Predictive value of post-treatment C-reactive protein-to-albumin ratio in locally advanced non-small cell lung cancer patients receiving durvalumab after chemoradiotherapy.

BACKGROUNDS: The PACIFIC trial established durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). However, little is known about the predictive factors of durvalumab efficacy in this population. This study aimed to validate the predictive use of inflammation-related parameters in patients with LA-NSCLC treated with CCRT plus durvalumab. METHODS: We recruited 76 LA-NSCLC patients who received CCRT followed by durvalumab from 10 Japanese institutions. The neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutrition index (PNI) were measured before (pre-treatment) and 2 months after (post-treatment) durvalumab induction. Cox proportional hazards analysis was used to examine prognostic factors associated with progression-free survival (PFS) after durvalumab therapy. RESULTS: The median follow-up time was 17 (range, 3.3-35.8) months. The median PFS and overall survival (OS) times were 26.1 and 33.7 months, respectively. Durvalumab was discontinued in 47 (61.8%) patients, with non-infectious pneumonitis being the most common reason. Post-treatment CAR (cutoff, 0.2) was a significant stratifying factor in survival comparison (<0.2 vs. ≥ 0.2, median PFS, not-reached vs. 9.6 months. Log-rank, p = 0.002). Multivariate analysis with a Cox proportional hazards model showed that post-treatment CAR was an independent prognostic factor for PFS (hazard ratio, 3.16, p = 0.003). CONCLUSIONS: This study suggests that post-treatment CAR has predictive value for LA-NSCLC patients treated with CCRT plus durvalumab consolidation therapy.

Blood urea nitrogen-to-serum albumin ratio and A-DROP are useful in assessing the severity of Pneumocystis pneumonia in patients without human immunodeficiency virus infection.

INTRODUCTION: There is an increasing incidence of Pneumocystis pneumonia (PcP) among individuals without human immunodeficiency virus (HIV) infection (non-HIV PcP). However, prognostic factors for patients with non-HIV PcP have not been identified. Moreover, A-DROP (for classifying the severity of community-acquired pneumonia) or the blood urea nitrogen-to-serum albumin ratio (BUN/Alb), which is reported to be a predictor of mortality of community-acquired pneumonia, has not been established as an efficient prognostic factor in patients with non-HIV PcP. In this study, we analyzed the prognostic factors for non-HIV PcP and evaluated the prognostic ability of A-DROP and the BUN/Alb ratio. METHODS: This retrospective study involved a chart review of the medical records of 102 patients diagnosed with non-HIV PcP between January 2003 and May 2019 at five medical facilities. RESULTS: Overall, 102 patients were involved in this study. The 30-day mortality rate for non-HIV PcP was 20.5% in this study population. Compared with survivors, non-survivors had significantly lower serum albumin levels and significantly higher age, corticosteroid dosage at the PcP onset, alveolar-arterial oxygen gradient, A-DROP score, lactate dehydrogenase levels, blood urea nitrogen levels, and BUN/Alb ratio. Multivariate analysis showed that a high BUN/Alb ratio at treatment initiation was significantly associated with 30-day mortality risk. The receiver operating characteristic curves showed that A-DROP score had the highest prognostic ability in estimating 30-day mortality. CONCLUSIONS: In patients with non-HIV PcP, a high BUN/Alb ratio is an independent prognostic predictor of mortality risk, and A-DROP is useful for classifying the severity.

Comparison of computed tomography findings with clinical risks factors for endoscopic therapy in upper gastrointestinal bleeding cases.

Several risk scoring systems exist for acute upper gastrointestinal bleeding (UGIB). The clinical Rockall score (clinical RS) and the Glasgow-Blatchford score (GBS) are major risk scores that consider only clinical data. Computed tomography (CT) findings are equivocal in non-variceal UGIB. We compared CT findings with clinical data to predict mortality, rebleeding and need for endoscopic therapy in non-variceal UGIB patients. This retrospective, single-center study included 386 patients admitted to our emergency department with diagnosis of non-variceal UGIB by urgent endoscopy between January 2009 and March 2015. Multivariable logistic regression analysis was used to investigate CT findings and risk factors derived from clinical data. CT findings could not significantly predict mortality and rebleeding in non-variceal UGIB patients. However, upper gastrointestinal hemorrhage in CT findings better predicted the need for endoscopic therapy than clinical data. The adjusted odds ratios were 10.10 (95% CI 5.01-20.40) for clinical RS and 10.70 (95% CI 5.08-22.70) for the GBS. UGI hemorrhage in CT findings could predict the need for endoscopic therapy in non-variceal UGIB patients in our emergency department. CT findings as well as risk score systems may be useful for predicting the need for endoscopic therapy.

