Intraoperative respiratory and hemodynamic strategies for reducing nausea, vomiting, and pain after surgery: Systematic review and meta-analysis.

BACKGROUND: Despite improved medical treatment strategies, postoperative pain, nausea, and vomiting remain major challenges. This systematic review investigated the relationship between perioperative respiratory and hemodynamic interventions and postoperative pain, nausea, and vomiting. METHODS: PubMed and Embase were searched on March 8, 2021 for randomized clinical trials investigating the effect of perioperative respiratory or hemodynamic interventions in adults undergoing non-cardiac surgery. Investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed when feasible. GRADE was used to assess the certainty of the evidence. RESULTS: This review included 65 original trials; of these 48% had pain, nausea, and/or vomiting as the primary focus. No reduction of postoperative pain was found in meta-analyses when comparing recruitment maneuvers with no recruitment, high (80%) to low (30%) fraction of oxygen, low (5-7 ml/kg) to high (9-12 ml/kg) tidal volume, or goal-directed hemodynamic therapy to standard care. In the meta-analysis comparing recruitment maneuvers with no recruitment maneuvers, patients undergoing laparoscopic gynecological surgery had less shoulder pain 24 h postoperatively (mean difference in the numeric rating scale from 0 to 10: -1.1, 95% CI: -1.7, -0.5). In meta-analyses, comparing high to low fraction of inspired oxygen and goal-directed hemodynamic therapy to standard care in patients undergoing abdominal surgery, the risk of postoperative nausea and vomiting was reduced (odds ratio: 0.45, 95% CI: 0.24, 0.87 and 0.48, 95% CI: 0.27, 0.85). The certainty in the evidence was mostly very low to low. The results should be considered exploratory given the lack of prespecified hypotheses and corresponding risk of Type 1 errors. CONCLUSION: There is limited evidence regarding the impact of intraoperative respiratory and hemodynamic interventions on postoperative pain or nausea and vomiting. More definitive trials are needed to guide clinical care within this area.

Fraction of inspired oxygen during general anesthesia for non-cardiac surgery: Systematic review and meta-analysis.

BACKGROUND: Controversy exists regarding the effects of a high versus a low intraoperative fraction of inspired oxygen (FiO2 ) in adults undergoing general anesthesia. This systematic review and meta-analysis investigated the effect of a high versus a low FiO2 on postoperative outcomes. METHODS: PubMed and Embase were searched on March 22, 2022 for randomized clinical trials investigating the effect of different FiO2 levels in adults undergoing general anesthesia for non-cardiac surgery. Two investigators independently reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and potential effect measure modification was assessed in subgroup analyses and meta-regression. The evidence certainty was evaluated using GRADE. RESULTS: This review included 25 original trials investigating the effect of a high (mostly 80%) versus a low (mostly 30%) FiO2 . Risk of bias was intermediate for all trials. A high FiO2 did not result in a significant reduction in surgical site infections (OR: 0.91, 95% CI 0.81-1.02 [p = .10]). No effect was found for all other included outcomes, including mortality (OR = 1.27, 95% CI: 0.90-1.79 [p = .18]) and hospital length of stay (mean difference = 0.03 days, 95% CI -0.25 to 0.30 [p = .84). Results from subgroup analyses and meta-regression did not identify any clear effect modifiers across outcomes. The certainty of evidence (GRADE) was rated as low for most outcomes. CONCLUSIONS: In adults undergoing general anesthesia for non-cardiac surgery, a high FiO2 did not improve outcomes including surgical site infections, length of stay, or mortality. However, the certainty of the evidence was assessed as low.

