Immediate-delayed lymphatic reconstruction after axillary lymph nodes dissection for locally advanced breast cancer-related lymphedema prevention: Report of two cases.

Approximately 60%-70% of breast cancer patients in Indonesia are diagnosed in the locally advanced stage. The stage carries a higher risk of lymph node metastasis which increases susceptibility to lymph obstruction. Hence, breast cancer-related lymphedema (BCRL) could present before axillary lymph node dissection (ALND). The purpose of this case report is to describe immediate-delayed lymphatic reconstructions with lymphaticovenous anastomosis in two subclinical lymphedema cases that present before ALND. There were 51 and 58 years old breast cancer patients with stage IIIC and IIIB, respectively. Both had no arm lymphedema symptoms, but arm lymphatic vessel abnormalities were found during preoperative indocyanine green (ICG) lymphography. Mastectomy and ALND were performed and proceeded with lymphaticovenous anastomoses (LVA) in both cases. One LVA at the axilla (isotopic) was done in the first patient. On the second patient, 3 LVAs at the affected arm (ectopic) and 3 isotopic LVAs were created. The patients were discharged on the second day without complications during the follow-up. The intensity of dermal backflow was reduced, and no subclinical lymphedema progression occurred during 11 and 9 months follow-up, respectively. Based on these cases, BCRL screening might be recommended for the locally advanced stage before cancer treatment. Once diagnosed, immediate lymphatic reconstruction after ALND should be recommended to cure or prevent BCRL progression.

Melatonin effect on hypoxia inducible factor-1α and clinical response in patients with oral squamous cell carcinoma receiving neoadjuvant chemotherapy: A randomized controlled trial.

CONTEXT: Chemoresistance is a major issue in patients with locally advanced oral squamous cell carcinoma (OSCC). In this study, we evaluated the effectiveness of melatonin in conjunction with neoadjuvant chemotherapy (NC) on hypoxia-inducible factor-1α (HIF-1α) expression and clinical response in locally advanced OSCC patients. AIMS: To study the effects of melatonin on HIF-1α expression and its effect on the clinical response of patients with locally advanced OSCC. SETTINGS AND DESIGN: A randomized controlled trial was conducted, wherein patients were recruited from several hospitals in Jakarta, Indonesia. Patients were randomized into two groups using computerized block randomization. SUBJECTS AND METHODS: Both groups were given NC, with treatment group receiving melatonin. Outcomes measured in this study were HIF-1α expression from tissue samples and clinical response based on the RECIST 1.1 criteria. Twenty-five patients completed the study protocol and were included in the data analysis. STATISTICAL ANALYSIS USED: Shapiro-Wilk test was used to test the data normality. For data with normal distribution, we conducted an independent t-test to compare between the two groups. Data with abnormal distribution were analyzed using Mann-Whitney U-test. The mean difference between the two groups was analyzed using Shapiro-Wilk normality test. RESULTS: Our study showed a significant decrease in HIF-1α expression in the melatonin group compared to the placebo group (P < 0.05, relative risk 3.08). However, the degree of reduction of HIF-1α expression in the melatonin group did not differ significantly (P = 0.301). CONCLUSIONS: Our study showed that melatonin administered at 20 mg/day could reduce the expression of HIF-1α and residual tumor percentage, but did not affect the clinical response in OSCC patients.

Universal health coverage in Indonesia: concept, progress, and challenges.

Indonesia is a rapidly growing middle-income country with 262 million inhabitants from more than 300 ethnic and 730 language groups spread over 17 744 islands, and presents unique challenges for health systems and universal health coverage (UHC). From 1960 to 2001, the centralised health system of Indonesia made gains as medical care infrastructure grew from virtually no primary health centres to 20 900 centres. Life expectancy improved from 48 to 69 years, infant mortality decreased from 76 deaths per 1000 livebirths to 23 per 1000, and the total fertility rate decreased from 5·61 to 2·11. However, gains across the country were starkly uneven with major health gaps, such as the stagnant maternal mortality of around 300 deaths per 100 000 livebirths, and minimal change in neonatal mortality. The centralised one size fits all approach did not address the complexity and diversity in population density and dispersion across islands, diets, diseases, local living styles, health beliefs, human development, and community participation. Decentralisation of governance to 354 districts in 2001, and currently 514 districts, further increased health system heterogeneity and exacerbated equity gaps. The novel UHC system introduced in 2014 focused on accommodating diversity with flexible and adaptive implementation features and quick evidence-driven decisions based on changing needs. The UHC system grew rapidly and covers 203 million people, the largest single-payer scheme in the world, and has improved health equity and service access. With early success, challenges have emerged, such as the so-called missing-middle group, a term used to designate the smaller number of people who have enrolled in UHC in wealth quintiles Q2-Q3 than in other quintiles, and the low UHC coverage of children from birth to age 4 years. Moreover, high costs for non-communicable diseases warrant new features for prevention and promotion of healthy lifestyles, and investment in a robust integrated digital health-information system for front-line health workers is crucial for impact and sustainability. This Review describes the innovative UHC initiative of Indonesia along with the future roadmap required to meet sustainable development goals by 2030.

