The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia

BACKGROUND: The prognosis of pulmonary fibrosis associated with scleroderma (PF-SSc) has been reported to be significantly better than that of IPF. Because the nonspecific interstitial pneumonia-pattern (NSIP), a newly defined subgroup of idiopathic interstitial pneumonias (IIP), has better prognosis than the usual interstitial pneumonia pattern (UIP), we postulated that NSIP may occur more frequently than UIP in patients with scleroderma who develop fibrosis. METHOD: We reviewed the pathologic, radiologic and clinical outcomes in 19 patients with PF-SSc. Two pulmonary pathologists reclassified the histopathology of surgical lung biopsies (SLBx) and consensus diagnosis was achieved in all patients. RESULTS: Thirteen patients had NSIP, five had UIP, and remained one showed only nondiagnostic honeycombing. No significant difference was noted in the initial pulmonary function test (PFT), bronchoalveolar lavage (BAL) findings, or other clinical parameters between UIP and NSIP groups. Comparison of the clinical outcome of 12 patients who were followed for more than 12 months (mean: 34.5 +/- 26.0 months) suggested a better prognosis for NSIP than UIP. Five of the eight NSIP patients improved and three were stable, whereas in patients with UIP, one worsened and three were stable. CONCLUSION: NSIP seems to be the major histopathologic pattern in patients with PF-SSc.     

Histopathological approach to patterns of interstitial pneumonia in patient with connective tissue disorders

It is well established that some patients with connective tissue disorders will suffer from pulmonary disease at some stage in their disease progression. This article concentrates on the interstitial pneumonias, seen in association with most types of connective tissue disorder, particularly in the ligh of non-specific interstitial pneumonia (NSIP) being recognised as a distinct histological pattern. Most published articles on this subject precede recognition of NSIP and, as such, the relative incidence of patterns of interstitial pneumonia, as defined by the International Consensus Classification Committee for Interstitial Lung Disease (ICCILD), as well as the clinical and prognostic significance of these patterns is undergoing further scrutiny. In this review, the recognised histological patterns, namely usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), organising pneumonia (OP), reactive pulmonary lymphoid hyperplasia, desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RBILD) are reviewed systematically in relation to the various subgroups of connective tissue disorders. As yet, there are few published studies, but current evidence suggests that many cases previously classified as fibrosing alveolitis are likely to show a pattern of NSIP rather than UIP, particularly in relation to systemic sclerosis. The histological pattern of usual interstitial pneumonia, the most frequently seen pattern in biopsies from patients with idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis, appears to be comparatively rare. Furthermore, any biopsy showing a combination of histological patterns, a pattern of non-specific interstitial pneumonia or a pattern of lymphoid interstitial pneumonia/follicular bronchiolitis should be thoroughly investigated for a background connective tissue disorder, if previously unsuspected. Finally, the recently published prognostic data relating to these histological patterns in idiopathic disease should not be extrapolated to patients with connective tissue disorders.     

Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias

BACKGROUND AND AIM OF THE STUDY: Idiopathic interstitial pneumoniae (IIPs) are characterized by fibroblast proliferation, extracellular matrix deposition and progressive lung function impairment. Because effective therapeutic strategies still remain limited, research has been directed toward the identification of novel targets for additional therapeutic options. The neurotrophins (NTs) nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, beside their importance in nervous, endocrine and immune system activities, participate in chronic inflammatory disorders and in repair processes. METHODS: We have investigated NT and high and low affinity NT receptor expression in IIPs using immunoblots and immunohistochemistry. Fourteen idiopatic pulmonary fibrosis/usual interstitial pneumoniae (IPF/UIP), eight non specific pneumoniae (NSIP) and eight respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) were analyzed. RESULTS: Immunoblots revealed that NT and high affinity NT receptor proteins were more abundantly expressed in IPF/UIP than NSIP and RB-ILD patients. In RB-ILD, a faint expression of NT-3 and NT receptors were detected. NT and NT receptor immunostaining was detected in interstitial cells from IPF/UIP, NSIP and RB-ILD patients by immunohistochemistry. Fibroblastic foci in IPF/UIP strongly stained for BDNF and its high affinity receptor TrkB and in lesser amount for NGF, NT-3 and their respective high affinity receptors TrkA and TrkC. Furthermore, in fibroblast culture derived from IPF/UIP patients, the proliferation rate of primary culture and clones derived from primary lines was stimulated by BDNF but down regulated by NT-3. In contrast, NGF did not influence IPF/UIP fibroblasts proliferation. CONCLUSIONS: Our data suggest that that NTs may exert differential activities on lung fibroblasts and may be considered as potential regulatory molecules influencing fibroblast behavior in IPF/UIP patients. Therefore, NTs may play a role in IIPs patho-physiology representing novel potential therapeutic targets.     