[Successful Treatment of Squamous Cell Lung Cancer without PD-L1 Expression Using Fourth-Line Nivolumab].

A 71-year-old woman was diagnosed with stage ⅢB locally advanced lung squamous cell cancer(cT0N3M0).Programmed death-ligand 1(PD-L1)immunostaining was negative.First -line nedaplatin plus docetaxel and second-line carboplatin plus nab-paclitaxel were followed by sequential thoracic radiation therapy(60 Gy).The patient developed radiation pneumonitis, but her condition improved with corticosteroids.However, chest computed tomography(CT)revealed multiple nodules in both lungs.Third -line carboplatin plus tegafur/gimeracil/oteracil potassium(S-1)was not successful, and fourth- line nivolumab(3mg/kg every 2weeks)was adopted.On day 9 after first administration, she developed fever and radiation recall pneumonitis.Multiple nodules rapidly formed, but they later gradually decreased in number.After 13 courses of nivolumab, the nodules had disappeared completely.Mediastinal lymph nodes decreased in size, but an abdominal lymph node remained enlarged.Nivolumab was continued, and after 24 courses, the abdominal lymph node began to shrink, and the multiple lung metastases continued to disappear.Currently, the best overall response is good partial response to nivolumab.

Clinical analysis of patients treated with afatinib for advanced non-small cell lung cancer: A Nagano Lung Cancer Research Group observational study.

BACKGROUND: Afatinib has been available in Japan for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) since May 2014. We conducted an observational study in patients treated with afatinib in Nagano prefecture, focusing on response and associated toxicities. METHODS: We analyzed the clinical records of NSCLC patients treated with afatinib between May 2014 and February 2015. RESULTS: The records of a total of 73 patients (27 men, 46 women) with a median age of 69 years (range: 42-85 years) were analyzed. Afatinib was administered to 11 patients as a first-line therapy, but it was predominantly administered as a fifth-line or beyond therapy (32 cases, 43.8%). The overall response rates for afatinib as a first-line therapy and beyond second-line therapy were 80% (95% confidence interval [CI]: 55.2-100.0%) and 27.1% (95% CI: 14.5-39.7%), respectively. The main toxicities grade >3 included diarrhea (8.2%), skin rash (6.8%), nausea (6.8%), and appetite loss (6.8%). A low body surface area (BSA) (<1.5m2) was significantly associated with a higher frequency of diarrhea grade >2, compared with a higher BSA (≥ 1.5m2). Forty-eight patients (63.0%) were treated without a dose reduction of afatinib. CONCLUSIONS: Although the survival benefit with afatinib remains unclear, our observational analysis demonstrated the feasibility of using afatinib for EGFR-mutated NSCLC in clinical practice. In particular, a relatively high level of drug delivery is possible. In addition, a lower BSA may be a predictor of diarrhea in patients treated with afatinib.

Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study.

The clinical efficacy and outcomes of gefitinib therapy as a first-line treatment for elderly patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations were analyzed retrospectively. We analyzed chemotherapy-naïve NSCLC patients aged 75 years or older who had EGFR mutations (exon 19 deletion mutation or L858R), who were initially treated with gefitinib (250 mg) once daily in Nagano Prefecture. A total of 55 patients (16 men, 39 women) with a median age of 81.1 years (range; 75-94 years) treated between April 2007 and July 2012 were analyzed. The overall response rate and disease control rate were 72.7 % (95 % confidence interval (CI); 59.5-82.9 %) and 92.7 % (95 % CI; 82.0-97.6 %), respectively. Median progression-free survival and overall survival from the start of gefitinib treatment were 13.8 months (95 % CI; 9.9-18.8 months) and 29.1 months (95 % CI; 22.4 months-not reached), respectively. Two-year survival rate was 59.5 % (95 % CI; 41.0-78.0 %). Major grade 3 toxicities were skin rash (1.8 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (7.3 %). First-line treatment with gefitinib for elderly EGFR-mutated NSCLC patients was effective and well tolerated. The results suggest that first-line gefitinib should be considered as a preferable standard treatment in elderly patients with advanced NSCLC harboring EGFR mutations.