Ventilation Strategies During General Anesthesia for Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal ventilation strategy during general anesthesia is unclear. This systematic review investigated the relationship between ventilation targets or strategies (eg, positive end-expiratory pressure [PEEP], tidal volume, and recruitment maneuvers) and postoperative outcomes. METHODS: PubMed and Embase were searched on March 8, 2021, for randomized trials investigating the effect of different respiratory targets or strategies on adults undergoing noncardiac surgery. Two investigators reviewed trials for relevance, extracted data, and assessed risk of bias. Meta-analyses were performed for relevant outcomes, and several subgroup analyses were conducted. The certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: This review included 63 trials with 65 comparisons. Risk of bias was intermediate for all trials. In the meta-analyses, lung-protective ventilation (ie, low tidal volume with PEEP) reduced the risk of combined pulmonary complications (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.28-0.49; 9 trials; 1106 patients), atelectasis (OR, 0.39; 95% CI, 0.25-0.60; 8 trials; 895 patients), and need for postoperative mechanical ventilation (OR, 0.36; 95% CI, 0.13-1.00; 5 trials; 636 patients). Recruitment maneuvers reduced the risk of atelectasis (OR, 0.44; 95% CI, 0.21-0.92; 5 trials; 328 patients). We found no clear effect of tidal volume, higher versus lower PEEP, or recruitment maneuvers on postoperative pulmonary complications when evaluated individually. For all comparisons across targets, no effect was found on mortality or hospital length of stay. No effect measure modifiers were found in subgroup analyses. The certainty of evidence was rated as very low, low, or moderate depending on the intervention and outcome. CONCLUSIONS: Although lung-protective ventilation results in a decrease in pulmonary complications, randomized clinical trials provide only limited evidence to guide specific ventilation strategies during general anesthesia for adults undergoing noncardiac surgery.

Treatment with senicapoc, a KCa 3.1 channel blocker, alleviates hypoxaemia in a mouse model of acute respiratory distress syndrome.

BACKGROUND AND PURPOSE: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary oedema and severe hypoxaemia. We investigated whether genetic deficit or blockade of calcium-activated potassium (KCa 3.1) channels would counteract pulmonary oedema and hypoxaemia in ventilator-induced lung injury, an experimental model for ARDS. EXPERIMENTAL APPROACH: KCa 3.1 channel knockout (Kccn4-/- ) mice were exposed to ventilator-induced lung injury. Control mice exposed to ventilator-induced lung injury were treated with the KCa 3.1 channel inhibitor, senicapoc. The outcomes were oxygenation (PaO2 /FiO2 ratio), lung compliance, lung wet-to-dry weight and protein and cytokines in bronchoalveolar lavage fluid (BALF). KEY RESULTS: Ventilator-induced lung injury resulted in lung oedema, decreased lung compliance, a severe drop in PaO2 /FiO2 ratio, increased protein, neutrophils and tumour necrosis factor-alpha (TNF-α) in BALF from wild-type mice compared with Kccn4-/- mice. Pretreatment with senicapoc (10-70 mg·kg-1 ) prevented the reduction in PaO2 /FiO2 ratio, decrease in lung compliance, increased protein and TNF-α. Senicapoc (30 mg·kg-1 ) reduced histopathological lung injury score and neutrophils in BALF. After injurious ventilation, administration of 30 mg·kg-1 senicapoc also improved the PaO2 /FiO2 ratio and reduced lung injury score and neutrophils in the BALF compared with vehicle-treated mice. In human lung epithelial cells, senicapoc decreased TNF-α-induced permeability. CONCLUSIONS AND IMPLICATIONS: Genetic deficiency of KCa 3.1 channels and senicapoc improved the PaO2 /FiO2 ratio and decreased the cytokines after a ventilator-induced lung injury. Moreover, senicapoc directly affects lung epithelial cells and blocks neutrophil infiltration in the injured lung. These findings indicate that blocking KCa 3.1 channels is a potential treatment in ARDS-like disease.

Goal-directed haemodynamic therapy during general anaesthesia for noncardiac surgery: a systematic review and meta-analysis.

BACKGROUND: During general anaesthesia for noncardiac surgery, there remain knowledge gaps regarding the effect of goal-directed haemodynamic therapy on patient-centred outcomes. METHODS: Included clinical trials investigated goal-directed haemodynamic therapy during general anaesthesia in adults undergoing noncardiac surgery and reported at least one patient-centred postoperative outcome. PubMed and Embase were searched for relevant articles on March 8, 2021. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. The primary outcomes were mortality and hospital length of stay, whereas 15 postoperative complications were included based on availability. From a main pool of comparable trials, meta-analyses were performed on trials with homogenous outcome definitions. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). RESULTS: The main pool consisted of 76 trials with intermediate risk of bias for most outcomes. Overall, goal-directed haemodynamic therapy might reduce mortality (odds ratio=0.84; 95% confidence interval [CI], 0.64 to 1.09) and shorten length of stay (mean difference=-0.72 days; 95% CI, -1.10 to -0.35) but with low certainty in the evidence. For both outcomes, larger effects favouring goal-directed haemodynamic therapy were seen in abdominal surgery, very high-risk surgery, and using targets based on preload variation by the respiratory cycle. However, formal tests for subgroup differences were not statistically significant. Goal-directed haemodynamic therapy decreased risk of several postoperative outcomes, but only infectious outcomes and anastomotic leakage reached moderate certainty of evidence. CONCLUSIONS: Goal-directed haemodynamic therapy during general anaesthesia might decrease mortality, hospital length of stay, and several postoperative complications. Only infectious postoperative complications and anastomotic leakage reached moderate certainty in the evidence.

