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.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

The influence of the presence of intraductal carcinoma of the prostate on the grade group system's prognostic performance.

BACKGROUND: Although the presence of intraductal carcinoma of the prostate (IDC-P) influences biochemical failure in radical prostatectomy patients, no data are available regarding the impact of its integration into the classification grade group system. Thus, the aim of this study was to enhance the utility of the grade group system by integrating the presence of IDC-P. METHODS: This study was a retrospective evaluation of 1019 patients with prostate cancer who underwent radical prostatectomy between 2005 and 2013 without neoadjuvant or adjuvant therapy. The data on age, prostate-specific antigen (PSA) level at diagnosis, pathological T stage (pT), presence of Gleason pattern 5 (GP5), presence of IDC-P, and surgical margin status were analyzed to predict PSA recurrence after prostatectomy. RESULTS: The median patient age was 67 (range, 45-80) years and the median initial PSA level was 6.8 (range, 0.4-82) ng/mL. The median follow-up period was 82 (range, 0.7-148) months. IDC-P was detected in 157 patients (15.4%). Among these patients, the increase in the positive rate of IDC-P correlated with tumor upgrading. The grade groups (GGs) were as follows: GG1 without IDC-P, 16.0% (n = 163); GG2 without IDC-P, 46.1% (n = 470); GG3 without IDC-P, 15.7% (n = 160); GG4 without IDC-P, 2.6% (n = 27); GG5 without IDC-P, 4.1% (n = 42); any GG with IDC-P, 15.4% [n = 157; GG 2 (n = 29); GG3 (n = 60); GG4 (n = 13); GG5 (n = 55)]. Any grade Group with IDC-P showed significantly worse prognosis than any other group without IDC-P (P < 0.0001). In a multivariate analysis, integration of the IDC-P into the Grade Groups, the PSA level at diagnosis, and the surgical margin status were significant prognostic predictors (P < 0.0001, < 0.0001 and < 0.0001, respectively). CONCLUSIONS: Integrating the presence of IDC-P into the grade group system will result in more accurate predictions of patient outcome.

Integrating tertiary Gleason pattern 5 into the ISUP grading system improves prediction of biochemical recurrence in radical prostatectomy patients.

Although the presence of tertiary Gleason pattern 5 is reportedly related to unfavorable prostate cancer characteristics, few data are available regarding the effects of tertiary Gleason pattern 5 on the new ISUP (International Society of Urological Pathology) grading system in radical prostatectomy patients. In this study, we evaluated the effect of tertiary Gleason pattern 5 on biochemical recurrence following radical prostatectomy in patients with prostate cancer. We retrospectively evaluated 1000 patients with prostate cancer who underwent radical prostatectomy. The ISUP Grades were as follows: Grade 1, 16.3%; Grade 2, 48.1% (with tertiary Gleason pattern 5, 8.0% and without tertiary Gleason pattern 5, 40.1%); Grade 3, 21.9% (with tertiary Gleason pattern 5, 9.1% and without tertiary Gleason pattern 5, 12.8%); Grade 4, 3.9%; and Grade 5, 9.8%. Biochemical recurrence-free survival differed significantly among the five groups (Grade 1-5) (P < 0.0001). Grade 2 with tertiary Gleason pattern 5 had a significantly worse prognosis than Grade 2 without tertiary Gleason pattern 5. Similarly, Grade 3 with tertiary Gleason pattern 5 demonstrated a significantly worse prognosis than Grade 3 without tertiary Gleason pattern 5. When Grade 2 and Grade 3 were divided with or without tertiary Gleason pattern 5, the survival curves differed significantly among Grade 1, Grade 2 without tertiary Gleason pattern 5, Grade 2 with tertiary Gleason pattern 5, Grade 3 without tertiary Gleason pattern 5, Grade 3 with tertiary Gleason pattern 5, and Grade 4 (P < 0.0001) (hazard ratios: 1, 1.14, 1.86, 2.23, 3.53, and 6.30). In a multivariate analysis, integrating tertiary Gleason pattern 5 into the ISUP Grade, PSA, and surgical margin status significantly predicted biochemical recurrence (P < 0.0001). Integrating tertiary Gleason pattern 5 into the ISUP grading system will improve the accuracy of patient outcome prediction following radical prostatectomy in patients with prostate cancer.

Outcomes of laparoscopic surgery for pathological T4 colon cancer.

PURPOSE: The surgical indication of laparoscopic surgery for pT4 colon cancer remains to be established because only a few studies have investigated the short- and long-term outcomes of laparoscopic surgery for them to date. Therefore, we aimed to elucidate the validity of laparoscopic surgery for them. METHODS: We retrospectively analyzed 81 patients with pT4 colon cancer who underwent surgical resection with a curative intent at Kobe University Hospital from January 2007 to December 2015. The short- and long-term outcomes were compared between the propensity score-matched patients who underwent laparoscopic colectomy (LAP group, n = 25) and those who underwent open colectomy (OP group, n = 25). RESULTS: Intraoperative blood loss was significantly less in the LAP group than in the OP group (p = 0.029). Operative time, R0 resection rate, and morbidity did not significantly differ between the two groups. The 5-year overall survival (OS) and the 5-year recurrence-free survival (RFS) did not significantly differ between the propensity score-matched groups. Univariate and multivariate analyses of the entire cohort showed the surgical approach (LAP vs OP) selected was not a significant prognostic factor for OS or RFS. CONCLUSIONS: The short and the long-term outcomes were similar between the LAP and OP groups. Laparoscopic surgery might be a safe and feasible option for pT4 colon cancer patients.

[Hepatic and Pancreatic Metastases of a Rectal Gastrointestinal Stromal Tumor in a Patient with Long-Term Survival following Combined Therapy-ACase Report].

