Relationship Between Submental Superficial Layer Hardness and Tongue Pressure Determined Using a Tissue Durometer.

Aging affects the tongue and suprahyoid muscles, causing dysphagia and undernutrition. We hypothesized that tongue function would affect submental superficial layer hardness. Tongue movements during water retention between the tongue and palate are the same as those required during bolus formation, involving internal and external tongue muscle movement. In 28 healthy adults (14 males, 14 females, average age 28.7 ± 2.9 years), we measured the submental superficial layer characteristics (frequency [tension], stiffness, decrement [inverse of resilience], relaxation, and creep [deformation over time]) using a simple tissue durometer (MyotonPRO®), and examined their relationship with maximum voluntary tongue pressure. The tissue durometer sensor was placed in the submental region, where there is no intervening bone. Measurements were performed at rest and while retaining 5 mL water. Tongue pressure was measured using a tongue pressure-measuring device. The submental superficial layer hardness differed significantly between rest and during water retention. During water retention, frequency and stiffness were high, while decrement, relaxation, and creep were low. When pressure is applied to the palate, such as during water retention the inner tongue muscle, which changes the tongue's shape, and the outer tongue muscle, which moves the tongue laterally, are active. However, the change in the hardness of the submental superficial layer during water retention may be related to the suprahyoid muscles that are present in this layer. The results of this study suggested that the hardness of the submental superficial layer changed during water retention, and that tongue movement could be measured from outside the mouth.

Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer.

BACKGROUND: Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms. METHODS: From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1). RESULTS: Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice. CONCLUSIONS: Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.

Plasma miR-1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer.

This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR-323, 345, 409, and 1254) based on the microRNA microarray comparing pre-treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR-1254 was more highly elevated in pre-treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver-operating characteristic curve 0.7621). High plasma miR-1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR-1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR-1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR-1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR-1254 levels might improve chemosensitivity in ESCC.

Mitoribosome sensitivity to HSP70 inhibition uncovers metabolic liabilities of castration-resistant prostate cancer.

The androgen receptor is a key regulator of prostate cancer and the principal target of current prostate cancer therapies collectively termed androgen deprivation therapies. Insensitivity to these drugs is a hallmark of progression to a terminal disease state termed castration-resistant prostate cancer. Therefore, novel therapeutic options that slow progression of castration-resistant prostate cancer and combine effectively with existing agents are in urgent need. We show that JG-98, an allosteric inhibitor of HSP70, re-sensitizes castration-resistant prostate cancer to androgen deprivation drugs by targeting mitochondrial HSP70 (HSPA9) to suppress aerobic respiration. Rather than impacting androgen receptor stability as previously described, JG-98's primary effect is inhibition of mitochondrial translation, leading to disruption of electron transport chain activity. Although functionally distinct from HSPA9 inhibition, direct inhibition of the electron transport chain with a complex I or II inhibitor creates a similar physiological state capable of re-sensitizing castration-resistant prostate cancer to androgen deprivation therapies. These data identify a significant role for HspA9 in mitochondrial ribosome function and highlight an actionable metabolic vulnerability of castration-resistant prostate cancer.

Pancreatic fistula as a pivotal prognostic factor among postoperative complications in gastric cancer.

Recent studies have identified that postoperative infectious complications (PICs) have contributed to poor prognosis in gastric cancer (GC). In this study, we investigated which complication among PICs most strongly contributes to a poor prognosis. This study included 1,653 consecutive patients who underwent curative gastrectomy for GC between 1997 and 2018. A Clavien-Dindo classification of grade II or higher was used as a cut-off for PICs. PICs occurred in 17.1% of all GC patients. Patients with a PIC had a poorer prognosis than those without [Hazard ratio (HR): 17.5, P < 0.001]. Among PICs, pancreatic fistula (PF) had the strongest effect on poor prognosis (HR: 3.16) compared to anastomotic leakage (HR: 2.41), pneumonia (HR: 2.11) and intra-abdominal abscess (HR: 1.98). Multivariate analysis on pStage II or III GC showed that PF had the strongest poor prognostic effect (P = 0.025, HR: 2.21, 95%-CI: 1.07-3.99). Patients with PF had significantly higher C-reactive protein (CRP) levels on postoperative days 1 (P = 0.039) and 3 (P = 0.044), tended to experience a prolonged period of high inflammation, with CRP levels above 10 mg/dL (P = 0.086), and had the highest incidence of recurrence compared to other PICs. Robotic gastrectomy had no incidence of PF, while open gastrectomy resulted in a 2% occurrence, and laparoscopic gastrectomy had a 1.8% occurrence. In conclusion, PF had the strongest effect on poor prognosis among PICs. Robotic gastrectomy might be the optimal approach for avoiding PF.