COVID-19 in Indonesia: Challenges and Multidisciplinary Perspectives for a Safe and Productive New Normal.

The COVID-19 pandemic has caused disruption in all aspects of life, and countries around the world have been combating this pandemic using multiple approaches. Success in one country does not guarantee a transferable approach to other countries with different contexts. This review describes the challenges of COVID-19 management in Indonesia as a populous, socially and culturally diverse, and archipelagic country. It aims to provide multidisciplinary perspectives for a safe, evidence-based, and productive new normal as well as a comprehensive and integrated actionable policy for COVID-19 control.

Y-Chromosomal Microdeletion in Idiopathic Azoospermic and Severe Oligozoospermic Indonesian Men.

AIM: to detect Y-chromosomal microdeletion in Indonesian men with azoospermia or severe oligozoospermia using multiplex PCR. METHODS: we performed 2 multiplex PCR amplifications of the Azoospermia Factor (AZF) region in 71 men. Criteria for including a patient were fulfilled if they presented with azoospermia or severe oligozoospermia, with or without additional abnormalities of sperm motility or of head morphology, raised or normal levels of FSH, normal levels of LH and testosterone, and with no evidence of testicular tumors or other abnormalities. Five men participated as control persons. RESULTS: partial deletion of AZFa was found in 11 men (15.49%), complete deletion of AZFb in 1 man (1.4%), and complete deletion of AZFc in 1 man (1.4%). The unspecific type of deletion was also detected, including the DBY gene in 2 men (2.81%), and partial deletion of both AZFa and AZFb in 2 men (2.81%). No AZF deletion was observed in the control probands. Related to the type of deletion, the AZFa and AZFb deletion showed spermatogenesis arrest in most tubules, while deletion of the DBY gene is associated with the sertoli cell only (SCO) syndrome. CONCLUSION: the frequency of partial deletion of AZFa was found to be relatively high in our center. The type of deletion is associated with the testicular histology.

Granulocyte Colony-stimulating Factor Improves Innate Immunity in Pediatric Pretransplant Patients.

Background: Children with decompensated cirrhosis (DC) awaiting LT suffer from infection linked to high pediatric end-stage liver disease (PELD) scores and mortality. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult DC. Our study investigated G-CSF as an optimizing treatment for pre-transplant DC, exploring its effect on cytokine activity. Methods: An open-label, randomized controlled trial included DC patients aged 3 months-12 years. The intervention group (n=26) received 12 G-CSF courses injected subcutaneously (5 µg/kg/day) plus DC standard medical treatment (SMT). The control group (n = 24) received SMT. We obtained PELD scores, tumor necrosis factor (TNF)-α, interleukin (IL)-10, hepatocyte growth factor (HGF), CD34+ mobilization, liver function, leukocyte and neutrophil counts. Infection and side effects were documented. Results: There was no significant difference in PELD scores between the groups after 3 months G-CSF treatment. Decreased TNF-α (p < 0.001) and increased IL-10 and HGF (p = 0.003 for both markers) were shown 1 month following G-CSF treatment. Alanine aminotransferase (ALT) levels improved significantly (p = 0.038). Significant increase in leucocyte and neutrophil counts (p < 0.001) and a lower incidence of sepsis (p = 0.04) were shown after intervention. There was no significant difference in survival (p = 0.372). Conclusion: Following 3 months of G-CSF treatment, PELD scores did not show significant improvement. G-CSF reversed the cytokine profiles in DC, resulting in reduced TNF-α and increased IL-10. HGF significantly improved, indicating hepatic regeneration. Significantly decreased occurrence of sepsis following G-CSF treatment indicated improved clinical outcome.

