Current situation of management of spontaneous pneumothorax in Japan: A cross-sectional cohort study.

BACKGROUND: Limited epidemiological information is available on spontaneous pneumothorax. To address this gap, the Japan Society for Pneumothorax and Cystic Lung Disease (JSPCLD) conducted a nationwide retrospective survey to investigate the current epidemiology of spontaneous pneumothorax in Japan. METHODS: In this study, we conducted a retrospective cross-sectional cohort study to demonstrate the clinical features of spontaneous pneumothorax in one year from April 2019 to March 2020, compare patient characteristics and treatment outcomes between primary (PSP) and secondary spontaneous pneumothorax (SSP), and investigate the risk factors associated with in-hospital mortality among patients with SSP. RESULTS: A total of 1784 patients from 28 institutions were enrolled in the study, with PSP observed in 956 cases (53.6%) and SSP in 817 cases (45.8%). The age distribution showed a biphasic peak caused by the different peaks between PSP and SSP. In-hospital mortality occurred in 42 cases (2.4%) among all patients, with 0 cases (0%) in PSP and 42 cases (5.1%) in SSP. Multivariable analyses revealed that interstitial pneumonia as an underlying disease (odds ratio: 2.4700, 95% confidence interval: 1.1100 to 5.4800, p = 0.0269), performance status≧3 (odds ratio: 7.3900, 95% confidence interval: 3.1900 to 17.2000, p < 0.0001), and lower value of serum albumin on admission (odds ratio: 0.4060, 95% confidence interval: 0.2140 to 0.7690, p = 0.0057) were significantly associated with in-hospital mortality among patients with SSP. CONCLUSIONS: SSP patients with poor baseline conditions are at a higher risk for in-hospital mortality. It is crucial to provide close and meticulous management for SSP patients with compromised conditions.

The Effectiveness of the Combination of Arterial Infusion Chemotherapy and Radiotherapy for Biliary Tract Cancer: A Prospective Pilot Study.

The standard treatment of unresectable biliary tract cancer (BTC) has shown an insufficient response rate (RR). Our retrospective setting revealed that a combination therapy consisting of intra-arterial chemotherapy plus radiation therapy (IAC + RT) provided a high RR and long-term survival benefits in unresectable BTC. This prospective study aimed to test the effectiveness and safety of IAC + RT as the first-line therapy. The regimen included one-shot IAC with cisplatin, 3-6 months of reservoir IAC (5-FU and cisplatin, q/week), and 50.4 Gy of external radiation. The primary endpoints include the RR, disease control rate, and adverse event rate. This study included seven patients with unresectable BTC without distant metastasis, with five cases classified as stage 4. RT was completed in all cases, and the median number of reservoir IAC sessions was 16. The RR was 57.1% for imaging and 71.4% for clinical assessment, and the disease control rate was 100%, indicating a high antitumor efficacy, which allowed two cases to be transferred to surgery. Five cases of leukopenia and neutropenia; four cases of thrombocytopenia; and two cases of hemoglobin depletion, pancreatic enzyme elevation, and cholangitis were observed, but with no treatment-related deaths. This study revealed a very high antitumor effect with IAC + RT for some unresectable BTC, and it could be useful for conversion therapy.

Multiplex Digital PCR Assay to Detect Multiple KRAS and GNAS Mutations Associated with Pancreatic Carcinogenesis from Minimal Specimen Amounts.

Digital PCR (dPCR) allows for highly sensitive quantification of low-frequency mutations and facilitates early detection of cancer. However, low-throughput targeting of single hotspots in dPCR hinders variant specification when multiple probes are used. We developed a dPCR method to simultaneously identify major variants related to pancreatic carcinogenesis. Using a two-dimensional plot of droplet fluorescence under the optimized concentration of two fluorescent probe pools, the absolute quantification of different KRAS and GNAS variants was determined. Successful detection of the multiple driver mutations was verified in 24 surgically resected tumor samples from 19 patients and 22 fine-needle aspiration samples from patients with pancreatic ductal adenocarcinoma. Precise quantification of the variant allele frequency was optimized by using template DNA at a concentration as low as 1 to 10 ng. Furthermore, amplicons targeting multiple hotspots were successfully enriched with fewer false-positive findings using high-fidelity polymerase, allowing for the detection of various KRAS and GNAS mutations with high probability in small amount of cell/tissue specimens. Using this target enrichment, mutations at a rate of 90% in small residual tissues, such as the fine-needle aspiration needle flush and microscopic lesions in resected specimens, were successfully identified. The proposed method allows for low-cost, accurate detection of driver mutations to diagnose cancers, even with minimal tissue collection.

