Detection of lymph node metastasis in non-small cell lung cancer using the new system of one-step nucleic acid amplification assay.

INTRODUCTION: The prognosis of non-small cell lung cancer greatly depends on the presence of lymph node metastasis, which limits the need for surgery and adjuvant therapy for advanced cancer. One-step nucleic acid amplification of cytokeratin19 (CK19) mRNA was used to detect lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of the new one-step nucleic acid amplification system, which has increased gene amplification efficiency by improving the reagent composition, have shorter preprocessing and measurement times than conventional systems. We aimed to compare the clinical performance of the new system with that of histopathology and the conventional system. MATERIALS AND METHODS: 199 lymph nodes from 58 non-small cell lung cancer patients who underwent lymph node dissection were examined intraoperatively using the new system, conventional system, and histopathology. RESULTS: Lymph node metastasis was diagnosed in 32, 42, and 44 patients using histopathological analysis, the new system, and the conventional system, respectively. Compared with histopathological analysis, the concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value of the new system were 92.0%, 90.6%, 92.2%, 69.0%, and 98.1%, respectively, and compared with the conventional system, the values were 95.0%, 86.4%, 97.4%, 90.5%, and 96.2%, respectively. CONCLUSION: The clinical performance of the new one-step nucleic acid amplification system in detecting lymph node metastasis of lung cancer is comparable to that of histopathology and the conventional system; its performance was sufficient for determining the appropriate clinical treatment. The new rapid system can be effectively utilized during lung cancer treatment intraoperatively and postoperatively.

Radiographic change over 11 years in a patient with asbestos-related pleural disease.

Asbestos-related pulmonary conditions such as benign asbestos pleural effusion (BAPE) and diffuse pleural thickening (DPT) can develop after many years of asbestos exposure. These conditions cause progressing constrictive deficit in pulmonary function which may lead to respiratory failure and death. We report the case of a 72-year-old man with asbestos-related BAPE and DPT which developed approximately 40 years after occupational asbestos exposure, leading to chronic respiratory failure and death. We were able to observe his clinical course including computed tomography (CT) scan evaluation over 11 years. In addition to this observation, moderate asbestos body concentration was confirmed in autopsy-derived lung tissue. There are few case reports that showed radiographic course of asbestos-related pulmonary disorder initiated as BAPE, followed by unilateral DPT and later bilateral DPT that was histologically proven with asbestos body. We consider his clinical course is important in managing this disease, especially in early phase.

Arc-welders' pneumoconiosis with atypical radiological and bronchoalveolar lavage fluid findings: A case report.

Arc-welders' pneumoconiosis (AWP) is an occupational lung disease and has nonspecific symptoms typically with the patterns of centrilobular and/or branching opacities on chest high-resolution computed tomography (HRCT) which are similar to those of hypersensitivity pneumonitis (HP) and/or respiratory tract infections. Therefore, the differential diagnosis is often difficult if they are not suspected. We report a case of AWP which was initially suspected to be pulmonary tuberculosis because of the chest HRCT findings: centrilobular opacities distributed predominantly on the right lobe. On detailed review of the work history, however, the patient was found to be involved in welding. Prussian blue staining of the lung tissues and the bronchoalveolar lavage fluid (BALF) ferritin analysis were useful for the final diagnosis and the appropriate treatment for AWP. The atypical lymphocytosis in BALF in this case suggested the involvement of HP in the pathogenesis due to the occupational sensitization to causal antigens. To the best of our knowledge, this is the first case report of AWP showing features of HP. AWP should be noted even in patients with the typical patterns of centrilobular opacities on chest HRCT. Medical history, iron staining of lung tissues, and the BALF ferritin analysis would be useful for the diagnosis of these patients. The BALF findings are sometimes indeterminate for the diagnosis because the occupational sensitization to causal antigens might be involved in some cases of AWP.

Congenital cystic adenomatoid malformation in adults detected after infection.

Congenital cystic adenomatoid malformation (CCAM) is a benign congenital tumour in which a part of the lung becomes polycystic. Case 1 was a 64-year-old male who was diagnosed with pneumonia, with multiple cysts in the right lower lung lobe, using chest computed tomography (CT). After treatment of the pneumonia, including Mycobacterium abscessus, a right lower lobectomy was performed. Case 2 was a 41-year-old male who had suffered from pneumonia many times since his youth. Polycystic and infiltrative shadows were observed on chest CT. After treatment of the pneumonia, a right lower lobectomy was performed. Pathologically, both the cases were diagnosed as CCAM type 1. Although CCAM in adults is very rare, it should be considered in the differential diagnosis of cases with repeated pneumonia due to suspected congenital cystic disease. CCAM is better detectable with chest CT and requires active surgical treatment.

