Citations

Laparoscopic Sleeve Gastrectomy (LSG) is the most common bariatric surgery in the world. While clinically effective, recent studies have shown increasingly higher rates of gastroesophageal reflux disease (GERD) and esophageal motility disorders. We reviewed all the literature and unraveled the underlying mechanism of post-LSG GERD. Finally, we propose a new classification to help us understand the disease and guide work-up, treatment, and future refinements in the surgical technique.

Abstract The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after.

Abstract Background Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients. Methods We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR. Results Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum. Conclusions In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.

Abstract Background Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi-fraction stereotactic ablative radiotherapy (SABR) have led to better outcomes and reduced treatment-related toxicities, sparking renewed interest in using RT to treat RCC. Moreover, numerous studies have revealed that certain therapeutic agents including chemotherapies can increase the sensitivity of tumors to RT, leading to a growing interest in combining these treatments. Here, we developed a rational combination of two radiosensitizers in a tumor-targeted liposomal formulation for augmenting RT in RCC. The objective of this study is to assess the efficacy of a tumor-targeted liposomal formulation combining the mTOR inhibitor everolimus (E) with the survivin inhibitor YM155 (Y) in enhancing the sensitivity of RCC tumors to radiation. Experimental Design: We slightly modified our previously published tumor-targeted liposomal formulation to develop a rational combination of E and Y in a single liposomal formulation (EY-L) and assessed its efficacy in RCC cell lines in vitro and in RCC tumors in vivo. We further investigated how well EY-L sensitizes RCC cell lines and tumors toward radiation and explored the underlying mechanism of radiosensitization. Results EY-L outperformed the corresponding single drug-loaded formulations E-L and Y-L in terms of containing primary tumor growth and improving survival in an immunocompetent syngeneic mouse model of RCC. EY-L also exhibited significantly higher sensitization of RCC cells towards radiation in vitro than E-L and Y-L. Additionally, EY-L sensitized RCC tumors towards radiation therapy in xenograft and murine RCC models. EY-L mediated induction of mitotic catastrophe via downregulation of multiple cell cycle checkpoints and DNA damage repair pathways could be responsible for the augmentation of radiation therapy. Conclusion Taken together, our study demonstrated the efficacy of a strategic combination therapy in sensitizing RCC to radiation therapy via inhibition of DNA damage repair and a substantial increase in mitotic catastrophe. This combination therapy may find its use in the augmentation of radiation therapy during the treatment of RCC patients.

Abstract Background: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods:The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

Abstract Background The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. Aim The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Methods Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Outcomes Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. Results A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Clinical Implications Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Strengths and Limitations Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. Conclusion CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

AbstractCollision tumors, defined as “two independent neoplasms that occur in close proximity to one another but maintain distinct boundaries,” are quite rare. We report an exceptional collision tumor composed of a genetically confirmed malignant glomus tumor and a fumarate hydratase (FH)‐deficient leiomyoma, presenting as a subcutaneous thigh mass in a 38‐year‐old male who was known to have hereditary leiomyomatosis and renal cell carcinoma syndrome. Microscopic examination identified a biphasic subcutaneous mass comprising sheets and nodules of glomus cells, with nuclear atypia and mitotic activity, and fascicles of mitotically inactive smooth muscle with variably pleomorphic nuclei and intracytoplasmic eosinophilic inclusions, features of FH‐deficient leiomyoma. Immunohistochemistry demonstrated loss of FH and robust 2‐succinocysteine expression in the smooth muscle, with a normal (FH‐retained) expression pattern in the glomus tumor. Next‐generation sequencing, performed on the glomus tumor component, identified CARMN::NOTCH2 fusion, characteristic of malignant glomus tumors. Awareness of the distinctive morphologic, immunohistochemical, and molecular genetic features of glomus tumors and FH‐deficient leiomyomas is important for correct clinical management of patients with exceptional collision tumors of this type.

Enteropathy-associated T cell lymphoma (EATL) is an aggressive subtype of non-Hodgkin’s lymphoma often associated with coeliac disease (CD). We describe a previously healthy man in his 50 s who presented with a history of abdominal pain, failure to thrive and significant weight loss over a 3-month period. Investigations revealed a positive coeliac serology, diffuse duodenal atrophy with multiple duodenal and jejunal ulcers on endoscopy and mesenteric lymphadenopathy on CT imaging. Duodenal tissue biopsy confirmed a diagnosis of EATL Stage IVB. Chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone regimen was initiated. This case highlights the need for greater awareness and consideration of EATL in individuals with worsening malabsorption and abdominal pain, irrespective of coeliac history.