A good surgical field for para-aortic nodal dissection in gastric cancer by the Cattell-Braasch maneuver.

PURPOSE: Gastric cancer patients with para-aortic lymph node metastases may achieve long-term survival with radical gastrectomy and para-aortic lymph nodal dissection (PAND) following neoadjuvant therapy. We introduced the Cattell-Braasch maneuver to facilitate safe and complete PAND for advanced gastric cancer with extensive lymph node metastases. METHODS: Between January 2014 and March 2020, 7 patients with highly advanced gastric cancer received preoperative chemotherapy followed by radical gastrectomy and PAND using the Cattell-Braasch maneuver. This maneuver consists of mobilization of the right hemi-colon and the total small intestine. RESULTS: Five patients received preoperative chemotherapy for para-aortic lymph node metastases and 2 for bulky lymph node metastases around the supra-pancreatic area. All patients received S-1 + cisplatin therapy, and one was additionally treated with paclitaxel chemotherapy followed by nivolumab. After chemotherapy, 2 patients with para-aortic lymph node metastases achieved down-staging on imaging tests. Total gastrectomy with PAND by the Cattell-Braasch maneuver was performed on all patients and was accompanied by splenectomy (n = 5) and distal pancreatectomy (n = 1). Pathological assessments revealed that 3 patients had para-aortic lymph node metastases, and the median number of retrieved para-aortic lymph nodes was 16. Three patients without para-aortic lymph node metastasis survived for more than 5 years without recurrence. CONCLUSION: The Cattell-Braasch maneuver provides a good surgical field and is useful for complete PAND for gastric cancer.

Clinical Statistics of Dysphagia Rehabilitation Provided on Dental Visits to a Partner Hospital.

Maintaining oral hygiene is an important yet often neglected aspect of rehabilitation medicine. Our visiting dental team, which provides dental treatments and swallowing rehabilitation, partnered with a medical hospital that had no dental department and began visiting and treating inpatients at this hospital. This study is aimed at evaluating the effects of dysphagia rehabilitation, and this was jointly conducted by medical and dental hospitals. The survey was conducted between May 2017 and March 2018. We retrospectively examined dysphagia rehabilitation provided to 25 patients (12 men and 13 women) aged 40-92 years (mean age: 77.1 ± 12.3 years). The largest number of requests for dental treatment was received from the internal medicine department (13 requests, 52.0%). A total of 39 videofluoroscopic or videoendoscopic examinations of swallowing interventions for dysphagia rehabilitation were conducted. All patients' oral and swallowing functions were evaluated using the functional oral intake scale (FOIS). At initial assessment, 9, 13, and 0 patients were at FOIS levels 1, 2, and 3 (use of tube feeding), respectively, and 1, 2, and 0 patients were at FOIS levels 4, 5, and 6 (only oral feeding), respectively. At the final assessment, 6, 10, and 4 patients were at FOIS levels 1, 2, and 3, respectively, and 0, 2, and 3 patients were at FOIS levels 4, 5, and 6, respectively. Oral and swallowing functions differed significantly between the first and final visits (p = 0.02). Visits conducted by a team of oral health practitioners to a medical hospital without a dental department appear to have a major impact and will become even more important in the future.

Structure-guided design enables development of a hyperpolarized molecular probe for the detection of aminopeptidase N activity in vivo.

Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-13C]Gly-d2-NMe2 as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.

[Effects of Conservative or Surgical Treatment of Anastomotic Leakage after Colorectal Surgery].

