Methods

Twenty-seven Saffan anaesthetized, mechanically ventilated pigs were randomized to a control group, a haemorrhage group with no resuscitation (25 per cent blood loss over 20 min) and an identical haemorrhage group but with reinfusion of shed blood over a further 20 min. Standard invasive haemodynamic monitoring was conducted, as well as digital recordings of blood pressure (via semiconductor catheter-tipped pressure transducers) at consecutive sites from the aortic arch to the femoral artery.

Results

The data are presented as time-averaged isobaric pulsatile contour plots of wave propagation from the aortic arch to the femoral artery. The colour contours encompass relative pressure measurements from the troughs of diastole (blue) to the peaks of systole (red). Distance from aortic arch to femoral artery was 50 cm in this series and the time axis travelled from left to right and over 0·7 s for each figure. Data were obtained before and after 25% haemorrhage and again after restoration of blood volume.

Conclusion

The time-domain morphology of the pulsatile blood pressure waveform and its systemic propagation is changed during a survivable haemorrhage. Furthermore, recovery is apparent following blood volume restoration.
Impact of the ‘2 week wait’ directive for suspected cancer on service provision in a symptomatic breast clinic
Authors: Cant P J , Yu D S L
Published: March 2003

Background

The ‘2 week wait’ directive (Health Service Circular (HSC) 1998/242) guaranteeing that ‘everyone with suspected breast cancer will be able to see a specialist within two weeks of their general practitioner (GP) deciding they need to be seen urgently’ is a unique audited approach to access for the British National Health Service, the effects of which have been assessed in a non-academic symptomatic breast clinic.

Methods

New GP referrals (n = 607) were reviewed prospectively in two comparable 3-month intervals, beginning 1 April 1998 and 1 April 1999, to determine the probability of a breast cancer diagnosis from the referral letter and the effects of the directive on waiting times for appointments and utilization of clinics.

Results

The urgency of referral was not specified in 53 per cent of GP referrals. For the ‘urgent’ cases (25 per cent of all new referrals) the probability of a final diagnosis of breast cancer was 0·19. The breast specialists prospectively achieved a rate of 0·26 from 99 per cent of the same referral letters. ‘Urgent’ referrals did not wait significantly longer in 1999 (median 9 versus 10 days) but waiting times for new appointments overall increased (13 versus 16 days; P < 0·01), and this was greatest for ‘routine’ referrals (14 versus 21 days; P < 0·001). These changes were caused by an increase in the number of clinic appointments, due to significant increases in median number of visits to diagnosis or discharge and clinic non-attendance in 1999, resulting in overbooking. Telephonic communications were associated with faster median access times (fax 8 days; telephone 2 days), relative to mailed referrals (19 days) (P < 0·01).

Conclusion

Breast specialists were better overall at assessing the probability of a breast cancer diagnosis. The waiting time for ‘urgent’ appointments was unchanged following HSC 1998/242, but there was an increased wait for other patients, especially those assessed as having a lower probability of cancer.
Rapid rehabilitation in elderly patients after laparoscopic colonic resection
Authors: Bardram L , Funch-Jensen P , Kehlet H
Published: March 2003

Background

Introduction of the laparoscopic surgical technique has reduced hospital stay after colonic resection from about 8–10 to 4–6 days. In most studies, however, specific attention has not been paid to changes in perioperative protocols required to maximize the advantages of the minimally invasive procedure. In the present study the laparoscopic approach was combined with a perioperative multimodal rehabilitation protocol.

Methods

After laparoscopically assisted colonic resection, patients were treated with epidural local anaesthesia for 2 days, early mobilization and enteral nutrition. Routine use of morphine and traditional tubes, drains and prolonged bladder catheterization was avoided.

Results

Laparoscopic resection was intended in 50 consecutive patients, of median age 81 years. The conversion rate to open resection was 22 per cent. In patients in whom the procedure was completed laparoscopically the median hospital stay was 2·5 days; defaecation occurred in 92 per cent of patients within 3 days. Patients were mobilized for more than 8 h daily from day 2.

Conclusion

Recovery after colonic surgery was improved considerably by combining the use of a laparoscopic technique with a multimodal rehabilitation protocol of pain relief, early mobilization and oral nutrition.
Compliance properties of conduits used in vascular reconstruction
Authors: Tai N R , Salacinski H J , Edwards A , Hamilton G , Seifalian A M
Published: March 2003

Background

Compliance mismatch between native artery and prosthetic graft used for infrainguinal bypass is implicated in the aetiology of graft failure. The aim was to quantify the elastic properties of a new compliant poly(carbonate)polyurethane (CPU) vascular graft, and to compare the compliance properties of grafts made from CPU, expanded polytetrafluoroethylene (ePTFE), Dacron and human saphenous vein with that of human muscular artery.

