NPHS2 mutations in sporadic steroid-resistant nephrotic syndrome in Japanese children

Podocin is an integral membrane protein encoded by NPHS2, which is mapped to 1q25-31 and is exclusively expressed in glomerular podocytes. NPHS2 mutations are responsible for autosomal recessive familial steroid-resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset (age less than 6 years) and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent/adult onset form of autosomal recessive familial FSGS with heavy proteinuria. It has been demonstrated that sporadic SRNS and heavy proteinuria are also due to NPHS2 gene mutations. We isolated genomic DNA from 36 Japanese children with chronic renal insufficiency caused by SRNS or heavy proteinuria, and analyzed all eight exons and exon-intron boundaries of NPHS2 using the polymerase chain reaction and direct sequencing. The age at onset of disease was 3.9+/-0.5 years. There were 29 patients with SRNS and 7 with heavy proteinuria without nephrotic syndrome at the onset, but all patients developed chronic renal insufficiency 4.6+/-0.8 years after the onset. A new homozygous missense variant of NPHS2, G34E (G101A) in exon 1, was detected in 1 of 36 patients. However, this homozygous variant was also found in 1 of 44 normal controls, suggesting that the mutation is a polymorphism. Two silent variants (T954C and A1038G) in exon 8 of this gene were also identified in some of the patients and normal controls, indicating that the silent variants are also polymorphisms. There was no significant difference in the genotypic and allelic frequencies of T954C and A1038G polymorphisms between the patients and normal controls. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by sporadic SRNS or heavy proteinuria in Japanese children.     

Hand assisted retroperitoneoscopic nephroureterectomy: comparison with the open procedure

PURPOSE: We report our initial experience with hand assisted retroperitoneoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma and compared our results to those of a contemporary series of open nephroureterectomy. MATERIALS AND METHODS: Clinical data on 34 consecutive patients who underwent hand assisted retroperitoneoscopic nephroureterectomy were reviewed and compared with those on 34 who underwent open nephroureterectomy. All specimens were extracted intact. RESULTS: Total operative time was similar in the 2 groups (233 versus 236 minutes). Estimated blood loss was significantly less in the hand assisted laparoscopy group (236 versus 427 ml.). During convalescence the frequency of parenteral analgesia postoperatively was significantly lower in the laparoscopy group than in the open surgery group. The former patients had a significantly shorter interval to oral intake and ambulation as well as a shorter hospital stay and convalescence compared with those who underwent open surgery. In each group the complication rate was 12% (4 of 34 cases). In the hand assisted laparoscopy group 1 conversion to an open procedure was due to bleeding. There was recurrence in 4 of the 34 patients (12%) in the laparoscopy group, including 2 with bladder recurrence and 2 with metastases, at an average followup of 13.1 months. CONCLUSIONS: Hand assisted retroperitoneoscopic nephroureterectomy is an effective and safe alternative to open nephroureterectomy for upper urinary tract transitional cell carcinoma.     

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies

Purpose  The aim of this study was to investigate the regional differences between the morphologic and functional changes in the same patients with frontotemporal dementia (FTD) using statistical parametric mapping and voxel-based morphometry (VBM). Methods  Thirteen FTD patients (mean age, 64.9 years old; mean MMSE score, 17.7), 20 sex-matched Alzheimer’s disease (AD) patients (mean age, 65.0 years old; mean MMSE score, 17.5), and 20 normal volunteers (mean age, 65.2 years old; mean MMSE score, 29.0) underwent both [¹⁸F]FDG positron emission tomography and three-dimensional spoiled gradient echo MRI. Statistical parametric mapping was used to conduct a VBM analysis of the morphologic data, which were compared voxel by voxel with the results of a similar analysis of glucose metabolic data. Results  FTD patients showed decreased grey matter volume and decreased glucose metabolism in the frontal lobe and anterior temporal lobe. In addition, there was a clear asymmetry in grey matter volume in FTD patients by the VBM analysis while the glucose metabolic data showed little asymmetry. In AD patients, glucose metabolic reduction occurred in the bilateral posterior cingulate gyri and parietal lobules while grey matter density decreased the least in the same patients. Conclusion  In FTD, metabolic and morphologic changes occur in the bilateral frontal lobe and temporal lobe with a limited asymmetry whereas there was considerable discordance in the AD group.     

Clinical impact of the callosal angle in the diagnosis of idiopathic normal pressure hydrocephalus

The utility of measuring the corpus callosal angle (CA) for the diagnosis of idiopathic normal pressure hydrocephalus (INPH) was investigated. Three-dimensional magnetic resonance imaging (MRI) was performed in 34 INPH patients, 34 Alzheimer’s disease (AD) patients, and 34 normal control (NC) subjects. Measurement of the CA on the coronal MR images of the posterior commissure perpendicular to the anteroposterior commissure plane was performed for all subjects. The CA of the INPH group (mean ± SD, 66 ± 14°) was significantly smaller than those of the AD (104 ± 15°) and NC (112 ± 11°) groups. When using the threshold of the mean − 2SD value of the NC group (= 90°), an accuracy of 93%, sensitivity of 97%, and specificity of 88% were observed for discrimination of INPH from AD patients. Measuring the CA helps in differentiating INPH patients from AD and normally aged subjects.     