Case series of pleomorphic carcinomas of the lung treated with nivolumab.

Pleomorphic carcinoma (PC) of the lung is a rare type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD-L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59-year-old woman (Case 1), a 66-year-old man (Case 2), and an 83-year-old man (Case 3). PD-L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression-free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD-L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD-L1 is highly expressed.

[Case of MPO-ANCA-positive Wegener's granulomatosis with hepatitis C virus infection].

A 77-year-old Japanese man was referred to our hospital because of the progression of renal dysfunction. Two months prior to the admission he had been diagnosed with otitis media. Urinalysis showed proteinuria and microscopic hematuria. Blood examination revealed renal dysfunction, hepatitis C virus (HCV)infection and positive myeloperoxidase (MPO)-ANCA. A chest CT revealed small infiltrates in the right middle lobe. The renal biopsy demonstrated crescentic glomerulonephritis with tubulitis. He was diagnosed as having Wegener's granulomatosis according to the American College of Rheumatology classification criteria. Methylprednisolone pulse therapy followed by oral prednisolone improved all of the otitis media, lung infiltrates and renal function. Recently, a high prevalence of ANCA has been reported in patients with HCV. It has also been reported that the prevalence of HCV infection is high in patients with Wegener's granulomatosis. Therefore, our case points to the clinical significance of HCV infection in ANCA-associated systemic vasculitis including Wegener's granulomatosis.

Alpha-fetoprotein producing ovarian clear cell carcinoma with a neometaplasia to hepatoid carcinoma arising from endometriosis: a case report.

We present a rare case of alpha-fetoprotein (AFP) producing ovarian clear cell carcinoma. This is the first report of a clear cell ovarian carcinoma with hepatoid carcinoma arising from endometriosis. A 54-year-old menopausal woman had a primary ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IIIc. Serum level of AFP was 4195 ng/mL. Histological examination revealed clear cell adenocarcinoma arising from endometriosis with hepatoid carcinoma. Metastatic liver and lymph node tumors were found after 25 months from the first surgery. However, the patient's serum AFP was within normal limits. The recurrent and metastatic tumors disappeared in response to combined liposomal doxorubicin and carboplatin chemotherapy. She has had a disease-free survival of 4 years. In conclusion, the patient had a clear cell ovarian carcinoma with hepatoid carcinoma arising clearly from endometriosis. The recurrent tumors did not show a component of hepatoid carcinoma. Therefore, it is possible to expect better survival with good sensitivity to chemotherapy.

Overlapped glomerular lesions of chronic rejection and recurrent lupus nephritis in transplanted kidney: a case report.

We describe a renal transplant recipient with systemic lupus erythematosus (SLE) who showed continuous proteinuria and low complement levels without clinical evidence of active SLE. Her first renal allograft biopsy, performed nine yr and eight months after transplantation, revealed unusual histological change of glomeruli, and it initially led us to make a contradictory diagnosis based on light and electron microscopic examinations. Diffuse global double- or multi-contour glomerular basement membrane was caused by chronic endothelial injury owing to chronic rejection, and mesangial proliferation associated with mesangial electron-dense deposit was a histological change characteristic of recurrent lupus nephritis (RLN). Immunofluorescence study displayed weak mesangial staining of IgM and C1q. We concluded that this case presented overlapped chronic rejection and RLN. Because both transplant nephropathy and lupus nephritis present constellations of various histologies, it is difficult to diagnose their overlap. Complete morphologic studies with both immunofluorescence and electron microscopic evaluations in addition to microscopic examination should be performed to elucidate complex histological findings.

Diffuse alveolar hemorrhage in lupus nephritis complicated by microscopic polyangiitis.

Diffuse alveolar hemorrhage (DAH) is a rare but fatal complication in patients with systemic lupus erythematosus (SLE). We describe a case of a 74-year-old woman who presented with DAH as an initial presentation of SLE. She also had microscopic polyangiitis clinically manifesting as crescentic glomerulonephritis and purpura with positive myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCA). The patient transiently improved when treated with plasma exchange and methylprednisolone pulse therapy; however, she died of recurrent pulmonary hemorrhage and concurrent cryptococcal pneumonia. This case indicates that MPO-ANCA is associated with severe organ involvement such as pulmonary hemorrhage and crescentic glomerulonephritis in SLE.

