Liver transplantation in a subject with familial hypercholesterolemia carrying the homozygous p.W577R LDL-receptor gene mutation

Mutations within the low density lipoprotein (LDL)-receptor gene result in familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical homozygous affected subjects die of premature coronary artery disease as early as in early childhood. We identified a girl at the age of five yr with clinical homozygous familial hypercholesterolemia presenting with achilles tendon xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL. Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R mutation. Despite intensive treatment interventions with the combination of diet, statins, colestipol, and LDL-apheresis, the patient developed symptomatic coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver transplantation was performed to cure the defective LDL-receptor gene. Clinical follow-up for almost nine yr post-transplantation revealed excellent liver function, normal liver enzymes, normal LDL-cholesterol, and regression of both tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver transplantation can effectively reduce LDL-cholesterol in a familial hypercholesterolemia recipient with subsequent regression of xanthomas and atherosclerosis. Timing is extremely important in these exceptional cases to exclude the demand for heart transplantation due to severe coronary artery disease. In addition, the identification of the LDL-receptor as etiology of clinical homozygous hypercholesterolemia is a prerequisite once liver transplantation is considered as therapeutic option.     

Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood

Background

A 12-year-old girl presenting with intermittent epigastric pains and diarrhea was referred to our clinic. Diagnostic workup revealed nonfunctional bilateral adrenal pheochromocytomas as well as a neuroendocrine tumor of the pancreatic head. This is the first report on the combination of a neuroendocrine pancreatic tumor with adrenal pheochromocytoma in a pediatric patient with von Hippel-Lindau (VHL) disease.

Methods

von Hippel-Lindau disease was confirmed by molecular genetic analysis of peripheral blood lymphocytes, which revealed the mutation VHL c. 695 G > A. The family history showed also VHL disease in the mother who carried the same mutation.

Results and Conclusion

Open laparotomy, organ-sparing enucleation of pheochromocytoma, and pylorus-preserving resection of the pancreatic head tumor were successfully performed. After an uneventful postoperative course, the child fully recovered. She was free of further manifestations of VHL disease 30 months after surgery.     

A case of multiple primary tumors of the anterior skull base.

We report a case of synchronous olfactory bulb meningioma and undifferentiated carcinoma of the nose and paranasal sinuses that involved and destroyed the anterior skull base and mimicked intracranial invasion by a carcinoma. The heterogeneity of tissue types in the skull base gives rise to a diverse variety of benign and malignant neoplasms which have totally different prognoses. Synchronous development of benign and malignant primary tumors both originating from and involving the skull base at the same location is very rare and may cause confusion for both the skull base surgeon and neuroradiologist.     

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.     

Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.

PURPOSE: To evaluate fluorine 18 ((18)F) dihydroxyphenylalanine (DOPA) whole-body positron emission tomography (PET) as a biochemical imaging approach for detection of pheochromocytomas. MATERIALS AND METHODS: (18)F DOPA PET and magnetic resonance (MR) imaging were performed in 14 consecutive patients suspected of having pheochromocytomas (five sporadic, nine with von Hippel-Lindau disease); metaiodobenzylguanidine (MIBG) scintigraphy was performed in 12 of these patients. The individual imaging findings were assessed in consensus by specialists in nuclear medicine and radiologists blinded to the results of the other methods. The findings of the functional imaging methods were compared with those of MR imaging, the reference standard. Histologic verification could be obtained in eight patients with nine tumors. RESULTS: Seventeen pheochromocytomas (11 solitary, three bifocal; 14 adrenal, three extraadrenal) were detected with MR imaging. (18)F DOPA PET and MR imaging had concordant results in all 17 tumors. In contrast, MIBG scintigraphy had false-negative results in four patients with three adrenal tumors smaller than 2 cm and one extraadrenal tumor with a diameter of 3.6 cm. On the basis of these data, sensitivities of 100% for (18)F DOPA PET and of 71% for MIBG scintigraphy were calculated. Specificity was 100% for both procedures. CONCLUSION: (18)F DOPA PET is highly sensitive and specific for detection of pheochromocytomas and has potential as the functional imaging method of the future.     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

First demonstration of leukemia imaging with the proliferation marker 18F-fluorodeoxythymidine