Phase I/II study of S-1 combined with biweekly irinotecan chemotherapy in previously treated advanced non-small cell lung cancer.

PURPOSE: This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40 mg/m(2) twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle. RESULTS: In the phase I part, irinotecan was given in escalating doses of 70 (Level 1), 80 (Level 2), and 90 mg/m(2) (Level 3). Three of the 5 patients given Level 3 had dose-limiting toxicity, and Level 2 (80 mg/m(2) of irinotecan) was designated as the recommended dose. In phase II, 38 patients received a median of 7.4 cycles of irinotecan at the recommended dose. The overall response rate was 15.8 % (90 % confidence interval (CI): 6.1-25.5 %), and the median progression-free and overall survival times were 4.5 months (95 % CI: 3.5-5.0) and 15.0 months (95 % CI: 9.5-20.6) months, respectively. Toxicity was generally mild. Grade 3 or higher toxicity included neutropenia in 17.9 % of the patients, thrombocytopenia in 5.1 % and nausea in 7.7 %. CONCLUSION: Combination chemotherapy with S-1 and irinotecan was considered an effective salvage regimen in patients with advanced or metastatic NSCLC.

Endoscopic diagnosis of Barrett's esophagus.

The Prague C and M Criteria have been developed for the objective endoscopic diagnosis of Barrett's esophagus (BE). BE arises between the squamocolumnar junction and the gastroesophageal junction at the proximal margin of the gastric folds. In this study, we reported that 43.0% of the subjects examined were diagnosed with BE based on the Prague C and M Criteria. Previous criticism by John Dent proposed that our data should be considered invalid because the prevalence of BE reported in our study was extraordinarily high and discordant with previous studies. Dent predicted that the position of the gastroesophageal junction in our study was judged to be lower than the actual position due to the effacement of the proximal ends of the gastric folds because of the routine use of a high degree of air distension during typical Japanese endoscopic examinations. The endoscopic evaluation of the superior gastric folds is certainly influenced by the degree of air distension of the esophagus. However, in our study, the proximal limit of the gastric mucosal folds was prospectively imaged while the oesophagus was minimally insufflated. Then, under a high level of air distension, the distal ends of the palisade-shaped longitudinal vessels were imaged because they are more easily observed when distended. In the majority of patients, the distal ends of the palisade-shaped longitudinal vessels correspond to the proximal limit of the gastric mucosal folds. Our endoscopic evaluation was appropriately performed according to the Prague C and M Criteria. We suspect that the high prevalence of BE in our study may be due to the inclusion of ultrashort-segment BE, which defines BE with an affected mucosal length under 5 mm, in our positive results.

A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer.

PURPOSE: There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors. METHODS: Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150 mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR). RESULTS: Thirty-one patients (23 men and 8 women; median age, 71 years; range, 31-89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7 months, respectively. CONCLUSION: Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.

Risk factors for mortality in patients with Mallory-Weiss syndrome.

BACKGROUND/AIMS: Although the majority of patients with Mallory-Weiss syndrome (MWS) have a benign course, in some patients MWS results in a fatal outcome. Therefore, this study was carried out to analyze the risk factors for mortality in patients with MWS. METHODOLOGY: The medical records of patients with MWS seen between March 1994 and July 2007 were reviewed retrospectively. The demographic characteristics, clinical and laboratory parameters, and endoscopic findings of the patients were analyzed and the risk factors for mortality were evaluated. RESULTS: A total of ninety-three patients (13 female and 80 male patients; median age, 53 years) were treated. The mortality rate was 9.7% (9/93). The patients with a fatal outcome were of advanced age and had a higher frequency of shock on arrival, lower hemoglobin level, more prolonged prothrombin time, higher AST and ALT levels, higher frequency of detection of exposed vessels on endoscopy, higher frequency of rebleeding, longer hospital stay, and required a larger volume of blood transfusion than those who did not have a fatal outcome. According to the results of a multivariate analysis, the significant risk factors for mortality in the MWS patients were advanced age (OR 1.222, 95% CI 1.015-1.028), very low hemoglobin level (OR 2.137, 95% CI 1.063-4.295), elevated AST level (OR 1.007, 95% CI 1.001-1.013), and presence of the clinical symptom of tarry stool (OR 45.45, 95% CI 1.080-1000). CONCLUSIONS: Intensive care with close monitoring is required for patients of advanced age with a low hemoglobin level, an elevated AST level, and the clinical symptom of tarry stool, since these are of prognostic importance in terms of the mortality in MWS patients.