BACKGROUND: Anastomotic leakage is associated with short- and long-term mortality and an increased risk of local and distant cancer recurrence. This study aimed to investigate the short- and long-term outcomes after surgical or conservative therapy for anastomotic leakage. METHODS: Patients with anastomotic leakage after undergoing colorectal resection between January 2011 and December 2018 were identified and grouped according to the therapy for anastomotic leakage: surgical or conservative. We analyzed the intergroup differences in clinicopathological factors and outcomes. RESULTS: Of the 33 patients with anastomotic leakage, 21(64%)and 12(36%)patients received surgical therapy and conservative therapy, respectively. Patients in the conservative therapy group had a shorter length of hospital stay after the first operation. In patients with UICC Stage Ⅱ/Ⅲ, both overall and recurrence-free survival were significantly worse in those who were treated conservatively than in patients who were surgically treated(p<0.01). CONCLUSION: Conservative therapy for anastomotic leakage could shorten the length of hospital stay, but could negatively affect long-term outcomes.

Association between antiulcer agents and Clostridioides difficile infection in patients receiving antibiotics: A retrospective cohort study using the diagnosis procedure combination database in Japan.

OBJECTIVES: To evaluate baseline risk for hospital onset Clostridioides difficile infection (HO-CDI) and the association with the use of antiulcer agents among patients undergoing antibiotic therapy in Japan. METHODS: We conducted a retrospective cohort study using Japanese Diagnosis Procedure Combination database. Between July 2018 and January 2019, patients aged ≥18 years were included if they started antibiotics within two days of hospital admission. We defined exposure as proton pump inhibitors or histamine 2 receptor antagonists starting from day 2 to day 4 and the primary outcome as HO-CDI within 30 days. We performed multivariable analyses with complete cases using the propensity score (inverse probability treatment weighting [IPTW]) and several sensitivity analyses. RESULTS: In total, 87,137 patients were included. The median age was 78 years; 52.0% were men, and 23.6% received antiulcer agents. Within 30 days of admission, HO-CDI were observed in 0.41% and 0.26% of the antiulcer agent and control groups, respectively. IPTW revealed a positive association between antiulcer agents and HO-CDI (adjusted odds ratio, 1.33; 95% confidence interval [CI]: 1.13, 1.56). In the IPTW method, the risk difference was smaller (0.09%, 95% CI: 0.04%, 0.15%). CONCLUSION: The use of antiulcer agents in patients with antibiotics was associated with HO-CDI in Japan. However, the baseline risk and the difference in HO-CDI event rates were small; thus, as per several clinical practice guidelines, it is important to monitor antiulcer agent use and discontinue unnecessary use. The baseline risk should be considered when clinically evaluating the association between antiulcer agents and HO-CDI.

Aggressive behavior of anaplastic undifferentiated carcinoma arising from the hilar bile duct.

BACKGROUND: Undifferentiated carcinoma of the biliary tree is extremely rare, and biliary undifferentiated carcinoma mostly originates from the gallbladder. We herein present a case of anaplastic undifferentiated carcinoma of the hilar bile duct and reviewed the literature. CASE PRESENTATION: The patient was an 81-year-old male with obstructive jaundice. Contrast-enhanced computed tomography (CT) showed a protruded tumor located at the hepatic hilum. Obstructive jaundice was relieved by endoscopic drainage. Endoscopic biopsy revealed carcinoma without glandular differentiation, and the patient was diagnosed with resectable hilar undifferentiated carcinoma. During the 5-week preoperative examination, the tumor increased in size from 23 to 45 mm. Left hemi-hepatectomy and extrahepatic bile duct resection were performed, and there were no postoperative complications. Histological findings demonstrated that the tumor was mainly composed of non-cohesive polygonal neoplasms with pleomorphic nuclei, and was diagnosed as anaplastic undifferentiated carcinoma of the common hepatic duct (T2a N0 M0 Stage II). One month after surgery, the patient was readmitted to our hospital with pyrexia due to cholangitis, and liver nodules suggestive of multiple liver metastases were detected by CT. Three months after surgery, the patient died of multiple liver metastases. CONCLUSIONS: This is the first case report of undifferentiated cholangiocarcinoma with anaplastic features. Anaplastic undifferentiated carcinoma of the hilar bile duct showed preoperative rapid growth and early relapse despite a cancer-negative surgical margin.

Clarification of the aspects of tongue-palate contacts during mastication with/without stage II transport.

