Lars-Erik Tisell

Improved survival of patients with papillary thyroid cancer after surgical microdissection.

Abstract. A total of 195 patients had surgery for papillary thyroid cancer. The mean age at operation was 50 years. A microdissection technique was used for total thyroidectomy and lymph node clearance. Postoperative radioiodine tests showed no uptake or an uptake close to the background activity in 77% of the examined patients. By counting the lymph nodes removed at surgery we were able to check on the quality of the lymph node dissection. Men had a higher incidence (70%) of lymph node metastases than women (45%). Only 4% of the patients had radioiodine ablation of the thyroid remnant. The median follow-up time was 13 years. None of the patients below 45 years of age at surgery died of thyroid cancer. In the older age group eight patients died of thyroid cancer at a mean age of 75 years. Five of those who died of a thyroid carcinoma had distant metastases at diagnosis. Among patients with resectable disease, three (1.6%) died of thyroid cancer, all of whom had lived for more than 17 years after surgery. Hence longer follow-up is needed before we know the final mortality in our series. The results suggest that surgical technique and strategy can positively influence the survival of patients with papillary thyroid cancer.

Survival of patients with disseminated midgut carcinoid tumors after aggressive tumor reduction

Abstract. Sixty-four consecutive patients with disseminated midgut carcinoids were treated during an 8-year period according to a single clinical protocol aimed at aggressive tumor reduction by surgery alone or with subsequent hepatic artery embolization. All patients had markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) levels (581 ± 79 μmol/24 h) and hormonal symptoms. Fourteen patients (22%) reached anatomic and biochemical cure by surgery alone. At follow-up, the mean 5-HIAA levels were still normal after 69.0 ± 6.2 months; two patients had died from unrelated causes. With the introduction of somatostatin receptor scintigraphy, subclinical disease was diagnosed in 7 of these 14 patients. Forty patients with bilobar hepatic disease underwent embolization in combination with octreotide. In this group, 5-HIAA levels were still reduced by 55% after 71 ± 11 months of follow-up, and the 5-year survival was 56%, estimated from the total death hazard function. After embolization, two subgroups could be identified with marked differences in their long-term response to treatment. Ten patients were not embolized owing to complicating diseases. The 5-year survival for the entire series was 58%. A significantly increased risk of cardiovascular deaths was seen, which underlines the importance of total survival analysis in a disease with multiple hormonal effects. It is concluded that an active surgical approach must be recommended to patients with the midgut carcinoid syndrome. In patients with bilobar hepatic disease, embolization combined with octreotide treatment markedly reduced the 5-HIAA excretion and suggested a prolonged 5-year survival.

Long‐term outcome of a large series of patients surgically treated for pheochromocytoma

Objective.  To analyse the morbidity, mortality and long‐term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997.

Hyperparathyroidism subsequent to neck irradiation: risk factors

A follow‐up examination of 444 persons treated with x‐rays for tuberculous cervical adenitis was performed to determine if the risk for hyperparathyroidism (HPT) following radiation exposure can be related to the age at treatment, the dose of x‐rays, or the sex of the patient. The overall incidence of HPT was 14%. There was no definite age‐dependent difference in susceptibility to the induction of HPT. The doses of radiation among the 63 subjects who developed HPT ranged from 0.6 to 45.7 Gy (60–4570 rad). There was a statistically significant positive correlation between the dose of radiation and the probability of developing HPT. After doses of 14 Gy (1400 rad) or more 29% of the subjects had developed HPT. After neck irradiation women had twice the relative risk of men of developing HPT. This sex ratio was lower than in the series of nonirradiated HPT patients treated at the same institution during the time of the follow‐up study. Cancer 56: 1529‐1533, 1985.

Somatostatin Receptor Subtypes, Octreotide Scintigraphy, and Clinical Response to Octreotide Treatment in Patients with Neuroendocrine Tumors

Abstract. Several types of neuroendocrine tumor express high numbers of somatostatin receptors (sstr). We have compared the expression of sstr subtypes with the outcome of octreotide scintigraphy in patients with carcinoids and medullary thyroid carcinoma (MTC) in comparison with Hürthle cell tumors. The effect of sstr activation (octreotide treatment) on tumor markers was also studied in patients with disseminated carcinoid tumors. Six patients with carcinoid tumors (four midgut and two foregut), and three patients with thyroid tumors (one MTC, one Hürthle cell carcinoma, and one Hürthle cell adenoma) were studied. Octreotide scintigraphy visualized tumor sites in all nine patients. Macroscopic tumor was verified at these sites at subsequent surgical exploration. Using Northern blotting and subtype-specific riboprobes, sstr could be detected in all tumors examined. All five sstr subtypes were detected in most of the carcinoid tumors. All six carcinoids expressed sstr2. This was in contrast to the findings for the thyroid tumors analyzed, which also expressed several sstr subtypes but in some cases lacked expression of sstr2. This was also the case for normal thyroid tissue. Clinically, octreotide treatment of the patients with midgut carcinoid tumors resulted in palliation of hormonal symptoms accompanied by a significant reduction of urinary 5-HIAA levels (28–71%). These results indicate that carcinoid tumors frequently express all five sstr subtypes. The thyroid tumors also expressed multiple sstr but could lack expression of sstr2. Nevertheless, these tumors were visualized by octreotide scintigraphy, indicating that sstr2 expression is not a prerequisite for tumor imaging.

Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide.

After injection of 111In-labelled DTPA-D-Phe1-octreotide, intraoperative tumour localisation was performed using a scintillation detector in 23 patients with neuroendocrine tumours. Count rates from suspect tumour lesions and adjacent normal tissue were expressed as a ratio before (Rin situ) and after (Rex vivo) excision. 111In activity concentration ratios of tumour tissue to blood (T/B) were determined in a gamma counter. In patients with midgut carcinoids, (all scintigraphy positive), false Rin situ recordings were found in 4/29 macroscopically identified tumours. T/B ratios were all high (27-650). In patients with medullary thyroid carcinomas (eight out of ten scintigraphy positive), misleading Rin situ results were found in 4/37 macroscopically identified tumours. T/B ratios were lower (3-39) than those seen in midgut carcinoids. Two out of four patients with endocrine pancreatic tumours had positive scintigraphy, reliable intraoperative measurements and very high T/B ratios (910-1500). One patient with a gastric carcinoid had correct measurements in situ and ex vivo with high T/B ratios (71-210). In situ measurements added little information to preoperative scintigraphy and surgical findings using the present detection system. Rex vivo measurements were more reliable. The very high T/B ratios seen in midgut carcinoids and some endocrine pancreatic tumours would be favourable for future radiation therapy via somatostatin receptors.

Biodistribution data from 100 patients i.v. injected with 111in-DTPA-D-Phe1-Octreotide

The aim of this study was to obtain accurate data on the biodistribution of 111In-DTPA-D-Phe1-octreotide in tumour and normal tissues to facilitate dosimetric evaluations. Patients with carcinoid tumours, medullary thyroid carcinoma (MTC), differentiated thyroid tumours, endocrine pancreatic tumour (EPT), breast carcinoma, and various other tumour types were i.v. injected with 111In-DTPA-D-Phe-1-octreotide. Tumour and normal tissue samples were collected during surgery 1–35 days later, and the 111In activity concentration determined. Results showed large inter- and intra-individual variations. The 111Inconcentration was in general higher in carcinoids and some EPT (range 0.33–77% IA/kg) than in MTC and other tumours (0.017–7.8% IA/kg). Tumour-to-blood ratios (T/B) higher than 100 were found in most patients with carcinoids, EPT, renal carcinoma, and neuroendocrine carcinoma (max value 1500), while T/B was below 80 in most other tumours. Normal-tissue-to-blood ratios were in general≤10 but higher values were found in liver, kidneys, and spleen. The results presented are important for dosimetric calculations, when radiolabelled octreotide is used for diagnostic or therapeutic purposes.

Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin

SummaryThe survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated.

Malignant pheochromocytoma in a population-based study: survival and clinical results.

Abstract:  One hundred fifty‐four consecutive patients with pheochromocytoma (PC, n= 137) or paraganglioma (PG, n= 17) were treated at our unit. Twenty patients had MEN 2, 15 VRD, and 1 VHL tumors. Twelve had malignant tumors and were classified according to mode of presentation: (1) Distant metastases (n= 4); three underwent surgical debulking (with chemotherapy in one); and three had 131I‐MIBG therapy. Within 4 years two patients died of tumor progression. (2) Locally advanced disease (n= 4), all resected for cure. (3) Malignancy disclosed during follow‐up after adrenalectomy with “benign” histopathology (n= 4). All patients in groups 2 and 3 developed recurrence 9 (1–17) years after primary surgery; four underwent resection, one remains tumor‐free. The others were treated chronically with phenoxybenzamine, combined with 131I‐MIBG in one. These eight patients were observed 20 (5–35) years after primary surgery and 11 (1–19) years after recurrence. This series is population‐based and may better reflect the natural history of malignant PC/PG than the series from national referral centers. Active surgical treatment and phenoxybenzamine resulted in low tumor‐related mortality in groups 2 and 3; five patients died 8–30 years after diagnosis, four of PC/PG (three from group 2 and one from group 3 ) and one of other causes. We propose tumor uptake studies (MIBG‐ and octreotide scintigraphy) in patients with nonresectable metastases; to select individual radionuclide therapy data on the expression of CA‐transporters/somatostatin receptors may be helpful. To diagnose PC/PG early, screening of adrenal incidentalomas has been suggested. In a regional population‐based prospective study, 503 incidentalomas were reported during 18 months, but only one patient with PG was identified.

Expression of somatostatin receptors in oncocytic (Hürthle cell) neoplasia of the thyroid

SummaryTen consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by 111In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood 111In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of 111In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.