Bilateral pheochromocytomas with von Hippel-Lindau disease: a case report

A case of bilateral pheochromocytomas with von Hippel Lindau disease (VHL) is reported. A 32-year-old man visited Kumamoto Red Cross Hospital for further examination of hypertension. Computed tomography revealed bilateral adrenal tumors and noradrenalin levels in serum and urine were elevated. Suspecting bilateral pheochromocytoma, he was reffered to our hospital for further examination and treatment. 131I-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Moreover, he had cerebellar and spinal hemangioblastomas. Bilateral adrenalectomies and left nephrectomy were performed because tumor thrombus extended into the left renal vein, and pathological diagnosis was pheochromocytoma. His sister had been diagnosed as VHL disease. We diagnosed the patient as VHL disease because of the existence of cerebellar and spinal hemangioblastomas, bilateral pheochromocytomas, missense mutation and his family history. This is the eleventh case of bilateral pheochromocytomas with VHL disease reported in Japanese literatures.     

Retroperitoneal Liposarcoma With Leiomyosarcomatous Differentiation

We herein describe a 60-year-old Japanese man with a giant retroperitoneal liposarcoma undergoing leiomyosarcomatous differentiation. He was admitted to our hospital because of a 5-month history of dysphagia and abdominal distention. Abdominal computed tomography showed a giant tumor that occupied the entire retroperitoneal space. The majority of the mass was lipomatous and low density; both a heterogenous and solid mass were also present. A giant retroperitoneal liposarcoma was diagnosed, and tumor resection was performed. At surgery, the tumor was mostly isolated from the retroperitoneum and other organs. Histopathologically, the tumor comprised well-differentiated and dedifferentiated liposarcoma with heterologous differentiation of the leiomyosarcomatous components, which is a rare phenomenon in liposarcoma. The patient was alive 3 years after the first treatment, although he has had 3 local recurrences (approximately one recurrence yearly) and has been treated by repeated resection and radiotherapy.Key words: Retroperitoneum, Liposarcoma, Leiomyosarcomatous differentiationDedifferentiated liposarcoma (DL) is one of the most frequent sarcomas of the retroperitoneum. It is defined by the association of an atypical lipomatous tumor, namely, areas of well-differentiated liposarcoma (WDL), with a dedifferentiated component. WDL is composed of mature adipocytes and atypical stromal cells with an enlarged, hyperchromatic nucleus. Usually, the dedifferentiated part of the liposarcoma is composed of either a spindle/pleomorphic high-grade sarcoma or a mixoid/spindle cell low-grade sarcoma. The WDL component may be easily overlooked, and DL may thus be mistaken for another high-grade sarcoma. It has been reported in one study that approximately 5% of the dedifferentiated component showed heterologous differentiation, such as leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, and angiosarcoma.¹ A less common phenomenon is the occurrence of WDL with leiomyosarcomatous (LMS) differentiation.² Limited to the retroperitoneum, only 8 cases of liposarcoma with LMS components have been reported.^3–7 We herein report a case of retroperitoneal liposarcoma comprising WDL and DL, with LMS components, treated by surgical resection.     

Aberrant Glycosylation and Localization of Polycystin-1 Cause Polycystic Kidney in an AQP11 Knockout Model