Methods

A pulsatile flow phantom was used to perfuse vessel and prosthetic graft segments at physiological pulse pressure and flow. Intraluminal pressure was measured using a Millar Mikro-tip catheter transducer and vessel wall motion was determined with duplex ultrasonography using an echo-locked wall-tracking system. Diametrical compliance and a stiffness index were then calculated for each type of conduit over mean pressures ranging from 30 to 100 mmHg by 10-mmHg increments.

Results

The compliance values of CPU and artery (mean over the pressure range) were similar (mean(s.d.) 8·1(0·4) and 8·0(5·9) per cent per mmHg × 10−2 respectively), although the elastic behaviour of artery was anisotropic unlike CPU, which was isotropic. Dacron and ePTFE grafts had lower compliance values (1·8(1·2) and 1·2(0·3) per cent per mmHg × 10−2 respectively, averaged over the pressure range). In both these cases, compliance and stiffness differed significantly from that of artery over a mean pressure range of 30–90 mmHg. Human saphenous vein exhibited anisotropic behaviour and, although compliant at low pressure (30 mmHg), was markedly incompliant at higher pressures.

Conclusion

Compliant polyurethane grafts offer a greater degree of compliance match than either ePTFE or Dacron.
Risk factors related to operative mortality and morbidity in patients undergoing emergency gastrectomy
Authors: So J B Y , Yam A , Cheah W K , Kum C K , Goh P M Y
Published: March 2003

Background

Emergency gastric resection for complicated peptic ulcer and gastric cancer is a major challenge for general surgeons. This study aimed to evaluate the results of emergency gastrectomy and to examine the factors that predict the operative outcome.

Methods

A total of 82 consecutive patients who underwent emergency gastrectomy were studied. The following variables were assessed: pathology, mortality rate, morbidity, reasons for reoperation and factors related to the outcome.

Results

There were 64 men and 18 women with a median age of 62 (range 30–90) years. The indications were bleeding and perforated gastric or duodenal ulcers in 45 and 20 patients respectively, and bleeding and perforated gastric tumours in seven and ten patients respectively. The overall mortality rate was 17 per cent (n = 14). The complication rate was 63 per cent and 11 patients (13 per cent) required reoperation. By multivariate analysis, age greater than 65 years and blood haemoglobin level less than 10 g/dl on admission were predictive of complications after emergency gastrectomy. Postoperative pulmonary and cardiac complications and hypotension on admission were independent risk factors associated with operative death.

Conclusion

Age more than 65 years, haemoglobin level less than 10 g/dl and hypotension on admission were associated with a poor outcome after emergency gastrectomy. The operative result was not affected by the underlying gastric pathology.
Surgery for colorectal liver metastases with hepatic lymph node involvement: a systematic review
Authors: Rodgers M S , McCall J L
Published: March 2003

Background

Liver resection for colorectal metastases is the only known treatment associated with long-term survival; extrahepatic disease is usually considered a contraindication to such treatment. However, some surgeons do not regard spread to the hepatic lymph nodes as a contraindication provided that these nodes can be excised adequately. A systematic review of the literature was undertaken to address this issue.

Methods

An electronic search using Medline, Cancerlit and Embase databases was performed for studies reporting liver resection for colorectal metastases from 1964 to 1999. Data were extracted from papers reporting outcome for patients with positive hepatic nodes and analysed according to predetermined criteria.

Results

Fifteen studies were identified that gave survival data on 145 node-positive patients. Five patients were reported to have survived 5 years after liver resection; one was disease free, two had recurrent disease and the disease status was not described in the remaining two. Five studies containing 83 patients specified a formal lymph node dissection as part of the surgical procedure and four of the five node-positive 5-year survivors were from these studies.

Conclusion

There are few 5-year survivors after liver resection, with or without lymph node dissection, for colorectal hepatic metastases involving the hepatic lymph nodes.
Endoscopic ultrasonography in the evaluation of idiopathic acute pancreatitis
Authors: Norton S A , Alderson D
Published: March 2003

Background

‘Idiopathic’ pancreatitis may be diagnosed when gallstones are excluded by transabdominal ultrasonography and less common causes are not implicated by history or other investigations. Transabdominal ultrasonography may not, however, detect small stones responsible for acute pancreatitis. The aim of this study was to determine if endoscopic ultrasonography (EUS) is able to identify undetected gallstones in cases of ‘idiopathic’ pancreatitis.

Methods

Consecutive patients presenting with ‘idiopathic’ pancreatitis were assessed using EUS for the presence of gallstones or other potential causes of the attack. A control group was also imaged.

Results

Forty-four patients with ‘idiopathic’ pancreatitis were assessed. Ten had suffered earlier attacks of pancreatitis before this study. EUS revealed proven pathology in 18 patients. Unconfirmed pathology was evident in 14. No abnormality was seen in only nine patients. EUS failed in one patient and there were two possible false-positive results.

