G. F. W. Scheumann

Compartment-oriented microdissection of regional lymph nodes in medullary thyroid carcinoma

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n=57) and hereditary (n=25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P<0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P<0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.

Liver transplantation for metastatic neuroendocrine tumors

OBJECTIVE This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.

Human thyrotropin receptor gene: expression in thyroid tumors and correlation to markers of thyroid differentiation and dedifferentiation.

Human thyrotropin (TSH) receptor steady-state transcript levels were analyzed by Northern blot analysis in thyroids of patients with thyroid carcinoma, with hyperfunctioning adenoma and in normal controls. In control tissue and benign tumors expression levels of TSH receptor mRNA were high whereas in anaplastic carcinomas no normal TSH receptor mRNA was detected. In papillary and follicular tumors it varied from normal to markedly reduced levels. Thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA were strongly expressed in normal tissue and in hyperfunctioning adenomas but were completely lost in all anaplastic tumors. In papillary tumors expression of TPO and Tg mRNA varied from normal to a complete loss of expression of either TPO, Tg or both. Tg and TPO steady-state expression did not correlate to TSH receptor transcript levels. C-myc mRNA was highly expressed in anaplastic carcinomas, very variable in normal controls and in differentiated thyroid tumors and low in hyperfunctioning adenomas. In summary, TSH receptor mRNA is persistently expressed in all differentiated thyroid tissues and tumors but lost in undifferentiated carcinomas. Its persistence far along the transformation pathway further supports the concept that this gene which inserts the thyrocytes in the physiological regulatory network is almost constitutively expressed in this cell.

The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study

Abstract. Clinical data of 139 patients with hereditary medullary thyroid carcinoma (HMTC) from nine european centres surgically treated from 1980 to 1991 were reviewed retrospectively to analyse the value of systematic versus selective lymphadenectomy (LA). Biochemical cure rate was significantly higher in patients who underwent LA compared to patients who did not. In nodal‐positive HMTC, systematic LA compared to selective LA improved biochemical cure in small but not large tumours. In nodal‐negative HMTC, systematic LA compared to selective LA could not improve biochemical cure in either small or large primary tumours. To prevent local recurrences with the risk of increased surgical and tumour‐related morbidity, systematic LA should be performed in all HMTC patients regardless of the primary tumour stage. However, an improvement of biochemical cure by systematic LA seems to be possible only in nodal‐positive small primary tumours without distant metastases.

Total hepatectomy and liver transplantation for metastatic neuroendocrine tumors of the pancreas - a single center experience with ten patients.

Abstract  Background: Metastatic neuroendocrine pancreatic tumors have a poor prognosis. We have studied retrospectively the efficacy of liver transplantation as ultimate therapy of otherwise untreatable symptomatic neuroendocrine hepatic metastases originating in the pancreas. Methods: We reviewed our experience of liver transplantation (LTx) for hepatic metastases of neuroendocrine pancreatic tumors in ten patients. The indication for liver grafting was seen in cases of irresectable metastases and when patients were suffering from otherwise untreatable tumor-associated symptoms due to massive hormonal release or large intra-abdominal tumor bulk. Results: In four patients, the primary tumors had been removed before LTx, in five patients simultaneously with LTx and in one case 46 months after grafting. There was no operative mortality. After hepatectomy and LTx, all patients had complete relief of symptoms and all preoperatively increased hormonal levels returned to normal. In nine of ten patients, the transplant procedure had the potential for cure, whereas, in one patient, the primary tumor had remained in situ at LTx and was removed 46 months later by an R2-resection. At present, nine patients are alive with a median follow-up of 33 months (range 13.5 months to 117 months). The one patient in whom the primary tumor was removed after transplantation died due to massive intra-abdominal tumor spread 68 months after LTx. Currently, two patients are without evidence of disease, but one of them after re-operation because of lymph-node metastases 8 months after transplantation. The longest disease-free survival is now more than 7 years. In seven of nine patients, tumor recurred between 1.5 months and 48 months after transplantation. Conclusions: Patients with otherwise untreatable symptomatic neuroendocrine hepatic metastases of pancreatic origin may benefit from total hepatectomy and liver transplantation with regard to symptomatic relief and long-term survival, despite frequent recurrence of disease. In some patients, liver transplantation may even offer the chance for cure.

