Citations

Background and Aims: The optimal treatment strategy for de novo perihilar cholangiocarcinoma (pCCA) remains debated. This study compares outcomes between liver transplantation following neoadjuvant chemoradiation (RT+LT) and liver resection (LR), with (LR+VR) and without vascular resection (LR w/o VR). Approach and Results: This single-center, retrospective study included patients with de novo perihilar cholangiocarcinoma treated at the Mayo Clinic Rochester (1993–2023) with curative-intent surgery. Patients underwent either (1) LR, classified as LR+VR or LR w/o VR, or (2) RT+LT following the transplant protocol. Overall survival (OS) and recurrence-free survival were analyzed using as-treated and intention-to-treat approaches, incorporating competing risk analysis and direct matching. In the as-treated analysis, RT+LT showed superior median OS compared with LR w/o VR (78.0 vs. 58.2 mo, p =0.03) and LR+VR (25.8 mo, p <0.001). Considering dropout rates (RT+LT: 41%, LR: 28%), intention-to-treat analysis showed no significant OS difference between LR and RT + LT (31.7 vs. 38.5 mo, p =0.19). In matched as-treated analysis, RT + LT had no significant survival benefit over LR w/o VR (50.6 vs. 140.6 mo, p =0.08) or LR+VR (25.8 mo, p =0.11). Perioperative mortality was 4% (RT+LT), 7% (LR w/o VR), and 8% (LR + VR). Conclusions: Both LR and RT+LT achieve excellent oncological outcomes in selected patients with de novo perihilar cholangiocarcinoma. Key challenges remain dropouts during neoadjuvant therapy in patients planned for LT and high perioperative mortality for patients undergoing LR. OS doubles in patients undergoing LR+VR compared with dropouts, supporting LR+VR as a viable option for patients who are ineligible for LT. Appropriate patient selection is crucial, as those not undergoing surgery suffer from a dismal prognosis.

Key Points This study demonstrates that peritoneal dialysis is a safe and feasible option for patients with autosomal dominant polycystic kidney disease, even with high cystic organ volumes. Larger organ volumes, including height-adjusted cumulative kidney and liver volume, were not associated with increased peritoneal dialysis–related complications. Background Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and the fourth leading cause of kidney failure. Peritoneal dialysis (PD), preferred for its home-based convenience and cost-effectiveness, is often underutilized in ADPKD because of concerns over enlarged kidneys and heightened risk of complications. Methods This retrospective cohort study used data from the Mayo Clinic Polycystic Kidney Disease Database to evaluate individuals with ADPKD undergoing PD. We analyzed demographics, clinical parameters, and PD-related parameters. Complications were correlated with kidney and liver volumes derived from pre-kidney failure imaging. Results A total of 155 individuals with ADPKD on PD were included, of whom 45.1% were male. The mean age at PD initiation was 54.3±12.8 years, and the mean body mass index was 28.0±7.0 kg/m 2 . The median duration of PD was 24.3 months (interquartile range [IQR], 10.7–43.1), with 21.9% transitioning to hemodialysis. The most common complications were abdominal hernias (30.3%) and peritonitis (23.9%), with a peritonitis rate of 0.11 episodes per patient-year. Imaging analyses performed on a subset of 50 patients showed a median height-adjusted total kidney liver volume of 2731.9 ml/m (IQR, 2102.5–3131.1) and a median height-adjusted total kidney volume of 1303.5 ml/m (IQR, 733.1–1829.4). Kaplan–Meier analysis demonstrated no differences in complications rates on the basis of height-adjusted total kidney liver volume or height-adjusted total kidney volume (above versus below median values) or body mass index categories. Multivariate Cox regression analysis revealed that higher height-adjusted cumulative organ volume was associated with a lower risk of PD-related complications (hazard ratio=0.56, P = 0.026). Conclusions PD is a safe and feasible treatment option for patients with ADPKD, with no increased risk of PD-related complications associated with larger height-adjusted cumulative organ volumes. Infectious complication rates in this cohort were within International Society of Peritoneal Dialysis guideline thresholds, further supporting the safety of PD in this population.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.

