The clinical value of PERCIST to predict tumour response and prognosis of patients with oesophageal cancer treated by neoadjuvant chemoradiotherapy.

AIM: To examine whether Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) is useful to predict tumour response and prognosis of patients with oesophageal cancer who received neoadjuvant chemoradiotherapy (NACRT) followed by surgery. MATERIALS AND METHODS: This multicentre retrospective study included 60 patients with oesophageal cancer who underwent 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (18F-FDG-PET/CT) before and after NACRT prior to surgery from January 2007 and June 2016. The correlation between pathological response and PERCIST was assessed by χ2 test. The prognostic significance was assessed by the Kaplan-Meier method and Cox regression analysis. RESULTS: There were 30 responders and 30 non-responders pathologically. The complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) were seen in 22, 29, seven, and two patients, respectively. There was a significant correlation between pathological response and PERCIST (p<0.001). Forty patients showed eventual progression, and 20 patients were alive without progression between the start of NACRT and last clinical follow-up (median follow-up period; 27 months [range, 3-107]). Pathological stage and PERCIST were significant for progression-free survival (PFS; p=0.044 and 0.006, respectively) and also significant for overall survival (OS; p=0.009 and 0.001, respectively) at univariate analysis. Pathological lymph node staging was also significant for OS at univariate analysis (p=0.018). At multivariate analysis, PERCIST remained significant and independent for PFS (hazard ratio [HR]: 1.59, p=0.046) and OS (HR: 1.82, p=0.008). CONCLUSION: PERCIST may be useful for predicting tumour response and prognosis of patients with oesophageal cancer who received NACRT.

The utility of FDG-PET for detecting multiple primary cancers in hypopharyngeal cancer patients.

AIM: To examine the utility of 2'-[18F]-fluoro-2'-deoxy-D-glucose positron emission tomography (FDG-PET) for detecting multiple primary cancers (MPC) in patients with hypopharyngeal cancer (HPC). PATIENTS, METHODS: Seventy patients with HPC underwent FDG-PET to determine the staging. Routine clinical examinations were carried out, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and oesophagealgastroduodenoscopy (EGDS). The detection rate of synchronous and metachronous cancer was calculated based on FDG-PET alone or FDG-PET combined with clinical routine examination. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and accuracy were used to diagnose oesophageal cancer using FDG-PET. RESULTS: Of the 70 patients, 12 (17.1%) had 15 synchronous tumours, and 2 of the 58 remaining patients (3.4%) had metachronous tumours. Oesophageal cancer was discovered most frequently: superficial type (n=6), advanced type (n=4). On a per-patient basis, 11 of 12 patients (91.6%) were diagnosed with synchronous tumours, and on a per-lesion basis, 12 of 15 lesions (80.0%) were detected by FDG-PET. The sensitivity, specificity, accuracy, PPV, and NPV of FDG-PET regarding oesophageal cancer were 70%, 100%, 95.7%, 100%, and 95.2% respectively. Three of the six superficial types were positive on FDG-PET. Both of the metachronous tumour lesions were detected by FDG-PET. CONCLUSION: FDG-PET is useful for estimating the MPC in HPC patients. Since 3 of 10 synchronous oesophageal cancer were missed with PET alone, a combination with EGDS should be considered to exclude synchronous oesophageal cancer.

Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis.

The most common pathologic form of idiopathic pulmonary fibrosis is usual interstitial pneumonia, which is characterized by patchy fibrotic areas, marked increase in the number of fibroblasts and type II pneumocytes, and excessive deposition of extracellular matrix proteins, especially collagen. Heat shock protein 47 is a collagen-binding stress protein and has a specific role in intracellular processing of procollagen molecules as a collagen-specific molecular chaperone. However, its role in the causation of fibrosis in usual interstitial pneumonia is unknown. In this study, we examined the expression of heat shock protein 47 and type I procollagen in 12 patients with usual interstitial pneumonia by immunohistochemistry on sequential sections. Heat shock protein 47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts and surfactant protein-A-positive type II pneumocytes in active fibrotic areas of usual interstitial pneumonia. Type I procollagen was also expressed in those cells. In contrast, heat shock protein 47 and type I procollagen were weakly or not at all expressed in myofibroblasts and type II pneumocytes in bronchiolitis obliterans organizing pneumonia and normal lung tissue samples obtained from excised lung cancer tissues. The numbers of heat shock protein 47- and type I procollagen-positive cells to type II pneumocytes or myofibroblasts were significantly higher in usual interstitial pneumonia than in bronchiolitis obliterans organizing pneumonia and normal lung tissue specimens. Our results suggest that myofibroblasts and type II pneumocytes play an important role in the progression of fibrosis through the induction of heat shock protein 47, which regulates the synthesis/assembly of type I procollagen in usual interstitial pneumonia. HUM PATHOL 31:1498-1505.

Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Bronchoscopic therapy for mucosa-associated lymphoid tissue lymphoma of the trachea.

The tracheal tumor of a 74-year-old female was detected on bronchoscopy and histologically diagnosed as mucosa-associated lymphoid tissue (MALT) lymphoma. We successfully treated the tumor with endoscopic neodyminum-yttruim-aluminium-garnet (Nd-YAG) laser photoresection followed by local ethanol injection. This is the first case in which tracheal MALT lymphoma was successfully treated with bronchoscopy. Bronchoscopic therapy seems to be one of the most valuable strategies for treatment of MALT lymphomas of the central airway.

Cholesterol emboli following percutaneous transluminal coronary angioplasty as speculated by toe skin biopsy.

A 55-year-old man required hemodialysis for acute renal failure 3 days after repeat percutaneous transluminal coronary angioplasty (PTCA). Bilateral acrocyanosis and necrotic lesions of the toes occurred 10 days after PTCA. Skin biopsy samples revealed needle-shaped cholesterol crystals of the intraluminal clefts in his small arteries. He was diagnosed with cholesterol emboli presenting as blue toe syndrome. The conditions improved with anticoagulation and vasodilation, but improvement in renal function was temporary. He later required maintenance hemodialysis. Cholesterol emboli following PTCA are life threatening because they are difficult to diagnose and can cause severe complications.

[A case of radiation lung injury with characteristics of bronchiolitis obliterans organizing pneumonia after radiation therapy for breast carcinoma].

We report a case of sputum and dyspnea with patchy migratory air space infiltrates that developed in a 49-year old woman after she started breast radiation therapy following surgery for breast carcinoma. Our case clearly differed from ordinary radiation pneumonitis. Chest roentogenography and computed tomographic (CT) scanning demonstrated alveolar opacities. Bronchoalveolar lavage showed a moderate elevation of the total cell concentration and a considerable increase of lymphocytes, and transbronchial lung biopsies revealed a histological pattern of bronchiolitis obliterans organizing pneumonia with intra-alveolar granulation tissue. The present case suggests that breast irradiation may contribute to the development of a histological pattern of bronchiolitis obliterans organizing pneumonia.

[Significance of right precordial ST elevation in experimental right ventricular infarction].

We produced experimental isolated right ventricular infarction (RVI) with closed chest method, and examined ECG changes of right precordial leads and changes of cardiac output (C. O) in 19 dogs. As a result, ECG showed ST depressions in leads, II, III, aVF and V2-V6 and ST elevations in a VR lead in all 15 cases of the proximal occlusion of right coronary artery (RCA). In 10 of 15 dogs ST elevations in some right precordial leads occurred, and the sensitivity of ST elevation in single right precordial lead was 60% (V5R), 53% (V4R) and 47% (V3R and V1), respectively for the detection of RVI. When left circumflex artery (LCX) was occluded, ST elevation in V4R lead after RCA occlusion was blocked. Therefore, it is thought that the sensitivity of ST elevation in right precordial lead may be lower than expectation in identifying RVI. Concerning anterior chest leads, none of 15 dogs with RVI showed ST elevations in leads V2-V6 in this study. If ST elevations in right precordial leads did not appear, variation of C.O was small and C.O reduced in proportion to the extension of ST elevations in right precordial leads.

High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia.

BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.