Surgical management of MEN 2.

The multiple endocrine neoplasia (MEN) syndromes are genetically transmitted endocrinopathies. In both types of MEN syndrome, usually one organ predominantly is affected; however, the individual manifestation of the disease with regard to time and extent of organ involvement varies considerably. Unlike in MEN 1, in MEN 2 surgical treatment represents the therapy of choice for each part of the disease.

Role of the intra-arterial calcium stimulation test in the preoperative localization of insulinomas.

Abstract. The aim of this study was determination of the significance of the arterial stimulation test with venous sampling (ASVS) in the preoperative localization of insulinoma. Eleven patients with endogenous hyperinsulinism underwent preoperative transabdominal US, spiral computer tomography (spiral CT), MRI, endoscopic ultrasound (EUS) as well as angiography (DSA) combined with ASVS. The results were compared with intraoperative findings, intraoperative ultrasound (IOUS) and histopathology. There were no complications related to the ASVS test. In 11 patients the tumor could be localized with the various modalities as follows: US 1 of 11 (9 %), MRI 3 of 10 (30 %), spiral CT 4 of 11 (36 %), EUS 5 of 10 (50 %), DSA 8 of 11 (73 %), and ASVS 10 of 11 (91 %). In 2 patients the tumors were intraoperatively neither palpable nor detectable by IOUS, and consequently the intraoperative management was governed by information provided by DSA combined with the ASVS test. Ten patients had solitary benign insulinomas and 1 patient with multiple endocrine neoplasia I had two tumors adjacent to each other in the pancreatic tail. Arterial stimulation test with venous sampling was the most sensitive preoperative test for regionalizing the insulinoma in our set of patients. It can be performed safely in the course of a regular DSA examination and may affect intra-operative management in patients in whom the tumors are not detectable by palpation or IOUS.

Surgery and radioablation therapy combined: introducing a 1-week-condensed procedure bonding total thyroidectomy and radioablation therapy with recombinant human TSH

OBJECTIVE The objective of this study was to determine whether the use of recombinant human TSH (rhTSH) to stimulate radioiodine uptake after thyroidectomy is as efficacious as a period of withholding thyroid hormones, while at the same time avoiding hypothyroidism, reducing sick leave time and shortening the hospital stay. DESIGN Our aim was to compare the standard procedure of differentiated thyroid cancer treatment, which consists of thyroidectomy followed by 4 weeks of hypothyroidism and a conclusive ablative activity of (131)iodine, with a new shortened treatment in which l-thyroxine (T(4)) medication is initiated a day after thyroidectomy, followed by application of rhTSH stimulation and subsequent ablation a few days after surgery. We presumed our treatment to represent the most sophisticated strategy for the reduction in sick leave days overall without any reduction in safety or the efficacy of ablative therapy. METHODS Patients (n=25) were randomized either for surgery and rhTSH stimulation or surgery and l-T(4) abstinence before the first application of radioiodine. Ablation success was determined by neck ultrasound and serum thyroglobulin during follow-up. RhTSH receivers were monitored for an average of 635 days (s.d.+/-289) and patients in l-T(4) abstinence for an average of 624 days (s.d.+/-205). Both groups were statistically compared for significant differences in treatment efficacy, safety and overall time of sick leave. RESULTS AND CONCLUSIONS Our shortened treatment proved to be equally efficacious and safe in comparison with the conventional therapy regimen. At the same time, it showed economic advantages through the reduction in average sick leave time from approximately 29 days (l-T(4) abstinence) down to approximately 6 days (rhTSH stimulation) as well as sustaining the patients quality of life by the complete avoidance of hypothyroidism.

