[The efficacy and safety of ibrutinib in the treatment of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia].

Objective: To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) . Methods: Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety. Results: A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion: Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

[Analysis of ultrasound images features and diagnostic model establishment of alveolar soft part sarcoma and intramuscular capillary-type hemangiomas].

Objective: The ultrasonography features of alveolar soft part sarcoma (ASPS) and intramuscular capillary-type hemangiomas (ICTH) were analyzed, and the diagnostic model of ASPS was established. Methods: A cross-sectional study was carried out. The clinical data of 52 patients [28 males and 24 females, aged (20.7±15.1) years] with pathologically confirmed ASPS and ICTH admitted to People's Hospital of Henan Province from January 2005 to February 2023 were included in the study. According to pathological types, the patients were divided into ASPS group and ICTH group. Clinical data of patients were retrospectively collected, and meaningful indicators in the univariate analysis were included in the regression analysis for screening. After comprehensive consideration of clinical significance and statistical significance, eligible indicators were selected for inclusion in the regression analysis. Binary logistic regression analysis was used to screen the factors that distinguished the pathological types of ASPS and ICTH, and the diagnostic model was established. The area under receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic effectiveness of the diagnostic model in distinguishing ASPS from ICTH. Results: There were 20 patients in ASPS group, 10 males and 10 females, aged (26.9±13.5) years, and 32 patients in ICTH group, 18 males and 14 females, aged (16.8±15.0) years. The age difference between the ASPS group and the ICTH group was statistically significant (P<0.05), and there were statistically significant differences in the ultrasound imaging features of "clear boundary" "peripheral lobe" "thin blood vessels inside the lesion are straight and out of shape" "intra-lesion liquification" "peripheral thick blood vessels" and "peripheral muscle fiber disruption" between the two groups (all P<0.001).Variables with clinical and statistical significance were selected as independent variables. Binary logistic regression analysis showed that peripheral muscle fiber interruption (OR=97.358, 95%CI:6.833-1 387.249) and internal thin blood vessels were flat and out of shape (OR=0.052, 95%CI:0.003-0.921) was the correlation factor to distinguish the pathological types of ASPS and ICTH. Two ultrasonic image features of "peripheral muscle fiber interruption" and "internal thin blood vessels are straight and out of shape" were used to establish the diagnostic model. The sensitivity of "peripheral muscle fiber interruption" diagnostic model was 81.3%, and the specificity was 95.0%. The AUC was 0.811(95%CI: 0.761-0.954). The sensitivity, specificity and AUC of the diagnosis model of "internal thin vessels with flat misshape" were 90.0%, 96.9% and 0.934(95%CI: 0.830-0.984). The sensitivity, specificity and AUC of the combined diagnosis model of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" were 96.9%, 90.0% and 0.974(95%CI:0.877-0.999). Conclusion: Ultrasonography can be used to distinguish ASPS from ICTH, and the combined diagnostic model based on the two ultrasonic imaging features of "peripheral muscle fiber interruption" and "internal thin blood vessel straight out of shape" can further improve the diagnostic efficiency.

[Prognostic factors of autologous hematopoietic stem cell transplantation in intermediate-risk acute myeloid leukemia patients with minimal residual disease negativity].