Histologic prognostic factors for small-sized squamous cell carcinomas of the peripheral lung

OBJECTIVE: Although the incidence of peripheral squamous cell carcinomas (SqCCs) of the lung has increased over recent years, histologic prognostic factors for small peripheral SqCCs have not been well established. The aim of this study is to identify clinicopathologic prognostic factors. MATERIALS AND METHODS: We evaluated various clinicopathologic parameters in 101 patients with peripheral lung SqCCs (defined as tumors located in or more peripheral to the fourth branching bronchus), measuring < or = 30 mm in diameter. RESULTS: Multivariate analysis showed that the size of the minimal tumor nest (MTN), a background of usual interstitial pneumonia (UIP) and lymph node metastasis were significant prognostic factors. MTN sizes were defined as large (>6 tumor cells), small (2-5 tumor cells) or single cell. The 5-year disease-free survival rate was significantly worse in patients with single cell nests (50 patients, 69.5%) than in those with small nests (42 patients, 94.1%) (P = 0.0035, log rank test). The MTN size had a significant impact on survival in patients with pathologic stage IA disease and tumors < or = 20 mm in diameter. A background of UIP, which correlated with the presence of a single cell invasive component and pleural involvement, was also a poor prognostic factor, suggesting that peripheral SqCC in UIP is highly malignant even if the tumor is small. CONCLUSION: The MTN size is a useful prognostic factor for small peripheral SqCCs. Tumors with a single cell invasive component appear to be highly malignant, and should be distinguished from invasive cancers with a low malignant potential (tumors with large or small tumor nest components).     

Which prognostic indicator should we use for clinical practice in the initial evaluation and follow-up of IIP: should we depend on PFT, HRCT or...what?

Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.     

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias

Background and aim:Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF.Methods:We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500–1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital.Results:This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3–5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02–0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06–1.33, p < 0.01) were independently associated with 90-day mortality.Conclusions:The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).     

Phenotypic clusters and survival analyses in interstitial pneumonia with myositis-specific autoantibodies

Background:Idiopathic inflammatory myopathy (IIM) is highly combined with interstitial pneumonia (IP), often as the initial or solo presentation with positive myositis-specific autoantibodies (MSAs) but does not fulfill the diagnostic criteria.Objectives:We aimed to explore the phenotypic clusters and prognosis of the patients with IP and positive MSA, which is called MSA-IP in the present study.Methods:A total of 178 patients with MSA-IP were prospectively enrolled for analysis. Serum MSAs were detected using Western blotting. Radiological patterns of IP were determined according to the classification of idiopathic IPs. Clusters of patients with MSA-IP were identified using cluster analysis. Predictors for acute/subacute onset, therapeutic response, IP progression and survival were also analyzed.Results:Patients with MSA-IP were classified into four distinct clusters. Cluster 1 were the elderly with chronic onset, nearly normal oxygenation and good survival. Cluster 2 had dyspnea on exertion and nonspecific IP pattern, with moderate survival. Patients in cluster 3 had chronic onset and were prone to IP progression (OR 2.885). Cluster 4 had multi-systemic involvements, positive anti-melanoma differentiation associated gene 5 antibody, and were prone to acute/subacute onset (OR 3.538) and IP progression (OR 5.472), with poor survival. Corticosteroids combined immunosuppressants showed therapeutic response in MSA-IP (OR 4.303) and had a protective effect on IP progression (OR 0.136).Conclusions:Four clusters of the patients with MSA-IP suggested the distinct clinical, radiological and prognostic features.     

The safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small cell lung cancer with idiopathic interstitial pneumonias

Background

Idiopathic interstitial pneumonias (IIPs) are one of the most common complications in patients with lung cancer. In lung cancer patients with IIP, the most serious toxicity is acute exacerbation of IIP caused by anticancer treatment in Japan. However, there has been no consensus and no evidence presented, regarding optimal treatment for advanced lung cancer with IIP.