Ultrastructural localization of IgG and TPO in autoimmune thyrocytes referring to the transcytosis of IgG and the antigen presentation of TPO

Abstract While autoantibodies against thyroid peroxidase (TPO) are known to produce cytotoxicity in vitro, their in vivo effects are still obscure. In addition, the mechanism of TPO autoantibody creation needs to be disclosed because the localization of TPO on thyrocytes is considered to be restricted to the apical membrane, which is not in contact with immunocompetent cells. In order to study these crucial processes in the pathogenesis of thyroid autoimmunity, the ultrastructural localization of TPO and IgG was determined and quantified in thyrocytes of normal thyroid gland and thyroid tissue of patients suffering from Graves’ disease. This was done by using ultrathin frozen sections and the immunogold method. IgGs were detected in the follicular lumen, close to the apical membrane, in transport vesicles, the endoplasmic reticulum, and the Golgi apparatus of thyrocytes from patients with Graves’ disease. The labeling of TPO in the basolateral membrane was distinctly lower than that of the apical membrane, but was significant in comparison to the plasma membrane labeling of fibroblasts present in the same sections. These data indicate that thyroid autoantibodies may perform their cytotoxic function in intracellular compartments besides the plasma membrane. TPO molecules on the basolateral membrane of HLA class II antigen-positive thyrocytes may initiate antigen presentation of TPO as well as the formation and uptake of TPO autoantibodies.

Der Kalziumstimulationstest (ASVS) bei Insulinomen des Pankreas: Vergleich mit der bildgebenden Lokalisationsdiagnostik

ZusammenfassungZielsetzung. Bestimmung des Stellenwertes des arteriellen Stimulationstests mit venöser Blutentnahme (ASVS) zur präoperativen Lokalisation von Insulinomen. Methodik. Dreizehn Patienten mit endogenem Hyperinsulinismus wurden bei nichtkonklusiver externer Vordiagnostik präoperativ mittels transabdominellem Ultraschall (US), Spiral-CT (CT),MRT, endoskopischem Ultraschall (EUS), digitaler Subtraktionsangiographie (DSA) in Verbindung mit dem ASVS-Test untersucht. Die Resultate wurden mit intraoperativen Befunden und den histologischen Ergebnissen korreliert. Ergebnisse. Die Sensitivitäten betrugen für US 8%,MRT 27%, CT 46%, EUS 50%,DAS 69% und ASVS 92%.Die intraoperative Palpation und Ultraschall (IOUS) erzielten eine Sensitvität von 77%.Bei 3 Patienten war das Insulinom intraoperativ weder palpabel noch durch IOUS lokalisierbar, die Resektion erfolgte anhand der präoperativen Diagnostik. Der ASVS-Test als funktionelles Verfahren war in der Detektion den präoperativen bildgebenden Verfahren überlegen. Schlussfolgerungen. Der ASVS-Test erwies sich als das zuverlässigste Verfahren für die Lokalisationsdiagnostik.Vor dem Hintergrund gesundheitsökonomischer Überlegungen sollte er bei negativer Schnittbilddiagnostik frühzeitig eingesetzt werden.AbstractPurpose. Evaluation of clinical relevance of the arterial stimulation procedure with venous sampling (ASVS) in the preoperative localization of insulinoma. Methods. Thirteen patients with endogenous hyperinsulinism underwent preoperative transabdominal ultrasound (US), helical CT (CT), MRI, endoscopic ultrasound (EUS), and angiography (DSA) in conjunction with the ASVS-test for the detection of insulinoma. The results were compared with intraoperative findings, intraoperative ultrasound (IOUS) and histology. Results. Sensitivity was as follows: US 8%, MRI 27%, CT 46%, EUS 50%,DSA 69%,and ASVS 92%.Intraoperative palpation and IOUS yielded a sensitivity of 77%. In 3 patients the tumors were neither palpable nor detectable by IOUS, the mode of resection was based on preoperative diagnostics.The ASVS procedure as a functional test was superior to all other modalities for the preoperative tumor detection. Conclusion. The ASVS was the most sensitive diagnostic modality. It should especially be considered in terms of health economical aspects when CT or MRI do not yield conclusive results.