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Purpose: To identify risk factors for delayed oral nutrition in infants with a congenital diaphragmatic hernia (CDH) and its impact on developmental delay at 18 months of age., Methods: This retrospective single-center cohort study compared the clinical parameters in patients with isolated CDH born and treated at our hospital between 2006 and 2020. We evaluated clinical features significantly related to delayed oral nutrition (defined as taking ≥ 30 days from weaning from mechanical ventilation to weaning from tube feeding)., Results: Twenty-six of the 80 cases had delayed oral nutrition. Univariate analyses showed significant differences. Multivariate analyses were performed on the three items of preterm delivery, defect size (over 50% to nearly entire defect), and ventilation for ≥ 9 days. We identified the latter two items as independent risk factors. The adjusted odds ratios were 4.65 (95% confidence interval, 1.27-7.03) and 6.02 (1.65-21.90), respectively. Delayed oral nutrition was related to a significantly higher probability of developmental delay at 18 months (crude odds ratio 4.16, 1.19-14.5)., Conclusion: In patients with CDH, a large defect and ventilatory management over 9 days are independent risk factors for delayed oral nutrition, which is a potent predictor of developmental delay that requires active developmental care., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteosarcoma (OS) is a heterogeneous, highly metastatic bone malignancy in children and adolescents. Despite advancements in multimodal treatment strategies, the prognosis for patients with metastatic or recurrent disease has not improved significantly in the last four decades. OS is a highly heterogeneous tumor; its genetic background and the mechanism of oncogenesis are not well defined. Unfortunately, no effective molecular targeted therapy is currently available for this disease. Understanding osteosarcoma's tumor microenvironment (TME) has recently gained much interest among scientists hoping to provide valuable insights into tumor heterogeneity, progression, metastasis, and the identification of novel therapeutic avenues. Here, we review the current understanding of the TME of OS, including different cellular and noncellular components, their crosstalk with OS tumor cells, and their involvement in tumor progression and metastasis. We also highlight past/current clinical trials targeting the TME of OS for effective therapies and potential future therapeutic strategies with negligible adverse effects.

Osteosarcoma (OS) is the predominant primary bone tumor in the pediatric and adolescent populations. It has high metastatic potential, with the lungs being the most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it has heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, and chromosomal loss and gain. Unfortunately, clinical outcomes have not significantly improved in over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation in the tumor suppressor genes, including p53 , RB , and ATRX, and hyperactivation of the tumor promoter genes, including MYC and MDM2 , in OS. Alterations in the major signaling pathways, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, NOTCH, Hedgehog/Gli, TGF-β, RTKs, RANK/RANKL, and NF-κB signaling pathways, have been identified in OS development and metastasis. Although OS treatment is currently based on surgical excision and systematic multiagent therapies, several potential targeted therapies are in development. This review focuses on the major signaling pathways of OS, and we propose a biological rationale to consider novel and targeted therapies in the future.