Solitary Peutz-Jeghers type hamartomatous polyps in the duodenum are not always associated with a low risk of cancer: two case reports.

INTRODUCTION: A hamartomatous polyp without associated mucocutaneous pigmentation or a family history of Peutz-Jeghers Syndrome is diagnosed as a solitary Peutz-Jeghers type hamartomatous polyp. As compared with Peutz-Jeghers Syndrome, Peutz-Jeghers type hamartomatous polyps are diagnosed with a lower risk of cancer and are regarded as a different disorder. CASE PRESENTATION: In case one, we describe an 84-year-old Japanese man with a 14 mm duodenal polyp. Endoscopic mucosal resection was performed and histological examination showed findings suggestive of a hamartomatous polyp with a focus of well-differentiated adenocarcinoma. In case two, we describe a 76-year-old Japanese man who had been treated for prostate, rectal and lung cancer. Upper gastrointestinal endoscopy revealed a duodenal polyp measuring 15 mm in diameter. Endoscopic mucosal resection was performed, and histological examination showed findings suggestive of a hamartomatous polyp. Liver and thyroid cancers were found after the endoscopic treatment. CONCLUSION: Although duodenal solitary hamartomatous polyps are associated with a lower risk of cancer, four patients, including our cases, have been diagnosed with cancerous polyps. Patients with duodenal solitary hamartomatous polyps should be treated by endoscopic or surgical resection and need whole-body screening.

Visceral obesity and the risk of Barrett's esophagus.

It still remains controversial whether simple obesity, as measured by the body mass index (BMI), is an independent risk factor for Barrett's esophagus (BE). Recent studies have shown abdominal obesity, as defined by the waist circumference (WC) and the waist-to-hip ratio (WHR), to be a risk factor for BE, independent of the BMI, with the association between BMI and BE being no longer observed after adjustment for the WC and WHR. Moreover, visceral obesity, as directly measured by the surface area of the visceral adipose tissue (VAT) on abdominal CT images, has also been reported to have an association with the risk of BE. In addition to the mechanical effects of abdominal obesity, that is, increase of the intra- abdominal pressure by the large amount of adipose tissue, circulating factors secreted from the VAT, such as tumor necrosis factor-α, interleukin-6, leptin, and adiponectin, have also been proposed to be pathogenetically linked to BE and esophageal adenocarcinoma. Obesity is associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal obesity, especially visceral obesity. This raises several questions regarding the pathogenesis of obesity-related BE. Larger studies with prospective enrollment of patients are required for further examination of this issue.

Management of acute lower intestinal bleeding: what bowel preparation should be required for urgent colonoscopy?

BACKGROUND/AIMS: The management of acute intestinal bleeding is not standardized. The aim of this study was to determine the most suitable method of bowel preparation for urgent colonoscopy. METHODOLOGY: One hundred and forty patients admitted with acute lower intestinal bleeding (ALIB) to our Hospital (April 1998 to March 2004) were studied. The preparation for colonoscopy consisted, usually, of oral administration of polyethylene glycol (PEG)-salt solution. For elderly patients or for those suspected of bleeding from a sigmoid colon lesion, colonoscopy was performed following glycerin enemas or water enemas. For patients with a suspected rectal lesion or soon after undergoing a polypectomy, colonoscopy was performed without any of the above procedures. RESULTS: Ischemic colitis was the most common cause of bleeding. The overall cecal completion ratio was 41%, compared with 74% in the PEG group. The percentage of those in whom colonoscopy was impossible (poor preparation) was 16% overall, compared with 5% in the PEG group. Endoscopic hematemesis were performed successfully for 26 patients who were mainly postpolypectomy cases or had rectal ulcers. CONCLUSIONS: In urgent colonoscopy, the preparation with PEG-salt solution may improve the patient's outcome. In postpolypectomy patients and those with rectal ulcers preparation was not always needed.

