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1.
Dig Dis Sci ; 67(9): 4492-4499, 2022 09.
Article in English | MEDLINE | ID: mdl-34993681

ABSTRACT

BACKGROUND: The role of Interstitial Cells of Cajal (ICC) in the pathogenesis of gastroparesis has been suggested by previous studies due to their involvement in the transmission of neuronal signaling to the smooth muscles of the GI tract. However, studies have been limited by the inability to obtain a gastric muscle sample, since routine endoscopy can only biopsy the mucosa. We present a new technique of muscle biopsy during per-oral endoscopic pyloromyotomy (GPOEM), a novel endoscopic procedure for treatment of gastroparesis. PATIENTS AND METHODS: All enrolled patients had diagnosed gastroparesis and had biopsies of the muscular layer at the antrum/pylorus during POEM. All GPOEM procedures took place from August 2019 to December 2019. Various demographic, disease-related, and procedure-related data were collected from chart review. ICC in the biopsy specimen was examined and quantitated. RESULTS: Through this method, we readily expose the gastric muscle of 21 patients through dissection of a gastric submucosal tunnel during GPOEM and provide reliable muscle sample for ICC quantification. Average number of ICC were higher in clinical responders (88 ICC ± 63 vs. 39 ICC ± 24, p = 0.02), defined as those who experienced significant improvement in nausea and vomiting symptoms after GPOEM. CONCLUSIONS: This study provides a reliable novel biopsy method for safely biopsy gastric muscle for quantitating the number of gastric ICC in patients with gastroparesis. The number of ICC may be related to the outcome of GPOEM therapy. However, further studies with larger number of patients are needed to confirm the results.


Subject(s)
Gastroparesis , Interstitial Cells of Cajal , Pyloromyotomy , Endoscopy, Gastrointestinal/adverse effects , Gastric Emptying/physiology , Gastroparesis/etiology , Gastroparesis/pathology , Gastroparesis/surgery , Humans , Interstitial Cells of Cajal/pathology , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Pyloromyotomy/adverse effects , Pylorus/pathology , Pylorus/surgery , Treatment Outcome
3.
J Muscle Res Cell Motil ; 42(1): 117-127, 2021 03.
Article in English | MEDLINE | ID: mdl-33590444

ABSTRACT

The method of kinetic analysis of the relaxation phase of the mechanical response of the smooth muscle previously proposed by Burdyga and Kosterin was applied to study the dynamics of the decay of oxytocin-induced calcium transients in cytosol of the rat myometrium smooth muscle cell detected by a fluorescence signal generated by a calcium-sensitive probe fluo-4 using a laser scanning confocal microscope. The experimental data were well linearized in the coordinates ln [(Fm - F)/F] vs lnt (F and Fm are the current fluorescence intensity of the calcium probe and the fluorescence intensity at the maximum of the calcium transient, respectively, while t is the time). The empirical parameters n and τ were determined by which the maximal normalized relaxation rate Vn was calculated for five different ROIs (regions of interest) in the myocyte cytosol. It proved to be almost the same for all ROIs. The maximal normalized relaxation rate calculated from the fluorescence intensity was always lower than that calculated from the corresponding calcium concentration, i.e. the cytosolic Ca2+ concentration in the relaxation phase decreases faster than the corresponding fluorescence intensity. The value of the maximal normalized relaxation rate calculated both from the fluorescence intensity and from the force of oxytocin-induced contractions of isolated rat uterus longitudinal smooth muscles (according to Tsymbalyuk and Kosterin) was exactly the same. This indicates that in the relaxation phase, the decreasing curves of both the fluorescence intensity and the contraction forces coincide.