A 4-year-old girl was admitted to our hospital because of precocious puberty. Radiologic findings revealed a fist-sized solid tumor in the left ovary without ascites, peritoneal dissemination, and distant metastasis. The patient underwent left salpingo-oophorectomy without spillage. The size of the excised tumor was 10.0×9.0×4.8 cm. On pathologic examination, the tumor was diagnosed as an ovarian steroid cell tumor, not otherwise specified. In the present case, although the diameter of the tumor (>7 cm) and three mitoses per 10 high-power fields represented some potential for malignancy, we opted for careful observation without chemotherapy as the tumor was of clinical stage Ia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Fetuses with persistent cloaca are known to develop urine or meconium backflow into the abdominal cavity caused by obstruction of the common channel, thus leading to fetal peritonitis with fetal ascites. We analyzed the impact of prenatal fetal ascites on postnatal clinical features and management., Methods: This retrospective single-center cohort study was conducted to compare the perinatal parameters of patients with isolated persistent cloaca who were born and treated at our hospital between 1991 and 2021. The clinical features and management of those with and without fetal ascites were compared., Results: Among the 17 eligible patients, fetal ascites were recognized in seven. The occurrence of fetal ascites was significantly related to preterm birth, higher birth weight z-score, birth via emergency cesarean delivery, low Apgar scores at 1 min and 5 min, higher C-reactive protein levels at birth, longer duration of oxygen administration, the need for a urinary drainage catheter at initial discharge, and shorter neonatal hospital stays., Conclusions: The postnatal management of patients with persistent cloaca with fetal ascites differed significantly from that of patients without fetal ascites. For patients with unexplained fetal ascites, magnetic resonance imaging may be helpful for determining the definite diagnosis of persistent cloaca., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The number of lung cancer patients with a history of other malignancies is increasing. Previous upper gastrointestinal cancer (UGIC) surgery may increase the risk of complications after lung cancer surgery due to malnutrition and susceptibility in patients; therefore, we investigated its short-term outcomes., Methods: We retrospectively examined patients with lung cancer who underwent thoracoscopic lobectomy between 2011 and 2021 and collected data regarding postoperative complications and postoperative pulmonary complications ≥ grade II of the Clavien-Dindo classification that developed within 3 months post-surgery. The effect of UGIC surgery on the postoperative complications was evaluated by multivariable analysis using logistic regression., Results: Among the 1,385 included patients, 377 patients had a history of cancer surgery and 65 (4.7%) of them had undergone UGIC surgery. Postoperative and pulmonary complications were observed in 155 (11.2%) and 39 (2.9%) patients, respectively. The frequency of pulmonary complications was significantly higher in patients with previous UGIC surgery (9.2% vs. 2.5%, P=0.003) with no significant difference in all complications (16.9% vs. 10.9%, P=0.137). Multivariable analysis showed that previous UGIC surgery is an independent factor associated with postoperative pulmonary complications (odds ratio =2.923, P=0.029). In contrast, previous surgery for cancer other than UGIC was not associated with postoperative pulmonary complications (the rate was 1.2% after lower gastrointestinal cancer surgery and 3.0% after non-gastrointestinal cancer surgery)., Conclusions: Previous UGIC surgery was an independent factor associated with postoperative pulmonary complications after lung cancer surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-798/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Purpose: Postoperative complications have a significant impact on perioperative outcomes; however, their association with the long-term prognosis remains unclear. We evaluated the impact of postoperative complications on the long-term outcomes after curative surgery in lung cancer patients., Methods: This study included 1129 patients with primary lung cancer who underwent lobectomy between April 2011 and March 2017. Univariate and multivariate analyses were performed to assess the association of postoperative complications with the overall and recurrence-free survival., Results: Postoperative complications were observed in 147 (13.0%) patients over a median follow-up period of 5-years. Compared to patients without complications, those with complications showed had worse long-term outcomes, including the 5-year overall survival (75.3% vs. 86.1%, p < 0.001) and 5-year recurrence-free survival (64.2% vs. 74.4%, p = 0.004). A multivariate analysis revealed that the incidence of postoperative complications was significantly associated with the overall survival (hazard ratio = 1.665, p = 0.006) and recurrence-free survival (hazard ratio = 1.416, p = 0.025) in all patients. The prognostic influence was greater in patients with pathological stages II and III cancer (overall survival: hazard ratio = 2.019, p = 0.005; recurrence-free survival: hazard ratio = 1.90, p = 0.001) than in those with pathological stage I cancer., Conclusion: Postoperative complications are independent predictors of the overall and recurrence-free survival in lung cancer patients, especially advanced-stage cancer patients., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Liver transplantation (LTx) is indicated for unresectable hepatoblastoma (HB) without distal metastasis. However, to our knowledge, there is no consensus on the management of unresectable HB with pulmonary metastases, or on the treatment of recurrent HB. We report a successful case of metastatic HB treated with repeated lung resection, chemotherapy, and LTx. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source., Case Report: Our case was a 1-year-old boy who developed pre-treatment extent of disease (PRETEXT) Ⅲ HB with multiple pulmonary metastases. The liver tumor was unresectable because it involved all hepatic veins. After 3 cycles of chemotherapy (cisplatin/carboplatin plus doxorubicin), the remaining 2 pulmonary metastases were resected and living donor liver transplantation (LDLT) was performed. Five months after LDLT, a tumor recurrence was detected in the right lung. Repeat lung resection was performed followed by 1 cycle of chemotherapy (carboplatin plus doxorubicin). There has been no recurrence for 18 months since the last lung resection., Discussion: Previous reports revealed that 14 patients, including the present case, underwent LTx after resection of metastatic HB pulmonary lesions. Of these patients, the 2-year survival rate after LTx was 91%. Recurrence was reported in 5 patients, 2 of whom were successfully treated with repeated resection of the metastatic lesions. LTx after resection of lung recurrence may be a potential treatment for unresectable HB with pulmonary metastases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Smoking has a major role in the risk of postoperative pulmonary complications. This study aimed to elucidate the correlation between smoking status and pulmonary complications after thoracoscopic surgery for lung cancer., Methods: A total of 1751 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between April 2011 and March 2020 were assessed. The rate of pulmonary complications was evaluated according to smoking status and preoperative duration of smoking cessation. Univariate and multivariate logistic regression analyses were performed., Results: Pulmonary complications were observed in 50 patients (2.9%), whereas 3 (0.2%) died within 90 days of surgery. The rate of pulmonary complications was higher in smokers than in nonsmokers (4.6% vs 0.9%; P < .001), and smoking history was an independent risk factor for pulmonary complications (odds ratio, 3.31; P = .007). The complication rate in patients with a cessation period of more than 2 months was significantly lower than that in patients who ceased smoking within 2 months (4.0% vs 8.5%; P = .043), but it was still higher than that in nonsmokers (4.0% vs 0.9%; P < .001). In the multivariable analysis for smokers, preoperative short-term smoking cessation within 2 months, male sex, histologic type, tumor size, and cardiopulmonary comorbidities were associated with pulmonary complications instead of pack-year smoking history., Conclusions: Smoking habits and preoperative smoking cessation were independently associated with pulmonary complications after thoracoscopic surgery for lung cancer. A preoperative smoking cessation period of 2 months or more is preferable for reducing the risk of such complications., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the risk factors for surgical site infections (SSIs) post-abdominal surgery in neonates., Methods: A retrospective, single-center cohort study was conducted using patient data from 2009 to 2018. Patient characteristics and several variables were analyzed to identify independent risk factors for SSI., Results: SSI occurred in 39/406 procedures (9.6%). Univariate analysis showed that the incidence of SSI was significantly higher in patients who had undergone multiple surgical procedures (P = 0.032), prolonged operations (P = 0.016), long-term hospitalization (P < 0.001), long-term antibiotic administration (P < 0.001), with methicillin-resistant Staphylococcus aureus (MRSA) colonization (P = 0.044), contaminated/dirty wounds (P < 0.001), and American Society of Anesthesiologists physical status of 3 or 4 (P = 0.021). Multivariate analysis identified prolonged operations [odds ratio (OR): 2.91 (1.21-8.01)] and contaminated/dirty wounds [OR: 5.42 (2.41-12.1)] as independent risk factors. Patients with SSI had a higher incidence of MRSA colonization (27.8% vs. 14.8%, P = 0.044), longer antibiotic administration (24 days vs. 8 days, P = 0.049), and longer hospitalization times (98 days vs. 43 days, P = 0.007) than those without SSIs., Conclusions: Long operations exceeding 100 min and surgical procedures with contaminated/dirty wounds are independent risk factors for neonatal SSIs after abdominal surgery. SSIs were related to MRSA colonization during hospitalization, long-term antibiotic administration, and long-term hospitalization., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recent studies have reported the high incidence of undescended testis (UDT) in patients with gastroschisis. Although various mechanical, hormonal, and genetic theories have been postulated to describe testicular descent, the mechanism contributing to this condition remains controversial. We aimed to investigate the incidence and risk factors of UDT in infants with gastroschisis., Methods: Male neonates who underwent surgery for gastroschisis between January 1982 and December 2019 were enrolled. Data were analyzed regarding the prevalence of UDT, including spontaneous testicular descent and the necessity of orchidopexy. Patients were grouped into those with or without UDT to identify the risk factors for UDT., Results: Among 38 patients with gastroschisis, six (15.8%) developed UDT. There were no significant differences in gestational age or birthweight between patients with and without UDT. The patients with UDT had a significantly larger defect size than those without UDT (P = 0.037). In addition, the timing of abdominal closure was significantly later in patients with UDT than in those without UDT (P = 0.004). None of the patients with UDT exhibited spontaneous testicular descent requiring subsequent orchidopexy., Conclusions: Patients with gastroschisis had a high prevalence of UDT. In gastroschisis, the incidence of UDT was related to the defect size and the timing of abdominal wall closure, indicating that an insufficient increase in intra-abdominal pressure during the fetal period may affect the development of UDT., (© 2021 Japan Pediatric Society.)

