Martha Fjälling

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.

Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours

We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.

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.

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.

BILE ACID MALABSORPTION AFTER CONTINENT URINARY DIVERSION WITH AN ILEAL RESERVOIR

PURPOSE We determine the effect of urinary diversion with a Kock ileal reservoir on bile acid absorption and bowel habits. MATERIALS AND METHODS We asked 96 patients with a Kock ileal urinary reservoir to record bowel habits and abdominal symptoms for 1 week. Data on 75 patients were further analyzed. Bile acid absorption was determined in 29 healthy control subjects, in 17 before and 6 months after continent urinary diversion, and in 21, 2 to 14 years postoperatively. Bile acid absorption was considered pathological when retention of less than 10% of an oral capsule containing selenium-75 labeled tauroselcholic acid (SeHCAT) was noted after 1 week. RESULTS Mean number of defecations plus or minus standard deviation was 9.4 +/- 6.1 (75 cases). Of the patients 13% had 15 or more stools per week and 15% complained of always having loose stools. Mean value for the SeHCAT test was 32 +/- 19% preoperatively and 17 +/- 16% 6 months postoperatively (p = 0.0023). The corresponding value for healthy controls was 39 +/- 18%. Significant relationships were found between the results of the SeHCAT test postoperatively, and the number of stools per week and consistency of the feces. All patients with more than 10 defecations per week had a pathological SeHCAT test. CONCLUSIONS Most patients with an ileal urinary reservoir have fairly normal bowel habits. Bile acid absorption is significantly reduced postoperatively and approximately a third of the patients have a pathological SeHCAT test. Preoperative investigation of bowel habits is recommended and a SeHCAT test should be performed in patients with frequent, loose defecations. Other types of diversion should be offered when preoperative retention is below 10 to 20% especially in patients with impaired anal control.

Assessment of spleen size using gamma camera scintigraphy in newly diagnosed patients with essential thrombocythaemia and polycythaemia vera

Abstract:  By using gamma camera imaging the spleen size was assessed in 18 consecutive patients with essential thrombocythaemia (ET) and in 18 consecutive patients with polycythaemia vera (PV). All ET and PV patients were newly diagnosed and had not received any myelosuppressive therapy prior to study. The spleen areas in both posterior and left lateral projections were determined. Eighteen consecutive patients with idiopathic thrombocytopenic purpura (ITP) served as a control group since by definition they do not present with splenic enlargement; in these latter subjects the mean posterior and left lateral splenic areas were almost identical (48 ± 15 and 47 ± 17 cm2, respectively). In comparison with this control group patients with ET and PV had significantly larger spleens. In both ET and in PV patients the left lateral spleen scan area exceeded the posterior one. Patients with PV had larger splenic areas in both projections than did patients with ET, but the differences were not statistically significant. Compared to the ITP patients it was found that at least 50% of the ET patients and at least 61% of the PV patients at diagnosis presented with splenomegaly.

Indium-111-octreotide Scintigraphy, Intraoperative Gamma-detector Localisation and Somatostatin Receptor Expression in Primary Human Breast Cancer

Abstract12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the 111In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1–2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10–41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstr1, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.

Effects of preoperative parathyroid localisation studies on the cost of operations for persistent hyperparathyroidism

OBJECTIVE To find out whether preoperative parathyroid localisation studies are cost-effective in patients with persistent hyperparathyroidism (HPT). DESIGN Retrospective study. SETTING University hospital, Sweden. PATIENTS 29 consecutive patients with persistent HPT who were reoperated on with or without localisation studies. 15 other patients had initial operations for HPT without localisation studies. INTERVENTIONS Initial or repeat operation for HPT, localisation studies with 99mTc sestamibi scintigraphy, and catheterisation of large cervical and mediastinal veins with measurements of serum concentrations of parathyroid hormone. MAIN OUTCOME MEASURES Operative time. Cost of operations, frozen section biopsy and localisation studies. RESULTS The mean durations of reoperation with localisation studies and for the initial operation without them, were 124 and 135 minutes, respectively, while it was 269 minutes for reoperation without studies. For patients who had localisation studies the mean total cost of the investigations, operating time, and frozen section biopsy was 28% less than for patients who were reoperated on without such studies. CONCLUSION Preoperative localisation studies before repeat operations for HPT were cost-effective. Even if it has not been shown in this series, the reduction in operating time and the extent of dissection by localisation studies has the potential to decrease morbidity.