Patients and methods

Chemotherapy-naïve patients of inoperable stage, or post-operative recurrent non-small cell lung cancer (NSCLC) with IIPs were enrolled. Patients received paclitaxel at a dose of 100 mg/m² on Days 1, 8, 15, and carboplatin every 28 days at a target dose of area under the curve (AUC) 5.0 on Day 1.

Results

Between May 2004 and October 2008, 18 patients, including 6 with idiopathic pulmonary fibrosis (IPF), were enrolled and treated for a median of four cycles (range, 1-6). One patient (5.6%; 95% confidence interval (CI), 0-17%) with histologically confirmed IPF had acute exacerbation of IIPs associated with the treatment. The overall response rate was 61% (95% CI, 36-86%). The median progression-free survival, median survival time, and 1-year survival rate were 5.3 months, 10.6 months, and 22%, respectively.

Conclusion

This is the first report indicating that advanced NSCLC patients with IIP may benefit from chemotherapy. Weekly paclitaxel and carboplatin combination chemotherapy was as effective as conventional regimens in advanced NSCLC patients without IIP and was safer than previously reported for NSCLC patients with IIP. The results from this study would support, on ethical grounds, the conduct of a large-scale study to confirm the feasibility of this regimen.     

Interstitial pneumonia--diagnosis and therapy

Interstitial pneumonia is defined as a fibrotic lung disease in which the main lesion sites are in the alveolar interstitium, and develops into respiratory failure due to progression of fibrosis. Idiopathic interstitial pneumonia comprises seven types of different clinico-radiological-pathological disease entities. Among them, idiopathic pulmonary fibrosis (IPF) in which the histology is characterized as usual interstitial pneumonia (UIP) has a worse prognosis, and the histology is fundamentally different from other types of disease entities in terms of fibrotic nature. However, the histology of UIP shows a better prognosis when associated with collagen vascular diseases. Here, we attempt to review the whole spectrum of interstitial pneumonia, its classification, differential diagnosis, prognosis, and therapeutic problems.     

B细胞非霍奇金淋巴瘤患者应用R-CHOP方案化疗后发生间质性肺炎的危险因素和临床特征

背景与目的：由于利妥昔单抗(rituximab)在B细胞非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)中的广泛应用,与其相关的间质性肺炎(interstitial pneumonia,IP)陆续报道,后者诊断和治疗的特殊性越来越受到重视。本研究探讨B细胞NHL患者在应用利妥昔单抗联合环磷酰胺+多柔比星+长春新碱+泼尼松(R-CHOP)方案化疗后发生IP的危险因素和临床特征,以期分析早期诊断的方法和有效治疗手段。方法：回顾性分析徐汇区中心医院肿瘤科103例初治的B细胞NHL的临床资料,其中61例接受R-CHOP方案化疗,42例接受CHOP方案化疗。结果：初治接受R-CHOP方案化疗后IP的发生率显著高于单用CHOP方案化疗(14.8% vs 2.4%,Ρ＜0.05)。R-CHOP方案组男性吸烟(38.1% vs 2.5%)、有B症状(发热、盗汗、6个月内体重减轻10%,33.3% vs7.0%)的患者发生IP的发生率明显增高(Ρ＜0.05)。IP的主要症状是发热、胸闷和干咳,胸部CT检查目前是主要诊断依据。10例IP患者全部使用激素联合抗菌药物治疗,9例患者症状和肺部体征明显改善,1例患者因出现严重的并发症和混合性感染治疗无效而死亡。R-CHOP组发生IP患者与未发生IP患者比较化疗前T淋巴细胞亚群各项指标无明显差异;化疗后CD4、CD4/CD8值呈现下降趋势,但差异无统计学意义(Ρ＞0.05),CD8值(化疗前37.11±8.87,化疗后42.44±6.52)则明显增高(Ρ＜0.05)。结论：B细胞NHL患者在应用R-CHOP方案化疗后应警惕IP的发生,尤其是吸烟、有B症状的患者。早期诊断和激素治疗可明显改善患者症状。化疗前、后监测T细胞亚群有一定临床指导意义。     

Low Body Mass Index Is an Independent Predictive Factor after Surgical Resection in Patients with Non-Small Cell Lung Cancer