Purpose: In 2004, the Japanese government halted nationwide mass screening for neuroblastoma in 6-month-old infants as it led to overdiagnosis of localized tumors with favorable prognoses and failed to reduce neuroblastoma-related mortality. However, a new mass screening program for neuroblastoma in 18-month-old infants (18MS) was conducted in the Osaka prefecture. We assessed the efficacy of the 18MS in screening unfavorable cases., Methods: Public health centers in Osaka prefecture, excluding the Osaka city area, provided test kits to the guardians of infants who received a check-up at 18 months of age between 2004 and 2017. For patients whose standardized urinary levels of vanillylmandelic acid or homovanillic acid exceeded the threshold, they were further examined and treated in two specific hospitals Osaka University Hospital and Osaka Women's and Children's Hospital. Screening-positive patients with and without neuroblastoma were retrospectively reviewed., Results: Among 142,423 children screened during the 18MS, 85 tested positive, and 14 were diagnosed with neuroblastoma. Twelve patients were classified as very low risk, while 2 were classified as high risk, based on the International Neuroblastoma Risk Group risk classification., Conclusion: The 18MS did not screen unfavorable cases with neuroblastoma efficiently, although few participants benefited from it., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This is the first report of an immature sacrococcygeal teratoma with inguinal lymph node metastasis, providing the histologic transformation of an immature teratoma in association with chemotherapy. Incomplete tumor resection with coccygectomy was performed, and the histopathologic diagnosis was a grade 3 immature teratoma. Following the initial surgery, the residual tumors enlarged and the tumors metastasized to the inguinal lymph node, demonstrating immature teratoma without yolk sac tumor components. Although the tumor markers normalized after chemotherapy, the residual tumors had enlarged significantly. Therefore, a complete resection of the residual tumors was performed, and they were found to be mature teratomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: It is important to confirm the existence of pulmonary metastases in pediatric patients with malignancies. Therefore, we aimed to investigate if computed tomography CT-guided marking is a feasible and safe method for the identification and resection of tiny pulmonary lesions in pediatric cancer patients., Methods: We retrospectively reviewed the medical records of pediatric cancer patients who underwent CT-guided marking procedures in our institutions between Jan 2011 and Apr 2020. After 2015, these procedures were combined with an indocyanine green (ICG) navigation-guided surgery for hepatoblastoma cases., Results: We targeted a total of 22 nodules in 12 patients. Of these, marking was successful in 18 (81.8%) nodules, 10 of which contained viable malignant cells. Complications caused by the marking procedures included mild pneumothorax and mild atelectasis in two patients, respectively. Of the eight resected nodules in patients with hepatoblastoma, four were ICG-positive and contained viable malignant cells. Two additional ICG-positive nodules, which were unidentified before surgery, were observed intraoperatively., Conclusion: CT-guided marking is a feasible and safe method that can be used to identify and resect tiny pulmonary lesions in pediatric cancer patients. An ICG navigation-guided surgery is useful when combined with CT-guided marking, particularly in hepatoblastoma cases., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Postoperative severe respiratory adverse events (SRAEs) are the major cause of perioperative morbidity in patients after thoracic surgery. In particular, SRAEs often occur in lung cancer patients concomitant with chronic inflammatory lung diseases (CILDs) such as interstitial lung disease, emphysema, infectious disease, and asthma. We aimed to clarify whether the measurement of the maximum of standardized uptake value in the noncancerous lung area (NCA-SUVmax) and CILDs on high-resolution computed tomography were useful for predicting the risk of SRAEs., Methods: A total of 984 patients with lung cancer undergoing preoperative computed tomography, F-18 fluorodeoxyglucose-positron emission tomography/computed tomography followed by surgery between July 2012 and March 2019 were assessed. NCA-SUVmax was measured using a 3-dimensional workstation. We extracted the records of patients with CILDs and their disease history. Predictive factors associated with SRAEs were identified., Results: SRAEs were observed in 75 patients (7.6%), and 7 patients (9.3%) died of SRAEs within 90 days after surgery. NCA-SUVmax in patients with CILDs (n = 325; emphysema = 161, interstitial lung disease = 134, infectious disease = 17, asthma = 13) were higher than that in patients without CILDs (n = 659; 1.3 ± 0.7 vs 1.1 ± 0.4, respectively; P < .001). On multivariate analysis, CILDs, percent vital capacity, and NCA-SUVmax were independently associated with SRAEs (P < .001). Rate of SRAEs in patients with CILDs, NCA-SUVmax ≥1.3, and percent vital capacity ≤ 110 was 31.8%., Conclusions: NCA-SUVmax was independently associated with the incidence of SRAEs in patients with resected lung cancer and was significantly increased in patients with CILDs., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The coexistence of interstitial lung disease (ILD) is associated with poor prognosis in patients with lung cancer. The tumor doubling time (TDT) of lung cancer reflects cancer aggressiveness and is related to its prognosis. However, the relationship between the TDT of lung cancer and underlying ILD has not been fully evaluated. This study aimed to identify this crucial relationship., Materials and Methods: Patients with lung cancer who underwent surgery between 2007 and 2020 were reviewed retrospectively. The propensity score matching method was used to balance the characteristics of patients with ILD (n = 100) and those without ILD (n = 100). TDT was calculated based on the difference of three-dimensional volumes defined from the two-time CT scans before surgery. We compared the TDT of lung cancer and other characteristics between the two groups., Results: The median TDT of all patients was 149 days. The TDT was significantly shorter in patients with ILD (134 days) than in those without (204 days). The rate of short-term tumor enlargement (TDT < 90 days) was significantly higher in patients with ILD than in those without ILD, and ILD was an independent factor related to short-term tumor enlargement (odds ratio, 2.30; p = 0.015). We focused on 25 patients with usual interstitial pneumonitis (UIP) findings of patients with ILD. However, the presence of the UIP pattern was not related to the TDT among patients with ILD., Conclusion: ILD was an independent predictor of short-term tumor enlargement in lung cancer patients, regardless of the presence of the UIP pattern., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study aimed to evaluate the incidence and factors associated with long-term functional outcomes of sacrococcygeal teratoma (SCT) after resection in neonates and infants., Methods: Twenty-nine patients with a minimum of 3 years of follow-up who underwent resection and were histologically diagnosed with SCTs between 1982 and 2017 at our institution were included., Results: The median age at the time of the study was 10.0 years. Functional disorders occurred after surgery in 6 (20.7%) patients. Anorectal dysfunction, urologic dysfunction, and lower-extremity motor disorders occurred in 6 (20.7%), 4 (13.8%), and 3 (10.3%) patients, respectively. One patient with all three types of functional disorders developed intestinal perforation due to ileus and died of sepsis at 13 years of age. The overall mortality rate after tumor resection was 3.4%. The patients who developed functional disorders presented a low 1-min Apgar score, larger tumors requiring abdominosacral resection, surgical injury to the pelvic organs, and immature or malignant histological findings., Conclusion: Although the mortality rate was low, the long-term rate of functional disorders after SCT resection was approximately 20%. SCT patients with large tumors, surgical injury to the pelvic organs, and immature or malignant histological findings require thorough follow-up.

