Christian Scheuba

Current value of intraoperative sonography during surgery for hepatic neoplasms

Noninvasive liver imaging has developed rapidly resulting in increased accuracy for detecting primary and secondary hepatic tumors. Intraoperative ultrasonography (IOUS) was commonly considered to be the gold standard for liver staging, but the current value of IOUS is unknown in view of more sophisticated radiologic tools. The purpose of this prospective study was to evaluate the impact of IOUS on the treatment of 149 patients undergoing liver surgery for malignant disease (colorectal metastasis, 61 patients; hepatoma, 52 patients; other hepatic malignant tumors, 36 patients). The sensitivities of computed tomography (CT), helical CT, magnetic resonance imaging, and IOUS in patients with colorectal metastases were 69.2%, 82.5%, 84.9%, and 95.2% in a segment-by-segment analysis; in patients with hepatoma their sensitivities were 76.9%, 90.9%, 93.0%, and 99.3%; and in patients with other hepatic malignancies they were 66.7%, 89.6%, 93.3%, and 98.9%, respectively. Additional malignant lesions (AMLs) were first detected by inspection and palpation in 20 patients (13.4%). In another 18 patients (12.1%) IOUS revealed at least one AML. Overall, the findings obtained only by IOUS changed the surgical strategy in 34 cases (22.8%). It was concluded that IOUS, having undergone some refinement as well, still has immense diagnostic value in hepatectomy candidates. Frequently avoiding palliative liver resection and occasionally disproving unresectability as assessed by preoperative imaging, IOUS still has a significant impact on surgical decision making and should still be considered the gold standard.RésuméOn a récemment assisté à une amélioration importante dans la précision de la détection des tumeurs primitives et secondaires du foie par l’imagerie non-invasive. L’échographie peropératoire (EPO) a été considérée comme l’examen de référence («gold standard») dans le Staging du foie, mais la valeur de l’EPO est discutée à présent en raison de l’apparition d’investigations radiologiques plus sophistiquées. Le but de cette étude prospective a été d’évaluer l’impacte de l’EPO au cours d’une résection hépatique pour maladie maligne chez 149 patients (métastases d’origine colorectale: 61 patients; carcinome hépatocellulaire: 52 patients; autres tumeurs hépatiques malignes: 36 patients). Chez les patients ayant des métastases d’origine colorectale, la sensibilité de la tomodensitométrie simple (TDM), de la tomodensitométrie hélicoïdale (TDMh), de la résonance magnétique (RM) et l’EPO a été de 69.2%, 82.5%, 84.9% et 95.2% dans une analyse du foie segment par segment. Chez les patients porteurs de carcinome hépatocellulaire, la sensibilité de ces différentes méthodes était, respectivement, de 76.9%, 90.9%, 93% et 99.3%; chez les patients ayant d’autres tumeurs malignes du foie, la sensibilité était, respectivement, de 66.7%, 89.6%, 93.3% et 98.9%. D’autres lésions malignes ont été détectées à l’inspection et à la palpation chez 20 patients (13.4%). De plus, chez 18 autres patients (12.1%), l’EPO a décelé au moins une lésion maligne supplémentaire. Globalement, les données obtenues par l’EPO ont changé la stratégie chirurgicale dans 34 cas (22.8%). On conclue que l’EPO, grâce à quelques raffinements, a toujours une immense valeur diagnostique pour les candidats à l’hépatectomie. En évitant à certains patients une résection palliative, et en permettant, de temps à autre, une résection jugée impossible par les investigations préopératoires, l’EPO garde un impacte significatif sur la décision chirurgicale et devrait continuer à être le «gold standard».ResumenEl rápido desarrollo de los métodos no invasivos ha conferido una mayor precisión diagnóstica de los tumores hepáticos tanto primarios como secundarios. La ecografÍa intraoperatoria (IOUS) se consideró como el mejor método diagnóstico para la estadificación hepática, pero en la actualidad, su valor está en entredicho ante los nuevos y sofisticados estudios radiológicos. El objetivo de este estudio prospectivo fue evaluar el valor de la IOUS en el tratamiento quirúrgico de 149 pacientes con neoplasias malignas de hÍgado (metástasis colorrectales n=61; hepatomas n=52; otros tumores hepáticos malignos n=36). El análisis secuencial segmentario demostró en pacientes con metástasis colorrectales una sensibilidad para la tomografÍa axial o helicoidal computarizada (CT y hCT) del 69.2% y 82.5%, para la resonancia magnética nuclear (MR) del 84.9% y para la IOUS del 95.2%. En pacientes con hepatomas la sensibilidad de estos métodos fue del 76.9%, 90.9%, 93% y 98.9%. En 20 pacientes (13.4%) lesiones malignas adicionales (AML) se diagnosticaron por inspección y palpación. En otros 18 pacientes (12.1%) la IOUS fue capaz de detectar al menos una AML. En 34 casos (22.8%) el conjunto de hallazgos obtenidos exclusivamente con la IOUS propició un cambio de estrategia quirúrgica. En conclusión, la IOUS, con sus recientes mejoras, sigue teniendo un inmenso valor diagnóstico para aquellos que son candidatos a una hepatectomÍa. Previene, con frecuencia, las resecciones hepáticas paliativas y, ocasionalmente, contradice el diagnóstico de irresecabilidad obtenido con otros medios diagnósticos. La IOUS sigue teniendo un importante valor a la hora de establecer una decisión quirúrgica y continúa siendo el mejor método diagnóstico.