BACKGROUND: During mastication, the tongue presses the bolus into the pharynx by a "squeeze-back" motion, known as stage II transport (St2Tr). However, the pressure of St2Tr tongue-palate contact has not been examined. OBJECTIVES: We aimed to clarify aspects of St2Tr occurrence and tongue-palate contact during mastication by measuring tongue pressure. METHODS: Ten healthy adults (eight men, two women, aged 26.8 ± 2.2 years) were enrolled. Tongue pressure was measured (Swallow Scan) during mastication. Sensors were placed on the palate near the incisive papilla (Ch.1), in the middle (Ch.2), at the posterior (Ch.3), and near the first molars on the habitual (Ch.H) and non-habitual (Ch.Nh) masticatory sides. Nasopharyngeal endoscopy confirmed St2Tr and swallowing. Tongue pressures were measured repeatedly, from mastication onset through the first swallow, until eight sets of data were obtained. Tongue-palate contact frequencies, integrated values of tongue pressure, and mastication times were recorded for St2Tr(+) and St2Tr(-) mastication conditions. RESULTS: St2Tr occurred in 43 of 80 trials (53.8%). St2Tr(+) exhibited the highest tongue-palate contact frequency at Ch.H; it exhibited higher contact frequencies at Ch.2, Ch.3 and Ch.H than St2Tr(-). St2Tr(+) exhibited higher tongue pressures at Ch.1, Ch.2 and Ch.H than at Ch.3; it exhibited higher tongue pressures at Ch.1 and Ch.2 than St2Tr(-). CONCLUSION: The study suggested that during St2Tr, the tongue frequently touched the palate at the central and posterior regions, as well as at its habitual masticatory side. It applies the strongest pressure at the anterior and central palate to transport the bolus to the pharynx.

Collagen hydrogels with controllable combined cues of elasticity and topography to regulate cellular processes.

The elasticity, topography, and chemical composition of cell culture substrates influence cell behavior. However, the cellular responses toin vivoextracellular matrix (ECM), a hydrogel of proteins (mainly collagen) and polysaccharides, remain unknown as there is no substrate that preserves the key features of native ECM. This study introduces novel collagen hydrogels that can combine elasticity, topography, and composition and reproduce the correlation between collagen concentration (C) and elastic modulus (E) in native ECM. A simple reagent-free method based on radiation-cross-linking altered ECM-derived collagen I and hydrolyzed collagen (gelatin or collagen peptide) solutions into hydrogels with tunable elastic moduli covering a broad range of soft tissues (E= 1-236 kPa) originating from the final collagen density in the hydrogels (C= 0.3%-14%) and precise microtopographies (⩾1 µm). The amino acid composition ratio was almost unchanged by this method, and the obtained collagen hydrogels maintained enzyme-mediated degradability. These collagen hydrogels enabled investigation of the responses of cell lines (fibroblasts, epithelial cells, and myoblasts) and primary cells (rat cardiomyocytes) to soft topographic cues such as thosein vivounder the positive correlation betweenCandE. These cells adhered directly to the collagen hydrogels and chose to stay atop or spontaneously migrate into them depending onE, that is, the density of the collagen network,C. We revealed that the cell morphology and actin cytoskeleton organization conformed to the topographic cues, even when they are as soft asin vivoECM. The stiffer microgrooves on collagen hydrogels aligned cells more effectively, except HeLa cells that underwent drastic changes in cell morphology. These collagen hydrogels may not only reducein vivoandin vitrocell behavioral disparity but also facilitate artificial ECM design to control cell function and fate for applications in tissue engineering and regenerative medicine.

[A PRIMARY BLADDER ALVEOLAR SOFT PART SARCOMA: A CASE REPORT].

A 32-year-old woman was admitted to our department for hematuria and dysuria.Computed tomography (CT) and cystoscopy revealed a 2-cm pedunculated tumor with rich blood supply and a smooth surface in the bladder trigone. We performed a transurethral resection of bladder tumor. The pathologic diagnosis was alveolar soft part sarcoma (ASPS). CT, bone scintigraphy, positron emission tomography, and pelvic magnetic resonance imaging revealed no other lesions; thus, she was diagnosed as having a primary bladder ASPS. Postoperative follow-up with regular cystoscopies and CTs over 10 years have shown no local recurrence or metastasis.Primary ASPS of the bladder is exceedingly rare, and this case is the 8th case (the 2nd case in Japan) reported in literature.

Determination of the Relationships Between intra- and Extraoral Tongue Hardness, Thickness, and Pressure Using Ultrasonic Elastography.