INTRODUCTION: Chronic pancreatitis (CP) remains difficult to manage with few treatment options. Prior studies have implicated prostaglandin E 2 (PGE 2 ) in mediating chronic inflammation in the pancreas. Therefore, we aimed to evaluate whether indomethacin, a cyclooxygenase-2 enzyme inhibitor, would reduce PGE 2 levels in CP. METHODS: In this pilot multicenter randomized controlled trial, participants with CP received oral indomethacin (50 mg) or placebo twice daily for 28 days. Measurement of PGE 2 levels in pancreatic fluid collected endoscopically after secretin administration at baseline and posttreatment (day 28) was performed. Quality of life and pain were also assessed at baseline and posttreatment. RESULTS: A total of 27 participants were randomized (indomethacin = 13, placebo = 14). Although PGE 2 levels decreased after treatment in pancreas fluid, plasma, and saliva in the indomethacin group, there was no significant difference in mean change in pancreas fluid PGE 2 levels between the indomethacin and placebo groups (−457.7 pg/mL vs −840.4 pg/mL, P = 0.25). There was also no significant change in pain severity composite score (−1.3 indomethacin vs −0.5 placebo, P = 0.33), but the improvement in pain interference score (−2.9 indomethacin vs −0.4, P = 0.058) trended toward significance. There was no difference in adverse events between the 2 groups. DISCUSSION: In this phase 1/2 study, oral indomethacin was safe and well tolerated by patients with CP. Although there was no significant difference in change in PGE 2 levels, further studies are needed to determine the effect of indomethacin on the inflammatory pathway of CP and patient-centered outcomes.

Background: Invasive and non-invasive neuromodulation in psychiatry represents a burgeoning field that leverages advanced neuromodulation techniques to address substance use disorders (SUDs). Aims: This narrative review synthesizes findings from multiple reviews to evaluate the efficacy of neuromodulation in treating SUDs. Methods: A comprehensive literature search was conducted between December 2024 and April 2025, focusing on systematic reviews and meta-analyses that examined various neuromodulation modalities, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The selected reviews were analyzed to identify common themes, outcomes, and gaps in the current understanding of these treatments for SUDs. Results: 11 reviews met the final inclusion criteria; 5 focused on non-invasive neuromodulation (rTMS, tDCS) and 6 on invasive neuromodulation (DBS). Non-invasive neurostimulation was associated with modest improvements in craving and cognitive dysfunction in individuals with SUDs. Similarly, invasive neuromodulation (DBS), through high-frequency stimulation of the bilateral nucleus accumbens, appeared to reduce cravings and improve comorbid psychiatric symptoms in both preclinical and human studies. Importantly, small sample sizes, heterogeneity in targets and stimulation protocols, and short follow-up periods significantly limit the generalizability of current findings from both non-invasive and invasive neuromodulation studies. Conclusions: As novel and more effective therapies for the treatment of SUD are desperately needed, procedural interventional psychiatry holds promise. However, despite encouraging results, existing evidence is still preliminary, and larger, rigorously designed studies are warranted to further establish the safety and efficacy of neuromodulatory interventions for SUD treatment.

Abstract The therapeutic landscape of Graves’ hyperthyroidism has been rapidly evolving in the past few years. There has been a shift worldwide toward antithyroid drugs as the preferred first-line therapy with significant interest in thyroid function preservation, even if it requires more than 2 years of antithyroid drug treatment. This approach, long term antithyroid drug therapy, has gained traction as a therapeutic option after it has been shown to be safe and associated with significantly higher rates of remission than the traditional 18-month course of medical treatment. In parallel, we see, after 80 years of antithyroid drugs as the only medical therapy available for Graves’ disease, a strong interest in new drug development that follows more closely the pathophysiology of the disease. These approaches span the spectrum of targeting antigen presentation, B cell activation, TSHR antibody cycle and TSHR signaling. Separately, advances in wearable devices and artificial intelligence models present new opportunities for more timely diagnosis, monitoring, and treatment of patients with Graves’ disease. Finally, new therapies will pose novel challenges in the management of patients that will necessitate adjustments to our clinical practices and development of guidelines suited for these new therapeutic options.

