Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

BACKGROUND: The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. METHODS: This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70 years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. RESULTS: Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80 years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. CONCLUSION: In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

The integration of the intracorporeal triangular anastomotic technique in robotic distal gastrectomy: advancing patient safety and procedural simplicity.

BACKGROUND: Robotic distal gastrectomy (RDG) with Billroth I (BI) reconstruction is predominantly performed due to its physiological congruence and simplicity. The Intracorporeal Triangular Anastomotic Technique (INTACT) aims to reduce ischemic areas compared to the conventional Delta-shaped anastomosis using the unique characteristics of robotic surgery to standardize procedures, thereby ensuring safe, simple, and reliable reconstruction. This study aims to investigate the efficacy of the INTACT in RDG with BI reconstruction, focusing on its robotic precision in minimizing ischemic zones and improving surgical reliability. SURGICAL TECHNIQUE: The posterior duodenal wall is dissected before reconstruction, and the hepatoduodenal ligament is severed to facilitate passive duodenal manipulation. A quarter-circumference incision is created centrally on the anterior wall of the duodenal stump to avoid excessive tension during anastomosis and to ensure an adequate anastomotic diameter. A small opening is established on the greater curvature of the remaining stomach, and the posterior walls of the stomach and duodenum are joined using a Linear stapler in the first fire. A V-shape is created, and two EndoWrist instruments (robotic first and fourth arms) are utilized to grip and extend the anastomosis diameter, completing the anastomosis with a shared hole closure using the Linear stapler. The robotic arms' features improve the physiological integrity and stability of the BI reconstruction. RESULTS: A total of 81 patients underwent RDG with INTACT from September 2020 to January 2024. The median age was 72 years (range: 31-91), with 49 males and 32 females. The median blood loss was 0 ml (range: 0-200 ml), and the median postoperative hospital stay was 8 days (range: 6-20 days). No cases required reanastomosis during surgery, and no postoperative anastomotic leakage, surgery-related reoperations, or anastomotic strictures were reported. CONCLUSION: INTACT in RDG can be safely performed. The characteristics of the EndoWrist instruments helped in stabilizing the technique, making it a viable option in robotic-assisted surgeries.

A case of hepatoid adenocarcinoma of the lung harboring KRAS G12C responded favorably to sotorasib.

Hepatoid adenocarcinoma of the lung is a rare variant of adenocarcinoma. We describe a case of hepatoid adenocarcinoma of the lung that harbored KRAS G12C and responded favorably to sotorasib. A man in his 70s was found to have an abnormality on his chest X-ray. He underwent right middle lobectomy, and a pathological examination of the surgical specimen showed conventional invasive adenocarcinoma with highly focal hepatoid adenocarcinoma. He received chemoradiotherapy and concurrent radiation, followed by durvalumab for postoperative recurrence. After three doses of durvalumab, he reported feeling short of breath. A computed tomography scan showed emerging broad consolidation in the right lower lobe. Transbronchial lung biopsy specimens from the consolidation showed hepatoid adenocarcinoma harboring KRAS G12C mutation. Therefore, he was started on sotorasib 960 mg daily. Eight days later, a computed tomography scan showed that the area of consolidation had reduced in size. Progressive disease was detected after 42 days of treatment with sotorasib. The patient died 1 month after cessation of sotorasib and 3 months after postoperative recurrence. We have encountered what we believe to be the first case of hepatoid adenocarcinoma of the lung with KRAS G12C mutation that responded favorably to treatment with sotorasib.

Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Combination of transbronchoscopic oxygen insufflation and a digital chest drainage system in endobronchial occlusion: a hybrid technique for localization of fistula in intractable pneumothorax.

BACKGROUND: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. CASE PRESENTATION: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. CONCLUSION: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.

Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Effects of Maturation on Antibacterial Properties of Vietnamese Mango (Mangifera indica) Leaves.