Acute myeloid leukemia (AML) is a neoplasm of hematopoietic stem cells with partial or complete loss of the ability to differentiate but with preserved proliferation capacity. The aim of our study was to evaluate if the in vivo proliferation marker 3'-deoxy-3'-18F-fluorothymidine (FLT) is suitable for visualizing leukemia manifestation sites and if 18F-FLT is a surrogate marker for disease activity. METHODS: In this pilot study, 10 patients with AML underwent pretherapeutic imaging with 18F-FLT PET or 18F-FLT PET/CT. The biodistribution of 18F-FLT was assessed 60 min after intravenous injection of the radiotracer. Standardized uptake values were calculated for reference segments of bone marrow, spleen, and normal organs. 18F-FLT PET in 10 patients with benign pulmonary nodules and the absence of malignant or inflammatory disease served as controls. RESULTS: Retention of 18F-FLT was observed predominantly in bone marrow and spleen and was significantly higher in AML patients than in controls (mean 18F-FLT SUV in bone marrow, 11.5 and 6.6, P < 0.05; mean 18F-FLT SUV in spleen, 6.1 and 1.8, P < 0.05). Outside bone marrow, focal 18F-FLT uptake showed extramedullary manifestation sites of leukemia in 4 patients (meningeal disease, pericardial, abdominal, testicular, and lymph node), proven by other diagnostic procedures. CONCLUSION: This pilot study indicated that PET using 18F-FLT is able to visualize extramedullary manifestation sites of AML and reflects disease activity. Because 18F-FLT uptake in bone marrow is caused by a combination of both neoplastic and normal hematopoietic cells, the correlation of 18F-FLT uptake in bone marrow and leukemic blast infiltration did not reach statistical significance.     

A comparison of the laryngeal tube with the laryngeal mask airway during routine surgical procedures

The laryngeal mask airway (LMA; Laryngeal Mask Company, Henley-on-Thames, UK) is an established airway device, whereas the laryngeal tube (LT) is relatively new and therefore not as well investigated. Therefore, the purpose of the present prospective, randomized, controlled trial was to compare the LT with the LMA in routine clinical practice. In 50 patients undergoing general anesthesia for minor routine surgery, standardized anesthesia was induced and maintained with alfentanil and propofol. Patients were randomized to controlled ventilation (fraction of inspired oxygen = 0.4; fraction of inspired nitrous oxide = 0.6; tidal volume = 7 mL/kg; respiratory rate = 10 breaths/min) with the LT (n = 25) or the LMA (n = 25). Oxygen saturation was recorded before the induction of anesthesia and after the administration of oxygen. After 2 and 10 min of ventilation with the LT or LMA, oxygen saturation, end-expiratory carbon dioxide, expiratory tidal volume, and peak airway pressure were recorded. Capillary blood gas samples were taken before the induction of anesthesia and after 10 min of ventilation. Time of insertion and airway leak pressure of each device were measured. The time of insertion was comparable with both devices (LT versus LMA, median 21 s versus 19 s; P = not significant). Blood gas samples and ventilation variables revealed sufficient ventilation and oxygenation with either device (P = not significant). Peak airway pressure (LT, 17 +/- 3 cm H(2)O; LMA, 15 +/- 3 cm H(2)O) and airway leak pressure (LT, 36 +/- 3 cm H(2)O; LMA, 22 +/- 3 cm H(2)O) were significantly (P < 0.05) higher when using the LT compared with the LMA. In conclusion, using the LT and LMA resulted in comparable ventilation and oxygenation variables in this model of ASA physical status I and II patients undergoing routine surgical procedures. The newly developed LT may be a simple alternative device to secure the airway. IMPLICATIONS: The laryngeal tube, a newly developed airway device, and the laryngeal mask airway were used to ventilate patients in the operating room. Both airway devices proved to be effective and safe; however, the laryngeal tube allowed greater airway pressure during ventilation.     

Juxtacondylar Approach in Temporal Paraganglioma Surgery: When and Why?

As it became clear that patients with paraganglioma (PGL) syndromes had a higher risk of multifocal tumors, we changed our surgical strategy to avoid the possibility of bilateral cranial nerve paralysis. The juxtacondylar approach offers advantages for some jugular foramen tumors, including types C and D temporal PGLs. This approach allows exposure of the jugular foramen without skeletonizing or transposing the facial nerve. It improves the surgeon's ability to distinguish between the pars vascularis and the pars nervosa at the jugular foramen, and it helps to save functioning of the lower cranial nerves. There is already considerable experience using the juxtacondylar approach for patients suffering from schwannomas and meningiomas involving the jugular foramen. Some limitations have been noted for using the juxtacondylar approach with jugular PGLs that are related to their vascular nature. In this article we demonstrate its use for the management of eight patients with locally advanced temporal PGLs and how it can be combined with an infratemporal fossa approach.