Subject(s)
Muscle, Smooth/surgery , Myocytes, Smooth Muscle/metabolism , Animals , Calcium , Female , Kinetics , Oxytocin , Rats
4.
Am J Surg Pathol ; 45(6): 803-811, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33481390

ABSTRACT

Segmental absence of the intestinal musculature (SAIM) can cause intestinal perforation in adults. However, its prevalence and clinicopathologic features have not been well-described. This study aimed to determine the prevalence of SAIM-associated perforation and characterize its clinicopathologic features. We retrospectively examined 109 cases of intestinal perforation that underwent surgical resection from January 2009 to December 2019. SAIM was defined as the complete absence of the muscularis propria without extensive inflammation and fibrinous exudation around the perforation. SAIM was the second most frequent cause of perforation (26 cases: 24%), the most frequent cause being related to diverticulitis (39 cases: 36%). The most common site was the sigmoid colon (12 cases: 46.2%). The younger group (aged below 65 y) exhibited more frequent perforation of the upper segments of the gastrointestinal tract (from the duodenum to the descending colon) than the older group (65 y and above) (P=0.0018). No patients developed recurrence. The most common gross features were well-defined circular or small punched-out lesions, and the histologic features were complete absence of the muscularis propria and absence of hemorrhage and necrosis around the area of perforation. The characteristic features of SAIM were unique and their prevalence was higher than previously reported. The precise recognition of SAIM can aid in understanding the cause of perforation and avoiding further unnecessary examinations.


Subject(s)
Digestive System Abnormalities/epidemiology , Intestinal Perforation/epidemiology , Intestines/abnormalities , Muscle, Smooth/abnormalities , Adult , Aged , Aged, 80 and over , Digestive System Abnormalities/pathology , Digestive System Abnormalities/surgery , Diverticulitis/epidemiology , Diverticulitis/pathology , Female , Humans , Intestinal Perforation/pathology , Intestinal Perforation/surgery , Intestines/surgery , Male , Middle Aged , Muscle, Smooth/surgery , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome , Young Adult
5.
Int J Med Sci ; 18(2): 505-510, 2021.
Article in English | MEDLINE | ID: mdl-33390819

ABSTRACT

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC. Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively. Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I2=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P<0.00001, I2=64%). In terms of OM and recurrence, outcomes were pooled only after RC, which both turned out to be higher for SMIBC (OM: HR 1.50, 95%CI 1.30-1.73, P<0.00001, I2=0%; Recurrence: HR 1.66, 95%CI 1.36-2.02, P<0.00001, I2=48%). No obvious publication bias was observed from funnel plot. Conclusion: The current study suggested SMIBC had higher risk of CSM, OM and recurrence after RC, but lower risk of CSM after initial diagnosis.


Subject(s)
Muscle, Smooth/pathology , Neoplasm Recurrence, Local/epidemiology , Urinary Bladder Neoplasms/mortality , Urinary Bladder/pathology , Cystectomy , Disease Progression , Disease-Free Survival , Follow-Up Studies , Humans , Muscle, Smooth/surgery , Neoplasm Invasiveness/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery
6.
Cancer Sci ; 112(3): 1084-1094, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33368857

ABSTRACT

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.


Subject(s)
Carcinoma, Transitional Cell/mortality , Kidney Neoplasms/pathology , Neoplasm Recurrence, Local/epidemiology , Ureteral Neoplasms/pathology , Urinary Bladder Neoplasms/mortality , Administration, Intravesical , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/therapy , Chemotherapy, Adjuvant , Cystectomy , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Male , Middle Aged , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoadjuvant Therapy , Neoplasm Recurrence, Local/pathology , Nephroureterectomy , Propensity Score , Retrospective Studies , Risk Factors , Ureteral Neoplasms/mortality , Ureteral Neoplasms/therapy , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/secondary , Urinary Bladder Neoplasms/therapy
7.
Am J Respir Crit Care Med ; 203(2): 175-184, 2021 01 15.
Article in English | MEDLINE | ID: mdl-32721210

