[Esophagectomy for Bronchogenic Cyst within the Esophageal Muscle Layer with Dysphagia:Report of a Case].

A 26-year-old man referred to our hospital because of dysphagia and a mediastinal tumor detected on chest computed tomography (CT). A contrast-enhanced CT revealed a 12 cm long cystic tumor along the right thoracic esophagus. An upper gastrointestinal endoscopy showed no abnormalities in the esophageal mucosa, and an unclear boundary between the tumor and the esophageal wall was observed by echography. In surgery, the tumor and the esophagus were in one lump, and esophagectomy was performed. On the fourth postoperative day, esophagogastric anastomosis was performed with poststernal reconstruction, and the patient was discharged home on the 38th postoperative day. Pathological examination revealed that the mass was a cystic lesion within the esophageal muscular layer, and the cyst wall was coated with airway-like multi-lineal hairy epithelium, which led to the diagnosis of a bronchogenic cyst. Even if the cyst is within the esophageal muscularis layer, bronchogenic cyst should be considered in the differential.

[Pulmonary Herniation Requiring Reconstructive Surgery Caused by Minimally Invasive Cardiac Surgery:Report of a Case].

A 72-year-old man who underwent aortic valve replacement by a minimally invasive cardiac surgery (MICS) approach two years ago was visited our hospital complaining of swelling and pain in the right anterior chest. A chest computed tomography (CT) scan showed that the right upper lobe protruded beyond the right second intercostal space and outside the thorax. He was diagnosed as a right intercostal lung hernia and underwent chest wall reconstruction with a substitute method. Postoperative course was uneventful without any evidence of recurrence. Postoperative intercostal lung hernias in MICS may increase with the increment in MICS, and it is necessary to accumulate cases as one of the complications.

Clinical application of a lung cancer organoid (tumoroid) culture system.

Despite high expectations for lung tumoroids, they have not been applied in the clinic due to the difficulty of their long-term culture. Here, however, using AO (airway organoid) media developed by the Clevers laboratory, we succeeded in generating 3 lung tumoroid lines for long-term culture (>13 months) from 41 lung cancer cases (primary or metastatic). Use of nutlin-3a was key to selecting lung tumoroids that harbor mutant p53 in order to eliminate normal lung epithelial organoids. Next-generation sequencing (NGS) analysis indicated that each lung tumoroid carried BRAFG469A, TPM3-ROS1 or EGFRL858R/RB1E737*, respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAFG469A, crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFRL858R/RB1E737*) significantly suppressed the growth of each lung tumoroid line. AO media was superior to 3 different media developed by other laboratories. Our experience indicates that long-term lung tumoroid culture is feasible, allowing us to identify NGS-based therapeutic targets and determine the responsiveness to corresponding small molecule drugs.

Distinguishability and Disturbance in the Quantum Key Distribution Protocol Using the Mean Multi-Kings' Problem.

We introduce a quantum key distribution protocol using mean multi-kings' problem. Using this protocol, a sender can share a bit sequence as a secret key with receivers. We consider a relation between information gain by an eavesdropper and disturbance contained in legitimate users' information. In BB84 protocol, such relation is known as the so-called information disturbance theorem. We focus on a setting that the sender and two receivers try to share bit sequences and the eavesdropper tries to extract information by interacting legitimate users' systems and an ancilla system. We derive trade-off inequalities between distinguishability of quantum states corresponding to the bit sequence for the eavesdropper and error probability of the bit sequence shared with the legitimate users. Our inequalities show that eavesdropper's extracting information regarding the secret keys inevitably induces disturbing the states and increasing the error probability.

Iatrogenic femoral vein pseudoaneurysm.

Femoral vein pseudoaneurysm is a rare complication during percutaneous interventions. We report the case of a patient with common femoral vein pseudoaneurysm caused by unsuccessful manual compression. A 68-year-old woman underwent catheter ablation for atrial fibrillation at another institution. Postoperatively, she experienced right groin pain and leg edema. Doppler ultrasound examination revealed a 2-cm venous pseudoaneurysm as a compressible and hypoechoic lesion. We successfully performed venous aneurysmectomy after failed ultrasound-guided compression therapy. Appropriate procedures must be selected for patients with femoral pseudoaneurysm. The efficacy of hemostatic techniques for preventing vascular complications after venous sheath removal should not be underestimated.

A case report of left lower lobe segmentectomy for pulmonary metastasis from retroperitoneal liposarcoma.

