Improved quality of life following total pancreatectomy and auto-islet transplantation for chronic pancreatitis.

BACKGROUND: Total pancreatectomy (TP) with auto-islet transplant (AIT) is an extreme treatment for chronic pancreatitis, and we reviewed our experience to assess the impact on quality of life (QOL). METHODS: A prospective cohort study from 2007 through 2010 with pre- and postoperative assessments of the Depression Anxiety Stress Scale, Pain Disability Index, and visual analogue pain scale was performed. RESULTS: Twenty patients underwent TP-AIT with a median follow-up of 12 months (6.75-24 months). All patients reported moderate (45 %) to severe (55 %) pain prior to surgery. TP-AIT resulted in significant decreases in abdominal pain (p < 0.001), 80 % reporting no or mild pain. Despite pain improvement, only 30 % discontinued narcotics. Improvements in all PDI QOL domains improved from 79 to 90 % (p = 0.002), with greatest improvements seen in those without prior pancreatic surgery, younger patients, and in those with higher levels of preoperative pain. Patients were less affected by depression and anxiety prior to surgery, but 60 and 70 % did show improvement in depression and anxiety, respectively (p = 0.033). Sixteen patients (80 %) required exogenous insulin at last follow-up (mean total dose of insulin 11.6 U/day). CONCLUSIONS: TP-AIT significantly improves pain and QOL measures in appropriately selected patients with CP.

Diagnostic characteristics of late-night salivary cortisol using liquid chromatography-tandem mass spectrometry.

OBJECTIVE: The objective of the study was to describe the diagnostic performance of a commercially available late-night salivary cortisol (NSC) assay using liquid chromatography tandem mass spectrometry. METHODS: We retrospectively identified 90 patients who had one or more NSC determinations: 52 patients in whom Cushing syndrome (CS) was excluded or could not be confirmed [group 1 (G1)] and 38 patients in whom CS was confirmed [group 2 (G2)]. Eighteen healthy volunteers served as controls. RESULTS: Baseline demographics in all groups were similar with regards to age, ethnicity, gender, and body mass index. NSC levels [median (range)] were higher in G2, 381 (64-13,500) ng/dl [10.51 (1.77-372.46) nmol/liter], compared with controls, 19.3 (2.1-416) ng/dl [0.53 (0.06-11.48) nmol/liter], and G1, 26 (4-176) ng/dl [0.72 (0.11-4.86) nmol/liter, P < 0.001]. The highest combined sensitivity (92%) and specificity (92%) was achieved at a cut point of 107 ng/dl (2.95 nmol/liter). Two or more NSCs were done in 32 of 52 G1 and 31 of 38 G2 patients. In G1 eight of 32 (25%) had at least one elevated [>100 ng/dl (2.76 nmol/liter)] NSC including two in whom both NSCs were elevated. In contrast, four of 31 (13%) in G2 had at least one normal NSC including one with four of five normal NSC values. None of the patients with CS had a NSC less than 60 ng/dl (<1.66 nmol/liter). Comparing G1 and G2, obtaining more than one saliva sample did not improve the diagnostic accuracy of NSC measurement (P = 0.64). CONCLUSION: The liquid chromatography tandem mass spectrometry assay to measure NSC is a simple and reliable test to screen patients suspected to have CS. Clinicians should be aware of appropriate cutoff values for proper interpretation of NSC and use additional tests when necessary.

Islet transplantation for brittle type 1 diabetes: the UIC protocol.

This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1-3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460 080 +/- 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537 495 +/- 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 +/- 0.6 at baseline to 5.6 +/- 0.5 after 2-3 Tx in Group 1 vs. 7.8 +/- 1.1 to 5.8 +/- 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets.

Use of low dose tacrolimus, mycophenolate mofetil and maintenance IL-2 receptor blockade in an islet transplant recipient.

The utilization of dual maintenance therapy with tacrolimus and sirolimus (the Edmonton protocol) has been widely adopted as standard immunosuppression for islet cell transplantation. This immunosuppression regimen has numerous toxicities including renal dysfunction, anemia, and recurrent aphthous ulcers. We present a case of a 63-yr-old Caucasian female who received an isolated islet transplant. Over the first six months post-transplant, the patient developed severe anemia, intractable aphthous ulcers, and renal dysfunction. Islet transplant function was excellent and the patient is insulin-independent since the end of the second month post-transplant. However, because of the above toxicities, a decision was made to change her immunosuppression regimen eight months post-transplant to low dose tacrolimus, mycophenolate mofetil, and a monthly maintenance infusion of daclizumab. Since then, her aphthous ulcers have disappeared, renal function has improved, and islet cell function remains stable.

Intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma: case report & literature review.