This study, for the first time, has investigated the relationships between alterations of mangiferin contents in mango leaves at different maturity stages and their antibacterial properties. Leaves were classified into six different maturity stages based on their color: (1) young dark reddish brown, (2) young yellow, (3) young light green, (4) mature green, (5) old dark green, and (6) old yellow leaves. Ethanol extracts were then examined against Gram-positive and Gram-negative bacteria, applying broth dilution and agar well diffusion methods. In addition, we also measured the mangiferin contents in leaves at different stages for the purpose of evaluating how the changes in this phytochemistry value affects their activities against bacteria. The results showed that extracts from leaves at young ages had better antibacterial properties than those from old leaves, as evidenced by the lower minimum inhibitory concentrations and larger inhibitory zones. In addition, we also found that the contents of mangiferin were significantly decreased followed the maturation process. These results suggest that mango leaves at young stages, especially dark reddish brown and young yellow leaves, are preferable for application in bacterial infections and other therapies related to mangiferin's constituents.

Anti-Inflammatory, Wound Healing, and Anti-Diabetic Effects of Pure Active Compounds Present in the Ryudai Gold Variety of Curcuma longa.

Turmeric (Curcuma longa) contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of Curcuma longa, on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.

Fibroblast-derived Extracellular Vesicles Induce Lung Cancer Progression in the Idiopathic Pulmonary Fibrosis Microenvironment.

Idiopathic pulmonary fibrosis (IPF) is a progressive aging-related lung disease associated with increased lung cancer risk. Although previous studies have shown that IPF worsens the survival of patients with lung cancer, whether IPF independently affects cancer malignancy and prognosis remains inconclusive. Extracellular vesicles (EVs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication in lung homeostasis and pathogenesis. EV cargo-mediated fibroblast-tumor cell communication might participate in the development and progression of lung cancer by modulating various signaling pathways. In this study, we examined the impact of lung fibroblast (LF)-derived EVs on non-small cell lung cancer (NSCLC) malignancy in the IPF microenvironment. Here, we showed that LFs derived from patients with IPF have phenotypes of myofibroblast differentiation and cellular senescence. Furthermore, we found that IPF LF-derived EVs have markedly altered microRNA compositions and exert proproliferative functions on NSCLC cells. Mechanistically, the phenotype was attributed mainly to the enrichment of miR-19a in IPF LF-derived EVs. As a downstream signaling pathway, mir-19a in IPF LF-derived EVs regulates ZMYND11-mediated c-Myc activation in NSCLC, potentially contributing to the poor prognosis of patients with NSCLC with IPF. Our discoveries provide novel mechanistic insights for understanding lung cancer progression in the IPF microenvironment. Accordingly, blocking the secretion of IPF LF-derived EV miR-19a and their signaling pathways is a potential therapeutic strategy for managing IPF and lung cancer progression.

Response Prediction Model of Atezolizumab plus Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Retrospective Study.

INTRODUCTION: Atezolizumab plus bevacizumab (ATZ+BV) treatment has become the first-line regimen for unresectable hepatocellular carcinoma (u-HCC). Prediction of response to it might be clinically beneficial. Using peripheral blood parameters, we aimed to construct a prediction model for ATZ+BV treatment. METHODS: Clinical records of 119 patients with u-HCC treated by ATZ+BV were retrospectively analyzed. The primary outcome measurement was defined as any-size reduction at the initial image evaluation. Using baseline values of peripheral blood parameters, a prediction model was constructed by univariate and multivariate logistic regression analysis. Validation was performed internally by bootstrap method. RESULTS: The primary outcome was achieved in 46 patients. Univariate analysis showed that C-reactive protein (CRP), alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were possible predictors. CRP and DCP, and NLR and PLR had correlation (correlation coefficient >0.3), so we used CRP and NLR as representative factors, respectively. Multivariate analysis constructed the following prediction model: Logit = 1.62-0.61×[CRP] -0.38×[Log10AFP] -0.37×[NLR]. Bootstrapped median (95% confidence interval) of coefficients of CRP, Log10AFP, NLR were -0.64 (-1.46 ∼ -0.11), -0.40 (-0.82 ∼ -0.03), and -0.38 (-0.74 ∼ -0.05), respectively. The area under the receiver operating characteristic curve (95% confidence interval) was 0.73 (0.60-0.80). Median overall survival of the favorably and unfavorably predicted groups were 17.0 and 11.0 months (p = 0.03), respectively. DISCUSSION: In patients with u-HCC treated by ATZ+BEV, a prediction model constructed using baseline values of CRP, AFP, and NLR had impact on any-size reduction at the initial image evaluation and on prognosis.