Supermicrosurgery lymphaticovenous and lymphaticolymphatic anastomosis: Technical detail and short-term follow-up for immediate lymphatic reconstruction in breast cancer treatment-related lymphedema prevention.

OBJECTIVE: We describe the feasibility and short-term outcome of our surgical technique to repair the lymph vessel disruption directly after axillary lymph node dissection during breast cancer surgery. This procedure is called immediate lymphatic reconstruction to prevent breast cancer treatment-related lymphedema (BCRL), which frequently occurs after axillary lymph node dissection. The surgical technique consisted of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis. We named the procedure lymphatic bypass supermicrosurgery (LBS). METHODS: This study used a retrospective cohort design of patients with breast cancer between May 2020 and February 2023. LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels lymphaticolymphatic anastomosis. RESULTS: A total of 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, and most had stage III breast cancer (n = 59 [72%]). LVA was the most common type of lymphatic bypass (94.6%). The median number of LVA was 1 (range, 1-4) and 1 (range, 1-3) for lymphaticolymphatic anastomosis. The median follow-up time was 12.5 months (range, 1-33 months). The 50 patients who had postoperative indocyanine green lymphography described arm dermal backflow stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. The proportion of BCRL was 11 (22%), and subclinical lymphedema was 19 (38%) in this period. Most cases were in stable subclinical lymphedema (10, 58.8%). The 1-year and 2-year BCRL rates were 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively. CONCLUSIONS: Along with the emerging immediate lymphatic reconstruction, LBS is a feasible supermicrosurgery technique that may have a potential role in BCRL prevention. A randomized controlled study would confirm the effectiveness of the technique.

Effects of endopeptidase inhibition on the contraction-relaxation response of isolated human vaginal tissue.

INTRODUCTION.: Vasoactive peptides, such as bradykinin, C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP), and endothelin 1 (ET-1), are assumed to be involved in the control of female genital vascular and nonvascular smooth muscle. Tissue levels of said peptides are controlled by the activity of endopeptidase enzymes. Theoretically, in female genital tissues, inhibiting the degradation of bradykinin, CNP, and VIP, or the conversion of Big ET-1 into ET-1 should result in an enhancement in smooth muscle relaxation and, thus, an improvement in sexual response. AIM.: Elucidate the effects of the endopeptidase inhibitor KC 12615 on the contraction/relaxation response of isolated human vaginal smooth muscle to Big ET-1, bradykinin, CNP, or VIP. METHODS.: Tissue bath experiments were carried out to ascertain the responses of human vaginal tissue challenged by ET-1 (0.1 µM) to increasing concentrations of bradykinin, CNP, and VIP (0.01 µM, 0.1 µM, and 1 µM, respectively). The effects were also evaluated following preexposure to KC 12615 (10 µM, for 20 minutes). MAIN OUTCOME MEASURES.: Measure the effects of KC 12615 on the relaxation of isolated human vaginal smooth muscle brought about by bradykinin, CNP, or VIP and the contraction mediated by Big ET-1. RESULTS.: The tension induced by ET-1 was reversed by bradykinin, CNP, or VIP (-25 ± 6.6%, -13.3 ± 2.2%, and -17.6 ± 10%, respectively). Big ET-1 induced contraction of the vaginal tissue. Preexposure of the tissue to KC 12615 increased the relaxation exerted by bradykinin, CNP, or VIP (to -39.2 ± 5.8%, -40.7 ± 7.3%, and -44.6 ± 19%, respectively). The contraction induced by Big ET-1 was attenuated in the presence of KC 12615 (to approximately 25% of the initial response). CONCLUSION.: Inhibition of endopeptidase activity can antagonize the contraction of human vaginal tissue induced by Big ET-1 and increase the relaxation induced by vasoactive endogenous peptides.

VICTORY project: a study of counterfeit PDE5 inhibitor (sildenafil) in Indonesia.