We report an uncommon case of an intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma as the first manifestation of multiple myeloma. A 57 year old woman was referred to our department with a presumed diagnosis of a non-functioning pituitary macro-adenoma. She reported a 3 month history of headaches and a 2 week history of sudden onset of right facial numbness. Preoperative endocrine evaluation was remarkable only for a modestly elevated serum prolactin. A magnetic resonance imaging (MRI) scan revealed 3.6 x 5 x 4 cm enhancing homogeneous intrasellar mass with extension into the sphenoid and cavernous sinuses bilaterally; the optic chiasm was not displaced. She underwent transphenoidal surgery of the sellar lesion. The surgical specimen was heavily infiltrated with abnormal plasma cells, which stained almost exclusively for Kappa light chain immunoglobulins. An extensive investigation was undertaken to look for occult myelomatous disease. A diagnosis of multiple myeloma was made 1 month later based on a combination of clinical, pathological and radiologic features. She underwent radiation therapy directed towards the residual sellar tumor, followed by chemotherapy and autologous stem cell transplantation. Review of the world literature revealed only 22 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first presented as a sellar mass; in all cases mimicking clinically and radiologically a non-functioning invasive pituitary adenoma however with additional cranial nerve involvement. Intrasellar plasma cell tumors are rare tumors which may mimic non-functioning invasive pituitary tumors. The diagnosis should be suspected in patients with well preserved anterior pituitary function and cranial nerve neuropathies in the presence of significant sellar destruction.

Immediate conversion from tacrolimus to cyclosporine in the treatment of posttransplantation diabetes mellitus.

Posttransplantation diabetes (PTDM) is a frequent complication of tacrolimus (TAC)-based immunosuppressive therapy after kidney transplantation. We investigated whether immediate conversion from TAC to Cyclosporine (CSA) could reverse or at least improve new-onset PTDM. Between February 2002 and February 2004, 28 adult kidney transplant recipients maintained on TAC were diagnosed with new-onset PTDM. Eight adult patients with new-onset PTDM were enrolled in the study and converted from TAC to CSA, the remaining 20 patients served as controls and were continued on the TAC-based immunosuppression. The conversion to CSA was performed immediately after establishing the diagnosis of PTDM at an average of 11 months posttransplantation. We did not document any episodes of acute rejection or worsening renal function after conversion. After conversion to CSA, among the 3 patients started on insulin, 1 has come completely off antidiabetic medications, whereas 1 required decreased doses of insulin, and the third has been converted to oral medications. Of the 5 patients originally on oral medications, 3 completely discontinued therapy, whereas the other 2 were well controlled on single-drug therapy at reduced doses. After a mean follow-up of 17 months, in the control group 9 of the 16 patients started on oral antidiabetics ultimately required insulin treatment and no patient could stop antidiabetic or insulin therapy. These findings indicate that conversion from TAC to CSA is a simple, safe, and efficacious way to reverse or at least improve PTDM.

Fine-needle aspiration of thyroid nodules in radiation-exposed patients.

External radiation used to treat benign conditions in the head and neck area results in an increased risk of thyroid cancer in exposed individuals. Fine-needle aspiration (FNA) biopsy is the standard procedure used to evaluate suspicious thyroid nodules. Its accuracy has been extensively studied, but little is known about FNA in irradiated patients. We analyzed the FNA experience of 136 irradiated subjects. Fifty-two had surgery enabling a comparison of the histologic diagnosis with the FNA results. In these 52 patients with a total of 53 FNAs, 20 were reported as benign, 14 as follicular neoplasms, 6 as papillary cancer, and 13 as inadequate samples. Seven malignant nodules were aspirated; 4 were reported as papillary cancer, 1 was reported as benign and 2 had inadequate specimens. An additional 11 patients had thyroid cancer in foci that were not subjected to FNA. For the nodules that were aspirated, and considering an FNA report of follicular neoplasm as a false-positive when a follicular adenoma or a colloid nodule was found at surgery, the calculated sensitivity was 80%, specificity 54%, positive predictive value 20%, and negative predictive value 95%. Of the 14 follicular neoplasm FNA diagnoses, 10 were colloid nodules (71%), and 4 only were follicular adenomas. We conclude that the sensitivity of FNA in irradiated patients is similar to what is reported for the general population. However, smaller malignant nodules are common and are not diagnosed by the FNA. Also, the FNA diagnosis of follicular neoplasm is often inaccurate and inadequate aspirations are frequent in this patient group.

Selective endocytosis of thyroglobulin: a review of potential mechanisms for protecting newly synthesized molecules from premature degradation.

In 1976 Cortese, Schneider and Salvatore (Eur. J. Biochem. 68 (1976) 121-129) showed that the thyroid gland protects newly synthesized, iodine and hormone poor thyroglobulin from immediate degradation. Since then there has been substantial progress in understanding the mechanism by which this selectivity of degradation occurs. Thyroglobulin in the follicular lumen is internalized mainly by receptor-specific endocytosis. Recycling of immature, poorly iodinated thyroglobulin back to the follicular lumen is the pathway most likely responsible for selectivity. Since additional carbohydrate groups are added to the immature thyroglobulin, it appears that this recycling occurs via the Golgi compartment. The molecular signal for recycling most likely involves the complex carbohydrates and probably is exposed GlcNAc groups. A thyroid-specific GlcNAc receptor has been identified and cloned. Other Tg-binding sites have been identified in the thyroid, but their physiological role remains to be determined.