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Objectives  Descending necrotizing mediastinitis (DNM) is a poor prognosis disease. This study aims to examine the patient background and treatment of DNM and to identify more effective treatments for DNM. Methods  The patient background and treatment of 11 patients who underwent surgery for DNM between November 2010 and June 2021 were studied. The patients were divided into six patients who underwent continuous saline irrigation (group I) and five patients who did not (group N). The differences in the drainage duration and length of hospital stay between the two groups were retrospectively investigated. Results  Eleven patients were treated for DNM: six male and five female, with a median age of 61 years (35-79). Comorbidities included diabetes mellitus in three cases; one patient was administered steroids. The pathways of occurrence were anterior tracheal gap/vascular visceral gap/posterior visceral gap in group I (2/1/2) and group N (0/2/4). Progression was I/IIA/IIB according to Endo's classification in group I (1/1/4) and group N (3/1/1). The mean duration of irrigation was 9.0 ± 3.7 days, and the drainage duration in group I was 17.5 ± 8.2 days, which was significantly shorter than 31 ± 13.6 days in group N ( p  < 0.048). The hospital stays in group I was 29.3 ± 8.4 days, which was significantly shorter than that in group N (68 ± 27.1 days; p  < 0.015). Conclusions  Irrigation therapy significantly shortened the drainage duration and hospital stay. Irrigation is a useful treatment for DNM., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Purpose: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose-response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA)., Methods: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other "special-type" cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve., Results: Hormesis was observed in 9 of the 22 cases; ED 50 of cytotoxic effect was significantly higher ( P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 μg/mL)., Conclusion: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Context: Nonislet cell tumor hypoglycemia (NICTH) is a rare but serious paraneoplastic syndrome associated with large tumors. The high molecular weight IGF2, known as "big" IGF2, is produced by culprit tumors and leads to severe hypoglycemia. The detailed mechanism of its production in NICTH, however, remains unclear., Objective: To clarify the mechanism of production of big IGF2 in light of the processing of pro-IGF2 in patients with solitary fibrous tumor (SFT) and NICTH., Design: We enrolled 14 patients with SFT and divided them based on the presence or absence of hypoglycemia. In light of the processing of pro-IGF2 in SFT with hypoglycemia, we, retrospectively, compared the production levels of big IGF2 and the expression levels of IGF2 and proprotein convertase subtilisin/kexin type 4 (PCSK4), a proteolytic enzyme of pro-IGF2., Results: In all patients with NICTH, big IGF2 was detected in serum by western immunoblotting analysis. Moreover, we showed that two patients without hypoglycemia also had a small amount of big IGF2 in their serum. By immunohistochemical analysis, the protein expression level of IGF2 was significantly higher in the NICTH group than in the non-NICTH group (P = 0.043). The IGF2/PCSK4 protein expression-level ratio in the NICTH group was significantly higher than that in the non-NICTH group (P = 0.021)., Conclusion: In patients with SFT and hypoglycemia, an imbalance of IGF2 and PCSK4 expression could lead to increased serum levels of big IGF2.

Background: The benefits of continuing bevacizumab (BEV) beyond progressive disease (PD) in patients with non-small cell lung cancer (NSCLC) remain unclear. We present our experience of continuing chemotherapy with BEV in patients with recurrent NSCLC after surgery., Patients: From January 2010 to December 2016, chemotherapy with BEV was continued beyond PD in 20 patients. These patients included 10 men and 10 women, and their mean age at surgery was 71±10 years. Recurrence was observed at 630±460 days after surgery., Results: The average number of protocols with BEV was 3±1 (1-6). The presented side effects were acceptable. Eight patients died of cancer. The 5-year survival rates after surgery, recurrence, and initiation of BEV were 78.8%, 50.1%, and 34.3%, respectively, and the median survival times were 2,465, 2,017, and 1,120 days, respectively., Conclusion: The majority of patients with operable NSCLC had a good performance status. We could detect recurrence early on, before the symptoms appeared, by regular examination. Therefore, these patients had an advantage in that more chemotherapeutic regimens could be administered to them and their prognosis could be improved by the continuation of BEV beyond over PD.

Fistula between the trachea and esophagogastric anastomosis after esophagectomy is rare. We successfully treated a 75-year-old woman with such a lesion by single-stage repair. The patient had undergone radical esophagectomy 20 years ago, and repeatedly developed aspiration pneumonia for recent 5 years. Radiological and endoscopic examinations demonstrated the fistula between the trachea at the level of sternal notch and esophagogastric anastomosis. The fistula was separated and the defects on both sides were closed. A sternocleidomastoid muscle flap was inserted between the two structures. The postoperative course was uneventful.