Conclusion

EUS is able to identify significant pathology in patients in whom a diagnosis of ‘idiopathic’ pancreatitis has been made following standard investigations. Patients with untreated gallstones are at risk of recurrent attacks. Idiopathic pancreatitis should not be diagnosed unless EUS has been performed.
Risk factors for surgery and recurrence in 907 patients with primary ileocaecal Crohn's disease
Authors: Bernell O , Lapidus A , Hellers G
Published: March 2003

Background

Previous studies on risk factors for resection and postoperative recurrence in Crohn's disease have given inconclusive results. The aim of this study was to assess the risk for resection and postoperative recurrence in the treatment of ileocaecal Crohn's disease and to define factors affecting the course of the disease.

Methods

A population-based cohort of 907 patients with primary ileocaecal Crohn's disease was reviewed retrospectively.

Results

Resection rates were 61, 77 and 83 per cent at 1, 5 and 10 years respectively after the diagnosis. Relapse rates were 28 and 36 per cent 5 and 10 years after the first resection. A younger age at diagnosis resulted in a low resection rate. The presence of perianal Crohn's disease and long resection segments increased the incidence of recurrence, and resection for a palpable mass and/or abscess decreased the recurrence rate. A decrease in recurrence rate during the study period (1955–1989) was observed.

Conclusion

In ileocaecal Crohn's disease the probability of resection is high and the risk of recurrence moderate. Crohn's disease in childhood carries a lower risk of primary resection. Perianal disease and extensive ileal resection increase the risk of recurrence.
Quality of life in long-term survivors after curative transhiatal oesophagectomy for oesophageal carcinoma
Authors: de Boer A G E M , Oñorbe Genovesi P I , Sprangers M A G , van Sandick J W , Obertop H , van Lanschot J J B
Published: March 2003

Background

Transhiatal resection for oesophageal cancer is a major operation with potentially severe physical, emotional and social consequences. The aim of this study was to assess various aspects of quality of life in long-term survivors following oesophageal resection for cancer.

Methods

Between January 1993 and May 1996, 100 consecutive patients with cancer of the oesophagus or oesophagogastric junction underwent a potentially curative transhiatal oesophagectomy. Patients with a minimum follow-up of 2 years and with no tumour recurrence (n = 35) were mailed questionnaires which consisted of: (a) the Short Form-36 Health Survey to assess general quality of life, (b) an adapted Rotterdam Symptom Checklist to assess disease-specific quality of life, and (c) additional questions about other effects of the operation.

Results

All patients returned the questionnaire. General quality of life was comparable with reference values for the same age group. However, more than half of the patients still experienced at least some early satiety, fatigue, dysphagia, heartburn and/or psychological irritability. Nine of 13 patients who worked in paid employment before operation continued to do so.

Conclusion

Patients who survive 2 years or more after transhiatal oesophageal resection for cancer can lead satisfactory lives. Although some residual symptoms may persist, their general quality of life is similar to that of healthy individuals of the same age.
Multicentre study comparing aggressive behaviour of familial non-medullary thyroid carcinoma and sporadic thyroid cancer
Authors: Alsanea O , Wada N , Ain K , Wong M , Taylor K , Ituarte P , Tressler P , Weier H-U , Freimer N , Siperstein A , Duh Q , Takami H , Clark O H
Published: March 2003

Background

Familial non-medullary thyroid cancer represents about 5 per cent of all thyroid cancers of follicular cell origin. Whether familial non-medullary thyroid cancer is more aggressive than sporadic thyroid cancer is controversial.

Methods

Each patient with familial non-medullary thyroid cancer was matched with three controls for age, sex and tumour node metastasis (TNM) stage of disease. Possible prognostic factors were compared in relation to recurrence, metastases and mortality rate in both groups. Univariate analysis was performed using contingency table analysis and McNemar's χ2 test for paired measurements. Multivariate analysis was used to evaluate factors significant in univariate analysis.

Results

Forty-eight cases (ten men) and 144 matched controls (30 men) were analysed with a mean follow-up of 102 and 94 months respectively. The mean age was 39 years for cases and 46 years for controls. Some 29 per cent of the cases and 12 per cent of the controls had history of prior or coexistent benign thyroid disease (P < 0·05). Ninety-four per cent of cases and 90 per cent of controls had papillary cancers; the remainder were Hurthle cell cancers. Based on TNM staging, there were 66 per cent stage I, 21 per cent stage II and 13 per cent stage III tumours in the familial non-medullary thyroid cancer group; the distribution was similar in the control group. Modified radical neck dissection was performed in 42 per cent of cases and 22 per cent of controls. Multifocal or bilateral disease was seen in 75 per cent of cases and 41 per cent of controls (P < 0·05); 35 per cent of cases and 16 per cent of controls had at least one recurrence (P < 0·05). Ten per cent of cases and 2 per cent of controls developed distant metastases (P < 0·05). Six per cent of cases but no controls died from thyroid cancer (P < 0·05). In patients with familial non-medullary thyroid cancer aged over 45 years (n = 14), distant metastases affected four, of whom three died. In multivariate analysis, age was the only significant variable that affected the disease outcome (P < 0·01).