Background: The effect of body mass index (BMI) on postoperative survival in non-small cell lung cancer (NSCLC) has been controversial. We retrospectively analysed the effect of preoperative BMI on postoperative outcomes of NSCLC surgery. Methods: Consecutive 384 NSCLC patients were enrolled. Patients were subdivided into 3 groups: low BMI group (BMI2), normal BMI group (BMI=18.5-24.0 kg/m2) and high BMI group (BMI>24.0 kg/m2). The prognostic significance of BMI was examined retrospectively. Results: The 5-year survival of patients with low, normal and high BMI groups were 46.3%, 74.3% and 84.3%, respectively. The low BMI group had a poorer prognosis than the other groups (p<0.001). The survival of high BMI group had a more favorable trend than that of normal BMI group, but this did not reach statistical significance (p=0.057). On multivariate analysis, significant risk factors for cancer-specific survival were male gender (p=0.0061), non-adenocarcinoma histology (p=0.0003), pN1-2 status (p=0.0007), high serum CEA level (p<0.0001) and low BMI (low vs. others: p <0.0001). Conclusions: Preoperative BMI is an independent prognostic factor for NSCLC patients after surgical resection, with low BMI patients having an unfavorable prognosis.     

MPO-ANCA positive interstitial pneumonia: Current knowledge and future perspectives

Although interstitial pneumonia is an important respiratory manifestation in microscopic polyangiitis (MPA), no studies have examined the detailed pathogenesis of interstitial pneumonia during the clinical course of MPA. In addition, it is considered that MPA develops at a certain incidence rate from myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positive interstitial pneumonia. However, there is a lack of consensus among pulmonologist and rheumatologist regarding whether MPO-ANCA positive interstitial pneumonia, which does not accompany other organ damage related to ANCA-associated vasculitis (AAV) other than interstitial pneumonia, should be included in AAV. In this review article, the clinical questions regarding MPO-ANCA positive interstitial pneumonia have been set, and evidence to date and problems to be solved in future are outlined.     

Chronic interstitial pneumonia with honeycombing in coal workers

BACKGROUND: Coal worker's pneumoconiosis (CWP) results from coal mine dust inhalation. PATIENTS AND METHODS: We report here the presence of a chronic interstitial pneumonia (CIP) with honeycombing in 38 cases of coal miners, with or without CWP. The 38 patients were selected on the basis of clinical criteria which are unusual in CWP, i.e. fine inspiratory crackles and severe dyspnea. There were 37 men and one woman; mean age was 67.5 +/- 9.1 years. Thirty-two were smokers. Duration of exposure was 26.7 +/- 9.9 years. All the patients had clinical examination, chest radiography, computed tomography (CT), lung function, laboratory investigations, wedged fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In eight cases, lung specimens were obtained (lung biopsy n = 6, explanted lungs n = 2). RESULTS: Seventeen out of 38 had finger clubbing. 17 had radiological signs of CWP limited to the upper lobes (n = 11) or diffusely distributed (n = 6). CT showed honeycombing (36 cases), and/or ground glass opacities (30 cases) with traction bronchiectasis (8 cases) predominant in the lower lobes. BAL analysis demonstrated an increased percentage of neutrophils (9.4% +/- 6). Lung function showed a restrictive pattern (TLC = 75.1% +/- 16 and FVC = 79.7% +/- 17 of predicted values) associated with a decreased DLCO (50.4 % +/- 22.9 of predicted values) and hypoxemia (at rest = 65.9 mmHg +/- 13.5, upon effort = 56.5 mmHg +/- 13.4). Lung specimens demonstrated in 2 cases a homogenous interstitial fibrosis of intra-alveolar septum with an accumulation of immune and inflammatory cells without temporal variation and with obvious honeycombing. The 6 other cases showed features of usual interstitial pneumonia. CONCLUSION: In presenting these cases, we would like to alert other clinicians to a possible association between CIP with honeycombing and coal dust exposure, with or without associated CWP.     