Background: Sonographic findings of lymph nodes on endobronchial ultrasonography (EBUS) images have been reported to be useful to predict lymph node metastasis (LNM) in lung cancer patients. F-18 fluorodeoxyglucose (FDG) uptake in lymph nodes was also found to be useful. In this study, we aimed to clarify whether a combination of sonographic features and maximum standardized uptake values of lymph nodes (LN-SUVmax) is useful for predicting LNM in lung cancer patients., Methods: From January 2014 to December 2019, a total of 147 lymph nodes from 104 patients with lung cancer, who underwent preoperative EBUS and FDG-positron emission tomography (PET)/computed tomography (CT) followed by surgery were retrospectively assesses. The characteristics of the patients, LN-SUVmax, and sonographic findings of lymph nodes were reviewed. Predictive factors associated with LNM were identified using the logistic regression model., Results: The average size of the lymph nodes was 8.55 (range, 3-22) mm and the average LN-SUVmax was 5.36 (range, 1.79-31.19). The prevalence of nodal metastasis was 26/147 (17.4%), including 22 in mediastinal lymph nodes and 4 in hilar lymph nodes. Multivariate analysis demonstrated four independent predictive factors for LNM; size, round or oval shape, absence of a central hilar structure, and LN-SUVmax. The optimal cutoff value for lymph node size and LN-SUVmax were 10 mm and 6.00, respectively. By combinating of the two modalities, we obtained the results with sensitivity of 76.9%, specificity of 95.1% and accuracy of 93.2%., Conclusions: A combination of sonographic findings and LN-SUVmax showed a higher diagnostic rate of LNM than either modality alone in lung cancer patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1888). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Background/purpose: The aim of this study was to evaluate our prenatal risk stratification system for risk-adjusted management in fetuses with isolated congenital diaphragmatic hernia (CDH)., Methods: Ninety-four infants prenatally diagnosed with isolated CDH treated between 1998 and 2017 at our institution were included in this retrospective single-center cohort study., Results: The patients were prenatally classified into four risk groups: Group A (n = 54), which consisted of infants with neither liver-up nor a contralateral lung-to-thorax transverse area (L/T) ratio <0.08. The infants in group A were divided into two subgroups: Group A-1 (n = 24) consisted of mild conditions; and Group A-2 (n = 30) consisted of severe conditions; Group B (n = 23), which consisted of infants with either liver-up or L/T ratio <0.08; and Group C (n = 17), which consisted of infants with both liver-up and L/T ratio <0.08. The rates of survival to discharge in Groups A-1, A-2, B, and C were 100.0%, 100.0%, 87.0%, and 58.8%, respectively. The rates of intact discharge were 91.7%, 90.0%, 52.1%, and 23.5%, respectively., Conclusions: Our prenatal risk stratification system demonstrated a significant difference in the severity of postnatal status and clinical outcomes between the groups., Study Type: Case Series, Retrospective Review., Levels of Evidence: LEVEL IV., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Idiopathic pulmonary fibrosis is defined as a specific form of progressive fibrosing interstitial pneumonia. Postoperative acute exacerbation is considered a lethal comorbidity for patients with lung cancer, particularly when it is accompanied with idiopathic pulmonary fibrosis. Thus, pretherapeutic risk stratification for acute exacerbation has been anticipated. In this study, we aimed to investigate whether the maximum standardized uptake value of F-18 fluorodeoxyglucose is useful for assessing the postoperative risk of acute exacerbation and severe respiratory adverse events in patients with lung cancer after surgical resection., Methods: A total of 822 patients with lung cancer who underwent preoperative high-resolution computed tomography, fluorodeoxyglucose-positron emission tomography/computed tomography, and pulmonary resection between July 2012 and July 2018 were assessed. Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were measured using a 3-dimensional workstation. Multivariable analyses for acute exacerbation and severe respiratory adverse events were performed using the logistic regression model., Results: Among all patients, 120 (14.6%) had idiopathic pulmonary fibrosis findings on high-resolution computed tomography whereas severe respiratory adverse events were observed in 35 (4.2%) patients, including those with acute exacerbation (n = 15, 1.8%). Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with both acute exacerbation and severe respiratory adverse events on multivariable analysis, both in all patients and in the 120 patients with idiopathic pulmonary fibrosis. Risk stratification analysis showed that 19.0% and 30.2% of patients who were positive for idiopathic pulmonary fibrosis on high-resolution computed tomography and with a maximum standardized uptake value of the main tumor and that of the noncancerous lung area 1.69 or greater (the optimal cutoff value relevant to acute exacerbation) experienced acute exacerbation and severe respiratory adverse events, respectively., Conclusions: Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with the incidence of postoperative acute exacerbation and severe respiratory adverse events in patients with lung cancer., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The prognostic nutritional index is a potential predictive indicator in other cancers and can be easily determined at low cost. To identify useful prognostic markers for high-grade neuroendocrine carcinomas, we examined the prognostic significance of the prognostic nutritional index in patients with resected high-grade pulmonary neuroendocrine carcinoma., Methods: We retrospectively reviewed perioperative clinical and laboratory data of patients who underwent pulmonary resection for high-grade neuroendocrine carcinoma between January 2000 and December 2014. Associations between the preoperative prognostic nutritional index and the patients' clinicopathological characteristics were analyzed to determine its prognostic significance., Results: The study comprised 61 patients, the majority of whom were men (85%). The median age was 70.0 years, and the median follow-up period was 42 months. No significant differences in the clinicopathological characteristics were observed between the high and low prognostic nutritional index groups. The 5-year overall survival and recurrence-free survival times were significantly shorter in the low prognostic nutritional index group than in the high prognostic nutritional index group (78.8% vs. 51.4% and 71.7% vs. 34.5%, respectively; p < 0.05). The prognostic nutritional index was confirmed as an independent prognostic factor (hazard ratio: 2.419, 95.0% confidence interval: 1.044-5.606; p < 0.05). A significantly greater proportion of patients developed distant metastases in the low prognostic nutritional index group than in the high prognostic nutritional index group (p < 0.05)., Conclusion: A low prognostic nutritional index is associated with poor survival in patients with resected high-grade pulmonary neuroendocrine carcinoma.