Conclusion

Familial non-medullary thyroid cancer is more aggressive than sporadic thyroid cancer and is associated with increased recurrence, metastasis and death, especially in patients over 45 years of age.
Surgery for primary hyperparathyroidism
Authors: Dudley N E
Published: March 2003

Background

Routine open bilateral neck exploration without preoperative localization or intraoperative parathyroid hormone assay has been repeatedly challenged over recent years as the optimal surgical strategy for the treatment of idiopathic primary hyperparathyroidism (HPT). This has prompted a review of the Oxford experience with adherence to traditional practice, questioning whether results could have been improved upon or cost justified by targeting unilateral exploration and immediate hormonal assay.

Methods

The records of all patients undergoing first-time surgery for idiopathic primary HPT over a 32-year period have been reviewed. In every patient bilateral neck exploration was performed and an attempt made to identify all four parathyroid glands. All macroscopically enlarged glands were removed and the operating time recorded. A successful outcome was defined as normocalcaemia without any therapy at 3-month review after surgery, with good cosmesis.

Results

Between 1968 and 2000, 688 patients were operated upon; a total of 2520 parathyroids were identified, of which 968 were abnormal. A single adenoma was found in 542 patients (79 per cent) (eight in a fifth gland), multiple gland disease in 120 (17 per cent) and parathyroid carcinoma in ten (1 per cent). Mean operating time for all patients was 65 min, including those requiring thyroid lobectomy and cervical thymectomy. When a single adenoma was found in a normal anatomical site the mean operating time was 35 min. Some 672 patients (98 per cent) were treated successfully.

Conclusion

Open bilateral neck exploration and removal of all macroscopically enlarged parathyroid glands resulted in a high level of success in this series. No evidence has been found in a worldwide literature search to suggest that expensive high technology would have provided greater benefit for the group as a whole.
Metabolic abnormalities and treatment of mild asymptomatic primary hyperparathyroidism
Authors: Hagstrom E , Lundgren E , Lithell H , Berglund L , Hellman P , Rastad J
Published: March 2003

Background

Primary hyperparathyroidism (pHPT) is associated with increased morbidity and mortality rates, especially due to cardiovascular disease. This may be an effect of metabolic alterations in lipoprotein, glucose and urate turnover. The few previous reports studying this matter have been inconclusive and have included only hypercalcaemic patients.

Methods

In a population-based screening of 5202 postmenopausal women, 109 were diagnosed with mild pHPT. Some 92 patients, together with matched controls, were investigated to analyse metabolic disturbances, and the effect of parathyroidectomy and hormone replacement therapy (HRT). Sixty-nine pairs completed the 5-year study.

Results

Patients had higher serum calcium and parathyroid hormone levels than controls. They had hypertriglyceridaemia and a significantly increased amount of triglyceride-rich lipoproteins. Furthermore, patients had pronounced hypercholesterolaemia, although the level of high-density lipoprotein–cholesterol was lower, and higher serum blood glucose and urate levels. While 5 years of surveillance only failed to affect these alterations, parathyroidectomy with or without addition of HRT normalized the metabolic changes. Thus, 4 years after surgery no differences were seen between cases and controls.

Conclusion

The metabolic alterations in mild pHPT span over many extraparathyroid metabolic systems and constitute an increased risk of cardiovascular disease and death. Parathyroidectomy has a reversing effect on these proatherosclerotic changes, while surveillance does not affect the outcome. Even in mild pHPT surveillance may be questioned.
Prospective case–control analysis of treatment of menopausal primary hyperparathyroidism: calcium and parathyroid hormone
Authors: Lundgren E , Naessen T , Ljunghall S , Rastad J
Published: March 2003

Background

Therapeutic options in primary hyperparathyroidism (HPT) have not been analysed in postmenopausal women recruited by population-based screening.

Methods

Postmenopausal women (n = 92) with HPT detected at population-based screening entered into a prospective case–control comparison at mean(s.d.) 66·5(6·0) years of age. Biochemical signs of HPT were mild (mean(s.d.) serum calcium 2·59(0·14) mmol l−1) and cases were considered overtly asymptomatic. Parathyroid surgery, oestrogen replacement therapy (ERT; ethinyloestradiol), ERT and surgery, and conservative surveillance were evaluated after 1, 2 and 5 years. Follow-up was complete in 75 per cent of the patients.