AIM: to quantify the extent of counterfeit sildenafil in Indonesia. METHODS: the study was conducted in 4 big areas: Jakarta, Bandung, East Java (Surabaya and Malang), and Medan. Sildenafil 100 mg tablets were purchased from pharmacies, drugstores, street peddlers, and 3 Indonesian websites. The outlets were chosen by random sampling in each stratum (type of outlet). Sildenafil tablets purchased were sent to Pfizer Quality Operations Division, Dalian, China, for authenticity evaluations (by infra red spectral analysis). All counterfeit tablets were then sent to Pfizer Counterfeit Medicines Laboratory, Sandwich, UK, a portion of which were analyzed quantitatively for sildenafil concentration per tablet (by HPLC). RESULTS: a total of 518 sildenafil 100 mg tablets were collected and sent to Dalian. Of these tablets, 284 tablets (55%) were genuine sildenafil and 234 tablets (45%) were counterfeit sildenafil. Counterfeit sildenafil were mostly found in street peddlers (100%), in drugstores (56%), and from internet (33%), but pharmacies also had (13%) counterfeit sildenafil. The sildenafil content of 106 counterfeit tablets analyzed varied from 24 to 157 mg per 100 mg tablet. No analysis was done to determine other active ingredient. CONCLUSION: 45% sildenafil 100 mg tablets in Indonesia were found counterfeit and widely distributed in street peddlers, drugstores, and pharmacies. This report is aimed to alert the potential consumers, health professionals and regulators of this problem.

Metachronous bilateral testicular germ cell tumors with different histopathology: A case report.

Background: Testicular cancer is the most common solid tumor affecting men aged 20-39 years old. About 95% of all testicular tumor is testicular germ cell tumor. Bilateral testicular tumor is a rare incident and has similar histopathology only in less than 5% of all testicular cancer patients. Besides oncological issues, bilateral testicular tumors could lead to further consequences, such as psychosocial and hormonal issues. This article shows a case of different histopathology in the metachronous bilateral testicular tumors. Case presentation: A 34-years-old male came with right radical orchiectomy due to testicular pure seminoma pT1N0M0S0 three and half years ago. He underwent bleomycin, etoposide phosphate (BEP) chemotherapy for progressive multiple lymphadenopathies in paracaval and interaortacaval region from positron emission tomography (PET)/computerized tomography (CT) scan a year later. Sperm banking was done before initiated chemotherapy. High metabolic activity was detected in contralateral testis from follow up PET-scan. Left testicle enlargement with hard consistency was found on physical examination and there is an elevation of alpha-feto protein (AFP) and ß-hCG. Intraoperatively, the frozen section identified a malignant tumor and the patient was decided to undergo radical left orchiectomy. Postoperative pathological results showed a mixed germ cell tumor of 3.5 × 2.5 × 2 cm consisting of immature teratoma, yolk sac tumor and embryonic carcinoma without lympho-vascular invasion and involvement of the spermatic cord. Post-operative imaging and testicular tumor marker did not identify any metastases. BEP chemotherapy, testosterone replacement therapy was planned for further management in this patient with complete blood count, prostate serum antigen (PSA) and digital rectal examination should be measured three to six weeks after initiation. Conclusion: Metachronous bilateral TGCT with different histopathology is a rare disease. The treatment depends on histology of second tumor and its stage. TRT is mandatory for patient undergoing bilateral orchidectomy to address lack if testosterone.

The efficacy of antibiotic and alpha-blocker combination therapy versus antibiotic monotherapy in chronic prostatitis/chronic pelvic pain syndrome: A systematic review.

OBJECTIVES: This study attempted to explore the efficacy of a combination of alpha-blockers and antibiotics compared with antibiotic monotherapy in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We searched PubMed/MEDLINE, Cochrane/CENTRAL, EBSCOHost/CINAHL, ProQuest, and Scopus on January 2020. Randomized controlled trials comparing antibiotic monotherapy with combination therapy of antibiotics and alpha-blockers in CP/CPPS patients lasting at least 4 weeks were included. The study eligibility assessment, data extraction, and study quality assessment were carried out by each author independently and in duplication. RESULTS: A total of six low- to high-quality studies with 396 patients were included in the study. Two reviews reported lower National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total scores in the monotherapy arm at Week 6. Only one study reported otherwise. On Day 90, the NIH-CPSI score was found to be lower in the combination group. In the pain, urinary, and quality-of-life domain, most studies agree that combination therapy is not superior to monotherapy. However, on Day 90, all domains were found to be lower in the combination therapy. Responder rates were found to vary between studies. Only four out of six studies reported a response rate. Responder rates were lower in the combination group at 6 weeks of observation. On Day 90, responder rates were found to be better in the combination group. CONCLUSIONS: The combination therapy of antibiotics and alpha-blockers is not substantially better than antibiotic monotherapy in the first 6 weeks of treatment for CP/CPPS patients. This might not be applicable to a longer duration of treatment.