Liver Transplantation for Cystic Fibrosis in Adults

Purpose To expand our knowledge on liver transplantation for cirrhosis associated with cystic fibrosis in adults. Methods Five patients who underwent a liver transplantation due to cystic fibrosis were reviewed. The outcome of the patients in terms of age, immunosuppression regimen, patient and graft survival, and pre- and post-transplant complications were investigated. Results Five adult liver transplant patients had cystic fibrosis (0.2%). These included 4 men and 1 woman with a mean age of 31 ± 10, ranging from 22 to 52 years old at the time of transplantation. All patients had lung problems. Four patients had exocrine and two had endocrine pancreatic insufficiency. Two are currently alive with a follow-up of 5.8 years and 4 months after transplantation, respectively. There were three deaths from pulmonary embolism at 4.5 years, myocardial infarction with cyclosporine nephrotoxicity at 10.7 years, and lymphoproliferative disorder at 5 months after transplantation. No deaths occurred from lung infection. Only one patient had postoperative pulmonary infectious complications, which were successfully treated with antibiotics and did not result in mortality. Conclusion Adult liver transplantation for end-stage liver disease associated with cystic fibrosis offers encouraging results with a rapid general improvement after surgery and it is now considered to be a safe and acceptable treatment for this disease population.     

Sentinel Node Concept in Clinically N0 Laryngeal and Hypopharyngeal Cancer

Background  Sentinel nodes (SNs) are the lymph nodes that directly receive lymphatic flow from a primary cancer lesion. The SN concept implies that lymphatic metastasis initially occurs at SNs. SN navigation surgery can be introduced for cancers in which the SN concept is established. In SN navigation surgery, lymph node dissection beyond SNs can be omitted if SNs are metastasis free. Although the SN concept has been investigated frequently for oral and oropharyngeal cancer, it has so far been investigated less for laryngeal and hypopharyngeal cancer. In this study, we investigated whether the SN concept is applicable for laryngeal and hypopharyngeal cancer. Methods  Twenty patients with T2–T4 and clinically N0 laryngeal and hypopharyngeal cancer were recruited. ^99mTc-phytate was injected into several sites surrounding the tumor on the day before surgery. Lymphoscintigrams were acquired from at least two different viewpoints. SNs were surveyed intraoperatively, and neck dissections including at least levels II, III, and IV were performed. Results  SNs had occult metastases in five cases. In the remaining 15 cases, neither SNs nor other lymph nodes contained metastases, consistent with the SN concept. There was one false-negative case showing delayed nodal metastasis 2 years after initial surgery. The overall accuracy of the SN concept was 95%. Conclusion  Our study shows that SN biopsy is a reliable strategy to determine correct lymph node status in N0 laryngeal and hypopharyngeal cancer. SN detection was valuable in evaluating the need for neck dissection, whether ipsilaterally or bilaterally. Presented at the 2004 Annual Meeting of the American Academy of Otolaryngology, New York.     

Reconstruction methods to achieve optimal postoperative bowel function following low anterior resection for rectal cancer

After low anterior resection for rectal cancer, approximately 50% of patients experience defecatory malfunction such as multiple evacuations, urgency, and soiling. Since the neorectum is constructed with the remaining colonic segment, it can only substitute for the rectum to a limited extent. A straight anastomosis is most frequently used when the rectal remnant is sufficient, such as in high anterior resection. When the height of anastomosis is close to the anal sphincter, a J-pouch, a side-to-end, or a transverse coloplasty pouch are constructed to achieve better postoperative bowel function. The advantage of J-pouch reconstruction is not only the increased volume but also may be decreased motility when compared with straight reconstruction. In terms of postoperative function, the side-to-end and transverse coloplasty pouch have both been reported to exhibit similar functional results to J-pouch reconstruction. To obtain optimal functional results, pouch reconstruction should be considered, especially when the height of anastomosis is at the levator plane.     

Renal cell carcinoma with unusual metastasis to the gallbladder

Gallbladder involvement in patients with renal cell carcinoma (RCC) is extremely rare. We present a report of a 61-year-old man with a synchronous RCC metastasis to the gallbladder presenting as an intraluminal polypoid mass simulating primary gallbladder carcinoma. Enhanced abdominal computed tomography demonstrated a well-enhanced polypoid lesion in the gallbladder. Intraoperative rapid pathological examination of the gallbladder tumor showed clear cell-type cancerous cells. Microscopically, tumor cells of both the resected kidney and gallbladder had round uniform nuclei, clear cytoplasm, and well-defined cytoplasmic borders, forming alveolar patterns. Immunohistochemically, the tumor cells were negative for cytokeratin 7 (CK7) and carcinoembryonic antigen (CEA), which is usually positive in primary clear cell carcinoma of the gallbladder. Therefore, the final diagnosis was RCC with a synchronous gallbladder metastasis.     

Influence of output energy and pulse repetition rate of the Er:YAG laser on dentin ablation

OBJECTIVE: We sought to improve the efficiency of dentin ablation with the Er:YAG laser by investigating the effects of output energy and pulse repetition rate on ablation. Background Data: The Er:YAG laser is superior to other lasers in ablating dental hard tissues. However, the factors affecting the efficiency of ablation with an Er:YAG laser remain unclear. METHODS: Fifty bovine root dentin plates were irradiated with an Er:YAG laser at an output power of 1.0 W, 1.5 W, or 2.0 W under a water spray while moving the plate at 1 mm/sec. After irradiation, the depth and volume of each ablated site were measured by laser microscopy and the ablated surfaces were examined by scanning electron microscopy. RESULTS: The output power showed a strong positive correlation with the depth and volume of ablation. The output energy had much more pronounced effects on the depth and volume of ablation compared to the pulse repetition rate. The shape of the ablated site varied with the output power, and no cracking or vitrification was observed under the irradiated dentin. The most effective parameters for dentin ablation were an output power of 2.0 W, with an output energy of 80 mJ/pulse at 25 pulses per second (pps) or 100 mJ/pulse at 20 pps. CONCLUSION: These findings suggest that the output energy is the main factor affecting the efficiency of dentin ablation with an Er:YAG laser. We propose that the efficiency of dentin ablation can be improved by choosing an optimal combination of output energy and repetition rate.