Results

Parathyroid surgery rendered the total and ionized calcium, and intact parathyroid hormone (PTH) values in blood, and the urinary calcium excretion indistinguishable between cases and controls. ERT was maintained during approximately 80 per cent of the follow-up period. It reduced the blood calcium levels significantly and tended to increase the serum PTH level. Significant discrepancies, however, persisted towards the controls. ERT added no significant changes to the biochemical outcome of parathyroidectomy. Conservatively treated cases had essentially stable parameters over the study period.

Conclusion

Parathyroidectomy was the only treatment option that normalized basic variables of the calcium homoeostasis to control levels in postmenopausal women with mild primary HPT.
Identification of a novel glucose transporter in medullary thyroid carcinomas and phaeochromocytomas
Authors: Phay J E , Hussain H B , Moley J F
Published: March 2003

Background

The authors previously reported that medullary thyroid carcinomas (MTCs) and phaeochromocytomas avidly take up the glucose analogue fluorodeoxyglucose (FDG) on FDG positron emission tomography. It was also shown that these tumours do not express any of the known human glucose transporters (Glut 1–5), which are responsible for glucose and FDG uptake into cells. It was hypothesized that a novel glucose transporter is responsible for glucose uptake in MTCs and phaeochromocytomas.

Methods

Using protein sequences from the known human glucose transporters (Glut 1–5), the National Center for Biotechnical Information expressed sequence tag database was screened for novel homologous sequences. Clones derived were used to screen a pooled kidney complementary DNA (cDNA) library, and cDNAs identified were used to identify patterns of expression by Northern blot analysis.

Results

A novel member of the human glucose transporter family, called Glut X2, was identified. This transporter had 33 per cent protein sequence identity to Glut 3. Hydropathic analysis showed exofacial and transmembrane domain structure consistent with a hexose transporter. Northern blot analysis showed expression of Glut X2 in all seven MTCs studied, all three phaeochromocytomas and in TT cells, an MTC cell line. These tumours did not express any of the other known facilitative glucose transporters (Glut 1–5).

Conclusion

A novel member of the human glucose transporter family has been identified which may be responsible for glucose uptake in MTCs and phaeochromocytomas.
Pitfalls of intraoperative (1–84) parathyroid hormone measurement during surgery for primary hyperparathyroidism in 154 consecutive operations
Authors: Mondragon-Sanchez A , Minuto M , Mullineris B , Lokey J , Pattou F , Smellie W J B , Proye C
Published: March 2003

Background

Rapid intraoperative assay of peripheral blood intact parathyroid hormone (PTH) levels has been proposed to supersede frozen-section analysis and assure complete removal of pathological tissue after unilateral (minimal access) exploration. This is a review of the author's surgical, pathological and rapid PTH assay results.

Methods

Some 152 patients (26 men) had 154 explorations for primary hyperparathyroidism (HPT) with rapid intraoperative assay of intact PTH at Centre Hospitalier Regional et Universitaire de Lille.

Results

After neck dissection, before removal of any tissue, the PTH level altered from 11 to 900 per cent of the level at induction of anaesthesia. Decay of blood PTH levels after excision was rapid but some late raised levels may be have been due to a pre-excision increase. Recurrent or persistent HPT was seen in eight patients. This was predicted correctly in two and missed in six by the PTH assay (i.e. PTH greater than 50 per cent at more than 5 min). One Schwannoma and one thyroid nodule were removed resulting in diagnostic drops of PTH. There was no instance of non-hyperparathyroid tissue removal and intraoperative PTH assay. Multiple pathological glands were missed by PTH assay in four patients and predicted in a further two. In five patients the fall in PTH was slow; one was taking lithium, one was in mild renal failure and one had such a high initial PTH level that the assay saturated and it appeared that the results remained static. In 140 operations HPT was identified correctly and excised with a concomitant drop in PTH.

Conclusion

The intraoperative PTH levels vary markedly in either direction between induction of anaesthesia and the end of dissection. After excision of hyperparathyroid tissue the PTH level normally falls briskly from the postdissection level. The number of patients with a potentially unfavourable outcome is small; these data suggest that rapid intrapoperative PTH assay would have missed further HPT in ten of 14 instances had the surgical strategy been solely dependent on PTH levels. The routine use of intraoperative PTH assay in surgery for primary HPT is therefore questioned.
Screening for genetic aberrations in papillary thyroid cancer using comparative genomic hybridization
Authors: Singh B , Lim D , Cigudosa J C , Rao P H , Ghossein R , Poluri A , Wreesmann V , Shaha A , Shah J P
Published: March 2003

Background

Papillary thyroid carcinomas (PTCs) are a heterogenous group of neoplasms that display a wide variability in clinical behaviour. Knowledge of the genetic composition of these tumours may help improve prognostication, but is currently limited. The aim of this study was to identify the genetic composition of pathologically low-risk papillary thyroid cancers and identify differences based on age, using a powerful, genome-wide analytical technique, comparative genomic hybridization (CGH).