Plaque excision with the Shah Penile Implant™ and tunica vaginalis graft in Peyronie's disease with erectile dysfunction: A case report.

Peyronie's disease (PD) is a condition characterized by the deposition of scar tissue in the tunica albuginea of the penis. Peyronie's disease often causes pain, worsens the quality of erections, a variable degree of penile deformation and shortening, which can cause severe distress for the patient and the partner and impact negatively on self-esteem and quality of life in general. Surgery still represents the gold standard treatment for PD in the chronic phase, and it aims to guarantee a penis straight and rigid enough to allow the patient to resume penetrative sex with confidence. Penile prosthesis implantation should be reserved for patients with refractory erectile dysfunction or in these patients with complex deformities and impaired erections. Herein is reported the case of a 51-year-old male with a large ossified PD plaque and erectile dysfunction who underwent simultaneous plaque excision and grafting and penile implantation surgery with a semirigid penile prosthesis. This was the first case of penile prosthesis implantation for Peyronie's disease in Indonesia.

Endogenous vasoactive peptides and the human vagina--a molecular biology and functional study.

INTRODUCTION: Endogenous peptides, such as vasoactive intestinal polypeptide (VIP), C-type natriuretic peptide (CNP), and bradykinin (BK), have been proposed to play a role in the female sexual arousal response by exerting relaxation of clitoral, labial, and vaginal smooth muscle. While the effects of endogenous peptides on the human male erectile tissue have already been described, only very few studies have been conducted to investigate the peptidergic control of female genital tissues, including the vagina. AIMS: To elucidate the expression of mRNA specifically encoding for peptide receptors in the human vagina and the effects of VIP, CNP, and BK on the tension induced by endothelin-1 (ET-1) of isolated human vaginal wall smooth muscle. The production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in response to exposure of the tissue to the peptides was also measured. METHODS: The expression of mRNA encoding for receptor proteins specific for VIP, CNP, and BK were investigated by means of molecular biology (reverse transcriptase polymerase chain reaction [RT-PCR] analysis). Using the organ bath technique, the effects of VIP, CNP, and BK (0.1 nM to 1 µM) on the tension induced by 0.1 µM ET-1 of human vaginal strips were investigated. The tissue was also exposed to three different concentrations of VIP, CNP, and BK (0.01 µM, 0.1 µM, 1 µM) and the production of cAMP and cGMP determined by means of radioimmunoassays. MAIN OUTCOME MEASURES: Characterize the expression of peptide receptors in the human vagina and measure the relaxation exerted by BK, CNP, and VIP on the contraction induced by ET-1 of isolated human vaginal tissue. In addition, the effects of the peptides on the production of cAMP and cGMP were also elucidated. RESULTS: RT-PCR analysis revealed the expression of mRNA transcripts encoding for the VIP receptors VIP1R/vasoactive intestinal polypeptide receptor type 1 (VPAC1) and VIP2R/VPAC2, CNP receptors natriuretic peptide receptor type A (NPRA), natriuretic peptide receptor type B (NPRB) and natriuretic peptide receptor type C (NPRC), and BK receptor B2R. The tension induced by ET-1 was reversed by the peptides with the following rank order of efficacy: BK (21.7%) > VIP (20.9%) > CNP (13.3%). The relaxing effects of VIP and BK were paralleled by a 4.8-fold and fivefold increase in cAMP, while the production of cGMP was stimulated 38-fold and 119-fold in the presence of CNP or BK, respectively. CONCLUSION: Our results are in support of the hypothesis that endogenous peptides may contribute to the control of human vaginal smooth muscle tone through the involvement of the cyclic nucleotide-dependent pathways.

Premature ejaculation in patients with lower urinary tract symptoms: a systematic review.