Theoretical insight of physical adsorption for a single component adsorbent+adsorbate system: II. The Henry region.

The Henry coefficients of a single component adsorbent + adsorbate system are calculated from experimentally measured adsorption isotherm data, from which the heat of adsorption at zero coverage is evaluated. The first part of the papers relates to the development of thermodynamic property surfaces for a single-component adsorbent+adsorbate system (Chakraborty, A.; Saha, B. B.; Ng, K. C.; Koyama, S.; Srinivasan, K. Langmuir 2009, 25, 2204). A thermodynamic framework is presented to capture the relationship between the specific surface area (Ai) and the energy factor, and the surface structural and the surface energy heterogeneity distribution factors are analyzed. Using the outlined approach, the maximum possible amount of adsorbate uptake has been evaluated and compared with experimental data. It is found that the adsorbents with higher specific surface areas tend to possess lower heat of adsorption (DeltaH degrees) at the Henry regime. In this paper, we have established the definitive relation between Ai and DeltaH degrees for (i) carbonaceous materials, metal organic frameworks (MOFs), carbon nanotubes, zeolites+hydrogen, and (ii) activated carbons+methane systems. The proposed theoretical framework of Ai and DeltaH degrees provides valuable guides for researchers in developing advanced porous adsorbents for methane and hydrogen uptake.

Theoretical insight of physical adsorption for a single-component adsorbent+adsorbate system: I. Thermodynamic property surfaces.

Thermodynamic property surfaces for a single-component adsorbent+adsorbate system are derived and developed from the viewpoint of classical thermodynamics, thermodynamic requirements of chemical equilibrium, Gibbs law, and Maxwell relations. They enable us to compute the entropy and enthalpy of the adsorbed phase, the isosteric heat of adsorption, specific heat capacity, and the adsorbed phase volume thoroughly. These equations are very simple and easy to handle for calculating the energetic performances of any adsorption system. We have shown here that the derived thermodynamic formulations fill up the information gap with respect to the state of adsorbed phase to dispel the confusion as to what is the actual state of the adsorbed phase. We have also discussed and established the temperature-entropy diagrams of (i) CaCl2-in-silica gel+water system for cooling applications, and (ii) activated carbon (Maxsorb III)+methane system for gas storage.

[A case of pulmonary coccidioidomycosis].

A 32-year-old Japanese woman who had been living in Arizona, United States since two years previously was admitted to our hospital because of an abnormal shadow. Her chest X-ray films revealed a small cavity in the right middle lung field which had not been identified two years ago. The chest CT showed that it was 15 mm in diameter and located in the right S6, and open lung biopsy was performed. Histological examination revealed caseous lesion of the epithelioid granulomas, that contained spherulitic forms of endospores. Fungal cultures demonstrated barrel-shaped arthroconidia. A diagnosis of pulmonary coccidioidomycosis was made.

[Clinical utility of in situ hybridization for diagnosing respiratory tract infection and sepsis].

We studied the clinical utility of in situ hybridization (Hybrisep) in diagnosing respiratory infection and/ or sepsis. Peripheral blood was taken from patients with respiratory infections and suspected sepsis for both routine blood culture and in situ hybridization, and focal samples including sputum, bronchoalveolar lavage, and central and thoracic catheter, were simultaneously examined for bacterial culture. Specimens numbered 46. The clinical diagnosis was 20 cases of septicemia, with 26 specimens diagnosed as respiratory infectious diseases including hospital-acquired pneumonia and pleurisy. Positive cases of in situ hybridization were seen in 19 specimens (41.3%) in all specimens, significantly higher than that in blood culture (17.4%). Respiratory infection showed a high positive rate in in situ hybridization. Interestingly, the bacterial pathogen detected by in situ hybridization was not always consistent with that taken from focal samples. Whether the pathogen isolated by in situ hybridization is accurate etiologically or diagnostically remains unknown, but our findings suggest a polymicrobial infection in patients with hospital-acquired respiratory infections. In situ hybridization thus provides important information on the etiological pathogen in different infectious diseases.