Methods

Tumour samples from patients with pathologically confirmed well differentiated PTC, less than 4 cm in size and without extrathyroidal extension or distant metastasis, were procured from the institutional tumour bank. CGH analysis was performed by differentially labelling tumour and normal DNA with fluorescent agents. The labelled DNAs were coprecipitated and simultaneously hybridized to normal metaphase chromosomes on glass slides. After chromosomal segregation, computerized image analysis was performed to detect fluorochrome intensity along the entire length of each chromosome. The ratio of fluorescent signal intensity was used to identify the presence of genetic abnormalities. Statistical age-group comparisons of the CGH findings were performed using Fisher's exact test.

Results

Genetic abnormalities were detected in ten of 21 cases. A recurrent pattern of aberrations was identified, involving losses at chromosomes 1p, 9q, 17, 19 and 22, and gains at 4, 6 and 13. The prevalence of CGH-detectable aberrations was not influenced by age, but loss of chromosome 22 was unique to patients aged less than 40 years (P = 0·05) and was associated with a higher rate of locoregional metastasis (19 versus 80 per cent; P = 0·02).

Conclusion

Two distinct patterns of genetic composition were observed in PTC. One group had no detectable abnormalities, while the other had a recurrent pattern of gains and losses that localized to identical chromosomal loci. Although a divergent pattern of involvement was seen in younger patients, the direct clinical significance of this finding needs to be elucidated. Moreover, the identified pattern of alterations suggests that novel oncologically consequential genes are present within the involved loci. Molecular cloning of the genes at each of these sites is warranted.
Risk profile for bone fractures in primary hyperparathyroidism
Authors: Westerdahl J , Valdemarsson S , Lindblom P , Bergenfelz A
Published: March 2003

Background

Contemporary patients with primary hyperparathyroidism (pHPT) have an increased fracture risk, although they are often otherwise asymptomatic with mild hypercalcaemia. Decreased bone density has, therefore, been considered an indication for surgery. However, many patients with pHPT are old with concomitant chronic diseases and therefore have a multifocal risk profile for osteoporosis and bone fractures. The aim of the present study was to evaluate bone density as well as other clinical and biochemical variables of importance for bone metabolism with regard to fracture risk in patients with pHPT.

Methods

Two hundred and five consecutive patients, 154 women and 51 men, operated for pHPT were investigated for bone mineral content (BMC), biochemical variables reflecting bone metabolism and severity of pHPT, medication and potential other risk factors for osteoporosis. Mean(s.d.) age of the patients was 64(14) years and serum level of calcium was 2·78(0·18) mmol l−1.

Results

Eighteen patients (9 per cent) had a history of at least one bone fracture during the 5 years before pHPT surgery. In univariate analyses age, BMC, serum level of PTH, 25-hydroxyvitamin D, alkaline phosphatase and collagen telopeptide (ICTP), cortisone treatment and a history of cardiovascular disease were found to be associated with a history of bone fractures. When these variables, and in addition sex, were included in a multiple logistic regression analysis, ICTP was the only variable independently related to bone fractures.

Conclusion

The present data highlight the multifocal bone fracture risk profile in pHPT including low bone density. However, bone resorption (ICTP) was the only variable in the multivariate analysis that was independently associated with bone fractures in pHPT. This finding supports the important role of bone resorption in the pathogenesis of fractures in pHPT. Furthermore, it suggests that ICTP may be a useful tool for risk evaluation of fractures in patients with pHPT.
Overexpression of haem oxygenase 1 protects allogeneic thyroid grafts from rejection in naive mice
Authors: Niimi M , Takashina M , Ikeda Y , Takami H , Wood K J
Published: March 2003

Background

Endocrine allografts are an option for the treatment of endocrine failure. This study examined whether anti-CD4 monoclonal antibody (mAb) could induce survival of allogeneic thyroid grafts and investigated the mechanisms involved in graft survival.

Methods and Results

One lobe of thyroid was transplanted under the kidney capsule and graft survival was examined histologically. C57BL/10 (H2b) thyroids were rejected in naive CBA (H2k) mice within 14 days after transplantation. When mice were treated with a depleting anti-CD4 mAb (YTA 3·1; 100 μg on day −1, 0 and 3), all C57BL/10 thyroid grafts survived for over 30 days. In order to determine if donor-specific tolerance had been induced, mice with the surviving C57BL/10 thyroid grafts were transplanted with second C57BL/10 or Balb/c (H2d) thyroids under the left kidney capsule at 30 days. Interestingly, all of the second grafts were rejected in the left kidney capsule but the first C57BL/10 thyroid grafts continued to survive in the right kidney capsule for a further 30 days. These findings suggest that grafts themselves were modified under anti-CD4 mAb treatment. To confirm this hypothesis, C57BL/10 thyroid grafts in mice treated with anti-CD4 mAb were resected and retransplanted into naive mice 30 days after transplantation. All of the grafts survived when retransplanted to naive mice and this was found to correlate with overexpression of haem oxygenase 1 in the thyroid grafts. In an attempt to demonstrate the pivotal role of haem oxygenase 1 on graft survival, an inhibitor of haem oxygenase 1 (zinc protoporphyrin) or control compound (copper protoporphyrin) that did not inhibit the enzyme was injected intraperitoneally (30 mmol l−1 every day) after transplantation of C57BL/10 thyroid grafts into the primary CBA recipients treated with anti-CD4 mAb. The grafts in mice treated with zinc protoporphyrin but not copper protoporphyrin were rejected when retransplanted to naive recipients.