ABSTRACT

Rationale: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT, but appropriate control groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT treatment is important.Objectives: First, to assess the effect of BT on ASM mass, and second, to identify patient characteristics that correlate with BT response.Methods: Patients with severe asthma (n = 40) were randomized to immediate (n = 20) or delayed (n = 20) BT treatment. Before randomization, clinical, functional, blood, and airway biopsy data were collected. In the delayed control group, reassessment, including biopsies, was performed after 6 months of standard clinical care, followed by BT. In both groups, post-BT data including biopsies were obtained after 6 months. ASM mass (% positive desmin or α-smooth muscle actin area in the total biopsy) was calculated with automated digital analysis software. Associations between baseline characteristics and Asthma Control Questionnaire and Asthma Quality of Life Questionnaire (AQLQ) improvement were explored.Measurements and Main Results: Median ASM mass decreased by >50% in the immediate BT group (n = 17) versus no change in the delayed control group (n = 19) (P = 0.0004). In the immediate group, Asthma Control Questionnaire scores improved with -0.79 (interquartile range [IQR], -1.61 to 0.02) compared with 0.09 (IQR, -0.25 to 1.17) in the delayed group (P = 0.006). AQLQ scores improved with 0.83 (IQR, -0.15 to 1.69) versus -0.02 (IQR, -0.77 to 0.75) (P = 0.04). Treatment response in the total group (n = 35) was positively associated with serum IgE and eosinophils but not with baseline ASM mass.Conclusions: ASM mass significantly decreases after BT when compared with a randomized non-BT-treated control group. Treatment response was associated with serum IgE and eosinophil levels but not with ASM mass.


Subject(s)
Asthma/surgery , Bronchi/surgery , Bronchial Thermoplasty , Muscle, Smooth/surgery , Adolescent , Adult , Aged , Airway Remodeling , Asthma/diagnosis , Asthma/pathology , Asthma/physiopathology , Biopsy , Bronchi/pathology , Bronchoscopy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Muscle, Smooth/pathology , Severity of Illness Index , Treatment Outcome , Young Adult
8.
World J Urol ; 39(7): 2475-2481, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33112984

ABSTRACT

BACKGROUND AND PURPOSE: Urinary continence (UC) represents the main non-oncological goal in patients undergoing robotic-assisted radical prostatectomy (RARP). To evaluate the efficacy in early UC achievement, we described a new sling technique using the retrotrigonal muscular layer (TZ sling) combined with total anatomical reconstruction (TAR). PATIENTS AND METHODS: We prospectively enrolled 407 consecutive prostate cancer (PC) patients undergoing RARP between May 2017 and January 2020. The first 250 patients underwent only TAR, while the following 157 patients TAR + TZ sling, by isolating and anchoring the retrotrigonal muscular layer to the pubic bone with 2 bilateral sutures. We defined UC as ≤ 1 pad/die, which was assessed after catheter removal at 1, 4 and 12wk using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Sling-related operative time and post-operative complications were analyzed. RESULTS: In the TAR group, the UC rates at the 1, 4 and 12wk were 58%, 66% and 86%; in the TAR + TZ sling group 72%, 76% and 88%, respectively. A statistically significant difference was observed in the two groups at 1wk (p = 0.0049) and 4wk (p = 0.035) favoring the TZ sling surgical strategy. This difference in UC rates was lost at 12wk (p ≥ 0.05). No statistically significant differences in operative time, acute urinary retentions and other complication rates were observed between the two groups (p = NS). CONCLUSIONS: We have described a new, safe, feasible modification of RARP using a sling with the retrotrigonal muscular layer associated with TAR. We have demonstrated a statistically significant improvement in early UC rate in patients who are undergoing TAR and TZ sling compared to undergoing only TAR.


Subject(s)
Muscle, Smooth/surgery , Prostate/surgery , Prostatectomy/methods , Prostatic Neoplasms/surgery , Robotic Surgical Procedures , Aged , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies , Time Factors , Urinary Incontinence/prevention & control , Urination
9.
Eur Urol Oncol ; 3(6): 728-738, 2020 12.
Article in English | MEDLINE | ID: mdl-33177001