Prognostic role of pneumonia in supracricoid and supraglottic laryngectomies

The goal of this study was to identify host and tumour factors associated with postoperative pneumonia (PP) in a selected population of laryngeal cancer patients, treated by partial laryngectomy in 20 years at our Institution and to assess its potential prognostic impact. Clinical records of 416 consecutive patients were retrospectively reviewed. Tobacco consumption, body mass index (BMI), previous pulmonary disease, age, sex, preoperative blood gas analysis values, tumour stage and type of surgery were tested as potential risk factors for PP. Finally, the prognostic impact of these variables, including PP, in terms of disease-free and actuarial survival by Kaplan-Meier and Cox analyses were evaluated. PP developed in 73 patients (16.8%). We identified two groups of patients: 26 patients experienced an early PP within the first 7-9 days after surgery, whilst 44 experienced an ab ingestis PP following attempts of oral food intake restoration, three patients died for PP related sepsis. At multivariate Cox analysis, age older than 60 years and BMI greater than 30 were statistically associated with early PP; whereas male gender and laryngectomy with neck dissection were statistically related to a higher risk of ab ingestis PP. Interestingly, the occurrence of early PP was a negative independent prognostic factor for 5-years disease-free and actuarial survival (p=0.049 and p=0.001, respectively). The occurrence of early-onset pneumonia in laryngeal cancer patients selected for conservative laryngectomies is predictable and associated with poor clinical outcome.     

Clinical features,anti-cancer treatments and outcomes of lung cancer patients with combined pulmonary fibrosis and emphysema

Background

Combined pulmonary fibrosis and emphysema (CPFE) patients may be at significantly increased risk of lung cancer compared with either isolated emphysema or pulmonary fibrosis patients. Acute exacerbation (AE) of interstitial lung disease caused by anticancer treatment is the most common lethal complication in Japanese lung cancer patients. Nevertheless, the clinical significance of CPFE compared with isolated idiopathic interstitial pneumonias (IIPs) in patients with lung cancer is not well understood.

Methods

A total of 1536 patients with lung cancer at Nippon Medical School Hospital between March 1998 and October 2011 were retrospectively reviewed. Patients with IIPs were categorized into two groups: (i) CPFE; IIP patients with definite emphysema and (ii) non-CPFE; isolated IIP patients without definite emphysema. The clinical features, anti-cancer treatments and outcomes of the CPFE group were compared with those of the non-CPFE group.

Results

CPFE and isolated IIPs were identified in 88 (5.7%) and 63 (4.1%) patients respectively, with lung cancer. AE associated with initial treatment occurred in 22 (25.0%) patients in the CPFE group and in 8 (12.7%) patients in the non-CPFE group, irrespective of treatment modality. Median overall survival (OS) of the CPFE group was 23.7 months and that of the non-CPFE group was 20.3 months (P = 0.627). Chemotherapy was performed in a total of 83 patients. AE associated with chemotherapy for advanced lung cancer occurred in 6 (13.6%) patients in the CPFE group and 5 (12.8%) patients in the non-CPFE group. Median OS of the CPFE group was 14.9 months and that of the non-CPFE group was 21.6 months (P = 0.679).

Conclusion

CPFE was not an independent risk factor for AE and was not an independent prognosis factor in lung cancer patients with IIPs. Therefore, great care must be exercised with CPFE as well as IIP patients when performing anticancer treatment for patients with lung cancer.     

Current status and measures for lung injuries in cancer treatment

The current status and measures for anticancer drug-induced lung injury and radiation pneumonia in cancer treatment were reviewed. Interstitial pneumonia induced by anticancer drugs is pathologically classified into the following: chronic interstitial pneumonia (CIP) or nonspecific interstitial pneumonia (NSIP), eosinophlic pneumonia (EP), bronchiolitis obliterans-organizing pneumonia (BOOP), diffuse alveolar damage (DAD), and hypersensitivity pneumonia (HP). In these pulmonary reactions to anticancer drugs, interstitial pneumonia manifested by DAD, which shows the acute or chronic clinical course, presents high mortality rates. Therefore, special care should be taken when DAD develops. Radiation pneumonia has two clinical phases, an acute phase of injury termed radiation pneumonitis, and a chronic phase of injuring termed lung fibrosis. It is usually confined to the irradiated area. On the other hand, sporadic radiation pneumonitis occurring outside the irradiated area has been reported besides classic radiation pneumonitis. Pathologically, it shows lymphocytic alveolitis or BOOP. Although radiation pneumonia has a good prognosis, mortality is rarely observed when lesion spreads outside the irradiated area.     