BACKGROUND: The principle treatment for retroperitoneal liposarcoma is surgical resection, however there are many cases of recurrence. In addition to local recurrence, retroperitoneal liposarcoma, particularly dedifferentiated liposarcoma is known to occasionally cause lung metastases. CASE REPORT: A 72-year-old woman with a diagnosis of retroperitoneal liposarcoma and probable right upper lobe early pulmonary adenocarcinoma underwent sequential local tumor resection and right upper lobectomy. Twenty months after liposarcoma resection, a computed tomography (CT) scan of the chest revealed a nodule located in the left lower lobe. A CT-guided biopsy was performed and she was subsequently diagnosed with pulmonary metastasis from retroperitoneal liposarcoma. The nodule enlarged chronologically, however a left lower lobectomy could not be performed because respiratory function after the right upper lobectomy was not sufficient. Therefore, in order to preserve the left superior segment (S6), the basal segments (S8+S9+S10) were resected. Seven months after the surgery, she is living a self-reliant life without recurrence of liposarcoma. CONCLUSION: Here we have reported a case of pulmonary metastasis from retroperitoneal liposarcoma following limited surgery. In cases where respiratory function is limited, lower lobe segmentectomy can be an effective treatment. For the treatment of a single pulmonary metastasis from retroperitoneal liposarcoma, metastasectomy was considered to be effective as long as no local recurrence was seen after initial primary tumor resection.

Development of an integrated CRISPRi targeting ΔNp63 for treatment of squamous cell carcinoma.

TP63 encodes TAp63, which is functionally similar to the tumor suppressor TP53, and ΔNp63, which lacks the transcription-activating domain of TAp63 and appears potently oncogenic in squamous cell carcinomas (SCCs). In this study, we developed an integrated CRISPR interference (CRISPRi) system to selectively suppress ΔNp63 (CRISPRiΔNp63). We engineered this CRISPRi using tandemized guide RNA expression cassettes that targeted the 50 to 100 bp downstream of the transcription start site of ΔNp63 in combination with inactivated Cas9 linked to the transcription repression module Krüppel-associated box repressor domain. The plasmid vector harboring CRISPRiΔNp63 repressed ΔNp63 transcription in lung and esophageal SCC cells. Likewise, Ad-CRISPRiΔNp63, an all-in-one adenoviral vector containing the tandemized gRNAs and dCas9/KRAB expression cassette suppressed ΔNp63 expression in SCC cells. Ad-CRISPRiΔNp63 also effectively decreased cell proliferation and colony formation and induced apoptosis in lung and esophageal SCC cells in vitro and significantly inhibited tumor growth in a mouse lung SCC xenograft model in vivo. These results indicate that ΔNp63 suppression using CRISPRiΔNp63 may be an effective strategy for treating lung and esophageal SCC.

Analysis of the DNA methylation level of cancer-related genes in colorectal cancer and the surrounding normal mucosa.

BACKGROUND: Two molecular pathways promote the development of colorectal cancer (CRC). One is termed "microsatellite stable" (MSS) whereas the other is characterized by "microsatellite instability" (MSI or MIN). In addition, the CpG island methylation phenotype is known to be an important alteration as a third molecular type. Thus, DNA methylation is thought to provide potential biomarkers for assessment of cancer risk in normal mucosa. In addition, it is also known that colonic location is an important parameter in the development of CRC. METHODS: We examined the surrounding normal mucosa in three parts of the colon. Next, we quantified DNA methylation levels of SFRP1, SFRP2, SFRP5, DKK2, DKK3, mir34b/c, RASSF1A, IGFBP7, CDKN2A, and MLH1 in isolated cancerous glands and crypts of normal colorectal mucosa adjacent to CRCs using a pyrosequencer. RESULTS: DNA methylation levels of SFRP1, SFRP2, DKK2, and mir34b/c were significantly higher in CRCs with an MSS phenotype than in those with an MSI phenotype. The average level of methylation in normal crypts did not decrease with the distance from the tumor, irrespective of microsatellite status or the tumor location. DNA methylation levels in SFRP1 and SFRP2 genes in normal crypts were significantly higher in left-side than right-side CRC with an MSS phenotype. Finally, the genes were classified into three types based on the methylation frequencies in normal crypts, including type I (SFRP1 and SFRP2I), type II (DKK2 and mir34b/c), and type III (others). CONCLUSIONS: Our results showed that DNA methylation of SFRP1 and SFRP2 might be useful to predict cancer risk of surrounding normal mucosa. In addition, a field effect may be present in CRC, affecting both adjacent and non-adjacent normal mucosa.