We previously reported that disruption of the aquaporin-11 (AQP11) gene in mice resulted in cystogenesis in the kidney. In this study, we aimed to clarify the mechanism of cystogenesis in AQP11(−/−) mice. To enable the analyses of AQP11 at the protein level in vivo, AQP11 BAC transgenic mice (Tg^AQP11) that express 3×HA-tagged AQP11 protein were generated. This AQP11 localized to the endoplasmic reticulum (ER) of proximal tubule cells in Tg^AQP11 mice and rescued renal cystogenesis in AQP11(−/−) mice. Therefore, we hypothesized that the absence of AQP11 in the ER could result in impaired quality control and aberrant trafficking of polycystin-1 (PC-1) and polycystin-2 (PC-2). Compared with kidneys of wild-type mice, AQP11(−/−) kidneys exhibited increased protein expression levels of PC-1 and decreased protein expression levels of PC-2. Moreover, PC-1 isolated from AQP11(−/−) mice displayed an altered electrophoretic mobility caused by impaired N-glycosylation processing, and density gradient centrifugation of kidney homogenate and in vivo protein biotinylation revealed impaired membrane trafficking of PC-1 in these mice. Finally, we showed that the Pkd1(+/−) background increased the severity of cystogenesis in AQP11(−/−) mouse kidneys, indicating that PC-1 is involved in the mechanism of cystogenesis in AQP11(−/−) mice. Additionally, the primary cilia of proximal tubules were elongated in AQP11(−/−) mice. Taken together, these data show that impaired glycosylation processing and aberrant membrane trafficking of PC-1 in AQP11(−/−) mice could be a key mechanism of cystogenesis in AQP11(−/−) mice.Aquaporin-11 (AQP11) is a membrane-channel protein. Although AQP11 is reported to be permeable to the water molecule,^1–3 the permeability of AQP11 to other solutes remains unclear. AQP11(−/−) mice die in the neonatal period because of renal failure and retarded growth.^4,5 Moreover, AQP11(−/−) mice develop renal cysts, suggesting that AQP11 can play a role in cystogenesis.^4,5 However, the mechanisms of cystogenesis in AQP11(−/−) mice have yet to be clarified. One of the reasons for the difficulties in investigating AQP11 has been the lack of a good antibody for detecting endogenous AQP11 in mouse tissues.Autosomal dominant polycystic kidney disease (PKD) is the most common inherited renal disorder, occurring in 1:400 to 1:1000 live births. It is characterized by gradual renal cyst development and expansion, ultimately resulting in massive kidney enlargement and ESRD. Among autosomal dominant PKD patients, 85%–90% of cases result from mutations in the PKD1 gene, whereas another 10%–15% of cases are accounted for by mutations in the PKD2 gene. PKD1 encodes polycystin-1 (PC-1), a 462-kD, 4303–amino acid integral membrane protein with 11 transmembrane domains, a long extracellular N terminus with multiple binding domains, and a short cytoplasmic C terminus that interacts with multiple proteins, including the protein product of PKD2, polycystin-2 (PC-2).⁶ PC-2 is a significantly smaller 110-kD protein with six transmembrane domains. PC-1 and PC-2 are located in the plasma membrane and cilia of renal epithelia.^6–8To enable the analyses of AQP11 in mice at the protein level in vivo, we generated AQP11 BAC transgenic mice (Tg^AQP11) that express AQP11 tagged with 3×hemagglutinin (HA) sequence at its N terminus and showed that AQP11 localizes to the endoplasmic reticulum (ER) of proximal tubule cells in vivo. Moreover, to investigate the mechanisms of cystogenesis in AQP11(−/−) mouse kidneys, we focused on PC-1 and PC-2. Impaired glycosylation processing and membrane trafficking of PC-1 in AQP11(−/−) mouse kidneys were found, which could represent a key mechanism of cyst formation in AQP11(−/−) mice.     

Update on Intensive Neuromonitoring for Patients with Traumatic Brain Injury: A Review of the Literature and the Current Situation

Intracranial pressure (ICP) measurements are fundamental in the present protocols for intensive care of patients during the acute stage of severe traumatic brain injury. However, the latest report of a large scale randomized clinical trial indicated no association of ICP monitoring with any significant improvement in neurological outcome in severely head injured patients. Aggressive treatment of patients with therapeutic hypothermia during the acute stage of traumatic brain injury also failed to show any significant beneficial effects on clinical outcome. This lack of significant results in clinical trials has limited the therapeutic strategies available for treatment of severe traumatic brain injury. However, combined application of different types of neuromonitoring, including ICP measurement, may have potential benefits for understanding the pathophysiology of damaged brains. The combination of monitoring techniques is expected to increase the precision of the data and aid in prevention of secondary brain damage, as well as assist in determining appropriate time periods for therapeutic interventions. In this study, we have characterized the techniques used to monitor patients during the acute severe traumatic brain injury stage, in order to establish the beneficial effects on outcome observed in clinical studies conducted in the past and to follow up any valuable clues that point to additional strategies for aggressive management of these patients.     

Spirometric and radiological evaluation of the remnant lung long after major pulmonary resection: can compensatory phenomena be recognized in clinical cases?

Purposes

The purpose of this study was to investigate the compensatory phenomena after lung resection in clinical cases by evaluating the spirometric and radiological parameters.

Methods

Forty patients undergoing lobectomy for stage IA lung cancer were divided into the following groups: (A) patients with <10 (n = 20) and (B) patients with ≥10 resected subsegments (n = 20). Comparisons were made of the predicted and observed postoperative values of spirometry and radiological parameters, such as lung volumetry and the “estimated lung weight”. Predicted values were based on the number of resected subsegments. The postoperative time to re-evaluation was at least 1 year for both groups.

Results

The predicted postoperative values of spirometry underestimated the actual values, and the differences were more significant in group B (forced vital capacity, p = 0.006, forced expiratory volume in 1 s, p = 0.011). Focusing on the remnant lungs on the surgical side, group B had significantly larger % postoperative lung volumes (161 ± 6.0 %) and % estimated lung weight (124 ± 5.4 %) than did group A (114 ± 3.8 %, p < 0.0001; 89.5 ± 4.4 %, p < 0.0001, respectively).