Involved with various bodily functions, including ingestion and swallowing, the tongue is an important organ. We measured resting tongue hardness using real-time tissue elastography (RTE) to establish a simple tongue evaluation for patients who may have limited capacities to follow commands. Relationships between tongue hardness, thickness, and pressure were investigated, using both intra- and extraoral probes. Assessments were performed for a total of 27 healthy adults (11 male, 16 female, average age 26.4 ± 1.8 years). Measurements of tongue hardness and thickness were made using strain ratios (SR), and averaged across nine images. Maximum tongue pressure was determined using a tongue pressure device. A negative correlation was observed between intraorally measured tongue hardness and maximum tongue pressure (r = -0.76, p < 0.01). A positive correlation between extraorally measured tongue thickness and maximum tongue pressure was observed (r = 0.59, p < 0.01). Additionally, significant differences were observed between males and females with regards to intraorally measured tongue hardness (p = 0.02), maximum tongue pressure (p = 0.02), and extraorally measured tongue thickness (p < 0.01). The results of this study demonstrated the clinical applicability of RTE-based tongue hardness measurements, and suggest the feasibility of predicting tongue strength based on extraoral tongue thickness measurements.

Use of barometric pressure and electromyography measurement techniques to elucidate the mechanisms by which bolus passes from the oral cavity to the oropharynx during swallowing.

OBJECTIVES: The exact timings associated with swallowing are difficult to measure with the currently available methods. In this study, we aimed to elucidate the timings of action of the swallowing organs in the oral and pharyngeal stages of swallowing by recording the barometric pressure (BP) and tongue muscle activities. METHODS: Dry and water swallows were studied in 10 adults using electromyography and small barometers. BPs were recorded during swallowing in the oral cavity (BP-o) and pharynx (BP-p), associated with muscle activities of the anterior (TA) and posterior (TP) parts of the tongue and of the suprahyoid (SHy) muscle. To analyze the temporal pattern of each activity, times of onset, cessation, and peak were measured. RESULTS: Two characteristic waveforms were obtained. BP-o peaked immediately after onset and decreased to atmospheric pressure following a short plateau. However, BP-p gradually increased, reached a peak, and returned to the atmospheric pressure immediately before the end of BP-o. Since pressure increments indicated that the sensor was compressed in a closed space, onset and cessation of BP-p could correspond to the duration of nasopharyngeal closure. The onset of BP-p and the peak time of BP-o occurred in close succession. Thus, nasopharyngeal closure could be evaluated from BP-o. The sensor and EMG measured durations of oral and pharyngeal stages as 0.4 and 0.6 sec, respectively. TA activation began earlier than the TP. TA and TP peaks appeared before the BP-o peak, suggesting that the tongue begins the activity for swallowing before nasopharyngeal closure. CONCLUSIONS: This study revealed movements of swallowing organs in the two stages with high temporal resolution. BP-o detected the duration of nasopharyngeal closure.

IgA nephropathy in a patient receiving infliximab for generalized pustular psoriasis.

BACKGROUND: IgA nephropathy is the most common glomerulonephritis. Secondary IgA nephropathy complicated with systemic diseases, including psoriasis, is also often reported. Generalized pustular psoriasis is a form of psoriasis characterized by sterile pustules on reddened skin and fever. Infliximab, one of the first-line therapies for severe psoriasis, has also been reported to cause systemic vasculitis and IgA nephropathy. We herein report a case of IgA nephropathy activated during infliximab treatment for generalized pustular psoriasis. CASE PRESENTATION: A 28-year-old woman presented with episodic gross hematuria, increasing proteinuria, and renal dysfunction. She had been receiving anti-TNFα therapy with infliximab because of generalized pustular psoriasis for 3 years, but her skin symptoms worsened following withdrawal during pregnancy. After delivery, her skin symptoms improved with the resumption of infliximab, but clinical signs suggested glomerulonephritis, and renal biopsy showed active IgA nephropathy. Infliximab was discontinued, and the combination of corticosteroids, tonsillectomy, and secukinumab, an IL-17A inhibitor, improved both the skin symptoms and the glomerulonephritis. CONCLUSIONS: In our case, the activity of IgA nephropathy was exacerbated by anti-TNFα therapy but was improved by the combination of corticosteroids, tonsillectomy, and an IL-17A inhibitor against the original disease. Autoimmune diseases may underlie the development of secondary IgA nephropathy associated with anti-TNFα therapy, and so further studies are needed to better understand the association between molecular-targeted drugs and IgA nephropathy.