In the present article, we quantitatively evaluated the dose-response relationship of hormetic reactions of anticancer agents in vitro. Serial dilutions of gemcitabine, cisplatin, 5-fluorouracil, vinorelbine, and paclitaxel were administered to the A549 non-small-cell lung cancer cell line. The bi-phasic sigmoidal curve with hormetic and cytotoxic effects is given by the formula y=(a-b/(1+exp(c(*)log(x)-d)))/(1+exp(e(*)log(x)-f)), that was used to perform a non-linear least square regression. The dose-responses of the five anticancer agents were fitted to this equation. Gemcitabine and 5-fluorouracil, which had the lowest ED50 for their hormetic reaction, had the most pronounced promotive effects out of the five anticancer agents tested. The hormetic reaction progressed exponentially with culturing time. Our theoretical model will be useful in predicting how hormetic reactions affect patients with malignant tumors., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: In order to clarify whether class III beta-tubulin (TUBB3) is a predictive marker for paclitaxel (PTX) chemotherapy, chemosensitivity was examined using an in vitro drug sensitivity assay., Patients and Methods: Twelve specimens from non-small cell lung cancer (NSCLC) patients were obtained for dose-response curve analysis and measurement of the half-maximal effective dose (ED50) of PTX using the histoculture drug response assay (HDRA). Forty-one specimens were evaluated using the HDRA and the inhibition ratio (IR) at a concentration of 25 μg/ml PTX (IR25) was measured. TUBB3 expression was evaluated by H-score in immunohistochemical staining., Results: The ED50 of PTX was 24.5 ± 8.06 μg/ml. The median H-score was significantly higher (p=0.0076) in the high effective dose (HE)-group (ED50 >25 μg/ml) than in the low effective (LE)-group (ED50 ≤ 25 μg/ml). The mean IR25 was 53.8 ± 26.6%. The median H-score for the high-inhibition ratio (HI)-group (IR25 >50%) was significantly higher (p=0.0337) than the low-inhibition ratio (LI)-group (IR25 ≤ 50%)., Conclusion: High TUBB3 expression in NSCLC appeared to correlate with lower PTX sensitivity., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Purpose: The outlines of primary lung cancers are more complicated than those of metastatic lung tumors on computed tomography (CT) images. This feature is useful for clarifying the diagnosis of pulmonary nodules before surgery. We applied fast Fourier transform (FFT) analysis for quantification of complexity of tumor outline., Methods: Sequential cases of 72 primary lung cancers (Group PL) and 54 metastatic lung tumors (Group MT) were included. The outline of each tumor on chest CT images was described using polar coordinates, and converted to rectangular coordinates, yielding wave data of the tumor outline. The FFT was then used to analyze the wave data. The complexity index (Cxi) was defined as the sum of the amplitude of all harmonics over a fundamental frequency., Results: The Cxi was higher (P <0.0001) for group PL (10.3 ± 6.7 mm) than for group MT (3.2 ± 2.4 mm), and it was correlated with tumor diameter in both groups. The cut-off equation "Cxi = 0.127 DT + 2.23" provided the highest diagnostic accuracy for distinguishing Group PL from Group MT such as a sensitivity of 95.8%, a specificity of 81.5%, and an accuracy of 89.7%., Conclusion: FFT analysis appears useful for quantification of complexity of the tumor outline.

