Surgeon-administered regional nerve blocks during radical cystectomy: a feasibility study.

OBJECTIVE: To describe the technique for surgeon-administered, ultrasound-guided transversus abdominis plane (SU-TAP) blocks performed during radical cystectomy as a component of multimodal, perioperative pain management. METHODS: Retrospective, case series of patients receiving SU-TAP blocks just prior to incision for RC. TAP blocks were performed by the surgeon with a standard technique using US guidance to instill an anesthetic solution. The primary outcome was opioid consumption at the intervals of 0-12, 12-24, 24-36, and 36-48 h postoperatively. Opioid consumption was reported as oral morphine milligram equivalents (MME). Secondary outcomes included time to perform SU-TAP blocks, and safety of block procedure. RESULTS: 34 patients were included. During the median length of stay of 4 days (interquartile range [IQR] 3-7), only 30/34 (88%) of patients required opioids within the first 12 h post-op, decreasing to 38% by 48 h post-op. The median consumption decreased in the first 48 h from 21 MMEs (IQR 9-38) to 10 MMEs (IQR 8-15) at the 0-12 and 36-48 h intervals, respectively. The median time to perform block procedure was 6 min (IQR 4-8 min) and there were no safety events related to the SU-TAP blocks. Limitations include no comparative arm for opioid consumption. CONCLUSION: Our data suggest that urologists may feasibly perform US-guided TAP blocks as a practical, efficient, and safe method of regional anesthesia. SU-TAP blocks should be considered in ERAS protocols for RC. Future comparative studies on opioid consumption compared to local infiltration and alternative block techniques are warranted.

Sequential Intravesical Chemotherapy for Treatment Naïve, High-Risk Non-Muscle Invasive Bladder Cancer: Oncologic Outcomes, Tolerance, and Comparison to Contemporary Controls.

OBJECTIVE: To assess if receiving sequential intravesical chemotherapy (Gemcitabine-Docetaxel, Gem-Doce) therapy was associated with similar oncologic efficacy to bacillus Calmette-Guérin (BCG) in patients with treatment-naïve, high-risk non-muscle invasive bladder cancer (HR-NMIBC). METHODS: Single-center, retrospective cohort study of 80 patients with HR-NMIBC initiating first-line Gem-Doce or BCG between August 2020 and August 2023. Surveillance was conducted with cystoscopy, urine cytology, and cross-sectional imaging. The primary oncologic outcome was high-grade bladder tumor recurrence during surveillance. Kaplan-Meier method was applied to determine 12- and 24-month recurrence-free survival (RFS) after initiation of therapy. Tolerance of each intravesical therapies was assessed. RESULTS: About 53/80 (66%) received Gem-Doce and 27/80 (34%) received BCG with overall 18-month median follow-up. There were 10 recurrences after Gem-Doce and 7 after BCG. The RFS at 12- and 24-months for Gem-Doce (12-months: 87%, 24-months: 75%) was not significantly different than BCG (12-months: 85%, 24-months: 81%). Lastly, Gem-Doce had significantly fewer patients with AEs compared to BCG (40% vs 74%). Limitations include retrospective design, small cohort size, and intermediate oncologic follow-up. CONCLUSION: Our data suggest that sequential intravesical Gem-Doce is an oncologically efficacious and, potentially better tolerated, alternative to BCG for treatment-naïve HR-NMIBC.

Adoption of robot-assisted radical nephroureterectomy permits a minimally invasive option for management of upper tract urothelial carcinoma in geriatric patients: comparison with non-geriatric patients with intermediate-term oncologic follow-up.

To assess the oncologic efficacy and safety of robot-assisted approach to radical nephroureterectomy (RARNU) in geriatric versus younger patients with upper tract urothelial carcinoma (UTUC). A single-center, retrospective cohort study was conducted from 2009 to 2022 of 145 patients (two cohorts: < 75 and ≥ 75 years old) with non-metastatic UTUC who underwent RARNU. Primary endpoint was UTUC-related recurrence of disease during surveillance (bladder-specific and metastatic). Safety was assessed according to 30-day, modified Clavien-Dindo (CD) classifications (Major: C.D. III-V). Survival estimates were performed using Kaplan-Meier method. There were 89 patients < 75 years (median 65 years) and 56 patients ≥ 75 years (median 81 years). Comparing the young versus geriatric cohorts: median follow-up 38 vs 24 months (p = 0.03, respectively) with similar 3-year bladder-specific recurrence survival (60% vs 67%, HR 0.70, 95% CI [0.35, 1.40], p = 0.31) and metastasis-free survival (79% vs 70%, HR 0.71, 95% CI [0.30, 1.70], p = 0.44). Expectedly, the younger cohort had a significant deviation in overall survival compared to the geriatric cohort at 1-year (89% vs 76%) and 3-years (72% vs 41%; HR 3.29, 95% CI [1.88, 5.78], p < 0.01). The 30-day major (1% vs 0) and minor complications (8% vs 14%, p = 0.87). Limitations include retrospective study design of a high-volume, single-surgeon experience. Compared to younger patients with UTUC, geriatric patients undergoing RARNU have similar oncologic outcomes at intermediate-term follow-up with no increased risk of 30-day perioperative complications. Thus, age alone should not be used to disqualify patients from definitive surgical management of UTUC with RARNU.

Outcomes After Laparoscopic Cholecystectomy in Hyperkinetic Biliary Dyskinesia.

BACKGROUND: Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms. METHODS: Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar's test. Risk differences with standard errors were employed to estimate percent reduction in symptoms. RESULTS: Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders. DISCUSSION: Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.

TGF-ß-mediated enhancement of TH17 cell generation is inhibited by bone morphogenetic protein receptor 1α signaling.

The cytokines of the transforming growth factor-ß (TGF-ß) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-ß, in regulating the immune responses has been extensively studied. TGF-ß is critical to prevent the spontaneous activation of self-reactive T cells and sustain immune homeostasis. In contrast, in the presence of proinflammatory cytokines, TGF-ß promotes the differentiation of effector T helper 17 (TH17) cells. Abrogating TGF-ß receptor signaling prevents the development of interleukin-17 (IL-17)-secreting cells and protects mice from TH17 cell-mediated autoimmunity. We found that the receptor of another member of TGF-ß family, bone morphogenetic protein receptor 1α (BMPR1α), regulates T helper cell activation. We found that the differentiation of TH17 cells from naive CD4+ T cells was inhibited in the presence of BMPs. Abrogation of BMPR1α signaling during CD4+ T cell activation induced a developmental program that led to the generation of inflammatory effector cells expressing large amounts of IL-17, IFN-γ, and TNF family cytokines and transcription factors defining the TH17 cell lineage. We found that TGF-ß and BMPs cooperated to establish effector cell functions and the cytokine profile of activated CD4+ T cells. Together, our data provide insight into the immunoregulatory function of BMPs.