Focal segmental glomerulosclerosis with intramembranous vesicle-like microstructures and podocytic infolding lesion

A 42-year-old woman was admitted to Kyushu University hospital because of 6 months' history of bilateral leg edema. Upon admission, ascites and pleural effusion as well as systemic edema were noted. Laboratory tests revealed hypoalbuminemia of 1.5 g/dl and massive proteinuria of 10 g/day. She was diagnosed with nephrotic syndrome. Renal biopsy revealed diffuse thickening of the glomerular basement membrane (GBM) and a crescent-like extracapillary lesion with segmental sclerosis in four of 11 glomeruli. Immunoglobulins and complements were negative by immunofluorescence examination. Therefore, we diagnosed this as focal segmental glomerulosclerosis (FSGS) rather than membranous nephropathy. Using an electron microscope, we observed a thickening of the GBM with numerous intramembranous vesicle-like microstructures and an infolding of the podocyte into the GBM. Since the microstructures were partly demarcated by a unit membrane and some of them were located very closely to the infolded podocyte, we speculated that the microstructures were derived from the podocyte. The unique electron microscopic finding of our case is a disease entity rather than a reactive phenomenon.     

Tubulointerstitial nephritis and IgA nephropathy in a patient with advanced lung cancer treated with long-term gefitinib

A 52-year-old Japanese female was admitted to our hospital for microhematuria, proteinuria and progressive renal dysfunction. Two years prior to admission, she was diagnosed with lung adenocarcinoma and multiple bone and brain metastases, and was treated with gefitinib (250 mg/day). Treatment for 6 months induced partial response with 30% regression of the primary lung tumor, and resolution of metastatic tumors. After confirmation of the partial remission state, we performed percutaneous renal biopsy. Glomeruli showed mild to moderate mesangial proliferation, segmental endocapillary proliferation and occasional fibrocellular crescent formation. In addition, severe interstitial fibrosis and tubular atrophy relative to the degree of glomerular sclerosis were noted. Immunofluorescence microscopy showed predominant IgA deposition in the mesangial area. Electron microscopy revealed subepithelial and paramesangial electron-dense deposits. In consideration of the prognosis of lung cancer and complication of immunosuppressive treatment, we continued gefitinib only and closely followed-up the clinical course in the outpatient clinic. Sixteen months later, she continued to have proteinuria and microhematuria, and the severity of renal dysfunction was still the same. However, the lung cancer started to increase in size. This is quite an unusual case presenting histologically with tubulointerstitial nephritis and IgA nephropathy in a patient on long-term treatment with gefitinib.     

Preserving functional lung using perfusion imaging and intensity-modulated radiation therapy for advanced-stage non-small cell lung cancer

PURPOSE: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. RESULTS: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. CONCLUSION: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients.     

Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma

PURPOSE: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma. METHODS AND MATERIALS: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at the University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non-cancer-related death within 6 months of IMRT. RESULTS: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving >or=20 Gy (V(20); p = 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V20 was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08-2.08) or non-cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02-1.45). CONCLUSION: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V20 was the only independent determinant for risk of PRD or non-cancer-related death. The mean V20 of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V20 should be kept as low as possible after extrapleural pneumonectomy.     

Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy

PURPOSE: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade > or = 3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. RESULTS: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade > or = 3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). CONCLUSIONS: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade > or = 3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.     

Fixed drug eruption due to allylisopropylacetylurea

We report a case of fixed drug eruption due to allylisopropylacetylurea. A 21-year-old female developed purplish-red round eruptions on her neck and left thigh after taking an analgesic containing isopropylantipyrine, allylisopropylacetylurea, phenacetin and anhydrous caffeine. Patch testing with the analgesic and its ingredients on the eruptive area showed positive reactions to the analgesic and allylisopropylacetylurea, while patch testing on the non-eruptive area showed negative reactions, We diagnosed her condition as a fixed drug eruption due to allylisopropylacetylurea in an analgesic.     

Screening for discomfort as the fifth vital sign using an electronic medical recording system: a feasibility study

Late referral to a specialized palliative care service hinders quality symptomatic management. The aim of this article is to describe the feasibility and clinical usefulness of screening for patient discomfort as the fifth vital sign using an electronic medical recording system to identify patients with undertreated physical symptoms. For the electronic medical recording system, all admitted patients received routine nurse assessment of discomfort (defined as any physical symptom) at every vital signs check using Item 2 of the Support Team Assessment Schedule Japanese version (STAS). All medically treated cancer patients admitted to seven oncology units were automatically screened at one-week intervals. Positive screening was defined as a STAS score of 2 or more at least two times during the previous week. For each patient identified by screening, a palliative care team reviewed the medical record and provided written recommendations when other treatments might improve the patient's physical symptoms. Of 629 patients screened, 87 (14%) initially met the positive screening criteria. Fifteen (17%) were false positive due to psychiatric symptoms without physical symptoms or due to misrecording. Of 72 cases with actual discomfort, 33 had already been referred to the palliative care team, 14 had received adequate palliative care as determined by the palliative care team, 14 had self-limiting transient discomfort, and one patient died before the screening day. In the remaining 10 cases (11% of symptomatic patients, 1.7% of all screened patients), the palliative care team recommended potentially useful interventions for symptom control; seven patients were referred to the palliative care team within one week. The time required for all screening processes was about 30 minutes per week. This experience demonstrates that screening for patient discomfort as the fifth vital sign using an electronic medical recording system can be successfully implemented and may be useful in facilitating early referral of distressing patients to the specialized palliative care service.     

Nodular glomerulosclerosis in patients without any manifestation of diabetes mellitus

AIM/METHODS: Diabetic nodular glomerulosclerosis is considered to be the specific renal lesion of diabetes mellitus (DM). However, some cases, in which nodular glomerulosclerosis was found without any manifestation of DM, have also occasionally been reported. We clinicopathologically examined seven cases without a prior history of DM. They consisted of six men and one woman with a mean age of 57 years, and included three cases with family history of DM and six cases with hypertension. RESULTS: Mean body mass index was 26.2 +/- 5.9 (means +/- SD) kg/m(2) and haemoglobin A1c 5.3 +/- 1.1% or haemoglobin A1 7.0 +/- 0.6%. Mean plasma glucose levels were 5.3 +/- 0.7 mmol/L at fasting and 10.1 +/- 1.9 mmol/L at 2 h of 75 g OGTT (normal: 1 patient; impaired glucose tolerance: 4 patients; DM: 2 patients). None of them showed diabetic retinopathy in fundoscopic ophthalmoscopy. Mean serum creatinine was 268 +/- 215 micromol/L, urinary protein 5.2 +/- 4.0 g/day, and three patients had mild haematuria. Renal biopsy revealed typical nodular glomerulosclerosis, a negative deposition based on an immunofluorescence study, and neither any significant electron dense deposits nor fibrils on electron microscopy. CONCLUSION: These patients at presentation had no overt clinical manifestations of glucose intolerance. Diabetic nodular glomerulosclerosis can occur in patients without overt DM, suggesting the role of factors additional to prolonged hyperglycaemia in the pathogenesis of this disorder.     

Coexistence of Generalized Morphea with Histological Changes in Lichen Sclerosus et Atrophicus and Lichen Planus

We reported a 44-year-old Japanese woman with generalized multiple sclerotic plaques, which showed hisological findings of morphea. This patient also had an erosive lesion on her mouth; its histological findings were consistent with lichen planus. A sclerotic lesion on her thigh showed the histological findings of lichen sclerosus et atrophicus (LSA). These data suggest that similar etiologic events or closely related pathologic processes are involved in morphea, lichen planus, and LSA.