Hypoparathyroidism After Total Thyroidectomy: A Prospective Study

HYPOTHESIS Combined measurement of intact parathyroid hormone (iPTH) and serum calcium (sCa) levels is useful for predicting postoperative hypocalcemia with minimal laboratory effort and low costs. DESIGN Prospective analysis of 170 consecutive patients. SETTING University hospital referral center. PATIENTS One hundred seventy patients underwent total thyroidectomy. Defining hypoparathyroidism as albumin-adjusted sCa levels of less than 1.9 mmol/L with or without clinical symptoms or subnormal sCa levels (1.9-2.1 mmol/L) with neuromuscular symptoms, the influences of central lymph node dissection, experience of the surgeon, and parathyroid autotransplantation were observed. We measured the sCa and iPTH levels separately and in combination and the postoperative sCa slope to predict patients who were at risk of hypoparathyroidism. MAIN OUTCOME MEASURES Predictive values for iPTH and sCa levels were compared to identify postoperative hypoparathyroidism. RESULTS Of the 170 study patients, 41 developed transient hypoparathyroidism and 2 developed permanent hypoparathyroidism. The morphologic features and function of the thyroid gland, central neck dissection, experience of the surgeon, and parathyroid autotransplantation did not influence development of postoperative hypoparathyroidism. The best sensitivity for predicting postoperative hypoparathyroidism was 97.7% for measurement of iPTH levels, and the best specificity was 96.1% for measurement of sCa levels. Negative and positive predictive values reached their best (99.0% and 86.0%, respectively) when we combined sCa and iPTH values. CONCLUSIONS Patients with iPTH levels of 15 pg/mL or less and sCa levels of 1.9 mmol/L or less are at increased risk of developing postoperative hypoparathyroidism. Measuring iPTH levels 24 hours after total thyroidectomy in combination with sCa levels on the second postoperative day allows the prediction of hypoparathyroidism with a high sensitivity, specificity, and positive predictive value.