Conclusion

Overexpression of haem oxygenase 1 protects allogeneic thyroid grafts from rejection in recipients treated with anti-CD4 mAb. This observation may be applied for clinical endocrine grafts using gene transfer of haem oxygenase 1.
Surgical versus medical treatment for calciphylaxis
Authors: Kang A S , McCarthy J T , Rowland C , Farley D R , van Heerden J A
Published: March 2003

Background

Calciphylaxis is a rare, painful, life-threatening problem of cutaneous necrosis and refractory healing seen in patients with uraemia and secondary hyperparathyroidism. The pathogenesis involves abnormalities in calcium and phosphorus metabolism, and acute deposition of calcium in tissues.

Methods

The clinical course of 16 patients diagnosed with calciphylaxis at this institution from 1994 to 1998 was reviewed.

Results

Fourteen women and two men, with a mean age of 56 (range 39–70) years, presented with chronic renal disease of various causes, hyperparathyroidism and characteristic skin lesions. All patients underwent intensive medical therapy, including haemodialysis (n = 16), parathyroidectomy (PTX) (n = 7) and skin debridement of cutaneous lesions (n = 8). Mean preoperative serum values in surgical (PTX) versus non-surgical patients were: calcium 9·9 and 9·3 mg dl−1 (P = 0·25); phosphorus 5·8 and 4·9 mg dl−1 (P = 0·04); calcium–phosphorus product 61·6 and 45·2 (P = 0·03); and parathyroid hormone (PTH) 56·8 and 5·9 pmol l−1 (P = 0·0001) respectively. Mean postoperative values for calcium (8·7 mg dl−1), phosphorus (4·2 mg dl−1), calcium–phosphorus product (30·5) and PTH (4·0 pmol l−1) in surgical patients changed significantly (P < 0·05). Median overall survival was 9·4 months with 15 patients now deceased. Median survival was 14·8 and 6·3 months for PTX versus no PTX (P = 0·22), 14·1 and 6·1 months for skin debridement versus no debridement (P = 0·08), 12·4 and 6·6 months for proximal versus distal skin lesions (P = 0·60), and 6·5 and 13·9 months for diabetic versus non-diabetic patients was (P = 0·11).

Conclusion

Calciphylaxis appears to have a female preponderance with a very dismal prognosis. A multidisciplinary approach using frequent haemodialysis to normalize serum calcium and phosphorus levels, and local debridement of skin lesions seems prudent. PTX cannot be recommended routinely in all such patients unless severe secondary hyperparathyroidism with poorly controlled metabolic disturbance mandates surgery. The exact indications for PTX for calciphylaxis remain unclear.
Late parathyroid function following successful parathyroidectomy guided by intraoperative hormone assay compared with standard bilateral neck exploration
Authors: Carneiro D N , Irvin G L
Published: March 2003

Background

Controversy continues between bilateral neck exploration and limited parathyroidectomy guided by gland hyperfunction. While one approach depends on gland size and histopathology, the other limits excision to hypersecreting glands only. Although both methods claim early operative success, the late recurrence rate with limited exploration is unknown. Late biochemical outcomes from these two operative approaches are reported.

Methods

Some 301 consecutive patients with primary hyperparathyroidism were followed 6–495 months after successful parathyroidectomy; 164 patients had bilateral neck exploration with excision of enlarged glands (group 1) and 137 patients had glands excised based on hypersecretion (group 2). Calcium and intact parathyroid hormone (iPTH) levels were measured yearly. Recurrent parathyroid gland hypersecretion was determined by iPTH levels above the normal range.

Results

In group 1, a single gland was excised in 150 patients (91 per cent); 15 (9 per cent) of 164 had late raised iPTH levels (12 normocalcaemic). In group 2, 133 patients (97 per cent) had a single gland excised and 21 (15 per cent) of 137 had high iPTH levels (19 normocalcaemic). The number of patients with more than one gland excised in group 1 (9 per cent) was three times higher than that in group 2 (3 per cent) (P < 0·04). There was no statistical difference in the incidence of recurrent hyperfunctioning glands between the two operative approaches (χ2 test).