To explore prognostic factors in intermediate-risk acute myeloid leukemia (AML) patients with minimal residual disease (MRD) negativity (MRD<0.1%,MRD-)receiving autologous hematopoietic stem cell transplantation (auto-HSCT).A total of 59 intermediate-risk AML patients with MRD-were treated with auto-HSCT from January 2015 to September 2021 at Affiliated People's Hospital of Ningbo University. The clinical data and laboratory results were collected retrospectively. Efficacy, clinical outcome and prognostic factors were analyzed. Univariate analysis was conducted by using log-rank test, the multivariate analysis by Cox proportional risk model.Among 59 patients, there were 27 males and 32 females with median age of 55 (31-69) years old.The median follow-up was 761(317-1 861)days. The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 76.1%±11.4% and 73.4%±11.6% respectively.The univariate analysis showed that age older than 50 years, TET2 gene mutation (TET2+), achieving MRD negativity over 30 days (MRD30+) were unfavorable factors of OS (χ2=6.20, 33.20, 7.18;P=0.013,<0.001, 0.007). TET2+, WT1 gene mutation (WT1+), CD34+cells<2×106/kg, MRD30+were negative factors of EFS (χ2=17.29, 4.47, 3.94, 9.393;P<0.001, 0.035, 0.047, 0.002).Multivariate analysis showed that MRD30+, TET2+ were independent prognostic factors of OS and EFS (OS:HR=9.251, 25.839, P=0.036, 0.001;EFS:HR=5.851, 9.199, P=0.043, 0.002). Intermediate-risk AML patients with MRD30+or TET2+ have very poor prognosis after auto-HSCT. Alternative regimens should be investigated.

[Effects of subanesthetic dose of esketamine on opioid consumption after thoracoscopic surgery].

Objective: To investigate the effect of continuous intravenous infusion of subanesthetic dose of esketamine intraoperatively on postoperative opioid consumption in patients undergoing thoracoscopic surgery. Methods: A total of 71 patients with elective thoracoscopic lung surgery in the First Affiliated Hospital of Zhengzhou University from December 2020 to December 2021 were selected. Patients who were classified as grade Ⅰ or Ⅱ by the American Society of Anesthesiologists (ASA) and aged 18-70 years were included, including 32 males and 39 females, with a body mass index (BMI) of 18.5-30.0 kg/m2. The patients were randomly divided into three groups: (1) Control group (group C, n=24): continuous intravenous infusion of normal saline at the same rate during surgery; (2) Subanesthetic dose of esketamine 0.125 mg·kg-1·h-1 group (group ES1, n=23): continuous intravenous infusion of esketamine at a rate of 0.125 mg·kg-1·h-1 during surgery; (3) Subanesthetic dose of esketamine 0.250 mg·kg-1·h-1 group (group ES2, n=24): continuous intravenous infusion of esketamine at a rate of 0.250 mg·kg-1·h-1 during surgery. The main outcome measures were the total consumptions of hydromorphone of 3 groups within 24 and 48 hours after surgery. The secondary outcome measures were the extubation time, length of postanesthesia care unit (PACU) stay, the time of first feeding, and the incidences of adverse effects within 24 h after surgery in 3 groups. Results: The 24 h postoperative consumption of hydromorphone in group C, ES1 and ES2 was (5.4±1.0) mg, (4.5±1.5) mg and (4.0±0.8) mg, respectively. Likewise, the 48 h postoperative consumption of hydromorphone was (9.7±2.2) mg, (9.0±3.0) mg and (7.7±1.8) mg, respectively. Compared with group C, the 24 h postoperative hydromorphone consumptions were significantly reduced in group ES1 and ES2 (both P<0.05). The extubation time, length of PACU stay and the time of first feeding after surgery in group C were (23±10) min,(70±12) min,(17±3) h,in group ES1 were (22±4) min,(69±11) min,(14±5) h,in group ES2 were (16±8) min,(58±12) min,(14±3) h, respectively. Compared with group C and group ES1, both of the extubation time and length of PACU stay were shortened in group ES2 (both P<0.05). Compared with group C, the first postoperative feeding time of group ES1 and ES2 was shortened (both P<0.05). There were no differences in the incidences of adverse effects at postoperative 24 h among 3 groups (all P>0.05). Conclusion: Continuously intravenous infusion of subanesthetic esketamine at a rate of 0.250 mg·kg-1·h-1 can significantly reduce the postoperative opioid consumption and improve the patient's outcomes.

[Application strategy and effect of cuffed tracheostomy tube with inner cannula in the treatment of postoperative complications of laryngeal or hypopharyngeal cancer].