Acute Hepatitis E Infection during Chemotherapy for Lung Cancer: A Case Report.

Acute hepatitis E, one of the causes of acute liver injury, has been increasingly diagnosed in developed countries in recent years. Misdiagnosis of acute hepatitis E virus (HEV) infection as drug-induced liver injury (DILI) may lead to discontinuation of effective chemotherapy. Thus, viral hepatitis, including hepatitis E, must be ruled out in the diagnosis of DILI. A 78-year-old woman with lung adenocarcinoma and multiple bone metastases received maintenance therapy with pemetrexed + pembrolizumab for a year. Increased aspartate aminotransferase and alanine aminotransferase levels, indicating acute liver injury, were observed. Initially, DILI was suspected, and she was given medications to lower the levels of hepatic enzymes. She was later admitted to the hospital with the chief complaint of general malaise and anorexia. Serum aspartate aminotransferase and alanine aminotransferase levels were markedly elevated (381 and 854 U/L, respectively). Acute HEV infection was diagnosed based on the detection of serum HEV immunoglobulin A antibodies. The patient received liver support therapy, and the serum hepatic enzymes recovered to normal levels. Chemotherapy was resumed without any subsequent relapse of hepatic enzyme elevation. When DILI is suspected during chemotherapy, exclusion of viral hepatitis is mandatory, which can be achieved by measuring markers of hepatitis viruses, including HEV, and examining the patient's detailed medical history.

Diagnostic Utility and Safety of Non-Intubated Cryobiopsy Technique Using a Novel Ultrathin Cryoprobe in Addition to Conventional Biopsy Techniques for Peripheral Pulmonary Lesions.

BACKGROUND: Transbronchial cryobiopsy enables high-quality sample collection around the probe tip. Meanwhile, existing cryoprobes have less flexibility and a higher risk of bleeding. The ultrathin cryoprobe with a 1.1-mm diameter addresses these problems and allows specimens to be directly retrieved through the working channel of a thin bronchoscope. OBJECTIVE: This study evaluated the diagnostic utility and safety of non-intubated cryobiopsy using an ultrathin cryoprobe added to conventional biopsy for diagnosing peripheral pulmonary lesions (PPLs). METHODS: The data of patients who underwent conventional biopsy followed by non-intubated cryobiopsy to retrieve specimens through the thin bronchoscope's working channel for diagnosing PPLs at Osaka Metropolitan University Hospital from July 2021 to June 2022 were retrospectively collected. They were analyzed to evaluate the diagnostic utility and safety of adding non-intubated cryobiopsy to conventional biopsy for PPLs. The characteristics of PPLs that obtain additional diagnostic benefits from cryobiopsy over conventional biopsy were also investigated. RESULTS: The analysis included 113 patients. The diagnostic yields of conventional biopsy and non-intubated cryobiopsy were 70.8% and 82.3%, respectively (p = 0.009). The total diagnostic yield was 85.8%, higher than conventional biopsy alone (p < 0.001). Although one moderate bleeding occurred, no severe complications developed. The additional diagnostic benefits of non-intubated cryobiopsy over conventional biopsy were demonstrated when the radial endobronchial ultrasound (R-EBUS) showed "adjacent to" (60.3% vs. 82.8%, p = 0.017). CONCLUSIONS: Non-intubated cryobiopsy using an ultrathin cryoprobe has high diagnostic utility and safety for diagnosing PPLs, with additional diagnostic benefits over conventional biopsy depending on the R-EBUS image.

Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction.

BACKGROUND: Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique. CASE PRESENTATION: A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications. CONCLUSION: The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.