Background: Lung adenocarcinoma with morule-like components is an unusual variant of lung adenocarcinoma, comprising uniform, tightly packed spindle-shaped cells, which fill the lumen of the glandular structures of the carcinoma. The aim of the study was to outline the clinicopathologic features of this variant., Patients and Methods: We examined a series of 904 surgically resected adenocarcinomas. We defined morule-like components as small buds of spindle-cell proliferation in the tumor lumen of the glandular structures of the carcinoma and calculated their proportion of total tumor mass. Targeted genotyping was performed for KRAS, EGFR, HER2, and BRAF. ALK rearrangements were analyzed immunohistochemically. Immunopositive cases were confirmed using RT-PCR and/or FISH., Results: We detected 17 cases of adenocarcinoma with morule-like components. This variant, representing only 1.9% was associated with unfavorable outcomes and a mutation in the EGFR. Histologic examination revealed adenocarcinoma with morule-like components accounting for 5-50% of tumors. Among the morule-like components, 10 (58.8%) of the 17 samples showed intracytoplasmic lumina formation containing eosinophilic mucinous material. The presence of micropapillary components in adenocarcinoma with morule-like components suggests that morule-like components could be merely excessive growth of the micropapillary pattern. However, our results indicated no statistical differences in the MIB-1 indices of the morule-like components and the adjacent tumor components or the micropapillary components. The univariate and multivariate analyses revealed a correlation between the presence of a morule-like components and an unfavorable outcome., Conclusions: Our study clearly indicated that adenocarcinoma with morule-like components is distinct unfavorable prognostic and predictor for EGFR mutation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Intra-airway and intra-arterial administration of gelatin-embedded, sustained-release basic fibroblast growth factor has stimulated regeneration of emphysematous lungs in animal experiments, but these routes of administration may also cause harm. This study investigated the effectiveness of intrapleural administration of gelatin-embedded, sustained-release basic fibroblast growth factor. This animal experiment preceded our clinical trial of intrapleural administration of sustained-release basic fibroblast growth factor in patients with chronic obstructive pulmonary disease accompanied by pneumothorax., Methods: Pulmonary emphysema was induced in Sprague-Dawley rats using porcine elastase. Gelatin-embedded, sustained-release basic fibroblast growth factor was administered via the left pleural cavity. The rats were divided into a group that received gelatin-embedded, sustained-release basic fibroblast growth factor (FGF(+) group, n = 6), and a group that did not (FGF(-)group, n = 6). Animals were sacrificed after 14 days, and the results were evaluated by histologic examination., Results: In the FGF(+) group, the mean linear intercept value of the alveolar septa was significantly shorter on the treated side than on the untreated side (65.1 ± 7.0 vs 114.4 ± 7.5 μm; P = .0005). There was no significant difference in the mean linear intercept value between the treated and untreated sides in the FGF(-) group., Conclusions: Intrapleural administration of sustained-release basic fibroblast growth factor induced lung regeneration in rats with elastase-induced pulmonary emphysema., (Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.)

Background: The present study aimed to determine the ability of the revised International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification of lung adenocarcinoma to predict patient survivals and driver gene alterations., Patients and Methods: A reclassification of 904 surgically resected adenocarcinomas was performed. The results were statistically analyzed to examine the correlation between the classification and overall survival (OS) using Cox regression analyses, and integrated discrimination improvement (IDI) analyses., Results: The 5-year OS rates for adenocarcinomas in situ (AIS) or minimally invasive adenocarcinoma (MIA) were 98%. Five-year OS rates of Lepidic-, acinar-, papillary-, micropapillary-, and solid-predominant adenocarcinomas was 93%, 67%, 74%, 62%, and 58%, respectively. The IDI estimates revealed that classification of ADC into the 7 subgroups had a higher estimated (0.0175) than did the combined histological grouping (AIS + MIA, lepidic + acinar + papillary, micropapillary + solid + others) (0.0111). Epidermal growth factor receptor mutations, KRAS gene mutations, and anaplastic lymphoma kinase gene alterations were statistically prevalent in papillary-predominant (P = 0.00001), invasive mucinous (P = 0.00001), and micropapillary- and acinar-predominant (P = 0.00001) adenocarcinomas, respectively., Conclusions: The new classification reflects disease prognosis, and was also associated with driver gene alterations., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To examine the relationship between preoperative serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (I-CTP) levels and postoperative distant metastasis in patients with non-small-cell lung cancer (NSCLC)., Methods: We retrospectively reviewed 143 patients in whom preoperative serum I-CTP level was measured from January 2006 to March 2011, including 91 males and 52 females with an average age of 70.1 ± 8.2 years. Histological subtypes included adenocarcinoma (n = 95), squamous cell carcinoma (n = 34) and other (n = 14). Preoperative serum carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA) levels were also measured. Patients with abnormal renal function or preoperative bone fractures were excluded., Results: The mean preoperative serum I-CTP level was 4.1 ± 1.6 ng/ml, and the preoperative serum I-CTP level was elevated (>4.5 ng/ml) in 29 patients. Distant metastasis was detected in 21 patients during the 39 ± 18 (range 1-79) months of follow-up. The rate of distant metastasis was significantly higher in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (≤4.5 ng/ml) (P < 0.0001). The 5-year recurrence-free survival rate was lower in patients with elevated preoperative serum I-CTP levels than those with normal preoperative I-CTP levels (41.8 vs 92.9%; P < 0.0001)., Conclusions: An elevated preoperative serum I-CTP level predicts postoperative distant metastasis in patients with NSCLC.

Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

A 62-year-old asymptomatic woman was referred to the National Cancer Center Hospital in Japan because of an abnormal shadow on an annual checkup chest X-ray. Chest computed tomography(CT)showed a well-demarcated nodular lesion of 3 cm in diameter in the right lower lobe. Since the nodule was located at the right pulmonary hilum, she underwent a right lower lobectomy. Histologically, the tumor was composed of solid nests or anastomosing strands of cells that were embedded in a hyalinized, focally myxoid stroma. Some of the tumor cells showed a striking feature of the presence of intracytoplasmic lumina that were visualized as clear spaces or vacuoles. These lumina were negative for alcian blue and periodic Schiff, and contained erythrocytes. Immunohistochemically, the tumor cells were stained for CD31 and FLI1. The tumor was diagnosed as a pulmonary epithelioid hemangioendothelioma.Pulmonary epithelioid hemangioendothelioma is a relatively rare entity.

Objective: There are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA)., Methods: Surgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib., Results: The HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 microg/ml (IR(20)) in adenocarcinoma without smoking (39.2% +/- 35.1%, n = 6) was higher than that with smoking (2.2% +/- 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% +/- 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR(20) values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%-50% appeared to be suitable for a concentration of 20 microg/ml., Conclusion: HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.

Objective: Application of the histoculture drug response assay for lung cancer was investigated by using data acquired from lung cancer specimens., Methods: From May 1994 through February 2005, histoculture drug response assay data were obtained from 359 lung cancer specimens held in our institute. We examined chemosensitivities of the tissues to cisplatin, doxorubicin, mitomycin C, 5-fluorouracil, docetaxel, paclitaxel, etoposide, irinotecan, and gemcitabine. Cutoff inhibition rates were determined with each drug for non-small cell lung cancer and were used to calculate predictabilities for chemotherapy responses., Results: The evaluability of the histoculture drug response assay was high at 97.4%. Good predictability, including true-positive and true-negative rates of 73.2% and 100%, respectively, with an accuracy of 83.0%, was observed., Conclusion: The histoculture drug response assay appears to be applicable to non-small cell lung cancer for the prediction of responses to chemotherapy.

Background: The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique., Materials and Methods: Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(1-1/(1+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50., Results: A dose-response curve was obtained in all tumors. The mean value (+/-SD) of maximum response, slope factor, and ED50 were 90.2+/-5.5%, 9.4+/-4.3, and 36.8+/-17.2 microg/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors., Conclusion: An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.

We report a case of massive bleeding from a varicose vein in a calf. A 56-year-old man was brought into the emergency unit of our hospital with massive bleeding from an ulcer on his left calf. A duplex scan and arteriography revealed arteriovenous communication at the site of stasis ulceration. After primary hemostasis, coil embolization of the feeding artery to the arteriovenous communication was successfully performed, followed by stripping of the greater saphenous vein. Careful attention thus needs to be paid to arteriovenous communication that can cause life-threatening bleeding from stasis ulceration. Coil embolization of the feeding arterial branch can safely and effectively treat this disease.

Cut-off levels of docetaxel (DOC), paclitaxel (PAC), and gemcitabine (GEM) in histoculture drug response assay are determined by data acquisition of non-small cell lung cancer. Inhibition rates were 47.5 +/- 22.2% in DOC (n=181), 66.6 +/- 25.1% in PAC (n=57), and 25.4 +/- 18.4% in GEM (n=63), respectively. Cut-off levels were determined as 50% in DOC, 60% in PAC, and 30% in GEM. The positive rates such as 47.5% in DOC, 68.4% in PAC, and 33.3% in GEM were obtained.

A 49-year-old male was referred to our hospital because of an abnormal shadow in his left lower lung field on chest X-ray. Magnetic resonance imaging scans revealed a large mass on the left diaphragm. The tumor was surgically extirpated. The tumor, encapsulated and growing from the center of the left diaphragm, measured 18 x 8 x 4 cm and weighed 440 g. Microscopic examination revealed a solitary fibrous tumor with mitotic activity of 7/ 50 hpf. Immunohistochemically, the tumor was negative for cytokeratin, s-100 protein, desmin, and alpha-smooth muscle actin, while positive for vimentin and CD34. On a histoculture drug response assay using the resected tissue, the tumor was sensitive to 5-FU, adriamycin, mitomycin C and docetaxel, and resistant to cisplatin, irinotecan, and gemcitabine.