Objective: To Investigate the application strategy and effect of cuffed tracheostomy tube with inner cannula in the treatment of postoperative complications of laryngeal and hypopharyngeal cancer. Methods: A total of 60 patients with laryngeal and hypopharyngeal cancer occurred serious postoperative complications, including 31 cases of severe postoperative neck infection, 8 cases of dyspnea, 5 cases of massive hemorrhage and 16 cases of seriously intractable aspiration. The tracheal cannula with inner cannula and outer cuff was immediately worn on these patients and the cuff was inflated. Different treatments were carried out according to different complications. The outer cuffs were inflated for patients with severe neck infections to prevent a large amount of neck secretions inhaled to the trachea. Patients with dyspnea immediately received ventilator-assisted ventilation. For those with massive hemorrhage on the wound, doctors should prevent bleeding and stop bleeding under general anesthesia. Patients with severely coughing should perform eating training to prevent food aspiration. The inner cannula was regularly replaced once a month for all of these patients. Results: Through targeted treatment, the complications of 60 patients with cuffed tracheostomy tube with inner cannula were effectively controlled. After dressing change, the neck wounds of 31 patients with neck infection were shrunk or healed. Finally, all of the patients were replaced with metal tracheal tubes. Eight cases with dyspnea were rescued with the symptomatic and related special treatment, and finally replace by metal tracheal tube. Five cases with massive bleeding in the neck wound were successfully rescued and replaced with metal tracheal cannula. Thirteen patients among 16 cases with intractable aspiration were removed the tracheal cannula and other 3 cases of old and severely ill were replaced with metal tracheal cannula. Conclusions: The cuffed tracheostomy tube with inner cannula is of great value in the treatment of severe postoperative complications of laryngeal or hypopharyngeal cancer. It is strongly recommended that the operators should fully understand and use it reasonably after the operation of laryngeal or hypopharyngeal cancer.

[Characteristics of contrast-enhanced ultrasound in alpha-fetoprotein-negative recurrent small hepatocellular carcinoma].

Objective: To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC). Methods: The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups. Results: The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of P<0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of P<0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s (P>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, P>0.05). Conclusions: The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC.

[Effect of ultrasound contrast agent targeting gelatin on uptake of mouse ascites hepatocellular carcinoma cell lines with high lymphatic metastasis].

Objective: To analyze the effect of ultrasound contrast agent targeting gelatin on uptake of high lymphatic metastasis cell lines of mouse hepatocellular carcinoma with peritoneal effusion. Methods: The modified double emulsifying solvent evaporation method was used to construct the macromolecule contrast agent PLGA-Cooh. The carbodiimide was used to connect the monoclonal antibody of gelatin with the contrast agent PLGA-Cooh, and the targeted ultrasound contrast agent Gsn-PLGA was established. The particle size and Zeta potential of the targeted ultrasound contrast agent were measured by laser particle size analyzer. The surface binding of the contrast agent to the gelatin monoclonal antibody was evaluated by immunofluorescence. Hca-F cells with high lymphatic metastasis were cultured in mice with peritoneal effusion hepatocellular carcinoma. Target-seeking ability in vitro was evaluated by in vitro uptake test, and the imaging effect of the contrast agent in vitro was evaluated by in vitro developing test. Results: The contrast agent is white powder with good water solubility. The average particle size and surface potential were (569.68±6.96) nm and (-10.95±2.43) mV, respectively. The fluorescent antibody binding rate of non-targeted and targeted ultrasound contrast agent labeled with DiI were 0.84% and 95.89%, respectively. The results showed that the targeted ultrasound contrast agent Gsn-PLGA had a better of developing effect in vitro. Hca-F cells with high expression of gelsolin protein had stronger uptake ability of targeted ultrasound contrast agent and stronger green fluorescence in vitro than those with low expression of gelsolin protein (P<0.05). Moreover, targeted ultrasound contrast agent Gsn-PLGA had stronger targeting to the gelsolin protein. The echo of the targeted ultrasound contrast agent Gsn-PLGA was uniform and fine, without attenuating echo of the back. Simultaneously, the development effect was more obvious with the increase of contrast agent concentration (P<0.05). Conclusion: Ultrasound contrast agent Gsn-PLGA targeting gelatin can bind Hca-F cells with high expression of gelatin and display a good imaging effect in vitro.