Background Pancreatoduodenectomy (PD) is the only curative treatment for pancreatic cancer. Neoadjuvant therapy (NAT) has enhanced survival, especially for downstaging advanced tumors, while also introducing complexities and new complications. Despite surgical advances, some PD attempts remain unsuccessful. The management of these cases is not well defined. This study analyzes outcomes of repeat PD performed by two high-volume surgeons following previously unsuccessful attempts. Methods We retrospectively analyzed patients with pancreatic neoplasm undergoing successful pancreaticoduodenectomy (2013-2024) at two high-volume centers under two experienced surgeons. Only cases with prior aborted PD attempts for non-metastatic disease were included. Data from institutional records provided outcomes on failure reasons, procedure timing, surgical details, and 90-day complications. Results Of the 858 PD cases, 18 patients (2.1%; 12 males, 6 females; median age 69 years) had prior unsuccessful PD attempts at other institutions. Initial tumors were borderline resectable (33.3%), resectable (22.2%), or locally advanced (22.2%). Main causes for initial failure were vascular involvement (41.2%) and tumor infiltration (17.6%). Median time between attempts was 246 days, with 77.8% receiving chemotherapy before the second attempt. The second procedure achieved R0 resection in 94.4% of cases. Major 90-day complications occurred in 23.5% of patients, with no perioperative mortality. Disease recurrence occurred in 38.9% within the first year. Conclusion Repeat PD after an aborted attempt is feasible in select patients at specialized centers. However, complication and recurrence rates emphasize the need for careful patient selection. Further research is needed to optimize management strategies.

BACKGROUND AND OBJECTIVES: Gynecological cancers represent 10% to 15% of cancers in women, but brain metastases (BM) are uncommon, with limited evidence regarding their management. This study investigates the role of stereotactic radiosurgery (SRS) for BM from primary gynecological cancers. METHODS: Institutions of the International Radiosurgery Research Foundation participated in this study. Inclusion criteria required histological diagnosis of epithelial ovarian, cervical, or endometrial cancer, SRS between 2000 and 2020, and at least 1 imaging or clinical follow-up. RESULTS: A total of 276 patients having SRS for 977 BM were included. Median age at SRS was 62 years (IQR, 55-70). Primary cancer origin was ovarian in 128 (46%), cervical in 43 (16%), and endometrial in 105 patients (38%). Median Karnofsky Performance Scale was 80%, and systemic disease was active in 124 (45%) of patients. A median of 1 metastasis was treated (IQR, 1-3) per patient. Median individual metastasis volume was 0.27 cc (IQR, 0.05-1.59 cc). The majority (91%) received single-fraction SRS, using a median margin dose of 18 Gy (IQR, 16-20 Gy). Actuarial overall survival was 77%, 65%, and 44% at 6, 12, and 24 months, respectively. Predictors of worsened survival included older age, cervical and endometrial primary, previous whole-brain radiation therapy (WBRT), active systemic disease, worsened Karnofsky Performance Scale, absence of subsequent surgery, and increasing number of BM. Actuarial local control was 94% at 6 months, 89% at 12 months, and 78% at 24 months. Previous SRS or WBRT, tumor bed treatment, and cervical histology increased the risk of local failure. New remote BM and leptomeningeal dissemination occurred in 44% and 11% of patients, respectively. Adverse radiation effects (ARE) occurred in 13% of cases but were symptomatic in only 3%. Previous WBRT or SRS and increased tumor diameter increased the risk of ARE. CONCLUSION: SRS is an effective management for BM from gynecological cancers with low risks of symptomatic ARE.