ABSTRACT

CONTEXT: Immune therapy has emerged as a powerful treatment of metastatic urothelial carcinoma. Over 20 ongoing studies are exploring this strategy in the neoadjuvant setting in patients with localized muscle-invasive bladder cancer. OBJECTIVE: To summarize the rationale and the clinical outcomes regarding the use of immune checkpoint blockade in the neoadjuvant setting before radical cystectomy. EVIDENCE ACQUISITION: A systematic review of the literature in the MEDLINE database was performed. The central search strategy used the terms bladder cancer, urothelial carcinoma, mice, human, immunotherapy, neoadjuvant therapy, atezolizumab, pembrolizumab, durvalumab, nivolumab, avelumab, ipilimumab, and tremelimumab. The search was limited to publications between January 2008 and February 2020. Publicly available relevant abstracts from recent meetings were also included. EVIDENCE SYNTHESIS: Phase II trials investigating neoadjuvant immune checkpoint blockade as a single agent before radical cystectomy reported a rate of pathological complete response (CR), ranging from 31% with an anti-PD-L1 monoclonal antibody (mAb) atezolizumab (n = 27/88) to 37% with anti-PD-1 mAb pembrolizumab (n = 42/114). Overall, 92% (n = 87/95) and 98% (n = 112/114) of the patients underwent radical cystectomy. Neoadjuvant immune checkpoint blockade did not delay planned surgery. Checkpoint inhibitor monotherapy was well tolerated, with no unexpected toxicity in the presurgical setting. Early phase I/II trials investigating neoadjuvant combination chemotherapy strategies with immune checkpoint blockers reported enhanced antitumor efficacy, with a pathological CR ranging from 33% to 50%. CONCLUSIONS: Although limited clinical data are available on long-term survival, neoadjuvant immune checkpoint blockade demonstrated effective antitumor efficacy for localized muscle-invasive bladder cancer. Phase III trials are currently investigating this strategy in the presurgical setting. PATIENT SUMMARY: Immunotherapy prior to surgery has been evaluated for patients with muscle-invasive bladder cancer. Although long-term survival benefit is unknown, such treatment strategy revealed a promising antitumor response rate for patients who underwent radical cystectomy. Ongoing prospective clinical trials will define the potential advantage of this approach over current cisplatin-based chemotherapeutic regimens alone or in combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/therapy , Immune Checkpoint Inhibitors/therapeutic use , Neoadjuvant Therapy/methods , Urinary Bladder Neoplasms/therapy , Carcinoma, Transitional Cell/immunology , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Chemotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/statistics & numerical data , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Cystectomy , Disease-Free Survival , Follow-Up Studies , Humans , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoadjuvant Therapy/statistics & numerical data , Neoplasm Invasiveness/pathology , Prospective Studies , Treatment Outcome , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
10.
Cancer Treat Res Commun ; 24: 100195, 2020.
Article in English | MEDLINE | ID: mdl-32688293

ABSTRACT

BACKGROUND: The aim of this retrospective study was to evaluate the prognosis of patients who had been diagnosed with muscle invasive bladder cancer (MIBC) and did not receive anti-cancer treatment because of their physical characteristics. METHODS: Between January 2012 and October 2019, 96 patients were diagnosed with MIBC (cT2-4N0M0) in our institution. Of those, 64 patients had undergone radical cystectomy (RC), 6 had received palliative radiation therapy, and 26 had not received any anti-cancer treatment. We further evaluated the 26 patients who had received no anti-cancer treatment. RESULTS: The no anti-cancer treatment group were significantly older (91 vs. 75 years, p<0.001), comprised fewer men (42% vs. 72%, p=0.015), and had poorer performance status (PS) (mean 2.69 vs. 0.32, p<0.001) than the RC group. The follow periods were 9.5 months and 28.5 months, respectively. Median overall survival (OS) was 12 months in the no anti-cancer treatment group, whereas the median OS was not reached during the study period in the RC group. In univariate analysis, OS was significantly associated with estimated GFR (eGFR) less than 30 mL/min/1.73m2 (median OS, 10 vs 16 months, p = 0.044). Multivariate analysis demonstrated that eGFR was significantly associated with OS (hazards ratio 0.267 [95% CI 0.0858-0.8357]; p = 0.0023). CONCLUSIONS: We evaluated the prognosis of patients with untreated MIBC. Their median OS was 12 months and eGFR was a significant prognostic factor. These findings may help in counseling patients about prognosis if no anti-cancer treatment is given.