Findings of graft biopsy specimens within 90 days after ABO blood group incompatible living donor kidney transplantation compared with ABO-identical and non-identical transplantation.

As immunosuppressive therapy has advanced, we have markedly improved the outcome of ABO blood group incompatible living donor kidney transplantation. Consequently, graft survival at early phase after ABO-incompatible transplantation has been favorable than ABO-compatible transplantation in Japan. But in these days, it has been assumed that transplant glomerulopathy within one yr after ABO-incompatible kidney transplantation might be significantly precipitated. That may be because of chronic, active antibody-mediated rejection (AMR). We performed kidney graft biopsies at the early phase within 90 d after living donor kidney transplantation that involved the episode and protocol biopsies and studied findings of graft biopsy specimens when compared with ABO incompatible and compatible involving non-identical and identical transplantations. In ABO-incompatible transplant cases, the ratio occurring glomerulitis, especially severe injury of g 2-3, was significantly higher than that of identical and non-identical transplant cases (p < 0.01). There was no significant difference in t score, i score, ptc score and v score between three transplant groups. The cases occurring AMR were concordant with the cases recognized with severe glomerulitis. AMR was difficult to be diagnosed by C4d analysis in ABO-incompatible transplant cases. Glomerular injury score, g score, may be considered as more significant and the injury should be cured thoroughly.

Analysis of preexisting baseline kidney lesions revealed by biopsy in living kidney donors: relationship with clinical parameters at the time of donation.

Because the safety of living organ donors is essential, we have been performing donor kidney biopsy before donation in cases where decision-making regarding suitability is marginal. To clarify the degree to which pathological change in the kidney can be predicted on the basis of clinical data obtained non-invasively, we analyzed preexisting lesions found by one-h biopsy in 76 living kidney donors, and compared the findings with clinical parameters at the time of donation. Pathological change in living kidney donors was correlated to some extent with predonation clinical parameters including age, serum creatinine, estimated glomerular filtration rate and presence of hypertension, while the lesions influenced by glucose intolerance were not completely correlated with the results of oral glucose tolerance test. A follow-up study will be required to determine whether these mild histological findings at the time of donation influence long-term outcome in the donor.

Efficacy of tonsillectomy for patients with recurrence of IgA nephropathy after kidney transplantation.

From January 2007, we started to perform the tonsillectomy for every patient with recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September 2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They had also progressive hematuria or proteinuria from on the average 14.3 months after transplantation. Then their specimens diagnosed as recurrent IgAN were collected and they underwent tonsillectomies on the average 52.3 months after transplantation. Abnormal urinary findings of all patients favorably improved after tonsillectomy. All cases but one had mild renal injury, where the severity of glomerular lesions, glomerular hypercellularity, segmental lesions, and sclerosis was mild, and no deteriorated serum creatinine (SCr) before their tonsillectomies. Even the case with exacerbated SCr and severe renal injury, where the severity of glomerular lesions was severe, had her urinary findings ameliorated promptly after tonsillectomy likely as others. At present, they have almost no symptoms after tonsillectomy and no remarkable change of SCr level compared with before and after tonsillectomy and maintain ameliorated urinary findings continuously. Tonsillectomy had possibility to be a favorable treatment of hematuria or proteinuria in recurrent IgAN recipients.

Histopathologic evaluation of living kidney donor candidates by pre-operative kidney biopsy.

A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.

A case of living-related renal transplant from the donor with membranous nephropathy.

INTRODUCTION: When a patient who had renal replacement therapy becomes older, an elder donor candidate may be considered as a potential donor for living-related transplantation. Elder donor candidate might have pre-existing disease including mild renal dysfunction, such as proteinuria. Marginally appropriate donors might be considered for renal graft because of the shortage of donors. A successful outcome after kidney transplantation from a living-related donor diagnosed as membranous nephropathy is reported. CASE REPORT: A 38-yr-old male had been on continuous ambulatory peritoneal dialysis (CAPD) since the age of 37. His 63-yr-old father had mild proteinuria, and had been diagnosed with membranous nephropathy by needle biopsy at the age of 60. However, renal function of the father was found to be stable for three yr in a preoperative examination for donor; the father had normal renal function except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father, diagnosed with membranous nephropathy, to his son with a cyclosporine A-based immunosuppression regimen. In both the recipient and the donor, postoperative course was stable without complication such as rejection or infection. At 57 months after transplantation, the serum creatine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. At 39 months after transplantation, allograft needle biopsy showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Decreases in electron-dense deposits and electron-lucent washout lesions with thickening of the GBM were observed using electron microscopy. This was diagnosed as Stage IV membranous nephropathy, showing clearance of the immune complexes and histological repair of the GBM. CONCLUSION: Donation of the kidney did not affect the residual renal function of the father with membranous nephropathy. Pre-existing membranous nephropathy itself might show remission after transplantation in the recipient. However, long-term careful observation for both the donor and recipient is required.