Proteobacteria community compositions correlate with bronchiectasis severity.

BACKGROUND: Proteobacteria contributes to airway inflammation and poor clinical outcomes in bronchiectasis. OBJECTIVE: To compare sputum Proteobacteria compositions according to bronchiectasis severity. METHODS: Sputum samples collected from 106 patients with stable bronchiectasis and 17 healthy subjects were split for 16srRNA sequencing and biomarker measurement. Pairwise changes in Proteobacteria compositions among 22 of 106 patients during stability, exacerbations and convalescence were compared. Patients were stratified based on the Bronchiectasis Severity Index (BSI). RESULTS: Respectively 44, 34 and 28 patients had mild, moderate and severe bronchiectasis. A higher BSI was associated with a greater relative abundance of Proteobacteria and lower Shannon-Wiener diversity index, Simpson diversity index and bacterial richness. Similar findings applied at genera levels. Proteobacteria and Pseudomonas were the major phylum and genus, respectively, contributing to community similarity in moderate-to-severe bronchiectasis. These significant correlations were not observed in those in whom Pseudomonas aeruginosa was not isolated. Proteobacteria abundance correlated with lung function, but not sputum inflammatory biomarkers in severe bronchiectasis. Proteobacteria compositions in severe bronchiectasis were less likely to change significantly during exacerbations and convalescence. CONCLUSION: Proteobacteria compositions (particularly culturable Pseudomonas abundance) were correlated with bronchiectasis severity. Proteobacteria and Pseudomonas contributed most to community similarity in patients with a higher BSI, indicating microbial targets for interventions in severe bronchiectasis.

[Prognostic significance of miRNA-223 targeting SOX11 in mantle cell lymphoma].

Objective: To explore the expression and prognostic significance of miR-223 in patients with mantle cell lymphoma (MCL) and to investigate the possible mechanism. Methods: Twenty-one newly diagnosed MCL patients with bone marrow involvement were enrolled in the present study, 20 healthy donors as normal control. The expression level of miR-223 and SOX11 mRNA was determined by RQ-PCR. CCK-8 and flow cytometer assays were used to analyze cell proliferation, cell cycle and apoptosis of the constructed miR-223 overexpressing MCL cell line, Granta519 cells. SOX11 protein expression level was determined by Western blot. The target gene of miR-223 was confirmed by dual luciferase reporter assay. Results: ①Of the 21 newly diagnosed MCL patients, 15 were male and 6 female, the median age was 58 (37-72) years. The expression level of miR-223 was significantly down regulated in MCL patients compared with that of healthy donors (14.7±10.5 vs 1 244.1±1 935.2, P<0.001). The lower expression of miR-223 was inversely correlated with high-risk mantle international prognostic index (P=0.001), elevated LDH (P=0.001), ECOG score ≥2 (P=0.035). ②Using the median relative expression level of miR-223 as the cutoff value, 21 MCL patients were divided into high-expression group (n=10) and low-expression group (n=11) and found that the high-expression group had a significantly superior OS (median OS: 36 vs 12 months, P=0.021). ③In vitro results showed that compared with the control group, the proliferation of miR-223 overexpressed Granta519 cells was inhibited (the most significant reduction on 96h, P<0.001), manifested by lower proportion of cells in G2/M phase (P<0.001) and increased apoptosis (P<0.001), and the expression level of SOX11 protein in Granta519 cells was significantly lower than that of the control group. ④miR-223 could inhibited the 3' untranslated region of SOX11, and the expression level of miR-223 was significantly negatively correlated with mRNA level of SOX11 in MCL patients (r=-0.81, P<0.001). Conclusions: The expression of miR-223 was repressed in MCL and was associated with poor clinical outcomes, which may be probably attributed to its direct targeting SOX11.