Subject(s)
Urinary Bladder Neoplasms/mortality , Adult , Age Factors , Aged , Aged, 80 and over , Clinical Decision-Making , Counseling , Cystectomy/statistics & numerical data , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Muscle, Smooth/pathology , Muscle, Smooth/radiation effects , Muscle, Smooth/surgery , Neoplasm Invasiveness/pathology , Palliative Care/methods , Palliative Care/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Urinary Bladder/pathology , Urinary Bladder/radiation effects , Urinary Bladder/surgery , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy
11.
Urol Oncol ; 38(10): 774-782, 2020 10.
Article in English | MEDLINE | ID: mdl-32654948

ABSTRACT

PURPOSE: This systematic review assessed compliance to guidelines for the management of nonmuscle-invasive bladder carcinoma (NMIBC). METHODS: The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in November 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement. RESULTS: Fifteen studies incorporating a collective total of 10,575 NMIBC patients were eligible for inclusion in this systematic review. We found that the rates of compliance were 53.0% with a single immediate intravesical instillation in patients with presumed low or intermediate risk, 37.1% with intravesical bacillus Calmette-Guerin or chemotherapy in those with intermediate risk, 43.4% with performance of a second transurethral resection in high-risk patients, 32.5% with administration of adjuvant intravesical bacillus Calmette-Guerin in high-risk patients, 36.1% with radical cystectomy in highest-risk patients, and 82.2% with cystoscopy for follow-up. CONCLUSIONS: Compliance with NMIBC guidelines remains low. Better guideline education and understanding holds the key to achieving high compliance. Strategies to improve guideline compliance at the physician level are urgently required.


Subject(s)
Carcinoma, Transitional Cell/therapy , Guideline Adherence/statistics & numerical data , Medical Oncology/statistics & numerical data , Urinary Bladder Neoplasms/therapy , Urology/statistics & numerical data , Adjuvants, Immunologic/administration & dosage , Administration, Intravesical , Aftercare/standards , Aftercare/statistics & numerical data , Antineoplastic Agents/administration & dosage , BCG Vaccine/administration & dosage , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/pathology , Chemotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/standards , Chemotherapy, Adjuvant/statistics & numerical data , Cystectomy/standards , Cystectomy/statistics & numerical data , Cystoscopy/standards , Cystoscopy/statistics & numerical data , Humans , Medical Oncology/standards , Muscle, Smooth/diagnostic imaging , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoplasm Invasiveness , Practice Guidelines as Topic , Urinary Bladder/diagnostic imaging , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Urology/standards
12.
Respirology ; 25(9): 981-986, 2020 09.
Article in English | MEDLINE | ID: mdl-32567121

ABSTRACT

In this review, we trace (i) the origins of bronchial thermoplasty, (ii) the development of a solid evidence base for efficacy and safety, (iii) the emerging understanding of the pathophysiological mechanisms of action and (iv) the place in therapy today. Future challenges are then discussed.


Subject(s)
Asthma/surgery , Bronchial Thermoplasty , Muscle, Smooth/surgery , Asthma/physiopathology , Bronchi , Bronchial Thermoplasty/adverse effects , Bronchoscopy , Humans
13.
Eur Urol Oncol ; 3(6): 789-801, 2020 12.
Article in English | MEDLINE | ID: mdl-32553706

ABSTRACT

This case-based discussion describes the clinical course of a 63-yr-old patient who presented with gross hematuria and was diagnosed with a muscle-invasive bladder cancer at transurethral resection. Computed tomography revealed a locally advanced tumor, and the patient underwent neoadjuvant chemotherapy followed by open radical cystectomy with standard pelvic lymph node dissection. In a step-by-step fashion, we elaborate on diagnostic and therapeutic treatment options from two different vantage points: (1) guideline-adherent treatment with the state-of-the-art standard of care, and (2) a glimpse into the future discussing the evidence of potential additional or alternative approaches based on recent scientific advances. PATIENT SUMMARY: In this case-based discussion, we follow the clinical course of a patient with advanced bladder cancer and elaborate how the state-of-the-art treatment looks like in 2020, based on the best available evidence. This is compared with potential future treatment strategies, which may change and alternate our understanding of optimal bladder cancer care.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cystectomy/methods , Neoadjuvant Therapy/methods , Urinary Bladder Neoplasms/therapy , Urinary Diversion , Chemotherapy, Adjuvant/methods , Clinical Decision-Making , Cystoscopy , Dose-Response Relationship, Drug , Drug Administration Schedule , Humans , Lymph Node Excision , Male , Middle Aged , Muscle, Smooth/diagnostic imaging , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Tomography, X-Ray Computed , Urinary Bladder/diagnostic imaging , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology
14.
Int J Surg Pathol ; 28(8): 899-905, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32423259