Conclusion

Based on late parathyroid gland function, parathyroidectomy guided by gland hyperfunction yielded comparable results to bilateral neck exploration. Multiple gland excision based on gross appearance alone may result in unnecessary excision of normal glands and possible hypoparathyroidism.
Thyroid surgery with intraoperative neuromonitoring of the recurrent laryngeal nerve: a prospective multicentre study in Germany with 7617 patients
Authors: Thomusch O , Sekulla C , Dralle H
Published: March 2003

Background

Injury to the recurrent laryngeal nerve (RLN) is a frequently noted and serious complication in thyroid surgery. Several studies have established that identification of the RLN may reduce the incidence of RLN palsy. To date, no prospective study has evaluated whether the RLN palsy rate can be further reduced by intraoperative neuromonitoring of the RLN.

Methods

Between 1 January and 31 December 1998, surgery for benign and malignant goitre was performed on 7607 patients in 45 hospitals. Data were collected prospectively by questionnaire. RLN function was evaluated before and after operation in all patients. RLN palsy was defined as permanent when there was no evidence of recovery within 6 months after surgery. The RLN palsy rate was adjusted to nerves at risk in the three groups ‘no identification of the RLN’, ‘intraoperative identification of the RLN without neuromonitoring’ and ‘identification of the RLN with neuromonitoring’. Statistical analysis was by χ2 test.

Results

Mean patient age was 51·8 years; 72·7 per cent were women. Some 7256 patients were treated for benign goitre (multinodular goitre 74·0 per cent, uninodular goitre 16·6 per cent, recurrent goitre 6·1 per cent, Graves' disease 3·3 per cent, Hashimoto and De Quervain thyroiditis less than 0·1 per cent) and 351 patients for thyroid carcinoma, with a negative selection of recurrent goitre and thyroid carcinoma for the two groups with intraoperative RLN identification (P < 0·0001). With respect to the extent of resection, in cases of lobectomy the rate of permanent RLN palsy was 1·5 per cent with intraoperative neuromonitoring which was significantly lower than rate with intraoperative RLN identification without neuromonitoring (2·6 per cent) or no RLN identification (6·3 per cent) (P < 0·0001). Detailed analysis of the complete spectrum of extent of resection and indications for surgery showed a positive trend for intraoperative neuromonitoring in comparison to the group with RLN identification without the use of neuromonitoring, but this trend was not statistically significant because of the small number of permanent RLN palsies.

Conclusion

Intraoperative neuromonitoring of the RLN has a beneficial effect for high-risk patients with recurrent goitre and thyroid carcinoma in whom the RLN is at greatest risk in cases of lobectomy or total thyroidectomy.
Expression of the RET proto-oncogene and the RET/PTC oncogenes in papillary thyroid carcinomas and its correlation to clinical manifestations
Authors: Kjellman P C , Learoyd D L , Larsson C , Wallin G , Messina M , Robinson B G , Zedenius J
Published: March 2003

Background

Papillary thyroid carcinoma (PTC) is the commonest thyroid cancer. It has an excellent prognosis if the patients receive appropriate treatment. However, a subgroup of patients with PTC develop distant metastases and eventually die from the disease. There are considerable difficulties in identifying such patients before operation, and there is a need for better tools to do so. Genetic changes, such as expression of the oncogenic fusion proteins RET/PTC 1–5, have been described but their correlation with the clinical picture and prognosis is unclear.

Methods

Sixty-one PTCs (50 primary and 11 recurrent tumours) from 61 patients were selected and analysed for expression of the RET tyrosine kinase domain (RET-TK) and the oncogenes RET/PTC by reversed transcribed polymerase chain reaction, followed by restriction enzyme digestion and direct sequencing. This expression was then correlated with clinical features of lymph node metastasis, distant metastasis, poor differentiation, tall cell variant, extrathyroidal growth, previous external radiation, recurrent disease and death from disease.

Results

Thirty PTCs (49 per cent) showed expression of RET-TK. Thirteen of them appeared to express wild-type RET, as upstream exons were also expressed. Three were explained by RET/PTC expression: one RET/PTC1, one RET/PTC3 and one with a unique variant of RET/PTC3, previously only described in a patient with PTC from Chernobyl. Poor differentiation, but no other histopathological parameter, was significantly correlated with the expression of wild-type RET. Furthermore, in PTCs from 15 patients with a poor clinical outcome (death from disease or distant metastases) RET-TK expression was found significantly more often.

Conclusion

Half of the PTCs showed expression of RET-TK. Surprisingly, only three of them could be explained by known RET/PTC oncogenes. Probably, some of the PTCs express wild-type RET while others could be explained by new, or not yet identified, RET/PTC rearrangements. Regardless of the mechanism for RET-TK expression, this seems to be correlated with a poor prognosis. If this holds true in a larger sample, RET-TK expression could be used as an additional marker to identify patients with PTC who have a less favourable prognosis, and who may benefit from more extensive treatment.