Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

[Quality criteria for common surgical operations]. / Qualitätsmerkmale in der Schilddrüsenchirurgie. Woran Sie eine gute Klinik erkennen.

Personal contact with a hospital and patients who have received treatment there offer the best opportunity to assess its quality. A certification merely shows that a quality management system has been implemented, but says nothing about the quality of the actual outcomes achieved. Quality reports aid the family doctor to make an estimate of departments with which he has not so far cooperated. Objective information regarding the quality of outcomes are considerably more difficult to obtain. There appears to be a correlation between large numbers of operations and the quality of the surgery. In this area, the physician is dependent on voluntary publication of performance reports.

Radio-guided surgery for persistent differentiated papillary thyroid cancer: case presentations and review of the literature.

BACKGROUND AND AIMS: Persistent differentiated papillary thyroid cancer following radical locoregional surgery with metastases is an indication for limited reoperation or radioiodine therapy. Following injection of radioiodine, radio-guided surgery with application of an intraoperative gamma probe offers detection of metastases not seen by conventional imaging and control of completeness of resection. PATIENTS/METHODS: We demonstrate four patients with locoregional metastases, two of them with additional distant metastases of papillary thyroid cancer following radical neck surgery. Postoperative radioiodine scans demonstrated persistent ipsilateral or contralateral cervical and mediastinal lymph node and isolated rib metastases. RESULTS: Radio-guided surgery (RGS) leads to complete clearance of persistent lymph node metastases by limited recurrent neck surgery, resection of metastases not seen by conventional imaging and control of complete mediastinal lymph node dissection. Post-RGS scans allowed early diagnosis of occult diffuse or nodal pulmonary metastases in two patients. At last follow-up, 23 to 48 months following RGS and radioiodine therapy, there was no evidence of disease. CONCLUSIONS: Radio-guided surgery is an additive surgical technique with low morbidity in selected patients with persistent thyroid cancer individualizing tumor therapy options in multimode oncological therapy.

Ergonomic assessment of the static stress confronted by surgeons during laparoscopic cholecystectomy.

BACKGROUND: Only a few reports on static strain in the spine, neck, and head of the surgeon are available, describing it as "distinctly harmful." The aim of this study was to objectively prove the static burden during laparoscopic operations. For this, new industrial software called PCMAN was used, capable of measuring and comparing the postures of the surgeon at different monitor placements. METHODS: Two simultaneous and synchronized video recordings of laparoscopic cholecystectomies (LC) were done using miniDV digital camcorders with the cameras standing at a 90 degrees angle to each other. Twenty operations were performed using two different placements of the monitor. In 10 cases, the monitor was placed at the patient's head in the center, and in 10 cases at the left side of the patient. Using the time codes of the recordings, different steps of the operation were identified, and the duration of these measured in seconds. Very characteristic, longer lasting postures were imported to and analyzed with the software. Results of the different setups were compared to each other, and to an "ideal" comfort posture. RESULTS: During the intermediate steps of the operations the rate of static phases is significantly higher. Measuring the typical postures of these phases the trunk and head are significantly more rotated and bent than in comfort positions. When the monitor was at the side of the patient facing the surgeon, results were closer to the comfort posture. CONCLUSIONS: It was proven that surgeons are confronted by significant static burden during LC. The software used was able to evaluate objectively the static posture of the surgeon during series of LC. Results also confirmed that the position of monitors significantly influences the surgeon's posture. Best setups for the whole team can be achieved by adjustable multiple monitor systems.

[Preservation of the recurrent laryngeal nerve]. / Schonung des Nervus recurrens.

A strategy to protect the inferior laryngeal nerve (ILN, recurrent and non-recurrent) as well as the superior laryngeal nerve (SLN) includes the reason for and extend of the operation to avoid recurrent goiter, selection of an experienced institution and operating team, a cautious intubation, adequate and anatomical operating technique, recognition of risk factors and postoperative treatment with a sufficient dosage of hormone and/or iodine. The ILN should be dissected routinely in view of its anatomical variation. The "capsular dissection technique" should be applied. The "laterialisation technique" of the upper pole protects the SLN with regard to its anatomic variability. Neuromonitoring of both nerves can be helpful under difficult circumstances.

Distinct frequency of ret rearrangements in papillary thyroid carcinomas of children and adults from Belarus.

Rearrangements of the ret oncogene were investigated in papillary thyroid carcinomas (PTC) from 51 Belarussian children with a mean age of 3 years at the time of the Chernobyl radiation accident. For comparison, 16 PTC from exposed Belarussian adults and 16 PTC from German patients without radiation history were included in the study. ret rearrangements were detected and specified by RT-PCR and direct sequencing using specific primers for ret/PTC1, 2 and 3. Only ret/PTC1, and no ret/PTC3, was found in the adult patients, with a frequency of 69% for the Belarussian cases, but of only 19% in the German patients. In contrast, 13 ret/PTC3 (25.5%) and 12 ret/PTC1 (23.5%) rearrangements were present in PTC from Belarussian children. Thus, our study reveals about a 1:1 ratio of ret/PTC3 and ret/PTC1, in contrast to earlier studies with lower numbers of cases and exhibiting a high predominance of ret/PTC3 (ratio about 3:1). A ratio (2.5:1) similar to that in earlier investigations (diagnosed 1991-94) was obtained for cases included in our study that were diagnosed in 1993/94. The present data suggest that ret/PTC3 may be typical for radiation-associated childhood PTC with a short latency period, whereas ret/PTC1 may be a marker for later-occurring PTC of radiation-exposed adults and children.