Mutant GNAS limits tumor aggressiveness in established pancreatic cancer via antagonizing the KRAS-pathway.

BACKGROUND: Mutations in GNAS drive pancreatic tumorigenesis and frequently occur in intraductal papillary mucinous neoplasm (IPMN); however, their value as a therapeutic target is yet to be determined. This study aimed at evaluating the involvement of mutant GNAS in tumor aggressiveness in established pancreatic cancer. METHODS: CRISPR/Cas9-mediated GNAS R201H silencing was performed using human primary IPMN-associated pancreatic cancer cells. The role of oncogenic GNAS in tumor maintenance was evaluated by conducting cell culture and xenograft experiments, and western blotting and transcriptome analyses were performed to uncover GNAS-driven signatures. RESULTS: Xenografts of GNAS wild-type cells were characterized by a higher Ki-67 labeling index relative to GNAS-mutant cells. Phenotypic alterations in the GNAS wild-type tumors resulted in a significant reduction in mucin production accompanied by solid with massive stromal components. Transcriptional profiling suggested an apparent conflict of mutant GNAS with KRAS signaling. A significantly higher Notch intercellular domain (NICD) was observed in the nuclear fraction of GNAS wild-type cells. Meanwhile, inhibition of protein kinase A (PKA) induced NICD in GNAS-mutant IPMN cells, suggesting that NOTCH signaling is negatively regulated by the GNAS-PKA pathway. GNAS wild-type cells were characterized by a significant invasive property relative to GNAS-mutant cells, which was mediated through the NOTCH regulatory pathway. CONCLUSIONS: Oncogenic GNAS induces mucin production, not only via MUC2 but also via MUC5AC/B, which may enlarge cystic lesions in the pancreas. The mutation may also limit tumor aggressiveness by attenuating NOTCH signaling; therefore, such tumor-suppressing effects must be considered when therapeutically inhibiting the GNAS pathway.

Dual preparation of plasma and platelet concentrates in platelet additive solution from platelet concentrates in plasma using a novel filtration system.

BACKGROUND AND OBJECTIVES: Platelet concentrates suspended in a platelet additive solution (PAS-PC) are associated with a reduction in allergic response and are suitable for preparing pathogen-inactivated PC. We aimed to develop an efficient platform for the dual preparation of PAS-PC and platelet-poor plasma. MATERIALS AND METHODS: PAS-PC was prepared in six steps by using a hollow-fibre system based on cross-flow filtration: priming, loading PC, loading PAS, collection of filtered liquid (flow-through) and collection of platelets by washing with PAS followed by washing with air. In this study, the efficacy of platelet and plasma protein recovery and characteristics of recovered PAS-PC and flow-through plasma were analysed in detail. RESULTS: Recoveries of platelet in PAS-PC and plasma protein in the flow-through were 95.4% ± 3.7% and 61.6% ± 5.0%, respectively. The residual plasma protein in PAS-PC was 34.1% ± 2.8%. Although the expression level of CD62P, a platelet activation marker, in recovered platelets was approximately 1.2-fold of that in original platelets, swirling patterns were well retained, and aggregation in PAS-PC was not visible. Agonist-induced aggregabilities, platelet morphology and hypotonic shock recovery were conserved. The patterns of plasma protein and lipoprotein in the flow-through were comparable with those in the original PCs. The multimeric pattern analysis of VWF remained unaltered. CONCLUSION: We propose a highly efficient preparation system that enables the simultaneous production of PAS-PC and platelet-poor plasma. It also achieves a high recovery of functionally well-retained platelets with very low activation.

Prognostic significance of skeletal muscle decrease in unresectable pancreatic cancer: Survival analysis using the Weibull exponential distribution model.

BACKGROUND/OBJECTIVES: Decrease in skeletal muscle mass and function is associated with a poor prognosis following surgical resection of pancreatic ductal adenocarcinomas (PDAs). This study evaluated whether skeletal muscle mass decrease affects PDA outcomes. METHODS: Data of 112 patients with advanced and unresectable PDA who underwent chemotherapy in a single institution were retrospectively analyzed. Information on age, sex, hematological investigations, including systemic inflammation-based markers and nutritional assessment biomarkers, and imaging parameters of skeletal muscle mass and visceral adipose tissue were retrieved from the patients' medical records. The efficiency of the Cox, Weibull, and standardized exponential models were compared using hazard ratios and the Akaike Information Criterion (AIC). RESULTS: Results from the Weibull, Cox, and standardized exponential model analyses indicated that low skeletal muscle mass, Eastern Cooperative Oncology Group performance status (PS), and the requirement of biliary drainage were associated with the highest risk of death, followed by carcinoembryonic antigen (CEA) levels and the presence of ascites. The AIC value from the four significant parameters was lowest for the Weibull-exponential distribution (222.3) than that of the Cox (653.7) and standardized exponential models (265.7). We developed a model for estimating the 1-year survival probability using the Weibull-exponential distribution. CONCLUSIONS: Low-skeletal muscle index, PS, requirement of biliary drainage, CEA levels, and presence of ascites are independent factors for predicting poor patient survival after chemotherapy. Improved survival modeling using a parametric approach may accurately predict the outcome of patients with advanced-stage PDA.

Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance.

BACKGROUND: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). METHODS: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. RESULTS: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. CONCLUSIONS: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.

BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion. CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor. CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.

[Bronchial Occlusion with Endobronchial Watanabe Spigot for Massive Pulmonary Hemorrhage during Heart Surgery;Report of a Case].

Massive pulmonary hemorrhage, although rare, is a potentially life-threatening complications during heart surgery. We herein present 1 such case successfully treated by selective bronchial occlusion using an Endobronchial Watanabe Spigot (EWS). The 82-year-old female underwent mitral valve replacement, tricuspid annuloplasty, and maze procedure. An hour and a half after cessation of cardiopulmonary bypass, the patient suffered a massive pulmonary hemorrhage. A subsequent bronchoscopy identified the hemorrhage site at the right middle lobe bronchus (B5b), and an EWS was then selectively deployed into this bronchus to block the hemorrhage. The following day, bronchial arterial embolization was performed, enabling the removal of the spigot on the next day. The patient's respiratory condition gradually improved, allowing for extubation on the 21st postoperative day. By preventing bleeding into neighboring bronchi, which, in turn, avoids the risk of exacerbating hypoxia, bronchial occlusion with EWSs is highly effective in managing massive pulmonary hemorrhage during heart surgery.

Time-saving method for directly amplifying and capturing a minimal amount of pancreatic tumor-derived mutations from fine-needle aspirates using digital PCR.

It is challenging to secure a cytopathologic diagnosis using minute amounts of tumor fluids and tissue fragments. Hence, we developed a rapid, accurate, low-cost method for detecting tumor cell-derived DNA from limited amounts of specimens and samples with a low tumor cellularity, to detect KRAS mutations in pancreatic ductal carcinomas (PDA) using digital PCR (dPCR). The core invention is based on the suspension of tumor samples in pure water, which causes an osmotic burst; the crude suspension could be directly subjected to emulsion PCR in the platform. We examined the feasibility of this process using needle aspirates from surgically resected pancreatic tumor specimens (n = 12). We successfully amplified and detected mutant KRAS in 11 of 12 tumor samples harboring the mutation; the positive mutation frequency was as low as 0.8%. We used residual specimens from fine-needle aspiration/biopsy and needle flush processes (n = 10) for method validation. In 9 of 10 oncogenic KRAS pancreatic tumor samples, the "water-burst" method resulted in a positive mutation call. We describe a dPCR-based, super-sensitive screening protocol for determining KRAS mutation availability using tiny needle aspirates from PDAs processed using simple steps. This method might enable pathologists to secure a more accurate, minimally invasive diagnosis using minute tissue fragments.

Resection for pancreatic cancer metastases contributes to survival: A case report with sequential tumor genotype profiling during the long-term postoperative course.

INTRODUCTION: Surgical management is not a standard treatment option for metastatic recurrence of pancreatic adenocarcinoma. However, the surgical management of a solitary metastasis is useful in selected cases. PATIENT CONCERNS: A 42-year-old woman was referred to our hospital on account of epigastric pain associated with a mass in the pancreatic body. The patient had a family history of branch duct-type intraductal papillary mucinous neoplasm of the pancreas. DIAGNOSIS: The patient was diagnosed with pancreatic ductal adenocarcinoma (PDA) complicated with pancreatitis due to pancreatic duct involvement. INTERVENTIONS: The patient underwent distal pancreatectomy, and pathological examination revealed a tubular adenocarcinoma. Solitary liver and lung metastatic tumors were found 6 and 43 months after the initial presentation, respectively, and sequential metastasectomies were performed. OUTCOMES: The patient survived until 8 years after her initial presentation. The genetic profiles of the resected specimens, primary PDA, and recurrent tumors in the liver and lung possessed identical KRAS mutations at codon 12, whereas there were no mutations in the main tumor suppressor genes, such as TP53, CDKN2A, and SMAD4. Multiplex polymerase chain reaction-based microsatellite instability assay demonstrated microsatellite stability. CONCLUSION: In our case, the patient with pancreatic adenocarcinoma survived for over 8 years following the resection of the primary tumor and resections of metachronous metastatic tumors. The outcome of PDA may be associated with the genetic profile that regulates its biological behavior. Operative management of solitary metastatic tumors may be a therapeutic options for selected patients with pancreatic cancer.