Clinical significance of immunophenotype in diffuse non-Hodgkin's lymphoma: with special emphasis on the clinical characteristics of T-cell lymphoma

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas (NHL) is still controversial. Therefore, we evaluated the prognostic significance of T- and B-cell phenotype in 102 patients having diffuse non-Hodgkin's lymphoma who had been treated in a majority with Adriamycin-containing regimens. The significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of markedly elevated LDH (greater than or equal to X 2 normal) and the lower frequency of decreased cholesterol level in B-NHL (p less than 0.05). Patients with B-NHL had a higher complete remission (CR) rate (77% vs 59%: p = NS), a significantly better overall survival (62% vs 34% at 3-years: p less than 0.05) and longer duration of remission for all patients (50% vs 27% at 3-years: p less than 0.05). Among forty-five patients with stages III and IV disease of nodal origin (excluding those with diffuse small cleaved histology), the B-cell group was associated with a better prognosis; a higher CR rate (68% vs 41%: p = NS) and a longer duration of remission for all patients (44% vs 12% at 2-years: p less than 0.05). Furthermore, for patients with T-cell phenotype, the primary site was the only prognostic factor; the patients whose disease originated from Waldeyer's ring, nasal cavity, and paranasal sinuses, achieved a better CR rate (92% vs 40%: p less than 0.05) and a longer duration of remission for all patients (48% vs 15% at 2-years: p less than 0.05). We conclude that advanced T-cell lymphoma of nodal origin is a subgroup of patients with very poor prognosis if treated with less intensive chemotherapeutic regimens.     

Clinical significance of procalcitonin in critically ill patients with pneumonia receiving bronchoalveolar lavage

Background:As a useful tool in intensive care units (ICU), fiberoptic bronchoscopy (FOB) may cause a deterioration of infection. This study is to investigate the clinical significance of procalcitonin (PCT) in critically ill patients with severe pneumonia receiving bronchoalveolar lavage (BAL).Methods:A retrospective case-control study was performed in a single respiratory ICU (RICU) with 6-bed. Critically ill patients with severe pneumonia admitted to RICU were consecutively reviewed from March 2017 to October 2019. Chi-square test, Wilcoxon test, Mann Whitney U-test, Kaplan–Meier survival analysis or Cox’s proportional hazards regression model was used as appropriate.Results:A total of 72 eligible patients were included in the final analysis, 51 of which received BAL performed by FOB. Serum levels of PCT in group received BAL is markedly increased at 24 hours after FOB (p<0.001). Forty-eight hours later, BAL group with decreased serum levels of PCT had less SOFA score and decreased mortality compared with those with increased serum levels of PCT. Furthermore, Kaplan-Meier analysis indicated that patients with decreased serum levels of PCT had improved survival rate during hospital (Breslow test, p=0.041). However, increased PCT after BAL was not an independent risk factor for in-hospital mortality (hazard ratio: 1.689, 95% CI(0.626 ,4.563), p=0.301).Conclusions:BAL performed by FOB increased serum levels of PCT. However, PCT levels decreased at 48 hours after BAL predicted a good prognosis of patients with severe pneumonia.     

Prognostic significance of p27(kip-1) expression in colorectal adenocarcinomas is associated with tumor stage.

PURPOSE: Although the decreased expression of p27(kip-1), a cyclin-dependent kinase inhibitor, has been correlated with advanced tumor stage and short survival of patients with colorectal adenocarcinomas (CRCs), its prognostic value based on the tumor site, tumor stage, and patient ethnicity was not assessed. Therefore, in this study, we investigated whether the prognostic value of p27(kip-1) expression varies with the tumor site, tumor stage and patient ethnicity. EXPERIMENTAL DESIGN: We evaluated 206 (85 African Americans and 121 Caucasians) archival tissue specimens of first primary CRCs for immunohistochemical expression of p27(kip-1), and its prognostic significance was analyzed using univariate Kaplan-Meier and multivariate Cox regression survival methods. RESULTS: Although, similar proportion of CRCs with decreased p27(kip-1) expression was observed in all stages (range, 26-36%), the decreased p27(kip-1) expression has been shown as a marker of poor prognosis only for patients with stage III tumors both in univariate (log-rank test, P = 0.014) and multivariate (hazard ratio = 3.2, 95% confidence interval = 1.3-7.7; P = 0.01) survival analyses. The decreased expression of p27(kip-1) was associated with a high histologic grade (P = 0.016) in stage II CRCs, and with distal tumors (P = 0.001), tumor invasion (P = 0.044), and with local recurrence (P = 0.008) in stage III CRCs. CONCLUSIONS: No prognostic significance was found for p27(kip-1) expression in stages I, II, or IV CRCs, and its prognostic value was not associated with either ethnicity or tumor location. These studies suggest that decreased expression of p27(kip-1) is an indicator of poor prognosis and aids in identifying a subset of patients with aggressive forms of stage III CRCs.