Cytogenetic changes in radiation-induced tumors of the thyroid.

Thyroid carcinoma incidence is increased significantly after ionizing irradiation; however, the possible mechanisms have not yet been identified. To provide clues for an understanding of the radiation-induced transformation of thyroid epithelium, we analyzed the karyotypes of 56 childhood thyroid tumors that appeared in Belarus after the Chernobyl nuclear accident in 1986. We also studied eight secondary thyroid tumors that developed after radiotherapy. Metaphase preparations obtained from primary cultures were analyzed by G-banding. Clonal structural aberrations were found in 13 of 56 Belarussian cases and in 6 of 8 secondary tumors that developed after radiotherapy. Furthermore, we detected multiple chromosomal aberrations as well as complex rearrangements in some of these tumors and performed a detailed analysis of marker chromosomes from a single case using spectral karyotyping and comparative genomic hybridization in a childhood tumor from Belarus with a near-triploid karyotype. Both comparative genomic hybridization and spectral karyotyping analysis revealed structural alterations affecting identical chromosomes 1, 2, 9, and 13, among others. In addition to the known hot spots of alterations in papillary thyroid carcinomas on chromosomes 1q and 10q, a comprehensive breakpoint analysis in the pooled data set revealed novel breakpoints on chromosomes 4q, 5q, 6p, 12q, 13q, and 14q. The chromosomal aberrations in these tumors may provide suitable starting points for the positional cloning of genes involved in radiation-induced tumorigenesis.

p53 mutations in childhood thyroid tumours from Belarus and in thyroid tumours without radiation history.

Mutations in the p53 tumour-suppressor gene (exons 5-8) were investigated in 31 Belarussian childhood thyroid tumours (24 cases of papillary thyroid carcinoma, 3 benign tumours and 2 cases each of thyroiditis and goiter); 33 thyroid tumours from juveniles and adults without radiation exposures (25 carcinomas of various histological types, including 11 papillary carcinomas and 8 adenomas) and 6 tumours from adults (4 papillary carcinomas, 1 adenoma, 1 goiter) served as controls. The mutational spectrum of p53 differed greatly between the childhood thyroid carcinomas from Belarus and the control groups. In the control groups of 29 malignant thyroid tumours, 7 different mutations were detected on exons 5-8, none of which occurred among the 15 papillary carcinomas in this group. Five mutations were found in tissue samples of the 24 childhood papillary carcinomas, and they were all the same p53 point mutation (CGA --> CGG) on codon 213 of exon 6. To determine whether this mutation is simply a polymorphism or whether it is specific to the tumour cells, laser-assisted microdissection was applied to collect various areas of tumorous and non-tumorous cells (10-20 cells per sample) from each paraffin-embedded tissue section of 8 of the papillary thyroid carcinomas. Using PCR-SSCP and sequence analysis on these cells, the very same p53 mutation on codon 213 was detected in various microdissected tumour samples of 2 cases, but it was not found in any microdissected non-tumorous sample. The exclusive occurrence of this p53 mutation in selective microdissected samples of tumour cells, even as homozygous mutation in 1 case, reflects a distinct tumour heterogeneity within papillary childhood thyroid carcinomas.

Cytogenetic and molecular genetic characterization of a chromosome 2 rearrangement in a case of human papillary thyroid carcinoma with radiation history.

Karyotype analysis of a primary culture from a case of papillary thyroid cancer (PTC) showed an abnormal short arm of one homologue of chromosome 2 as sole abnormality in 4 of 16 metaphases. Based on G-banding analysis, two different aberration types on chromosome 2 could be assumed representing either a del(2)(p22-23) or a pericentric inversion. Further comparative genomic hybridization (CGH) analysis as well as fluorescence in situ hybridization (FISH) analysis were performed to confirm the assumed alterations. While CGH analysis showed no loss of chromosome 2 material, FISH with yeast artificial chromosome (YAC) probes homologous to the region 2p22-23 demonstrated two pericentric inversions of chromosome 2 involving different breakpoints on 2p in 6.8% and 4.2% of the metaphases, respectively. Polymerase chain reaction (PCR) analysis with degenerated oligonucleotide primers that bind within the conserved catalytic domain of tyrosine kinase (tk) genes resulted in amplification products with DNA of YAC 851D11 suggesting the presence of such genes at or near the translocation breakpoint.

Chromosome translocations in thyroid tissues from Belarussian children exposed to radioiodine from the Chernobyl accident, measured by FISH-painting.

Chromosome painting of chromosomes 1, 4 and 12 was performed on metaphase preparations of cultured thyroid cells to analyse the frequency of radiation-induced stable chromosome translocations in papillary thyroid carcinomas from 40 Belarussian children exposed to radioiodine from the Chernobyl accident, and from 31 reference case. As expected, we found the highest translocation frequencies in secondary thyroid tumours after radiotherapy, but there were also high frequencies in tumour tissues as well as in non-tumourous tissues from childhood papillary carcinoma samples from Belarus. Among the Belarussian tumours the cases from the Gomel region exhibited the highest frequency of translocations and five cases lie within the range of frequencies observed in secondary thyroid tumours after radiotherapy. The findings support the assumption that radiation was the principal cause of the tumours in Belarus, but they indicate also that only a minority of the Belarus cases, which have developed papillary carcinomas, were exposed to very high doses of radioiodine.