A more efficient preparation system for HLA-eliminated platelets.

BACKGROUND AND OBJECTIVES: Although HLA-eliminated platelets can facilitate transfusions to patients possessing HLA antibodies, no such products are currently available commercially perhaps because the platelet collection rate is not yet economically viable. We have improved this process' efficiency by employing a hollow-fibre system at the last step of the production process after an acid and a reaction buffer have been washed out conventionally by centrifugation. MATERIALS AND METHODS: HLA-eliminated platelets were prepared via four distinct steps: chilled on ice, treated with an acid solution, diluted and finally washed using the hollow-fibre system. The efficiency of this platelet recovery process was determined. The resulting products' platelet characteristics, including a capacity for HLA expression, were evaluated in vitro and compared in detail to their corresponding originals. RESULTS: The average efficiency of platelet recovery was 91%. Although the expression levels of CD62P, a molecular marker for platelet activation, were approximately threefold higher on new platelets than on the original platelets, their HLA expression levels were lower. The phagocytosis assay, with monoclonal antibodies and cognate HLA antibody-containing sera, suggested that HLA-ABC molecules on the cell surface were sufficiently removed. The platelet functions, including the agonist-induced aggregability and adherence/aggregability of the collagen-coated plates under certain conditions, were conserved and not significantly different from the original ones. CONCLUSION: We propose a novel preparation system for producing HLA-eliminated platelets without centrifugation, which ensures a highly efficient, and therefore, much more economical method of platelet recovery that also retains their key functionality.

Genetic analysis of postoperative recurrence of pancreatic cancer potentially owing to needle tract seeding during EUS-FNB.

Background and study aims Needle tract seeding during endoscopic ultrasound fine-needle biopsy (EUS-FNB) remains a concern. We investigated whether such seeding occurred in a patient with pancreatic ductal adenocarcinoma (PDA). Patient and methods Surgically resected and EUS-FNB-derived specimens were genotyped to determine if a gastric wall tumor that emerged 3 years after curative resection of an early-stage PDA was clonally related to the original tumor. Results The gastric tumor histologically resembled the primary PDA; the lesions also shared KRAS , SMAD4 , and RNF43 mutations. Genotyping of the preoperative EUS-FNB specimen, in which cancer was not detected, nevertheless revealed mutations that were identical to those in the resected primary and recurrent tumors. While the primary PDA had a low frequency of mutant SMAD4 , such mutations were highly prevalent in both the EUS-FNB and recurrent tumor specimens. Conclusions The genetic lineages of sampled tissues from our patient revealed that needle tract seeding may have incidentally occurred when a subset of neoplastic cells within a heterogeneous tumor ( i. e. , an aggressive clone) was targeted during EUS-FNB.

[Congenitial Pulmonary Airway Malformation in an Adult with Pneumonia].

Congenitial pulmonary airway malformation (CPAM) most commonly present respiratory distress in the prenatal or neonatal period, but may rarely be asymptomatic and is incidentally found in adult patients with acute or recurrent pneumonia. Herein, we report a case of a 26-year-old asymptomatic adult male patient with pneumonia of the right lower lobe. He was also found to have multiple cystic lesions in the same lobe which was suspected to be CPAM, and the right lower lobectomy was performed.

Obstructive cholangitis by mucus from an intraductal papillary mucinous neoplasm with pancreatobiliary fistula treated by endoscopic septotomy and direct peroral cholangioscopy: a case report.

Intraductal papillary mucinous neoplasms (IPMNs) occasionally form a fistula to adjacent organs, resulting in obstructive jaundice and cholangitis due to mucus obstruction. Although some procedures such as endoscopic nasobiliary drainage are attempted, they often do not work adequately because of high mucus viscosity. Herein, we report the case of an 87-year-old man with obstructive cholangitis treated by endoscopic septotomy and mucus suction with direct peroral cholangioscopy using conventional endoscopy. The patient incidentally showed a branched-type IPMN in the pancreatic head on computed tomography (CT) approximately 10-years ago. Although the patient's tumor had grown slowly and he occasionally developed cholangitis, he did not want surgery. He was admitted to our hospital because of cholangitis by mucus obstruction with a PB fistula. Endoscopic retrograde cholangiopancreatography (ERCP) and septotomy were performed. Septotomy made the duodenal papilla a large orifice, thereby facilitating spontaneous drainage of mucus. In addition, conventional endoscopy with a large working channel enabled direct access into the orifice and smooth mucus suction, thereby alleviating his cholangitis. In conclusion, septotomy and direct peroral cholangioscopy using conventional endoscopy could be useful to control biliary tract infection and obstructive jaundice due to mucus obstruction from an IPMNs with PB fistula.