[Hemoptysis in adults with bronchiectasis: correlation with disease severity and exacerbation risk].

Objective: To investigate the association between hemoptysis and disease severity and risks of acute exacerbations in patients with bronchiectasis. Methods: Between September 2012 and January 2014, we recruited 148 patients (56 males, 92 females, mean age: 44.6 years) with clinically stable bronchiectasis, who were classified into hemoptysis group (36 males, 70 females, mean age: 45.6 years) and non-hemoptysis group (20 males, 22 females, mean age: 41.8 years). We inquired the past history, and evaluated chest imaging characteristics, lung function, cough sensitivity assessed using capsaicin cough challenge tests, and airway inflammation. We also performed a 1-year follow-up to evaluate whether patients with hemoptysis would have greater risk of having acute exacerbations. Results: In the hemoptysis group, median 24-hour sputum volume was 20.0 ml, median Bronchiectasis Severity Index (BSI) was 7.0, median bronchiectatic lobes was 4.0, median chest CT score was 7.0, the geometric mean for eliciting 5 coughs following capsaicin cough sensitivity (C5) was 77 µmol/L, 67 cases (63%) had cystic bronchiectasis and 52 cases (49%) had pulmonary cavity shown on chest CT, and 35 cases (33%) had Pseudomonas aeruginosa colonization. In the non-hemoptysis group, median 24-hour sputum volume was 5.0 ml, median BSI was 4.0, median bronchiectatic lobes was 3.0, median chest CT score was 5.0, 15 cases (36%) had cystic bronchiectasis and 10 cases (24%) had pulmonary cavity, the geometric mean for C5 was 212 µmol/L, and 4 cases (10%) had Pseudomonas aeruginosa colonization. All the above parameters differed significantly between the hemoptysis and the non-hemoptysis group (P<0.05). In the hemoptysis group, 29 patients with pulmonary cavity (27%) had reported the use of intravenous antibiotics, and 44 cases (42%) had at least one hospitalization within the previous 2 years. In the non-hemoptysis group, 8 cases (19.0%) had reported the use of intravenous antibiotics, and 8 cases (19.0%) reported hospitalization within 2 years. A prior history of hemoptysis was associated with a greater risk of experiencing bronchiectasis exacerbations during follow-up, after adjusting for age, sex, smoking status and BSI (62 cases in the hemoptysis group, 18 cases in the non-hemoptysis group, χ(2)=16.06, P=0.03). In a multivariate model, cystic bronchiectasis was the sole risk factor for hemoptysis; 67 cases which accounted for 63% of patients in the hemoptysis group and 15 cases which accounted for 36% of patients in the non-hemoptysis group, odds ratio: 2.84, 95% confidence interval: 1.00-8.14, P=0.05 . Conclusions: In this study, 72% of bronchiectasis patients had experienced hemoptysis, which was associated with the severity of bronchiectasis. Patients with a prior history of hemoptysis had a greater risk of acute exacerbations during follow-up than those without.

Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia.