Background: Trochlear dysplasia is important in recurrent patellofemoral instability (PFI); reliable metrics are essential to understand this condition and help define optimal treatment. One such measurement is the entry point to transition point (EP-TP) angle, which describes 2 components of patellar tracking from full knee extension to flexion: (1) mediodistal movement and (2) pure distal movement. Currently, measurement of this metric relies on 3-dimensional (3D) models. Purpose: To further develop the EP-TP angle metric to allow its digital measurement, to establish cohort and interrater reliability values, and to evaluate its appropriateness for clinical use. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A data set composed of 30 recurrent PFI patient knees and 30 control knees was acquired. Each knee came with anterior views of the distal femur and curvature maps, which highlighted relevant structures such as the trochlear groove and the medial and proximal ridge. Three raters measured EP-TP angles utilizing a digital tool with and without the curvature maps. Significance of differences in means, presence of a TP, and interrater reliability with intraclass correlation coefficients were tested and evaluated according to an established guideline (<0.5, poor reliability; >0.5-0.75, moderate; >0.75-0.9, good; >0.9 excellent reliability). A significance level of .05 corrected with the Bonferroni method was assumed. Results: PFI knees had a significantly higher EP-TP angle than the control cohort (48.9° ± 10.8° vs 11.8° ± 14.6°; P < .001). Patients had a greater TP prevalence than controls (96.7% vs 10.0%). Interrater reliability for the EP-TP angle with curvature maps was significantly better than without (0.84 [95% CI, 0.76-0.89] vs 0.67 [95% CI, 0.55-0.78]; P < .001). Conclusion: The EP-TP angle is significantly different between PFI patients and controls. This study presents a digital approach for measuring the EP-TP angle, in contrast with the initially described method, which required 3D prints. This digital approach, when aided with curvature mapping, yields better reliability.

Background: Injuries of the medial ulnar collateral ligament (MUCL) among baseball pitchers are increasing. Surgical treatment is evolving to optimize outcomes. Purpose/Hypothesis: This study’s purpose was to highlight trends in MUCL repair and reconstruction in professional pitchers, describe outcomes such as return to any level of play (RTP), and identify factors impacting these outcomes. It was hypothesized that primary and revision MUCL surgery is increasing, with revision surgery requiring greater RTP time. Study Design: Case series; Level of evidence, 4. Methods: The Major League Baseball (MLB) Health and Injury Tracking System database was used to procure data during the study period (2010-2023). All professional pitchers who underwent MUCL surgery during this period were included. RTP was defined as a pitcher returning to at least 1 professional game after index surgery. Return to the same level of play (RTSL) was defined as return to at least 1 game in the same league of play as before surgery. Because of the coronavirus pandemic, the year 2020 was considered an outlier and omitted from time-trend analysis. Results: A total of 2281 pitchers who underwent MUCL surgery during the study period were included for analysis. The number of MUCL surgeries for pitchers increased yearly ( R 2 = 0.821; P < .001), as did the number of reconstructions with internal brace augmentation ( R 2 = 0.896; P < .001). The RTP rate for MLB pitchers was significantly higher than the RTSL rate (93% vs 71%; P < .001). This difference was not observed in Minor League Baseball (MiLB) pitchers (RTP 76% vs RTSL 74%; P = .142). RTP rates after revision surgery were lower than those after primary surgery (71% vs 80%; P = .020). The mean time to RTP was shorter (470 ± 135 days) than the mean time to RTSL (499 ± 153 days; P < .001). Conclusion: The incidence of MUCL surgery and revision surgery is increasing among professional pitchers. Overall, 79% of pitchers returned to any level of play at a mean of 470 days, while 74% returned to the same level of play at a mean of 499 days, but this varied based on level of play. This study will guide athlete expectations and surgeon decision-making.