Objective: The purpose of this study was to clarify the surgical outcome for HIV-infected patients with non-small-cell lung cancer (NSCLC)., Methods: Six HIV-positive patients underwent lung resection as treatment for NSCLC at our hospital from July 2010 to December 2017. Their clinical information was collected based upon review of their medical records., Results: All the patients included in this study had received highly active antiretroviral therapy (HAART) before lung resection with a mean duration of 99 months. Five patients underwent lobectomy and one patient underwent segmentectomy. Median preoperative CD4-positive T-cell count was 234/µL (range 138-428/µL). One patient contracted pneumonitis within 30 days post-surgery, whereas others had no postoperative complications. There was no postoperative mortality. For four patients, the pathological stage was upstaged compared to their clinical stage; IA1-IA3 (1 patient), IA3-IIB (1 patient), IB-IIIA (1 patient), and IB-IIIB (1 patient). Two patients died of lung cancer 2 years after surgery., Conclusion: Surgical treatment for HIV-infected patients with NSCLC receiving HAART therapy and keeping adequate CD4-positive T-cell counts is safe and feasible. Preoperative precise staging using diagnostic imaging is difficult for these patients.

Gastric cancer remains the most commonly-occurring cancer and the third most frequent cause of cancer-associated mortality in Japan. Solitary pulmonary metastasis of gastric cancer is rare and the outcome of pulmonary metastasectomy is still unclear. Herein we report the impact of pulmonary resection in patients with metastasis from gastric cancer. The present study retrospectively reviewed the preoperative data and clinical courses of 10 patients who underwent pulmonary resection for metastasis from gastric cancer at our institution between July 1986 and December 2017. The data on the outcomes, including morbidity, mortality and survival, were obtained from the patient records. All patients were followed-up from the time of pulmonary resection until mortality or referral to another hospital. The statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for the R software program (The R Foundation for Statistical Computing, Vienna, Austria). The study population included 7 male patients and 3 female patients. A total of 5 patients underwent total gastrectomy, and 5 underwent distal gastrectomy. The median disease-free interval after initial gastric resection was 34.5 months. Five patients received adjuvant chemotherapy, of the 10 thoracotomies, 5 were lobectomy, 3 were wedge resection and 2 were segmentectomy. The median overall survival following pulmonary metastasectomy was 59 months and the 5-year survival rate was 40.5%. Taken together, the results of the present study suggest that pulmonary resection may be an effective therapeutic option for metastatic gastric cancer when a patient has a solitary metastatic lesion.

The β-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/β-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/β-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFβ signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of β-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFβ signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/β-catenin signaling and required for HB progression.

Background: The prevalence of non-tuberculous mycobacteria (NTM) has been increasing in recent years, and thus the number of related surgeries. In recent studies, a few recent studies reported that NTM patients require preoperative treatment. In addition, some cases are found to be granuloma suspected to be NTM (gsNTM) after surgery. We conducted a clinico-bacteriological examination of resected NTM and gsNTM cases we managed., Methods: Between 2003 and 2017, 82 patients with NTM and gsNTM underwent video-assisted thoracoscopic (VATS) biopsy at our institution. The objectives of surgery, perioperative treatment, progression of NTM and gsNTM, and bacteriological data were analyzed., Results: We enrolled 42 men and 40 women with a median age of 65 years. The bacteriological findings were Mycobacterium avium in 38 cases, M. intracellulare in 6 cases, M. kansasii in 3 cases, and gsNTM in 35 cases. The objectives of surgery were the diagnosis in 77 cases, and resistance to treatment in 6 cases. We performed postoperative treatment in 8 cases. There was no surgery-related (30-day mortality) death or complication., Conclusions: We analyzed surgical outcome for pulmonary NTM infections. We need to reconsider the surgical procedure for single pulmonary NTM lesion and whether adjuvant chemotherapy is necessary for NTM treatment., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Pneumothorax induced by Pneumocystis jirovecii( P. jirovecii) pneumonia is often refractory to treatment. A man in his 30's who had malignant lymphoma and received chemotherapy developed P. jirovecii pneumonia. A month after treatment for pneumonia, he developed a secondary pneumothorax. Since drainage was not effective, he underwent right lower lobectomy and bulla resection. Air leakage stopped after surgery but recurred on postoperative day 5. Chest computed tomography showed a new bulla on his right lung. On postoperative day 15, we inserted an endobronchial Watanabe spigot( EWS),and air leakage completely stopped.