BACKGROUND: Genetic polymorphisms of the µ-opioid receptor gene OPRM1 A118G have been shown to influence opioid efficacy. The association of the OPRM1 A118G genetic polymorphism with side effects, such as nausea and vomiting, caused by opioids during analgesia has not been well-represented by the literature . This study aimed to investigate whether the genetic polymorphism of OPRM1 A118G contributed to the variability in nausea and vomiting during fentanyl analgesia in patients undergoing total abdominal hysterectomy or myomectomy. METHODS: One hundred sixty-five women, of Han nationality, aged 20-50 yrs, of ASA I or II, and scheduled for elective total abdominal hysterectomy or myomectomy under general anesthesia were enrolled. Intravenous fentanyl, patient-controlled analgesia was provided postoperatively for pain control. The presence and scores of postoperative nausea and vomiting for 24 hours were recorded and measured using rating scales. Pain was measured with a visual analog scale, and fentanyl consumption over 24 hours was recorded, as well. Genotyping of the A118G allele was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and patients were divided into three groups according to their genotype. RESULTS: The frequency of the A118G allele was 32.4% for the patients in this study. Patients homozygous for 118G required more fentanyl to achieve adequate pain relief compared with the other two patient groups (patients homozygous for 118A and heterozygous). However, there were no statistically significant differences among the frequencies and scores of nausea and vomiting. CONCLUSION: OPRM1 A118G has no effect on the individual variation of postoperative nausea and vomiting, the side effects of fentanyl analgesia, in Chinese women undergoing gynecologic surgery.

T-cell subsets required for intravesical BCG immunotherapy for bladder cancer.

Intravesical bacille Calmette-Guérin (BCG) has been shown in prospective randomized clinical trials to be the treatment of choice for superficial bladder cancer. In this investigation we evaluated the role of CD4 and CD8 lymphocytes in the antitumor response. Monoclonal antibodies to thy 1.2, CD8, CD4 and an isotype control were injected intravenously to deplete T cell populations. After depletion (verified by flow cytometry), BCG therapy was initiated. The results demonstrate that the depletion of either CD4 or CD8 T cell subsets eliminated BCG-mediated antitumor activity. Footpad delayed type hypersensitivity (DTH) was aborted only in CD4 depleted mice; it was essentially unchanged in CD8 depleted mice. However, the presence of DTH was not sufficient for induction of BCG-mediated antitumor activity. Exogenous IL-2 at levels sufficient to induce lymphokine activated killer cell activity did not substitute for CD4 cells. There was no evidence for the induction of protective immunity to the tumor after BCG therapy. These results demonstrate the requirement for T lymphocytes in BCG-mediated antitumor activity and further demonstrate that the presence of both CD4 and CD8 subsets are required. CD8 depletion experiments suggest that the presence of CD4-mediated DTH is not sufficient for the induction of antitumor activity. Furthermore, these data suggest that BCG-mediated antitumor activity is a localized phenomenon that does not induce protective immunity.

Effects of rectal examination, prostatic massage, ultrasonography and needle biopsy on serum prostate specific antigen levels.

Measurement of serum prostate specific antigen (PSA) is commonly used to evaluate the prostate gland in a variety of clinical settings. We examined the effects of prostatic manipulations, including digital rectal examination, prostate massage, transrectal ultrasonography and transrectal needle biopsy, on serum PSA levels in 199 men. We detected no clinically significant difference between serum PSA levels obtained immediately before and at 5 or 90 minutes after rectal examination in 43 men. We observed falsely increased PSA levels (to greater than 4 ng./ml., Tandem-R) in 1 of 17 men (6%) following prostatic massage and in 3 of 27 men (11%) following ultrasonography. Transrectal needle biopsy caused an immediate increase in serum PSA in 92 of 100 men. In 29 of these 92 men (32%) when followed weekly serum PSA levels did not return to baseline as expected according to the published serum PSA half-life of 2 to 3 days. Biopsies taking 3 or fewer cores (7 patients) resulted in a smaller increase in serum PSA (mean 1.63 +/- 1.12 times the baseline level versus 6.24 +/- 1.10 times baseline, p less than 0.03) and a proportionally shorter duration of PSA elevation (mean 1.43 +/- 0.48 weeks versus 2.13 +/- 0.14 weeks, p = 0.20) than those taking 4 or more cores (93 patients). Prostate size and the presence of cancer had no influence on the duration of PSA elevation following biopsy. We conclude that digital rectal examination, prostatic massage and ultrasonography have minimal effects on serum PSA levels in most patients. However, prostatic needle biopsy usually causes marked elevations of serum PSA levels with a persistent PSA leak into the blood stream lasting longer than expected from the serum half-life of PSA in approximately 25% of the patients.