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

BACKGROUND: High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. METHODS: We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. RESULTS: The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). CONCLUSIONS: The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.

Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

BACKGROUND: This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). PATIENTS AND METHODS: We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis. RESULTS: IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively). CONCLUSION: The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.

Kidney-specific Sonoporation-mediated Gene Transfer.

Sonoporation can deliver agents to target local organs by systemic administration, while decreasing the associated risk of adverse effects. Sonoporation has been used for a variety of materials and in a variety of organs. Herein, we demonstrated that local sonoporation to the kidney can offer highly efficient transfer of oligonucleotides, which were systemically administrated to the tubular epithelium with high specificity. Ultrasonic wave irradiation to the kidney collapsed the microbubbles and transiently affected the glomerular filtration barrier and increased glomerular permeability. Oligonucleotides were passed through the barrier all at once and were absorbed throughout the tubular epithelium. Tumor necrosis factor alpha (TNFα), which plays a central role in renal ischemia-reperfusion injury, was targeted using small interfering RNA (siRNA) with renal sonoporation in a murine model. The reduction of TNFα expression after single gene transfer significantly inhibited the expression of kidney injury markers, suggesting that systemic administration of siRNA under temporary and local sonoporation could be applicable in the clinical setting of ischemic acute kidney injury.

Steroid-resistant nephrotic syndrome as the initial presentation of nail-patella syndrome: a case of a de novo LMX1B mutation.

BACKGROUND: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by mutations in the LMX1B gene and is characterized by nail dysplasia, skeletal abnormalities, and nephropathy. We herein report a case of steroid-resistant nephrotic syndrome (SRNS) prior to overt orthopedic symptoms in a patient with NPS. CASE PRESENTATION: A 24-year-old woman presented to our hospital with knee pain. She had poorly developed nails, hypoplastic patellas, dislocation of the elbows, and iliac horns in the pelvis. At the age of 7, she developed nephrotic syndrome and was diagnosed with primary focal segmental glomerulosclerosis by renal biopsy. She received long-term corticosteroid therapy with no obvious response. Her clinical course and orthopedic manifestations indicated NPS, and a genetic analysis showed a de novo mutation in the LMX1B gene (c.819 + 1G > A). Nephropathy in this case was considered to be associated with NPS. Therefore, we discontinued corticosteroids without the exacerbation of nephrotic syndrome. CONCLUSIONS: Patients with NPS may develop nephrotic syndrome prior to overt orthopedic symptoms and only show non-specific findings in renal biopsy at an early stage of NPS nephropathy. Hereditary nephrotic syndrome, often presenting as childhood-onset SRNS, may also be difficult to diagnose in patients with the following conditions: renal symptoms prior to overt extrarenal symptoms, de novo mutations, and non-specific findings in renal biopsy. Therefore, in the management of SRNS in children, we need to reconsider the possibility of hereditary diseases such as NPS even without a family history.

Swallowing Rehabilitation Affects Period of Hospitalization after Surgery for Tongue Cancer.

Functional rehabilitation has been reported to improve swallowing. The effect of the presence or absence of such rehabilitation has yet to be compared in oral cancer patients, however. The purpose of this study was to investigate its effect on correlations between the period of hospitalization and the period of tube feeding (from the day of surgery to termination of tube feeding) and period of oral nutrition (from termination of tube feeding to discharge). Body weight was also measured on admission and discharge and the difference calculated. A correlation was observed between period of hospitalization and period of tube feeding in the rehabilitation group, and with the periods of tube feeding and oral nutrition in the non-rehabilitation group. In the rehabilitation group, the period of tube feeding appeared to affect period of hospitalization. On the other hand, termination of tube feeding did not tend to affect period of hospitalization. These results suggest that both periods were factors affecting period of hospitalization in the non-rehabilitation group. Not performing swallowing rehabilitation, therefore, resulted in the period of oral nutrition affecting the period of hospitalization. This suggests that it is essential that nutrients be ingested in moderation after termination of tube feeding, when they are only taken orally. Moreover, these results also indicate that rehabilitation is important in improving quality of life after discharge.

The presence of intraductal carcinoma of the prostate in needle biopsy is a significant prognostic factor for prostate cancer patients with distant metastasis at initial presentation.

Intraductal carcinoma of the prostate is an adverse prognostic factor in localized prostate cancer patients. However, whether it influences outcome of those patients with distant metastases discovered at initial diagnosis is unclear. Here, we evaluated whether the presence of intraductal carcinoma of the prostate in prostate needle biopsies is an adverse prognostic factor for cancer-specific survival and overall survival in such prostate cancer patients. We retrospectively enrolled 150 eligible patients. All patients received androgen-deprivation therapy and/or chemotherapy. Their age, performance status, pain, metastatic sites, clinical T stage, serum prostate-specific antigen, alkaline phosphatase, hemoglobin, Gleason score, and the presence of Gleason pattern 5 were analyzed. Primary end point was cancer-specific survival; secondary end points included prostate-specific antigen progression-free survival and overall survival. Fine and Gray's model and the Cox proportional hazards model were used as statistical tests. Intraductal carcinoma of the prostate was detected in 100 (67%) patients. At a median follow-up of 38 months, 79 patients (53%) had died of the disease and nine (6%) had died of other causes. The average time interval to cancer-related death was 28 months. On multivariate analysis, only intraductal carcinoma of the prostate was significantly associated with cancer-specific survival (P=0.018) and overall survival (P=0.001), and only the presence of Gleason pattern 5 was significantly associated with prostate-specific antigen progression-free survival (P=0.026). The presence of intraductal carcinoma of the prostate was the only significant prognostic parameter for cancer-specific survival and overall survival in prostate cancer patients with distant metastasis at presentation. These results may prove useful in planning future treatments.