Dynamic Imaging of LDH Inhibition in Tumors Reveals Rapid In Vivo Metabolic Rewiring and Vulnerability to Combination Therapy.

The reliance of many cancers on aerobic glycolysis has stimulated efforts to develop lactate dehydrogenase (LDH) inhibitors. However, despite significant efforts, LDH inhibitors (LDHi) with sufficient specificity and in vivo activity to determine whether LDH is a feasible drug target are lacking. We describe an LDHi with potent, on-target, in vivo activity. Using hyperpolarized magnetic resonance spectroscopic imaging (HP-MRSI), we demonstrate in vivo LDH inhibition in two glycolytic cancer models, MIA PaCa-2 and HT29, and we correlate depth and duration of LDH inhibition with direct anti-tumor activity. HP-MRSI also reveals a metabolic rewiring that occurs in vivo within 30 min of LDH inhibition, wherein pyruvate in a tumor is redirected toward mitochondrial metabolism. Using HP-MRSI, we show that inhibition of mitochondrial complex 1 rapidly redirects tumor pyruvate toward lactate. Inhibition of both mitochondrial complex 1 and LDH suppresses metabolic plasticity, causing metabolic quiescence in vitro and tumor growth inhibition in vivo.

[ENDOSCOPIC REMOVAL OF INTRAVESICAL RARE FOREIGN BODY USING FLEXIBLE CYSTOSCOPY: A CASE REPORT].

A 50-year-old man was admitted to our hospital for urinary retention. Computed tomography revealed a spherical intravesical foreign body, measuring 1.7cm in diameter, and cystoscopy revealed glass ball in the bladder. Considering the shape of the object and the possibility of self-insertion, we used a flexible cystoscope, foreign body forceps, and a transvaginal echo probe cover to remove the intravesical foreign body. The end of the echo probe cover was grasped with the foreign body forceps, and a glass ball was inserted into the probe cover and extracted manually with a scooping action similar to using a landing net. No intraoperative hemorrhage was observed, and the glass ball was safely removed with good visual field.The patient's postoperative courses was uneventful, and he has shown no recurrence one year postoperatively.

Response of intraductal carcinoma of the prostate to androgen deprivation therapy predicts prostate cancer prognosis in radical prostatectomy patients.

BACKGROUND: Intraductal carcinoma of the prostate (IDC-P) has a poor prognosis and is thought to be completely resistant to current therapies, including androgen deprivation therapy (ADT). However, to date, there are no data showing direct evidence of such resistance. METHODS: We retrospectively evaluated 145 patients with high-risk prostate cancer who underwent radical prostatectomy (RP) with neoadjuvant ADT between 1991 and 2005. All patient data were collected from slides prepared from needle biopsy (NB) samples of prostate tissue and RP specimens. Data were analyzed in terms of serum level of prostate specific antigen (PSA), Gleason score of NB samples, clinical T stage, the positive cancer core rate, maximum cancer extension rate, presence of Gleason pattern 5, and presence of IDC-P in both NB samples and RP specimens. RESULTS: The median initial PSA was 33.2 ng/mL (range, 2.4-296 ng/mL), and the median follow-up period was 109 months (range, 11-257 months). The preoperative median ADT period was 4 months (range, 1-20 months). IDC-P was present in 53 patients (37%) in NB samples and 65 (45%) in RP. The patients were divided into three groups based on the presence or absence of IDC-P in NB/RP samples (IDC-P-negative at biopsy: 92 cases, IDC-P-positive at biopsy with IDC-P disappearance: 15 cases, and IDC-P-positive at biopsy with IDC-P persistence: 38 cases). Overall, 28% of IDC-P-positive cases in NB samples showed the disappearance of IDC-P at RP. IDC-P persistence cases showed the poorest prognosis, while IDC-P disappearance cases had a similar prognosis to that of IDC-P-negative at biopsy cases in terms of disease-free survival, cancer-specific survival, and overall survival (P = .0018, P = .0087, and P = .0034, respectively). CONCLUSIONS: Some cases with IDC-P responded to ADT and demonstrated favorable clinical outcomes similar to those of cases without IDC-P. These findings indicate that cases with IDC-P are heterogeneous.