German Association of Endocrine Surgeons practice guidelines for the surgical treatment of benign thyroid disease

IntroductionBenign thyroid disorders are among the most common diseases in Germany, affecting around 15 million people and leading to more than 100,000 thyroid surgeries per year. Since the first German guidelines for the surgical treatment of benign goiter were published in 1998, abundant new information has become available, significantly shifting surgical strategy towards more radical interventions. Additionally, minimally invasive techniques have been developed and gained wide usage. These circumstances demanded a revision of the guidelines.MethodsBased on a review of relevant recent guidelines from other groups and additional literature, unpublished data, and clinical experience, the German Association of Endocrine Surgeons formulated new recommendations on the surgical treatment of benign thyroid diseases. These guidelines were developed through a formal expert consensus process and in collaboration with the German societies of Nuclear Medicine, Endocrinology, Pathology, and Phoniatrics & Pedaudiology as well as two patient organizations. Consensus was achieved through several moderated conferences of surgical experts and representatives of the collaborating medical societies and patient organizations.ResultsThe revised guidelines for the surgical treatment of benign thyroid diseases include recommendations regarding the preoperative assessment necessary to determine when surgery is indicated. Recommendations regarding the extent of resection, surgical techniques, and perioperative management are also given in order to optimize patient outcomes.ConclusionsEvidence-based recommendations for the surgical treatment of benign thyroid diseases have been created to aid the surgeon and to support optimal patient care, based on current knowledge. These recommendations comply with the Association of the Scientific Medical Societies in Germany requirements for S2k guidelines.

Anaplastic (undifferentiated) thyroid carcinoma (ATC)

Background: Old age, reduced general condition and far advanced tumor stage associated with poor prognosis induced the belief that, apart from verifying the diagnosis of anaplastic thyroid carcinoma (ATC) by biopsy, no additional surgery would be justified. However, in some cases, an ultraradical approach was recommended in order to improve the quality of life and survival. Methods: These are the results of a retrospective analysis involving 120 patients subjected to restricted radical surgery (excising as much as possible of the tumor and local metastases, foregoing ultraradical removal of vital organs such as esophagus, larynx and trachea). Results: Irrespective of the surgical approach used, 6±2% of the patients were alive after 5 years (median survival time: 3.1 months). Patients without tumor residues (R0-resections; extending to soft tissue only; Kaplan-Meier estimate – cumulative survival 15±5%) had a significantly better prognosis than patients with tumor residues (R1/R2-resections; no patient survived 5 years; P<0.001). Tumor morphology (spindle cells, giant cells, mixed cells) or differentiated parts of the tumor as well as lymph-node involvement had no statistically significant impact on the prognosis. Conclusions: In ATC, the objective should be to remove as much of the carcinoma as possible (in the ideal case, a thyroidectomy); if lymph nodes are affected, neck dissection should be the goal, if possible (restricted radical approach, improving quality of life). Ultradical surgery to include segmental resection of larynx, trachea or esophagus do not seem to be indicated, as prolonged survival is questionable and quality of life is certainly diminished.

C-cell hyperplasia and medullary thyroid carcinoma in patients routinely screened for serum calcitonin.

Routine screening of calcitonin serum levels in patients with nodular thyroid disorders has led to an increased rate of total thyroidectomies. We investigated prevalence and interrelationship of C-cell hyperplasia (CCH) and medullary thyroid carcinoma (MTC) in patients with thyroid and parathyroid disorders that showed increased calcitonin serum levels detected by routine screening. Within two years, 30 (mean age, 60 +/- 14 years) of 667 patients had a pentagastrin-stimulated calcitonin level of more than 100 pg/mL. All 30 underwent total thyroidectomy and were tested for germ-line mutations of the ret protooncogene. Entire surgical specimens were blocked, and C-cell disorders were assessed using conventional histology and immunohistochemistry. C-cell hyperplasia was defined by the presence of more than 50 C cells/l low-power field in both lobes and was classified as focal, diffuse, nodular, or neoplastic. Nineteen patients (female/male = 14/5) had MTC, and 11 males but no females had CCH only. Six of 16 patients with sporadic MTC had concomitant CCH. Three patients were index cases of new MTC families. We conclude that MTC with concomitant CCH is an unreliable marker for hereditary MTC risk and that CCH has a preneoplastic potential in the absence of germ-line mutations. In this series, CCH alone was not found in females.