Unusual manifestation of Helicobacter cinaedi infection: a case report of intracranial subdural empyema and bacteremia.

BACKGROUND: There have been various reports concerning Helicobacter cinaedi infections. However, few reports have examined central nervous system infections. CASE PRESENTATION: A 52-year-old man was transferred from the local hospital because of a persistent headache and suspected intracranial subdural empyema. Neurosurgical drainage was performed via burr holes. Gram staining and results from abscess cultures were negative. The blood culture yielded H. cinaedi. He was given an antibiotic regimen consisting of 2 g of ceftriaxone twice a day, but the size of the abscess was not reduced in size at all after 3 weeks of treatment. Neurosurgical drainage was performed again, and the antimicrobial regimen was switched to 2 g of meropenem 3 times a day. The size of the abscess was reduced after 2 weeks of the second drainage and antimicrobial drug change to meropenem. After 4 weeks treatment with meropenem, the patient was discharged, and his symptoms had completely resolved. CONCLUSIONS: H. cinaedi infection should be considered in the differential diagnosis of subdural empyema cases for which Gram staining and abscess culture results are negative. Meropenem can be a first-line drug of choice or an effective alternative treatment for H. cinaedi central nervous system infections.

A Case of Birt-Hogg-Dubé (BHD) Syndrome Harboring a Novel Folliculin (FLCN) Gene Mutation.

BACKGROUND Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder clinically characterized by pulmonary cysts, spontaneous pneumothorax, renal cell cancer, and skin fibrofolliculomas. The disorder is caused by germline mutations in the FLCN gene. CASE REPORT A 56-year-old female was admitted to our hospital with a diagnosis of bilateral spontaneous pneumothorax. A computed tomography (CT) scan of the chest revealed bilateral multiple bullae predominantly located in the subpleural and mediastinal areas in the bilateral upper and lower lobes. Although she was cured by thoracic cavity drainage, she underwent resection of bilateral lung bullae because she had a prior history of right pneumothorax at 37- and 45-years of age. She had no signs of renal tumor but had fibrofolliculoma in her face and a family history of pneumothorax, we therefore suspected BHD syndrome. DNA sequence analyses determined that there was a two base pair deletion in exon 4 of the FLCN gene, confirming the diagnosis of BHD syndrome. CONCLUSIONS Here we report a case of BHD syndrome with a previously unreported FLCN mutation.

PLU1 histone demethylase decreases the expression of KAT5 and enhances the invasive activity of the cells.

PLU1 is a candidate oncogene that encodes H3K4 (Lys(4) of histone H3) demethylase. In the present study, we found that ectopic expression of PLU1 enhanced the invasive potential of the weakly invasive cells dependent on its demethylase activity. PLU1 was shown to repress the expression of the KAT5 gene through its H3K4 demethylation on the promoter. The regulation of KAT5 by PLU1 was suggested to be responsible for PLU1-induced cell invasion. First, knockdown of KAT5 similarly increased the invasive potential of the cells. Secondly, knockdown of PLU1 in the highly invasive cancer cells increased KAT5 expression and reduced the invasive activity. Thirdly, simultaneous knockdown of KAT5 partially relieved the suppression of cell invasion imposed by PLU1 knockdown. Finally, we found that CD82, which was transcriptionally regulated by KAT5, might be a candidate effector of cell invasion promoted by PLU1. The present study demonstrated a functional contribution of PLU1 overexpression with concomitant epigenetic dysregulation in cancer progression.

The tumor suppressor Rb and its related Rbl2 genes are regulated by Utx histone demethylase.

Utx is a candidate tumor suppressor gene that encodes histone H3 lysine 27 (H3K27) demethylase. In this study, we found that ectopic expression of Utx enhanced the expression of retinoblastoma tumor suppressor gene Rb and its related gene Rbl2. This activation was dependent on the demethylase activity of Utx, and was suggested to contribute to the decreased cell proliferation induced by Utx. A chromatin immunoprecipitation assay showed that over-expressed Utx was associated with the promoter regions of Rb and Rbl2 resulting in the removal of repressive H3K27 tri-methylation and the increase in active H3K4 tri-methylation. Furthermore, siRNA-mediated knockdown of Utx revealed the recruitment of endogenous Utx protein on the promoters of Rb and Rbl2 genes. These results indicate that Rb and Rbl2 are downstream target genes of Utx and may play important roles in Utx-mediated cell growth control.

Similar etiologies of functional visual loss observed in children and adults.