Lower urinary tract symptoms (LUTS) refer to a group of symptoms related to bladder, prostate, and urethra. LUTS are common in men and the severity increases with age. LUTS are frequently associated with sexual dysfunction, such as premature ejaculation (PE), standing as the most common sexual dysfunction in men. Both LUTS and PE cause distress and dissatisfaction for the patient and his partner. This systematic review aims to determine the relationship between LUTS and PE in men. Two reviewers independently conduct a literature search in five online databases (PubMed, Scopus, Proquest, ClinicalKey, and ScienceDirect). In addition, reviewers also reviewed the reference list of chosen articles to identify additional relevant studies. Twelve articles were included in this systematic review that consists of one cohort study and 11 cross-sectional studies. The total scores of each identified study ranged from "poor" to "good." The prevalence of PE in LUTS ranged from 12 to 77%. Most of the studies showed a significant relationship between LUTS and PE. PE is more common in older age with the peak prevalence in age of 60-69 years old. There is a possible association between PE and LUTS. Further research using cohort or case-control study design on this topic is needed.

Genetic polymorphisms as prognostic factors for recurrent kidney stones: A systematic review and meta-analysis.

Genetic polymorphisms have been suggested as risk factors affecting the occurrence and recurrence of kidney stones, although findings regarding the latter remain inconclusive. We performed this systematic review and meta-analysis to clarify the associations between genetic polymorphisms and recurrent kidney stones. PubMed, SCOPUS, EMBASE, and Cochrane Library databases were searched through May 28th, 2020 to identify eligible studies. The Quality in prognostic studies (QUIPS) tool was used to evaluate bias risk. Allelic frequencies and different inheritance models were assessed. All analyses were performed using Review manager 5.4. A total of 14 studies were included for meta-analysis, assessing urokinase (ApaL1) and vitamin D receptor (VDR) (ApaI, BsmI, FokI, and TaqI) gene polymorphisms. The ApaLI polymorphism demonstrated protective association in the recessive model [odds ratio (OR) 0.45, P < 0.01] albeit higher risk among Caucasians in the heterozygous model (OR 16.03, P < 0.01). The VDR-ApaI polymorphism showed protective association in the dominant model (OR 0.60, P < 0.01). Among Asians, the VDR-FokI polymorphism recessive model showed significant positive association (OR 1.70, P < 0.01) and the VDR-TaqI polymorphism heterozygous model exhibited protective association (OR 0.72, P < 0.01). The VDR-BsmI polymorphism was not significantly associated with recurrent kidney stones in any model. Urokinase-ApaLI (recessive model), VDR-ApaI (dominant model), and VDR-TaqI (heterozygous model) polymorphisms were associated with decreased recurrent kidney stone risk whereas urokinase-ApaLI (heterozygous model) and VDR-FokI polymorphisms were associated with increased risk among Caucasians and Asians, respectively. These findings will assist in identifying individuals at risk of kidney stone recurrence.

Profile of hepatocyte apoptosis and bile lakes before and after bile duct decompression in severe obstructive jaundice patients.

BACKGROUND: Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions. Although decompression of the bile duct has been reported to improve liver functions in animal studies, the mechanism of obstruction differs from that in humans. This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting. METHODS: We conducted a "before and after study" on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression. Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin (HE) to identify bile lakes. All measurements were independently done by 2 observers. RESULTS: Twenty-one severe obstructive jaundice patients were included. In all patients, excessive hepatocyte apoptosis and bile lakes were apparent. After decompression, the hepatocyte apoptosis index decreased from 53.1 (SD 105) to 11.7 (SD 13.6) (P<0.05), and the bile lakes from 23.6 (SD 14.8) to 10.9 (SD 6.9) (P<0.05). CONCLUSION: Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice, similar to the findings in animal studies.

Effect of melatonin supplementation in combination with neoadjuvant chemotherapy to miR-210 and CD44 expression and clinical response improvement in locally advanced oral squamous cell carcinoma: a randomized controlled trial.

BACKGROUND: Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment. It is thought that neoadjuvant chemotherapy (NC) in locally advanced OSCC is able to shrink tumor size. Chemoresistancy is a problem due to hypoxic microenvironment characterized by increased expression of HIF-1α. It is also regulated by miR-210 as well as increased expression of CD44 and CD133. Melatonin has a powerful antioxidant and oncostatic effects that are expected to improve tumor hypoxia and clinical response. Fifty patients with OSCC were included and randomized. miR-210 and CD44 expression were measured before and after intervention using qRT-PCR absolute quantification, and clinical response was evaluated according to RECIST 1.1 criteria. This study aims to determine the effect of melatonin in improving the clinical response of patients with locally advanced oral squamous cell carcinoma (OSCC) after neoadjuvant chemotherapy to miR-210 and CD44 expression. RESULTS: Melatonin administration reduced miR-210 levels but not significant (p = 0.767). CD44 expression also decreased in the melatonin group compared with placebo yet was not significant (p = 0.103). There was a decrease in the expression of miR-210 and CD44 followed by a decrease in the percentage of residual tumor but not significant (p = 0.114). CONCLUSION: In OSCC, the addition of 20-mg melatonin to neoadjuvant chemotherapy (NC) reduced the expression of miR-210 and CD44 and decreased the percentage of tumor residue; however, no statistically significant result was observed. TRIAL REGISTRATION: This study is registered to ClinicalTrials.gov under trial registration number: NCT04137627 with date of registration on October 22, 2019-retrospectively registered, accessible from: https://clinicaltrials.gov/ct2/show/NCT04137627.