Sporadic versus familial medullary thyroid microcarcinoma: A histopathologic study of 50 consecutive patients

By means of calcitonin screening programs, sporadic and hereditary medullary thyroid carcinoma (MTC) can be detected at an early stage. We investigated the histopathologic findings of 16 familial (mean age 32 ± 21 years, female/male ratio 1.6:1) and 34 sporadic (mean age 58 ± 15 years; female/male ratio 2.4:1) MTCs with stage T1 comparatively. Patients with hereditary tumors were younger. Hereditary tumors were more often found multifocal (13 of 16 vs 3 of 34; p <0.001), bilateral (11 of 16 vs 3 of 34; p <0.001), displaying desmoplastic stroma (14 of 16 vs 19 of 34; p = 0.02), and accompanied by C cell hyperplasia (16 of 16 vs 24 of 34; p = 0.01), but all of these factors were present in some sporadic patients. Only tumors with desmoplastic stroma showed lymph node metastasis, which was observed in eight of the 50 patients. After surgery all patients showed permanent normalization of calcitonin levels. We conclude that 1) morphologic parameters considered to indicate familial MTC risk are of no value in the individual patient, 2) many sporadic MTCs develop on the background of CCH, 3) tumors with desmoplastic stroma are more likely to develop lymph node metastasis, and 4) early detection of MTC permits curative surgery in the majority of patients.

German Association of Endocrine Surgeons practice guideline for the surgical management of malignant thyroid tumors

IntroductionOver the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable (“low risk”) papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages.MethodsThe present German Association of Endocrine Surgeons practice guideline was developed on the basis of clinical evidence considering current national and international treatment recommendations through a formal expert consensus process in collaboration with the German Societies of General and Visceral Surgery, Endocrinology, Nuclear Medicine, Pathology, Radiooncology, Oncological Hematology, and a German thyroid cancer patient support organization.ResultsThe practice guideline for the surgical management of malignant thyroid tumors includes recommendations regarding preoperative workup; classification of locoregional nodes and terminology of surgical procedures; frequency, clinical, and histopathological features of occult and clinically apparent papillary, follicular, poorly differentiated, undifferentiated, and sporadic and hereditary medullary thyroid cancers, thyroid lymphoma and thyroid metastases from primaries outside the thyroid gland; extent of thyroidectomy; extent of lymph node dissection; aerodigestive tract resection; postoperative follow-up and surgery for recurrence and distant metastases.ConclusionThese evidence-based recommendations for surgical therapy reflect various “treatment corridors” that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.

Analysis of hepatic resection of metastasis originating from gastric adenocarcinoma

Few patients with metastatic gastric cancer have disease that is amenable to curative surgery. Thus far, little is known about liver surgery for metastases arising from gastric adenocarcinoma and prognostic factors. Of 73 patients operated on between 1980 and 1999 for noncolorectal, non-neuroendocrine hepatic metastases, 15 underwent liver resection for gastric adenocarcinoma metastasis. Ten patients underwent synchronous hepatic resection and five underwent metachronous hepatic surgery after a median diseasefree interval of 10 months (range 6.1 to 47.3 months). None of the patients died within the first 30 days after surgery, and the in-hospital mortality rate was 6.7%. Among patients in the synchronous group, 26.7% experienced major complications mainly associated with gastric surgery. Overall median survival was 8.8 months (range 4 to 51 months); two patients survived more than 3 years. Univariate analysis reealed that the appearance of liver metastasis synchronous vs. metachronous), the distribution of liver metastases (unilobar vs. bilobar), and the primary tumor site (proximal vs. distal) were marginally signifiant predictive factors regarding overall survival. Because of its high morbidity, synchronous liver resecion for metastases originating from gastric adenocarcinoma is rarely followed by survival longer than 2 years. Primary tumor localization within the proximal third of the stomach and bilobar liver involvement appear to be predictive of poor outcome. On the other hand, curative resection of metachronous liver metastases may allow long-term survival in selected patients.

Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial.