Human Allergen-Specific IgG Subclass Antibodies Measured Using ImmunoCAP Technology.

BACKGROUND: Knowledge of human IgG subclass antibody responses to various allergens has been hampered by a lack of reliable standardized assays. The aim here was to develop quantitative immunoassays for human IgG1, IgG2, and IgG3 antibodies using ImmunoCAP® technology and to evaluate their application. METHODS: Enzyme conjugates with isotype-specific monoclonal antibodies and calibrators composed of purified myeloma paraproteins were developed for each assay and used together with other standardized assay reagents for the Phadia® 100 instrument. The calibrators were adjusted to the international reference preparation IRP 67/86. The assays were characterized and used together with other standard ImmunoCAP assays to measure antibodies to various allergens in preliminary studies. RESULTS: The new assays had limits of quantitation of 1.0 (IgG1), 4.6 (IgG2), and 0.04 mgA/L (IgG3), and coefficients of variation of <20%. Only some minor cross-reactivity with IgG2 was observed for the specific IgG1 assay. The specific IgG2 assay showed a bias for the allotype G2m(23) and compensation factors were used to adjust the measured concentrations accordingly. Preliminary studies indicated a strong and stable IgG4 antibody response to ß-lactoglobulin in healthy individuals, a high IgG1 and even higher IgG2 antibody response to house dust mite in sensitized and nonsensitized subjects, and a mixed IgG subclass response to venom allergens in allergic patients with increasing IgG4 antibody levels during venom immunotherapy. CONCLUSIONS: The new research assays are valuable tools for immunological studies, enabling the characterization of antibody profiles using a standardized approach, and facilitating data interpretation and the comparison of results across studies.

Fine-Needle Aspiration with Immunohistochemistry Using a Modified Scrape Cell Block Technique for the Diagnosis of Thyroid and Parathyroid Nodules.

OBJECTIVE: To evaluate the diagnostic accuracy of a modified scrape cell block (SCB) technique in a large series of patients. The technique was especially developed and tested for fine-needle aspiration of thyroid and parathyroid nodules. STUDY DESIGN: Eighty-two ultrasound-guided fine-needle aspiration specimens with the sonographic aspect of a thyroid (n = 33) or a possible parathyroid nodule (n = 49) were studied. Immunohistochemistry (IHC) was used on cell blocks containing plasma, thromboplastin, and selected 3-dimensional cell aggregates scraped off Papanicolaou-stained smears. Antibodies for chromogranin A, thyroglobulin, parathyroid hormone, calcitonin, and carcinoembryonic antibody (CEA) were used. In cases of reduced immunosensitivity or suspected metastases or rare primary tumors, additional IHC markers were employed. RESULTS: Chromogranin A was expressed in all 28 parathyroid adenomas (PA), in 7 of 8 hyperplastic parathyroid glands, and in 13 of 14 medullary thyroid carcinomas (MTC). When combining positivity for chromogranin A and calcitonin/CEA, the specificity for the detection of MTC was 100%. Parathyroid hormone was expressed in 26 of 36 parathyroid nodules (72.2%). When combining follicular microarchitecture and expression of chromogranin A, the specificity for the detection of parathyroid tissue was 97%. CONCLUSION: With the modified SCB technique, accurate cytological diagnoses were obtained in 97.6% of 82 patients.

[Thyroid and pregnancy]. / Schilddrüse und Schwangerschaft.

Screening for thyroid dysfunction is recommended among certain groups of women, who plan a pregnancy, for example women with history of hyperthyroid or hypothyroid disease, with type 1 diabetes or other autoimmune disorders or women with previous therapeutic head or neck irradiation, in the case of infertility. Management of thyroid disease during pregnancy requires special consideration because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse affects on the pregnancy and the foetus. Under ideal conditions there is a cooperation among several healthcare professionals, such as endocrinologists, nuclear medicine physicians, gynaecologists, neonatologists and if necessary surgeons. This article surveys the physiological and pathological changes of thyroid, their diagnosis and therapy in the case of women in childbearing age, women with unfulfilled desire to have children, pregnant women, as well as women after delivery.