Evaluating the role of the serotoninergic system in the control of human seminal vesicle smooth muscle-an in vitro approach.

INTRODUCTION: It has been suggested that serotonin re-uptake inhibitors (SRIs) may retard the ejaculatory response by acting directly on the seminal vesicle (SV) and ductus deferens smooth muscle. However, until now, only a very few experimental studies have investigated such potential local (peripheral) effects. AIM: To elucidate the effects of serotonin (5-HT) and the SRIs clomipramine, fluoxetine and imipramine on the tension induced by norepinephrine (NE) of isolated human SV smooth muscle, as well as on the production of tissue cyclic AMP and cyclic GMP. MAIN OUTCOME MEASURES: To measure the inhibition exerted by serotonin and SRIs clomipramine, fluoxetine, and imipramine on the contractile response of isolated SV tissue. In addition, the effects of the drugs on the turn-over of cyclic nucleotides cAMP and cGMP were also elucidated. METHODS: The effects of the cumulative addition of serotonin and the SRIs clomipramine, fluoxetine and imipramine (1 nM-10 microM) on the tension induced by the alpha(1)-adrenoceptor agonist NE (10 microM) of SV strip preparations were studied using the organ bath technique. Cyclic AMP and cyclic GMP were measured by means of specific radioimmunoassays. RESULTS: The tension induced by NE was dose-dependently reversed by the drugs tested. The rank order of efficacy was: imipramine > or = fluoxetine > or = clomipramine > serotonin. Mean reversion of tension was measured between 66 +/- 6.6% and 52 +/- 6.6%. These effects were paralleled by a 1.3-fold to 2.7-fold increase in tissue cAMP in response to exposure to the drugs. In contrast, no significant enhancement in cGMP was noted. CONCLUSIONS: The findings, for the first time, present evidence that SRIs may antagonize the sympathetic contraction of SV smooth muscle via stimulation of tissue cyclic AMP.

Efficacy and tolerability of vardenafil in Asian men with erectile dysfunction.

AIM: To evaluate the efficacy and tolerability of vardenafil, a phosphodiesterase type-5 (PDE-5) inhibitor, in men of Asian ethnicity with erectile dysfunction (ED). METHODS: In this prospective, double-blind, multinational study, Asian men were randomized to receive vardenafil (10 mg) or placebo (4:1 ratio) for 12 weeks. The primary efficacy variables were the International Index of Erectile Function erectile function domain (IIEF-EF), and Sexual Encounter Profile (SEP) questions related to penetration and intercourse completion. Significant mean improvements were required in all three measures to show positive benefits of vardenafil treatment. Secondary efficacy variables included the Global Assessment Question (GAQ) on erection improvement. RESULTS: Least-squares mean baseline IIEF-EF domain scores (vardenafil 14.6, placebo 13.4) were consistent with moderate ED. After 12 weeks, vardenafil treatment was associated with significant increases from the baseline in IIEF-EF domain scores compared with the placebo (22.4 vs. 14.3; P<0.001). Vardenafil was associated with significant improvements from baseline in least squares (LS) mean success rates for SEP-2 (vardenafil 82.2 vs. placebo 43.6; P<0.001) and SEP-3 (vardenafil 66.1 vs. placebo 24.0; P<0.001). Positive GAQ responses were reported by 81.8% of vardenafil recipients vs. 24.3% of placebo recipients. Adverse events were reported by 25.4% of the vardenafil group, the majority mild and transient. CONCLUSION: Vardenafil (10 mg) is a highly effective and well-tolerated treatment for moderate ED in Asian men. These results add to the increasing amount of data demonstrating the safety and efficacy of vardenafil for the treatment of ED in a range of patient populations.