Objective:To determine risk factors for presence of lymph node or distant metastases in patients with follicular thyroid cancer (FTC) at the time of diagnosis and whether there is a relationship between the type of tumor invasion and metastases. Summary Background Data:FTC often presents distant metastases at the initial diagnosis. As distant metastases are independent prognostic factors in a patients survival, determination of clinicopathologic characteristics for patients who are at higher risk for developing metastases is of greater clinical importance. Methods:The prognostic significance of gender (male vs. female), age (≤40 years vs. <40 years), tumor size (≤40 mm vs. >40 mm), number of lesions (uni- vs. multifocality), type of invasion (minimally invasive vs. widely invasive), and oncocytic changes (with vs. without) were analyzed in 207 patients, according to presence of lymph node and distant metastases at the time of initial surgery. According to the type of invasion, the carcinoma-specific survival and the disease-free survival of minimally invasive (MI) and widely invasive (WI) FTC were estimated and compared. Results:None of the 127 patients with MI growth presented with lymph node metastases but 9.4% distant metastases. Overall risk factors for the presence of lymph node metastases at the initial diagnosis were multifocality (P = 0.02) and widely invasion (P = 0.0001) and for distant metastases age >45 years (P = 0.007), tumor size larger than 40 mm (P = 0.03) and widely invasion (P = 0.0001). WI-FTC patients show larger tumors (P = 0.0001), older age (P = 0.0001), and are presented more frequently in recurrent goiter disease (P = 0.0001). The estimated 10 years carcinoma-specific survival and disease-free survival for MI-tumors were significantly better than for WI-tumors (P = 0.0001). Conclusions:Total thyroidectomy is recommended in all patients with FTC because of early distant metastases. Patients with WI-FTC need a more aggressive surgical treatment because of higher tendency for lymph node metastases. MI-FTC has an excellent prognosis with no sign of lymph node metastases, which emphasizes a limited need for nodal surgery.

Application of Staging Systems for Differentiated Thyroid Carcinoma in an Endemic Goiter Region With Iodine Substitution

ObjectiveTo evaluate and compare staging systems for differentiated thyroid carcinoma and predicted outcome in an endemic goiter region with iodine substitution and to examine the risk profile of differentiated thyroid carcinoma and compare it against nongoiter regions. Summary Background DataDifferentiated (papillary or follicular) thyroid carcinoma has a favorable prognostic outcome. In numerous studies prognostic factors have been identified and staging systems created, particularly in Anglo-American centers (nonendemic goiter regions), to evaluate individual prognostic outcome. MethodsIn a retrospective study, the authors assessed 440 patients with differentiated thyroid carcinoma (papillary, n = 293; follicular, n = 147) and a long-term follow-up of median 10.6 years to determine the predictive accuracy of nine staging systems applicable to the study population; the systems were compared by calculating the proportion of variation explained. ResultsWith regard to cause-specific mortality, the difference between the respective stages and/or risk groups was highly significant for every staging system. By means of calculating the proportion of variation explained, MACIS scoring supplied the most reliable prognostic information for differentiated thyroid carcinoma (relative importance 16.93%). EORTC and UICC/AJCC systems had a relative importance of 16.34% and 13.96%, respectively, also a high level of accuracy; this implies that they are superior to the other six staging systems. If we separate papillary and follicular carcinoma, for the former the MACIS score with a relative importance of 15.05% is clearly superior to the other staging systems, whereas for the latter the EORTC score and the UICC/AJCC staging system, with relative importance of 17.04% and 16.58%, respectively, yield the best prognostic information. ConclusionsBy applying staging systems in an endemic goiter region with iodine substitution, the best prognostic information for papillary thyroid carcinoma has been achieved with the MACIS score, while for follicular thyroid carcinoma the EORTC score and the UICC/AJCC system have the best prognostic accuracy. Because of the individual factors, which are easy to obtain and generally available (age, T, N, M classification), the uncomplicated handling, and the widespread use and the good predictive accuracy, the UICC/AJCC classification is the staging system of choice for comparing published results.