[Bronchial Typical Carcinoid Tumor Treated with Two-stage Resection;Report of a Case].

A 45-year-old woman, who had been treated for bronchial asthma, was referred to our hospital with symptoms of dyspnea. Upon examination, we found the right main bronchus to be almost completely occluded by an endobronchial tumor. For the purpose of diagnosis and relieving the dyspnea, we performed a rigid bronchoscopic tumor resection with a high frequency snare. The tumor was pathologically diagnosed as a typical bronchial carcinoid, and a right upper lobectomy and wedge resection of the right main bronchus was carried out 1 month later.

Utility of "liquid biopsy" using pancreatic juice for early detection of pancreatic cancer.

Background Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions Our study indicates the potential of "endoscopic liquid biopsy" to capture the driver gene for PDA diagnosis.

[Case report:multiple gastrointestinal stromal tumors of the small intestine associated with von Recklinghausen disease].

Abdominal ultrasonography revealed a low echoic mass in the upper abdomen of a 65-year-old man. He was referred to our department, where abdominal CT revealed a tumor with a 30-mm contrast effect on the distal side of the inferior part of the duodenum. Endoscopy revealed a submucosal tumor in the same region, and ultrasonic endoscopy showed a low echoic mass with a clear boundary derived from the muscle layer. The duodenum was partially resected based on a diagnosis of suspected gastrointestinal stromal tumors (GIST), and the skin tumor was simultaneously resected. An elastic, soft, 30-mm tumor mass was found in the upper duodenum during surgery, and small nodules of 3-5mm were identified throughout the 110-cm length of the jejunum at intervals of 20-30cm. The histopathological diagnosis was GIST and immunostaining showed the mass to be c-kit and CD34 positive. We diagnosed the skin tumor as a neurofibroma (von Recklinghausen disease). Mutational analysis of c-kit in the resected specimen showed no mutation, therefore suggesting that imatinib would not be effective. Since the nodules remaining in the small intestine might also be GIST, we established a policy of regular imaging assessments.

An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker.

BACKGROUND: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. METHODS: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. RESULTS: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). CONCLUSIONS: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

Efficacy of stereotactic radiotherapy for brain metastases using dynamic jaws technology in the helical tomotherapy system.

OBJECTIVE: Dynamic jaws (DJ) are expected to be useful in stereotactic radiotherapy (SRT) for brain metastases (BM). The efficacy and optimal dose fractionation were investigated. METHODS: In a planning study, 63 treatment plans were generated for the following 3 conditions: 1.0-cm fixed jaws (FJ), 2.5-cm FJ and 2.5-cm DJ. In a clinical study, 30 Gy/3 fr, 35 Gy/5 fr or 37.5 Gy/5 fr were prescribed depending on tumour size. Clinical results of groups treated with 2.5-cm DJ plans and 1.0-cm FJ were compared. RESULTS: In the planning study, the treatment times in 2.5-cm DJ and FJ plans were less than that in 1.0-cm FJ plans (p < 0.001). The brain doses in 1.0-cm FJ plans and 2.5-cm DJ plans were smaller than those in 2.5-cm FJ plans (p < 0.05). In the clinical study, 34 patients with 68 BM were treated with SRT. Of those, 15 patients with 34 BM were treated with 2.5-cm DJ plans and 19 patients with 34 BM were treated with 1.0-cm FJ plans. The overall survival and local tumour control (LC) rates were 52 and 93% at 12 months, respectively. The DJ system achieved favourable LC and 29% shorter treatment time compared with the FJ system (p < 0.001). Grade 2 or 3 necrosis occurred more frequently in patients with 15 cc or larger tumour volumes (p = 0.05). CONCLUSION: DJ technology enables treatment time to be reduced without worsening the dose distribution and clinical efficacy. The prescribed doses in this study may be acceptable for patients with small tumour volumes. ADVANCES IN KNOWLEDGE: DJ technology enables treatment time to be reduced without worsening the dose.