ABSTRACT

Nodular granular muscle degeneration (NGMD) of the appendix is a rare histologic curiosity characterized by distinctive nests of polygonal epithelioid cells with abundant pale-pink eosinophilic granular cytoplasm, mostly distributed in the inner layer of the muscularis propria or submucosa of the appendix. Although the nature of the cells of interest in NGMD of the appendix has not been completely elucidated, it is believed that they denote degenerative smooth muscle cells of the appendiceal muscularis propria, a histologic finding described as granular cells/granular cell lesions of the appendix in the 1960s. In this article, we described a new case of NGMD of the appendix and documented for the first time that this peculiar lesion actually represents a form of perivascular epithelioid cell proliferation based on its dual immunopositivity for myogenic and melanocytic markers. We also analyzed the old medical literature on granular cells/granular cell lesions of the appendix to shed some light on this ill-defined morphologic finding and its relationship to NGMD of the appendix. Since NGMD of the appendix is a lesion of perivascular epithelioid cells, the term NGMD is a misnomer, and hence, the designation "local PEComatosis of the appendix" is proposed for this unusual phenomenon.


Subject(s)
Appendiceal Neoplasms/diagnosis , Appendix/pathology , Epithelioid Cells/pathology , Muscle, Smooth/pathology , Perivascular Epithelioid Cell Neoplasms/diagnosis , Adult , Appendectomy , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/surgery , Appendix/cytology , Appendix/surgery , Cell Proliferation , Female , Humans , Muscle, Smooth/cytology , Muscle, Smooth/surgery , Perivascular Epithelioid Cell Neoplasms/pathology , Perivascular Epithelioid Cell Neoplasms/surgery
15.
Urol Oncol ; 38(10): 796.e1-796.e6, 2020 10.
Article in English | MEDLINE | ID: mdl-32430255

ABSTRACT

PURPOSE: The American Urological Association (AUA) introduced evidence-based guidelines for the management of nonmuscle invasive bladder cancer (NMIBC) in 2016. We sought to assess the implementation of these guidelines among members of the Society of Urologic Oncology (SUO) with an aim to identifying addressable gaps. METHODS AND MATERIALS: An SUO approved survey was distributed to 747 members from December 28, 2018 to February 2, 2019. This 14-question online survey (Qualtrics, SAP SE, Germany) consisted of 38 individual items addressing specific statements from the AUA NMIBC guidelines within 3 broad categories - initial diagnosis, surveillance, and imaging/biomarkers. Adherence to guidelines was assessed by dichotomizing responses to each item that was related to recommended action statement within the guidelines. Statistical analysis was applied using Pearson's chi-squared test, where a P-value of <0.05 was considered statistically significant. RESULTS: A total of 121 (16.2%) members completed the survey. Members reported a mean of 71% guidelines adherence; adherence was higher for the intermediate- and high-risk subgroups (82% and 76%, respectively) compared to low-risk (58%). Specifically, adherence to guideline recommended cystoscopic surveillance intervals for low-risk disease differed based on clinical experience (60.9% [<10 years] vs. 36.8% [≥10 years], P = 0.01) and type of fellowship training (55.2% [urologic oncology] vs. 28.0% [none/other], P = 0.02). CONCLUSION: Adherence to guidelines across risk-categories was higher for intermediate- and high-risk patients. Decreased adherence observed for low-risk patients resulted in higher than recommended use of cytology, imaging, and surveillance cystoscopy. These results identify addressable gaps and provide impetus for targeted interventions to support high-value care, especially for low-risk patients.