FDG PET/CT in the detection of recurrent rectal cancer.

The purpose of this study was to assess the additional value of combined fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the follow-up of rectal cancer after surgery. Forty-eight examinations in 30 patients were evaluated retrospectively. CT and PET components were interpreted separately, and this was followed by a consensus reading. Sites of increased FDG uptake as well as PET/CT findings were categorized as benign (1), equivocal (2), or malignant (3). The standard of reference was histology or clinical and imaging follow-up for at least 6 months. Sensitivity, specificity, positive and negative predictive values, and accuracy for differentiating benign (14/31) from malignant (17/31) uptake sites in the small pelvis were 100%, 64%, 77%, 100%, and 84% for PET/CT, and 100%, 29%, 63%, 100%, and 68% for PET, respectively. Regarding extrapelvic abnormalities, PET/CT was able to distinguish benign (31/88) from malignant (57/88) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 100%, 87%, 93%, 100%, and 95%, compared with 96%, 68%, 85%, 91%, and 86% for PET. The rare case of an FDG uptake of adrenal adenoma is documented. PET/CT is valuable in the staging of rectal cancer, particularly for excluding recurrent disease suspected by PET interpretation alone in a considerable number of patients.

High cathepsin K levels in men with differentiated thyroid cancer on suppressive L-thyroxine therapy.

BACKGROUND: Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. METHODS: A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). RESULTS: In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). CONCLUSION: Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Combined PET/CT in the follow-up of differentiated thyroid carcinoma: what is the impact of each modality?

PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established method in the follow-up of patients with differentiated thyroid carcinoma (DTC), elevated thyroglobulin (Tg) and negative 131I scans. This retrospective clinical study was designed to evaluate the impact of computed tomography (CT) and that of FDG-PET in combined FDG-PET/CT examinations on the restaging of DTC patients. METHODS: Forty-seven FDG-PET/CT scans of 33 patients with a history of DTC, elevated Tg levels and negative 131I uptake or additionally suspected 131I-negative lesions were studied. PET and CT images were analysed independently by an experienced nuclear medicine specialist and a radiologist. Afterwards a final consensus interpretation, the gold standard in our department, was provided for the fused PET/CT images and, if available, for supplementary investigations. RESULTS: Thirty-five investigations (74%) revealed pathological FDG-PET/CT findings. In summary, 25 local recurrences, 62 lymph node metastases and 122 organ metastases (41 lung, 60 bone, 21 other organs) were diagnosed. In 36 out of 47 examinations (77%), the original PET diagnoses were modified in the final consensus interpretation owing to the CT assessments. In 8 of the 35 pathological FDG-PET/CT examinations (23%), the final consensus interpretation of the PET/CT images led to an alteration in the treatment plan. CONCLUSION: PET/CT is a powerful fusion of two pre-existing imaging modalities, which not only improves the diagnostic value in restaging DTC patients with elevated Tg and negative 131I scan, but also provides accurate information regarding subsequent treatment options and may lead to a change in treatment management.

Is there a role for sandostatin treatment in patients with progressive thyroid cancer and iodine-negative but somatostatin-receptor-positive metastases?

