Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Comparison of tissue injury between laparosonic coagulating shears and electrosurgical scissors in the sheep model.

STUDY OBJECTIVE: To compare laparosonic coagulating shears (LCS), which use ultrasonic energy, and unipolar diathermy scissors with respect to depth of tissue injury. DESIGN: Prospective observational study (Canadian Task Force classification I). SETTING: A reproduced surgical setting. SUBJECTS: An anesthetized sheep. INTERVENTION: We laparoscopically harvested uterine horn and bowel tissue. MEASUREMENTS AND MAIN RESULTS: Tissue was transected while hemostasis was maintained. Two pathologists examined tissue independently, and each was blinded as to the instrument used for harvesting. Clinical characteristics and tissue injury created by the instruments were compared. CONCLUSION: Subjectively, LCS appeared to produce less smoke plume than diathermy scissors. It also produced greater tissue damage than unipolar electrosurgery on settings of 35 W cut and 30 W coagulate.

Mediastinal epithelioid hemangioendothelioma in a patient with type IV Ehlers-Danlos syndrome: a case report and review of the literature.

Ehlers-Danlos syndrome (EDS) is a collection of inherited connective tissue disorders with at least 10 types, differentiated on clinical and genetic grounds. Malignancy has been described only rarely in association with the syndrome. Epithelioid hemangioendothelioma (EH) is a rare endothelial tumor, which displays clinical behavior intermediate between that of hemangioma and angiosarcoma. A case report of a 50-year-old man with type IV EDS who was extensively investigated for several years for multiple mediastinal nerve palsies and chest pain. Magnetic resonance imaging (MRI) demonstrated an anterior mediastinal mass, which at biopsy showed EH. Subsequent metastatic spread to liver and lungs is unique among reported cases of mediastinal EH. The patient experienced significant symptomatic improvement from external beam radiotherapy (RT) to the mediastinum. After metastatic disease developed, multiagent chemotherapy was administered, but without response. The literature is reviewed regarding treatment of EH and the potential problems associated with EDS. Although there appears to be no etiological association between EDS and EH, the connective tissue disease clearly contributed to a delay in diagnosis and raised concerns regarding RT tolerance. The potential predisposition to aggressive tumor invasion remains a possibility. In addition, mediastinal EH has the potential to metastasize, and in this case demonstrated resistance to a broad range of chemotherapy agents.

Review of objective tests for the hand-arm vibration syndrome.

The Health and Safety Executive has recommended health surveillance for all workers in jobs identified as giving rise to significant risk of the hand-arm vibration syndrome. Objective tests are not routinely recommended for workplace surveillance but may have a role in the assessment of accurate staging or if decisions on an individual's continuing exposure is in question. This paper covers the use of multiple objective tests, the collection of routine data, a proposed scoring system for the sensorineural component and discusses the role of cold provocation testing in the diagnosis of the vascular component.

The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families.

OBJECTIVE: The pentagastrin stimulation test is the traditional test used for the identification of asymptomatic individuals in multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). The identification of mutations in the RET proto-oncogene segregating with the disease phenotype in MEN 2A and FMTC families has made it possible to re-examine the validity of using this test for the identification of affected family members. DESIGN: Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. PATIENTS: RET mutations were identified in 16 Australian and New Zealand MEN 2A or FMTC families. An analysis of 39 individuals from these families was included in this study. Thirty-two individuals (14 males, 18 females) had previously been determined as RET mutation negative. Seven individuals (6 males, 1 female) had previously been determined as RET mutation positive. Two RET mutation negative males had thyroidectomy based on prior pentagastrin test results. MEASUREMENTS: Serum calcitonin levels in response to stimulation with pentagastrin were measured at 0, 1, 2, 5 and 10 minutes post injection. Mutation analysis of the RET proto-oncogene was performed in all individuals. In two RET mutation negative individuals from two MEN 2A families, thyroidectomy was performed and C-cells were quantitated in order to determine the diagnosis of C-cell hyperplasia. RESULTS: There was a statistically significant difference (P < 0.013) between RET mutation negative male and female mean peak calcitonin responses of 282 +/- 236 and 96 +/- 62 (mean +/- SD) ng/l respectively. False positive responses to pentagastrin stimulation were identified in seven individuals who were RET mutation negative in two of the 16 families. Histologic examination of the thyroid glands in the two RET mutation negative individuals who had thyroidectomy demonstrated C-cell hyperplasia in one but not in the other. CONCLUSIONS: There is considerable overlap between pentagastrin test results in individuals who are RET mutation positive and those who are RET mutation negative. These results indicate a need for routine performance of RET proto-oncogene analysis on all individuals at risk of developing MEN 2A or FMTC and a coupling of pentagastrin test results and RET proto-oncogene analysis in the decision to proceed with thyroidectomy.

Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy.

We conducted a retrospective study to assess the changes in bone marrow (BM) stromal antigenic profile and fibrosis in chronic myeloid leukemia (CML) under combined interferon-alpha (IFN) and Ara-c therapy. Bone marrow biopsies were taken before therapy and twice (at 4 and 15 months) during therapy in 10 CML patients and compared with non-CML samples. Collagen and reticulin fibrosis was assessed by histochemical methods and phenotypic changes were studied by immunohistochemistry (APAAP) with antibodies directed against endothelial cell antigens, cell adhesion molecules, and HLA-DR. It was found that: (1) BM endothelial cells in patient and in control specimens showed a specific pattern of antigen expression: high expression of FVIII and CD34 (except on sinusoids for the latter), variable expression of UEA I, and no expression of HLA-DR and E-selectin. (2) Compared to non-CML controls, CML specimens at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopoietic cells. (3) Treatment did not influence BM fibrosis, the vascular content of the BM, or the expression of the antigens tested except an increase in the number of CD34+ sinusoids (5/10 patients), an increase in the number of HLA-DR+, and a decrease in the number of CD34+ hemopoietic cells (6/10). (4) On therapy, difficulty in aspiration and/or reduced BM fragment numbers were noted in 8 of 10 patients whose bone marrow was still normocellular or slightly hypercellular. In conclusion, CML samples at diagnosis showed increased fibrosis and decreased CD31 and CD61 expression compared to controls. During the period of observation, combined therapy did not modify BM fibrosis; however, an increase in CD34+ sinusoids and a decrease in CD34+ hemopoietic cells were noted.

Subcutaneous fat necrosis following traumatic pancreatitis.

A 25 year old female who developed subcutaneous fat necrosis and polyarthritis secondary to post-traumatic pancreatitis is reported. This is a well documented but uncommon phenomenom, affecting less than 1% of patients with pancreatic disease.