Subject(s)
Guideline Adherence/statistics & numerical data , Medical Overuse/statistics & numerical data , Neoplasm Recurrence, Local/diagnosis , Practice Patterns, Physicians'/statistics & numerical data , Urinary Bladder Neoplasms/therapy , Biomarkers, Tumor/analysis , Cystectomy , Cystoscopy/standards , Cystoscopy/statistics & numerical data , Disease Progression , Evidence-Based Medicine/standards , Evidence-Based Medicine/statistics & numerical data , Humans , Medical Oncology/standards , Medical Oncology/statistics & numerical data , Muscle, Smooth/diagnostic imaging , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Risk Assessment , Societies, Medical/standards , Societies, Medical/statistics & numerical data , Surveys and Questionnaires/statistics & numerical data , Urinary Bladder/diagnostic imaging , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Urology/standards , Urology/statistics & numerical data , Watchful Waiting/standards , Watchful Waiting/statistics & numerical data
16.
Urol Oncol ; 38(10): 795.e9-795.e17, 2020 10.
Article in English | MEDLINE | ID: mdl-32417111

ABSTRACT

OBJECTIVES: To validate the substratification of high-risk in the European Association of Urology (EAU) guidelines and to develop the simplified substratification to improve usefulness and predictive accuracy on oncological outcomes in patients with primary high-risk nonmuscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. First, the efficacy of the EAU highest-risk on intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival was evaluated with univariate analyses. Second, we developed our simplified substratification based on multivariate analysis for intravesical RFS (lower- and higher-risk). We compared predictive accuracy on oncological outcomes using the receiver operating characteristic curve between the EAU and the simplified substratifications. RESULTS: Median age and median follow-up periods were 72 years and 51 months, respectively. The EAU highest-risk was not associated with shorter intravesical RFS and MIBC-free survival (P = 0.054 and P = 0.350, respectively). In multivariate analysis, tumor size, grade 3, and chronic kidney disease were significantly associated with shorter intravesical RFS, and we developed the simplified substratification including those 3 factors. Of 428 patients, 89 (21%) were substratified into the simplified higher-risk. The predictive accuracy of the simplified substratification on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality was significantly superior to the EAU substratification. CONCLUSION: Our simplified substratification might contribute to improving predictive accuracy on intravesical recurrence, MIBC and metastasis progression, and cancer-specific mortality in patients with primary high-risk NMIBC who underwent TURBT.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy/methods , Neoplasm Recurrence, Local/epidemiology , Urinary Bladder Neoplasms/surgery , Urinary Bladder/pathology , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Disease Progression , Disease-Free Survival , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoplasm Invasiveness , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Practice Guidelines as Topic , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment/methods , Risk Assessment/standards , Societies, Medical/standards , Urinary Bladder/surgery , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urology/standards
17.
Urol Oncol ; 38(10): 796.e7-796.e14, 2020 10.
Article in English | MEDLINE | ID: mdl-32446641

ABSTRACT

INTRODUCTION: Radical cystectomy (RC) is the standard of care for refractory high-risk non-muscle invasive bladder cancer (NMIBC). We aim to identify predictors of adequate lymph node dissection (LND) in a cohort of NMIBC patients undergoing RC, as well as its impact on clinical outcomes. METHODS: The National Cancer Database was queried for patients who underwent RC for urothelial cell carcinoma for clinical stage Tis/a/1 N0M0 disease between 2004 and 2013. Patients were stratified by LND: none, inadequate (<10) or adequate (≥10 nodes). Factors associated with LND were analyzed. Inverse-probability weighted propensity score matching was used to assess the impact of adequate LND on overall survival. RESULTS: The final cohort of 3,226 patients had a median follow-up of 39.0 months, had a mean age of 65.3 years, was 70% male, and was 81% Caucasian. Overall, 16.6% received no LND, 28.5% inadequate LND, and 55.0% adequate LND. Treatment at an academic facility, Charlson-Deyo Comorbidity score of 1, and later year of treatment were significantly associated with adequate LND. Overall survival was significantly higher with adequate LND compared to a matched-cohort of inadequate LND patients (68.7% vs. 60.6% at 5 years, P < 0.01). CONCLUSIONS: Nearly half of NMIBC patients undergoing RC do not receive an adequate LND, despite an association with increased overall survival. Treatment at an academic facility was associated with increased likelihood of adequate LND. Initiatives to improve adequate LND in this population may be warranted.