Intratumoral heterogeneity of MIB-1 labelling index in gastric gastrointestinal stromal tumor (GIST).

BACKGROUND: The MIB-1 labelling index (LI) is used as a prognostic indicator for gastrointestinal stromal tumors (GISTs). However, whether a biopsy-based LI represents the entire tumor is uncertain, because the LI is not always homogeneous. In this study, we examined the extent and characteristics of LI heterogeneity in gastric GISTs. METHODS: We analyzed ten c-kit-positive gastric GISTs with diameters exceeding 3 cm, of which six were multilobular and four were unilobular. For MIB-1-immunostained sections, continuous digital images were obtained through the maximum diameter of the lobules. We obtained LIs for images by carrying out computer-assisted image analysis, and calculated the means and standard deviations (SDs) of the LIs for the lobules. For each lobule, intralobular heterogeneity was evaluated on the basis of the SD. For multilobular tumors, interlobular heterogeneity was assessed on the basis of the mean LI difference between lobules. RESULTS: The SDs, which ranged from 0.8% to 9.8%, indicated intralobular heterogeneity. Moreover, considerable interlobular heterogeneity was noted in five (83%) of the six multilobular GISTs, in which the maximum interlobular mean LI difference ranged from 9.6% to 27.2%. Notably, although the high maximum mean LI (14.1%-32.3%) showed that these five GISTs were high-grade tumors, they also contained at least one lobule showing a low-grade mean LI value (2.7%-5.1%). CONCLUSION: Gastric GISTs often show intralobular or interlobular MIB-1 LI heterogeneity. In multilobular GISTs, multiple biopsy samples may be required for the accurate evaluation of tumor grade.

Ten-year protocol biopsy findings of renal allografts in the calcineurin inhibitor era.

Ten-year protocol biopsies were performed in 16 patients treated with calcineurin inhibitor (CNI) continuously. All kidney grafts were functioning well at the time of biopsy with the mean serum creatinine level of 1.6 +/- 0.8 mg/dL. The specimen of biopsy showed various degrees of tissue injury. According to the Banff grading, allograft glomerulopathy (cg) was observed in one case. Interstitial fibrosis (ci) and tubular atrophy (ct) were observed more frequently in 13 (81%) and 15 (93%) cases, respectively. Fibrous intimal thickening (cv) was seen in one (7%) case. Arteriolar hyaline thickening (ah) was seen in 14 (87%) cases. These findings were associated with chronic rejection in one case, recurrence of original disease in four (25%) cases, toxicity of CNI in 14 (87%) cases. Longer follow-up studies are needed to confirm whether CNI should be continued or not in the long-term period following kidney transplantation for better graft survival.

A case of non-metastatic giant mucinous carcinoma of the breast.

A surgically resected case of giant mucinous carcinoma of the breast that had remained untreated for 2 years is reported. A 64-year-old postmenopausal woman presented with a large right breast mass (17.4 x 16.5 x 14.5 cm). Although she had noticed a mass in the right breast 2 years previously, she had not sought treatment. Mucinous carcinoma was diagnosed by core needle biopsy and she underwent right modified radical mastectomy with a free skin graft. There were no lymph node metastases or distant metastases. Fourteen months postoperatively, she remains well without evidence of tumor recurrence. Although several reports have suggested that pure mucinous carcinoma of the breast has a favorable prognosis, we need to follow this case until the clinical behavior and the outcome become clear.

Resection of a pelvic schwannoma with partial removal of the sacral nerve root.

Because the symptoms do not appear in most cases until the tumor has grown quite large, schwannomas are often detected incidentally during work-up for some other condition. Benign schwannomas generally do not invade adjacent structures but making the diagnosis preoperatively can be difficult when the tumor is large. We report the case of a benign schwannoma which was diagnosed preoperatively by needle core biopsy under computed tomography guidance. The tumor was removed completely by partially resecting the S1 nerve root, which was subsequently reanastomosed. The postoperative course was uneventful with the exception of minimal left leg pain due to neurologic deficit.