The ability of systematic transrectal ultrasound guided biopsy to detect prostate cancer in men with the clinical diagnosis of benign prostatic hyperplasia.

Multiple directed and systematic ultrasound guided biopsies of the prostate were performed in 73 men with the clinical diagnosis of benign prostatic hyperplasia (BPH). Seven men (10%) had prostate cancer. Of the 67 patients with benign biopsies 40 underwent subsequent transurethral prostatectomy and 2 (5%) had prostate cancer. Multiple directed and systematic biopsies of the prostate detected 78% of the nonpalpable prostate cancers diagnosed in the study population. Radical prostatectomy was performed in all 9 men with prostate cancer: there were 3 small organ-confined tumors, 5 large organ-confined tumors and 1 stage C tumor with 1 focus of microscopic capsular penetration. Our results suggest that multiple directed and systematic ultrasound guided biopsies are capable of detecting low volume nonpalpable prostate cancer in men with BPH. However, the exact indication for pre-treatment ultrasound guided biopsy of the prostate in men with symptomatic BPH remains unclear. It may be that use of this modality is most appropriate for patients undergoing pharmacological therapy or balloon dilation of BPH rather than for those undergoing transurethral prostatectomy.

Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) is secreted exclusively by prostatic epithelial cells, and its serum concentration is increased in men with prostatic disease, including cancer. We evaluated its usefulness in the detection and staging of prostate cancer. METHODS: We measured serum PSA concentrations in 1653 healthy men 50 or more years old. Those with PSA values greater than or equal to 4.0 micrograms per liter then underwent rectal examination and prostatic ultrasonography. Ultrasound-directed prostatic needle biopsies were performed in the men with abnormal findings on rectal examination, ultrasonography, or both. The results were compared with those in 300 consecutively studied men 50 or more years old who underwent ultrasound-directed biopsy because of symptoms or abnormal findings on rectal examination. RESULTS: Serum PSA levels ranged from 4.0 to 9.9 micrograms per liter in 6.5 percent of the 1653 men (107). Nineteen of the 85 men in this group (22 percent) who had prostatic biopsies had prostate cancer. Serum PSA levels were 10.0 micrograms per liter or higher in 1.8 percent of the 1653 men (30). Eighteen of the 27 men in this group (67 percent) who had prostatic biopsies had cancer. If rectal examination alone had been used to screen the men who had biopsies, 12 of the 37 cancers (32 percent) would have been missed. If ultrasonography alone had been used to screen these men, 16 of the 37 cancers (43 percent) would have been missed. Serum PSA measurement had the lowest error rate of the tests, and PSA measurement plus rectal examination had the lowest error rate of the two-test combinations. CONCLUSIONS: The combination of measurement of the serum PSA concentration and rectal examination, with ultrasonography performed in patients with abnormal findings, provides a better method of detecting prostate cancer than rectal examination alone.

Adverse impact of fibrin clot inhibitors on intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.

Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.

Cystotomy, temporary urinary diversion and bladder packing in the management of severe cyclophosphamide-induced hemorrhagic cystitis.

Severe hemorrhage from cyclophosphamide-induced cystitis sometimes requires aggressive open management when conventional endoscopic and intravesical therapies have failed. We present 2 patients with intractable hematuria who were managed by open cystotomy, temporary urinary diversion via external ureteral stents, and continuous postoperative bladder packing with gauze and hemostatic agents. Both patients had a dramatic improvement in the hematuria immediately postoperatively and 1 with prolonged followup has no urological disability. We suggest that this procedure be considered for management of severe hemorrhagic cystitis as an alternative to more aggressive surgical therapies, such as formal urinary diversion with cystectomy.