Background: The complication rate of fungal disease is higher among patients with hematological malignancies. We investigated the clinicobacteriological outcomes of resected pulmonary fungal infections complicating hematological malignancies., Methods: Between 2001 and 2017, 21 patients with pulmonary fungal infections complicating hematological malignancies underwent resection, and their clinical records and survival were retrospectively reviewed., Results: The median age of the patients was 47 years, and 13 were male. The histological diagnoses were pulmonary aspergillosis (19 cases), mucormycosis (1 case), and cryptococcosis (1 case). The indications for surgery were resistance to antifungal therapy and the necessity of surgery before hematopoietic stem cell transplantation in 13 and 8 cases, respectively. The diagnoses of the hematological malignancies were acute myelogenous leukemia (10 cases), acute lymphocytic leukemia (5 cases), myelodysplastic syndrome (3 cases), and chronic myelogenous leukemia, malignant lymphoma, and extramedullary plasmacytoma (1 case each). The surgical procedures were partial resection (11 cases), segmentectomy (5 cases), lobectomy (4 cases), and cavernostomy (1 case). The size of the lesions was 0.9-8.5 cm. Fourteen cases had cavitation. There were no surgical-related deaths or fungal progression., Conclusion: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible., Competing Interests: Conflict of interest No potential conflict of interest relevant to this article was reported.

A primary desmoid tumor arising from the chest wall is extremely rare. We report the case of a 57-year-old man presenting with a desmoid tumor arising from his chest wall. Chest radiograph at a regular medical checkup indicated an abnormal shadow. By computed tomography-guided biopsy, he was diagnosed as having a desmoid tumor. He underwent right-sided chest wall resection and reconstruction. Desmoid tumor is histopathologically benign tumor, however, they tend to show high rates of local recurrence after surgery. In case of recurrence on unresectable case, radiotherapy or some medical treatment should be chosen as a treatment option.

Objectives: Large cell neuroendocrine carcinomas (LCNECs) are rare neuroendocrine pulmonary malignancies with poor survival. Towards the goal of identifying a useful prognostic marker for LCNEC, we examined the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in LCNEC patients after complete resection. The NLR is a potential predictive indicator in other cancers and can be easily determined at low cost., Methods: We retrospectively reviewed the perioperative clinical and laboratory data of patients who underwent complete resection for LCNEC between 1995 and 2014. Correlations between the preoperative NLR and clinicopathological parameters were determined to assess its prognostic significance., Results: Our study consisted of 26 patients, most of whom were men (88.5%) with a median age of 68.8 years. The median follow-up time was 54.4 months. Univariate analysis identified 3 clinically significant overall survival predictors: serum albumin level [≥4.0 g/dL (5-year overall survival rate; 80.0%) vs. <4.0 g/dL (30.0%), p = 0.048], pathological T stage [T1 and T2 (79.6%) vs. T3 and T4 (0%), p = 0.001], and preoperative NLR [<1.7 (90.9%) vs. ≥1.7 (51.7%), p = 0.012]. In a multivariate analysis, the NLR was an independent prognostic factor for overall survival (hazard ratio 8.559, 95% confidence interval 1.783-80.230, p = 0.011)., Conclusions: The preoperative NLR inversely correlates with post-resection survival rates in patients with LCNEC and thus is a viable prognostic marker in LCNEC.

Background: Pancreatic cancer is a highly aggressive solid tumor. Patients with metastases from pancreatic cancer have poor survival rates. Here, we report the outcomes of 6 patients for whom resection of lung metastases was performed after a pancreatectomy to treat pancreatic cancer., Methods: We retrospectively reviewed the perioperative clinical data of patients with lung metastases resulting from primary pancreatic cancer who were treated with lung resection between 2008 and 2015. We report 6 cases where lung resection was performed to treat lung metastases after a pancreatectomy., Results: The number of lung metastases was 1 in 5 cases and 2 in 1 case. The surgical procedures performed to treat the lung metastases included 4 wedge resections and 2 lobectomies. The cell type of the primary tumor and metastases was tubular adenocarcinoma in 5 cases and intraductal papillary-mucinous carcinoma in 1 case. All 6 patients survived with a mean follow-up period of 65.6 months, although the disease recurred in 2 patients., Conclusion: Resection of lung metastases resulting from primary pancreatic cancer may lengthen survival, provided the patient can tolerate surgery., Competing Interests: Conflict of interest No potential conflicts of interest relevant to this article are reported.