Effects of Roasting Conditions on Antibacterial Properties of Vietnamese Turmeric (Curcuma longa) Rhizomes.

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

[HUMIDIFIER LUNG WITH ORGANIZING PNEUMONIA DETECTED BY BRONCHOSCOPY: A CASE REPORT].

A 58-year-old man presented with dyspnea on exertion and diffuse ground-glass opacities with mosaicism on chest computed tomography in April 201X. A transbronchial lung biopsy revealed organizing pneumonia and lymphocytic infiltration, and steroids were administered. During steroid tapering, the shortness of breath and ground-glass opacities recurred, and a transbronchial lung re-biopsy revealed organizing pneumonia without a granuloma again. Based on the clinical history, imaging features, and amount of humidifier usage, hypersensitivity pneumonitis caused by a humidifier was suspected. The inhalation challenge test was considered positive, and the diagnosis was confirmed. There have been some reports of unidentified granuloma in patients with humidifier lungs. Therefore, this case suggests that humidifier lung should be considered as a possibility even if pathological examination does not reveal granulomas and inflammatory changes such as organizing pneumonia are the only findings.

[A Case of Locally Advanced Giant Sigmoid Colon Cancer Successfully Treated with Neoadjuvant Chemotherapy].

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05).

OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and ß = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.

Circulating Tumor DNA as a Potential Prognostic Marker in Patients with Borderline-Resectable Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy Followed by Pancreatectomy.

BACKGROUND: Circulating tumor DNA (ctDNA) might be a promising biomarker for pancreatic cancer in liquid biopsy. This study aimed to evaluate the usefulness of liquid biopsy for patients with borderline-resectable pancreatic cancer (BR-PC). METHODS: Patients with BR-PC according to the National Comprehensive Cancer Network guidelines (2017) and eligible for neoadjuvant chemotherapy (NAC) followed by pancreatectomy were recruited at Wakayama Medical University Hospital (UMIN000026647) between March 2017 and April 2020. The study enrolled 55 patients with locally advanced PC, and each patient consented to inclusion in the study. The study investigated the relationship between KRAS status in ctDNA and clinicopathologic features, analyzing ctDNA at three time points: pretreatment, post-NAC, and post-operation. RESULTS: Of the 55 enrolled patients with a diagnosis of BR-PC, 34 were scheduled to undergo pancreatectomy. From 27 patients with resected BR-PC, 81 blood samples were analyzed in triplicate for ctDNA. The patients with positive pretreatment and post-NAC ctDNA status had no significant decrease in median relapse-free survival (RFS) or overall survival (OS). However, the patients with positive postoperation ctDNA status had a significantly shorter median OS (723 days) than the patients with negative ctDNA results (not reached; P = 0.0148). A combined analysis of postoperative ctDNA and CA19-9 values showed the cumulative effect on both RFS (P = 0.0066) and OS (P = 0.0046). The adjusted hazard ratio for risk of survival computed for the patients carrying risk factors (either detectable ctDNA or CA19-9 > 37 U/ml) increased from 4.13-fold to 17.71-fold (both P = 0.0055) compared with the patients who had no risk factors. CONCLUSION: Positive ctDNA predicts poor survival for patients with BR-PC who undergo NAC followed by pancreatectomy.

[A Case Report of Stage â £b Thoracic Esophageal Cancer Responding to Multidisciplinary Treatment].

A 68-year-old man was referred to our hospital because of back pain during swallowing. Upper gastrointestinal endoscopy revealed a lower esophageal type 3 tumor. The patient was diagnosed with esophageal squamous cell carcinoma by the biopsy specimen. CT scan showed thoracic lower esophagus wall thickening, left paracardiac lymph node swelling, and a low-density area in the liver. Therefore, the patient was diagnosed with Stage Ⅳb esophageal cancer. After introducing cisplatin plus 5-FU combination therapy, the liver metastasis disappeared. After 9 chemotherapy courses, the patient received radical chemoradiotherapy. After completing chemoradiotherapy, the patient was followed up without any treatment. After 3 years since the treatment initiation, the patient is surviving without any relapse.