BACKGROUND AND PURPOSE: To describe four cases of functional visual loss which challenge the theory that its causes are different in children and adults (i.e., that financial gain is the primary cause in adults while in children it is an involuntary response to psychosocial problems). Rather, we will show a similar etiology of functional visual loss in children and adults. We also describe diagnostic testing and therapeutic approaches that are useful in both children and adults with functional visual loss. SUBJECTS AND METHODS: Two children (5 and 15 years old) and two adults (54 and 73 years old) with presumed functional visual loss and whose visual functions were assessed with verbal assurance, Starlight Test, Flicker Test, and trial glasses or contact lenses. RESULTS: Normal visual function was elicited in all four cases. In both pediatric patients we were able to elicit normal vision using verbal assurance and trial glasses or contact lenses. In both adult patients, we elicited dramatic improvements in vision with verbal assurance and discussion of the patients' psychosocial situation. CONCLUSION: Children and adults present with similar etiologies (psychosocial problems) of functional visual loss. In these cases we believe the children were motivated by their desire to wear glasses or contacts and the adults were involuntarily responding to psychosocial problems. These cases show that we cannot, as has been proposed, clearly categorize patients with functional visual loss based upon age.

Intervertebral disc cells produce tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 immediately after herniation: an experimental study using a new hernia model.

STUDY DESIGN: A new hernia model that simulates human disc herniations was developed in rabbits. The herniated discs were examined by gross appearance and histology and production of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 was investigated. OBJECTIVES: To clarify the early mechanism of spontaneous herniated disc resorption. SUMMARY OF BACKGROUND DATA: Macrophage infiltration in herniated discs is essential for disc resorption. However, surgically removed human herniated disc tissues and existing animal hernia models are not suitable for analyzing the mechanism of macrophage infiltration. Recently, we have demonstrated that intervertebral disc cells are capable of producing monocyte chemoattractant protein-1, a potent macrophage chemoattractant, after stimulation with tumor necrosis factor alpha and interleukin-1beta. METHODS: Intervertebral disc herniations were surgically developed in rabbits using a new technique. The herniated discs were excised at appropriate time intervals after the surgery, and the size and histologic findings were examined. Expressions of tumor necrosis factor alpha, interleukin-1beta, and monocyte chemoattractant protein-1 in herniated discs were investigated immunohistochemically. RESULTS: A new rabbit model of disc herniation was established. The herniated discs spontaneously reduced in size by 12 weeks postsurgery. Infiltrating cells, mainly composed of macrophages, were observed from day 3. Immunohistochemically, intervertebral disc cells in the herniated discs produced tumor necrosis factor alpha and interleukin-1beta on day 1, followed by monocyte chemoattractant protein-1 on day 3. CONCLUSIONS: The new hernia model appears to be very useful for studying herniated disc resorption. Intervertebral disc cells may produce inflammatory cytokines/chemokine immediately after the onset of disc herniation, possibly triggering subsequent macrophage infiltration that leads to disc resorption.

Expression of monocyte chemoattractant protein-1 in primary cultures of rabbit intervertebral disc cells.

Macrophages are considered essential for herniated disc resorption, and chemokines may play a role in their recruitment. Here we demonstrate that intervertebral disc cells are capable of producing monocyte chemoattractant protein-1 (MCP-1), a CC chemokine that is chemotactic for macrophages. Nucleus pulposus cells and anulus fibrosus cells were harvested from intervertebral discs of healthy rabbits, and the cells were stimulated with either interleukin (IL)-1beta or tumor necrosis factor (TNF)alpha. Reverse transcriptase polymerase chain reaction demonstrated that IL-1beta and TNFalpha induced mRNA expression for MCP-1 in nucleus pulposus and anulus fibrosus cells. Protein concentrations of MCP-1 in the culture supernatants were quantitated by fluoroimmunoassay, which showed that nucleus pulposus and anulus fibrosus cells dose- and time-dependently produced MCP-1 after IL-1beta- and TNFalpha-stimulation, an event that was completely abrogated by IL-1 receptor antagonist and anti-TNFalpha monoclonal antibody, respectively. Nucleus pulposus cells produced significantly higher levels of MCP-1 than did anulus fibrosus cells. Immunohistochemically, the intensity of MCP-1 positive cells in nucleus pulposus cells was stronger than that in anulus fibrosus cells. Altogether, our data clearly demonstrated the production of MCP-1 in intervertebral disc cells, suggesting the possible involvement of disc cells in an early stage of macrophage infiltration.