Conclusions

Major lung resection in clinical cases causes a compensatory restoration of the pulmonary function and tissue.     

Comparison of Near-Infrared Spectroscopy and Laser Doppler Flowmetry for Detecting Decreased Hepatic Inflow in the Porcine Liver

Hepatic artery and portal vein thrombosis are devastating complications of partial liver transplantation. Early detection of inflow complications is important, as re-reconstruction can salvage the graft. Near-infrared spectroscopy or laser Doppler flowmetry can be used to detect tissue oxygenation or microcirculation on the liver surface. The aim of this study was to examine which of these two methods better detects changes in hepatic inflow. Sangen-strain pigs (n = 5) were used. The tips of the near-infrared spectroscopy and laser Doppler flowmetry probes were placed separately on the surface of the right liver. Inflow to the liver was controlled during the following seven conditions: control (not clamped), half- and totally clamped portal vein, half- and totally clamped hepatic artery, and half- and totally clamped portal vein and artery. Tissue blood flow was calculated using laser Doppler flowmetry. Oxyhemoglobin, deoxyhemoglobin, and the tissue oxygenation index were measured and calculated using a near-infrared spectroscopy system. The tissue blood flow and oxygenation index could not be used to differentiate between the half-clamped portal vein, half-clamped hepatic artery, and totally clamped portal vein conditions. The oxyhemoglobin minus deoxyhemoglobin value was significantly decreased after half or total clamping of the portal vein or hepatic artery (p <. 001 for each condition). The findings of the present study indicate that near-infrared spectroscopy was more sensitive than Doppler flowmetry for detecting changes in hepatic tissue inflow from the liver surface.     

Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds

Hepatocyte growth factor (HGF) has a number of biological activities, e.g., mitogenic, motogenic, antiapoptotic, antifibrous, and morphogenic. It also has angiogenic and angioprotective activities for endothelial cells. The aim of this study was to characterize the role of HGF in wound healing by administering the HGF gene locally to acute incisional skin wounds created on the backs of rats. To create wounds, the backs of Wistar rats were clipped and three 2-cm-long incisional wounds were made deep to the fascia. The wounds contained pannicrus carnosum and were created at intervals of 2 cm. After suturing, the HGF gene was then administered intradermally. Apoptotic cells in wound lesions were identified by TUNEL method as well as by immunological detection of active caspase-3. In the HGF-treated animals, we found almost complete suppression of apoptosis and well-organized wound healing. Histopathological examination revealed that the proliferation of fibroblasts was suppressed and that scar formation was less apparent in the HGF-treated animals compared to the controls. It is thought that administration of the HGF gene immediately after surgery may enhance the healing process through suppressing apoptosis, which occurred in the controls 1 week after suturing the incisional wound. In addition, locally increased HGF expression due to the introduction of the HGF gene to cells around wounds enhances dermal regeneration, possibly by promoting regeneration of dermal tissue, which results in less scarring due to its antifibrotic effect. Thus, HGF supplementation through gene therapy may be an effective strategy for treating wounds, as it increases the regeneration of the dermis to allow for "scarless wound healing."     

Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Background. Transferrin binds extracellular iron and protectstissues from iron-induced oxidative stress. The binding of ironand transferrin is pH dependent and conventional peritonealdialysis (PD) solutions have unphysiologically low pH values.Herein, we investigated whether conventional PD solution releasesiron from transferrin and if the released iron causes oxidativestress. Methods. Effects of PD solutions on iron binding to transferrinwere examined with purified human transferrin and transferrinin dialysates drained from PD patients. Oxidative stress inducedby iron released from transferrin was evaluated in terms ofthe formation of thiobarbituric acid reactive substance (TBARS)and protein carbonylation in the human red blood cell (RBC)membrane. The iron deposition in peritoneal tissue from PD patientswas evaluated by Perls' staining with diaminobenzidine intensification. Results. Low pH PD solution released iron from transferrin.This iron release occurred within 1 min. Iron release was notobserved in neutralized PD solution. Iron released from transferrinin low pH PD solution increased TBARS formation and proteincarbonylation in the human RBC membrane. Iron deposition, whichis prominent in the fibrotic area facing the peritoneal cavity,was observed in the peritoneum of PD patients. Conclusions. Iron released from transferrin in low pH PD solutioncan produce oxidative stress in the peritoneum of a PD patient.Neutralizing PD solution can avoid this problem. Iron depositionin the peritoneum may participate in the pathogenesis of peritonealfibrosis in PD patients.     

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study

Annals of Nuclear Medicine - Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of...