INTRODUCTION: The aim of our study was to determine whether treatment with a long-acting somatostatin-receptor analogue is effective in patients with (131)I-negative but somatostatin-receptor-positive metastases from dedifferentiated and anaplastic thyroid cancer. MATERIALS AND METHODS: Twelve patients were screened for the study. All of them showed progressive disease confirmed by radiologic evaluation, increasing serum thyroglobulin (Tg), and negative diagnostic or posttherapeutic (131)I whole-body scans (WBS). Eight of 12 patients (4 males and 4 females; age range, 57-89 years; 1 papillary thyroid cancer; 4 poorly differentiated follicular thyroid cancer; 1 follicular and anaplastic thyroid cancer; 2 anaplastic thyroid cancer) showed positive somatosatin-receptor expression in Tc-99m depreotide WBS/SPECT (Tc-99m Dep.WBS). Initially, in all patients fluorine-18 2-fluoro-2- D-glucose-positron emission tomography-computed tomography ((18)F-FDG-PET-CT), Tc-99m Dep.WBS, and Tg measurements were performed. In the case of positive receptor scintigraphy, patients were treated with 20mg Sandostatin LAR (Novartis Pharmaceuticals, Basel, Switzerland) once per month intramuscularly over a period of 6 months followed by repeated (18)F-FDG-PET-CT, Tc-99m Dep.WBS, and Tg measurement to determine metabolic activity and tumor size. In case of tumor progression, the dose was increased to 30mg of Sandostatin LAR once per month. RESULTS: Only 3 patients were able to undergo long-term treatment. Two patients were treated with octreotide long-acting release (LAR) for 1 year and 1 patient for 1(1/2) years. All patients showed progressive disease during the treatment: an increase of serum Tg on one hand and an increase in the number of lesions and extent in tumor size visible on FDG-PET-CT and Tc-99m Dep.WBS on the other. During the treatment there was no change in receptor expression, nevertheless, clear tumor progression under therapy with a somatostatin analogue was visible in FDG-PET-CT and in Tc-99m Dep.WBS. CONCLUSION: Our data demonstrate that all of our patients treated with a somatostatin analogue showed clinical progression and that our attempt to achieve a stabilization of the disease failed.

Respective roles of thyroglobulin, radioiodine imaging, and positron emission tomography in the assessment of thyroid cancer.

Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is FDG-PET. In recent years the combination of PET and computed tomography has been introduced. The fusion of the metabolic and morphologic information was able to increase the diagnostic accuracy, reduces pitfalls and changes therapeutic strategies in a reasonable number of patients.

Role of Fluorodeoxyglucose PET in Inflammatory Bowel Disease: A Review.

Inflammatory bowel disease (IBD) requires a complex diagnostic workup. In contrast to endoscopy and cross-sectional imaging methods, scintigraphy enables a complete survey of the whole small and large bowel intestinal tract with a single noninvasive examination. For detection of IBD, 80% to 90% sensitivity and 92% to 100% specificity can be found for conventional scintigraphy. A new imaging method like fluorine-18 (F-18) fluorodeoxyglucose PET has been shown to be useful in tumor diagnostics. A major problem in PET is the limited anatomic information and nonspecific tracer uptake within the colon, however, which may lead to false-positive results. New imaging methods like combined PET/CT can help to solve the problem, because physiologic tracer uptake can be easily distinguished from pathologic lesions as a result of the anatomic detail provided by CT.

Post-surgical use of radioiodine (131I) in patients with papillary and follicular thyroid cancer and the issue of remnant ablation: a consensus report.

OBJECTIVE: To determine, based on published literature and expert clinical experience, current indications for the post-surgical administration of a large radioiodine activity in patients with differentiated thyroid cancer. DESIGN AND METHODS: A literature review was performed and was then analyzed and discussed by a panel of experts from 13 European countries. RESULTS: There is general agreement that patients with unifocal microcarcinomas = 1 cm in diameter and no node or distant metastases have a <2% recurrence rate after surgery alone, and that post-surgical radioiodine confers recurrence and cause-specific survival benefits in patients, strongly suspected of having persistent disease or known to have tumor in the neck or distant sites. In other patients, there is limited evidence that after complete thyroidectomy and adequate lymph node dissection performed by an expert surgeon, post-surgical radioiodine provides clear benefit. When there is any uncertainty about the completeness of surgery, evidence suggests that radioiodine can reduce recurrences and possibly mortality. CONCLUSION: This survey confirms that post-surgical radioiodine should be used selectively. The modality is definitely indicated in patients with distant metastases, incomplete tumor resection, or complete tumor resection but high risk of recurrence and mortality. Probable indications include patients with tumors >1 cm and with suboptimal surgery (less than total thyroidectomy or no lymph node dissection), with age <16 years, or with unfavorable histology.

Recombinant human thyrotropin is helpful in the follow-up and 131I therapy of patients with thyroid cancer: a report of the results and benefits using recombinant human thyrotropin in clinical routine.