Subject(s)
Carcinoma, Transitional Cell/surgery , Cystectomy/statistics & numerical data , Lymph Node Excision/statistics & numerical data , Lymphatic Metastasis/prevention & control , Urinary Bladder Neoplasms/surgery , Age Factors , Aged , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Cystectomy/methods , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Male , Middle Aged , Muscle, Smooth/pathology , Muscle, Smooth/surgery , Neoplasm Staging , Prognosis , Propensity Score , Registries/statistics & numerical data , Risk Factors , Treatment Outcome , United States/epidemiology , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
18.
Am J Clin Pathol ; 154(2): 208-214, 2020 07 07.
Article in English | MEDLINE | ID: mdl-32253420

ABSTRACT

OBJECTIVES: Bladder cancers invading the muscularis mucosae (MM) are treated differently from those invading the muscularis propria (MP). However, it may be difficult to determine the type of smooth muscle in transurethral resection (TUR) or biopsy specimens. We aimed to investigate the clinicopathologic features of bladder cancers involving smooth muscle of indeterminate type (SMIT) in TUR specimens in comparison with those invading the MM. METHODS: We identified 103 patients with bladder cancer involving SMIT (n = 27) or the MM (n = 76) in TUR specimens. All patients underwent subsequent restaging TUR or cystectomy. RESULTS: Bladder cancer with SMIT invasion showed a significantly higher rate of MP invasion in the subsequent specimens than those invading the MM (52% vs 29%). Lack of MP in the TUR specimens had a significantly higher risk of MP invasion in the subsequent specimens than those with the MP (61% vs 40%). The overall survival time for patients with SMIT invasion was significantly shorter than those with MM invasion. CONCLUSIONS: Bladder cancers with SMIT invasion in TUR specimens show more frequent cancer upstaging in the subsequent specimens and a poorer clinical outcome than those invading the MM, which highlights the importance of a cancer restaging procedure for these patients.


Subject(s)
Carcinoma, Transitional Cell/pathology , Mucous Membrane/pathology , Muscle, Smooth/pathology , Neoplasm Invasiveness/pathology , Urinary Bladder Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Carcinoma, Transitional Cell/surgery , Cystectomy , Female , Humans , Male , Middle Aged , Mucous Membrane/surgery , Muscle, Smooth/surgery , Treatment Outcome , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/surgery , Urothelium/pathology , Urothelium/surgery
19.
Hum Pathol ; 99: 27-35, 2020 05.
Article in English | MEDLINE | ID: mdl-32220606

ABSTRACT

Smooth muscle hyperplasia of the testicular adnexa (SMH-TA) is a rare mass-forming intrascrotal lesion. Although benign, it can be a diagnostic challenge, as we have seen in our consult practice. Herein, we discuss our experience with these lesions over 14 years. Twelve SMH-TA cases were identified in our institutional records between 2005 and 2019. The morphologic features were reviewed. Clinical information was obtained from physicians' notes. The mean age was 51 years (range, 24-82 years). Six cases were on the left side, five on the right, and one was bilateral. The most common presentations were orchialgia (n = 10) and mass (n = 6). Two patients had a concurrent incarcerated inguinal hernia, and one had a recent groin trauma. Past medical history included 5 patients with previous surgeries in the inguinal region, 2 with a history of treated infections, and 1 with persistent chronic orchitis. Eight patients have undergone ultrasound imaging which showed lesions (n = 4), hematoma (n = 1), undescended testis (n = 1), or no abnormalities (n = 2). Grossly, the mean size was 1.7 cm (range, 1.0-3 cm). The lesions had ill-defined, focally cystic, pink-tan nodular surface. Microscopically, the lesions were comprised of an ill-defined smooth muscle proliferation arranged in fascicles or haphazard fashion, growing in a periductal, perivascular, interstitial, or most commonly in a mixed pattern. SMH-TA is a rare benign entity that can present clinically as orchialgia and/or a suspicious intrascrotal mass. As suggested in previous studies, we believe that this lesion represents a reactive process.


Subject(s)
Cell Proliferation , Muscle, Smooth/pathology , Myocytes, Smooth Muscle/pathology , Testicular Diseases/pathology , Testis/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Databases, Factual , Diagnosis, Differential , Humans , Hyperplasia , Male , Middle Aged , Muscle, Smooth/surgery , Predictive Value of Tests , Testicular Diseases/surgery , Testis/surgery , Young Adult
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