Purpose Minute pulmonary meningothelial-like nodules are incidentally discovered in lung specimens. We analyzed the clinicopathologic features of 14 cases identified in surgically resected lungs. Methods Among patients who underwent lung resection in our hospital from October 2007 to March 2016, 14 were found to have minute pulmonary meningothelial-like nodules. The clinical parameters, radiologic findings, and pathologic features of these patients were retrospectively reviewed using the medical records. Results The patients included 4 men and 10 women, with a mean age of 69 years (range 53-82 years). The coexisting main disease was adenocarcinoma in 8 patients, squamous cell carcinoma in 1, atypical adenomatous hyperplasia in 1, and metastatic pulmonary tumor in 3. In one patient, the minute pulmonary meningothelial-like nodules presented as multiple lung nodules on chest computed tomography. The median size of the nodules was 1.4 mm (range 0.3-6.0 mm). Similar to meningioma, one case had immunoreactivity to progesterone receptor and epithelial membrane antigen, although the minute pulmonary meningothelial-like nodules were not associated with a meningioma. Conclusions The relationship between minute pulmonary meningothelial-like nodules and meningioma should be investigated. If minute pulmonary meningothelial-like nodules are found on preoperative computed tomography, thoracoscopic lung biopsy is helpful for differential diagnosis.

Purpose: The aim of this study was to clarify the prenatal and postnatal clinical courses of an urachus identified as an allantoic cyst in the umbilical cord., Methods: Allantoic cysts in the umbilical cord were identified in five fetuses over the past 12 years at our hospital. The prenatal and postnatal clinical courses of these patients were retrospectively reviewed., Results: The presence of allantoic cysts in the umbilical cord was first detected at 15 to 27 weeks of gestation. The cysts subsequently became enlarged, reaching a maximum diameter of 34 to 61 mm at 17 to 32 weeks of gestation. The cysts then suddenly disappeared due to spontaneous rupture at 26 to 35 weeks of gestation. After being born at 38 (35-39) weeks of gestation, four patients were diagnosed with a patent urachus requiring surgery in the infantile period and one was diagnosed with an urachal cyst, which is currently being observed without surgery., Conclusion: The presence of an urachus identified as an allantoic cyst in the umbilical cord is frequently associated with spontaneous rupture during the prenatal period, resulting in a patent urachus after birth that requires surgical intervention., (Georg Thieme Verlag KG Stuttgart · New York.)

Background/purpose: Although the usefulness of intraoperative indocyanine green (ICG) fluorescent imaging for the resection of hepatocellular carcinoma has been reported, its usefulness for the resection of hepatoblastoma remains unclear. This study clarifies the feasibility of intraoperative ICG fluorescent imaging for the resection of hepatoblastoma., Methods: In three hepatoblastoma patients, a primary tumor, recurrent tumor, and lung metastatic lesions were intraoperatively examined using a near-infrared fluorescence imaging system after the preoperative administration of ICG., Results: ICG fluorescent imaging was useful for the surgical navigation in hepatoblastoma patients. In the first case, the primary hepatoblastoma exhibited intense fluorescence during right hepatectomy, but no fluorescence was detected in the residual liver. In the second case, a recurrent tumor exhibited fluorescence between the residual liver and diaphragm. A complete resection of the residual liver, with a partial resection of the diaphragm, followed by liver transplantation was performed. In the third case with multiple lung metastases, each metastatic lesion showed positive fluorescence, and all were completely resected. These fluorescence-positive lesions were pathologically proven to be viable hepatoblastoma cells., Conclusion: Intraoperative ICG fluorescence imaging for patients with hepatoblastoma was feasible and useful for identifying small viable lesions and confirming that no remnant tumor remained after resection., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The patient was a 34-year-old man, who was referred to our hospital because of abnormal shadows in the right lower lung field on a chest radiograph during a medical screening. Chest computed tomography (CT) showed a pulmonary arteriovenous fistula 23 x 17 mm in size in the anterior basal segment of the right lung, together with a single artery and single vein. He had no symptoms and did not have Osler-Weber-Rendu syndrome. Coil embolization was performed in order to decrease the risk of complications associated with right-to-left shunting. Transcatheter embolization using interlocking detachable coils and detachable fibered coils was successfully performed without severe complications. Then, 320-row multidetector CT revealed that the blood flow from the pulmonary artery disappeared just after coil embolization, the blood flow from the pulmonary vein flowed backward, and the fistula was contrasted. The fistula had almost completely disappeared 8 months after embolization. We confirmed that blood flows were interrupted by 320-row CT and pulmonary angiography. 320-row CT was useful for the evaluation of pulmonary arteriovenous fistula and coil embolization.