There is no doubt that the availability of recombinant human thyrotropin (rhTSH) is one of the milestones in the management of patients with differentiated thyroid cancer (DTC). It offers the opportunity to obtain representative serum thyroglobulin (Tg) levels and diagnostic whole-body scanning (Dx WBS) with 131I under adequate TSH elevation, while the patient continues to receive thyroid hormone. But rhTSH is also used with success in the treatment of local recurrences and distant metastases. In this retrospective analysis we were able to show that our excellent clinical experiences with the use of rhTSH (rare side effects and high compliance) could also be demonstrated by sufficiently elevated TSH levels and representative stimulated Tg measurements. Since April 2001 most of the patients with thyroid cancer in our hospital have undergone diagnostic examination (205 patients underwent 319 examinations) and 131I therapy (a total of 68 treatments) with rhTSH stimulation excluding the first radioiodine ablation of remnants after initial thyroidectomy. Our results show that under rhTSH stimulation 83.5% (diagnostic group) and 88% (therapy group) of our patients with DTC obtained a TSH level of greater than 80 mU/L after two injections of rhTSH (Thyrogen, Genzyme Corp., Cambridge, MA) 0.9 mg intramuscularly 24 hours and 48 hours before the administration of 131I. Only 2.3% (diagnostic group) and 0% (therapy group) demonstrated TSH levels less than 50 mU/L. Serum Tg levels under rhTSH-stimulated conditions showed that in 81.2% the serum Tg maximum was obtained on day 5. Because of the costs associated with periodically rhTSH-assisted Tg testing and based on the data of other studies we are now testing mainly on day 5 to identify residual tumor mass and to compare these Tg levels in the follow-up. Our experience demonstrates that the administration of rhTSH is a safe, effective, and-from an economic point of view- valuable tool in the management of patients with DTC.

[Diagnosis, treatment and follow-up in the case of differentiated thyroid cancer]. / Diagnose, Therapie und Nachsorge des differenzierten Schilddrüsenkarzinoms.

For early diagnosis of thyroid cancer, ultrasonography (US) and US-guided fine-needle aspiration biopsy are the methods of choice. Thyroid scintigraphy using Tc-99m pertechnetate can underline the necessity of surgery in case of hypofunctioning nodules. Treatment of thyroid cancer includes total thyroidectomy and staging lymphadenectomy, in the case of lymph node metastases, radical neck dissection of the ipsilateral side. Four weeks after surgery, if TSH exceeds a value of 50 mU/l, with the exception of papillary thyroid cancer pT1a (TNM 1997), radioiodine remnant ablation using activities between 2960 and 3700 MBq I-131 is performed in all other cases. As growth of benign and malignant thyroid cells depends on TSH stimulation, thyroid hormone therapy using TSH suppressive doses (TSH, <0.03 mU/l) follows radioiodine remnant ablation. Additional fractionated external radiation therapy (50 Gy) may be administered in advanced cases (e.g., pT4 N1M0; TNM 1997). Standard follow-up of differentiated thyroid cancer includes measurement of serum thyroglobulin, US of the neck and I-131 whole-body scintigraphy (I-131 WBS). With about 98% the sensitivity of thyroglobulin is very high under TSH stimulation. In case of elevated thyroglobulin, US is the method of choice to detect local recurrences and lymph node metastases of the neck. At defined intervals of follow-up or in case of increasing thyroglobulin, I-131 WBS will be performed under TSH stimulation. With the availability of recombinant TSH (exogenous TSH stimulation) the need to withdraw thyroid hormone over a period of 3-4 weeks (endogenous TSH stimulation) is no longer necessary to perform I-131 WBS. However, in about 20-40% of cases or in the course of disease after several radioiodine therapies, recurrences or metastases may be or become iodine negative. In this case, cationic complexes such as Tc-99m Sestamibi or Tc-99m Tetrofosmin are available to detect less differentiated metastases. In the course of dedifferentiation of malignant thyroid cells, the ability of iodine uptake decreases and uptake of glucose increases. This elevated glucose metabolism can be imaged using FDG PET. Today the combination of PET (metabolic imaging) and CT (morphologic imaging) using PET/CT fusion imaging is the method of choice to image iodine-negative metastases.

Follow-up and management of differentiated thyroid carcinoma: a European perspective in clinical practice.

As differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We have proposed, in a previous issue of this Journal, an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. We report here the case of a paradigmatic patient with papillary thyroid carcinoma, with the goal of illustrating the benefits of applying this algorithm in routine clinical practice. We also offer expanded and additional comments on various issues in the management of DTC.