Complete Remission of Metastatic Melanoma of the Scalp Following Treatment With Nivolumab Plus Relatlimab.

Melanoma is an aggressive malignancy accounting for approximately 1% of all skin cancers. The standard of care for distant melanoma of the skin is immunotherapy with PD-1 inhibitors (nivolumab) or CTLA-4 inhibitors. In March 2022, the FDA approved the combination of nivolumab with relatlimab, a lymphocyte-activation gene 3 antibody. There are few reports on the efficacy of treating widespread multivisceral metastatic melanoma with nivolumab plus relatlimab with a complete clinical response. We describe the diagnosis and management of a patient with metastatic nodular melanoma treated with palliative resection of the primary tumor followed by immunotherapy with nivolumab and relatlimab. Four months after his first treatment, he had no evidence of disease on PET scan. He continued to show no evidence of disease at recent follow-up. Treatment of metastatic melanoma of the skin with nivolumab and relatlimab is an effective approach showing greater benefit to patients than nivolumab alone.

Robotic Cytoreductive Surgery With Heated Intraperitoneal Chemotherapy.

Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS-HIPEC) is traditionally an open operation given the dissection required during cytoreduction. There are reports of minimally invasive HIPECs, but CRS to an accepted completeness of cytoreduction (CCR) has been described less frequently. We report a patient with metastatic low-grade mucinous appendiceal neoplasm (LAMN) to the peritoneum treated with robotic CRS-HIPEC. A 49-year-old male presented to our center following a laparoscopic appendectomy at an outside facility with final pathology showing LAMN. He had a peritoneal cancer index (PCI) score of 5 determined by diagnostic laparoscopy. Given the small amount of peritoneal disease, he was deemed a candidate for robotic CRS-HIPEC. Cytoreduction was completed robotically with a CCR score of 0. He then received HIPEC with mitomycin C. This case shows the feasibility of robotic-assisted CRS-HIPEC for select LAMNs. When appropriately selected, we advocate for the continued use of this minimally invasive approach.

Pediatric Cardiology Fellowship Standards for Training in Exercise Medicine and Curriculum Outline.

Over the past 2 decades, fundamentals of exercise medicine, including clinical exercise testing, assessment and promotion of physical activity, exercise prescription, and supervised exercise training/rehabilitation programming have demonstrated considerable clinical value in the management of children and adolescents with congenital and acquired heart disease. Although the principles of exercise medicine have become an integral component in pediatric cardiology, there are no standardized training recommendations for exercise physiology during pediatric cardiology fellowship at this time. Thus, the Pediatric Cardiology Exercise Medicine Curriculum Committee (PCEMCC) was formed to establish core and advanced exercise physiology training recommendations for pediatric cardiology trainees. The PCEMCC includes a diverse group of pediatric cardiologists, exercise physiologists, and fellowship program directors. The expert consensus training recommendations are by no means a mandate and are summarized herein, including suggestions for achieving the minimum knowledge and training needed for general pediatric cardiology practice.

Rosai-Dorfman Disease of the Chest Wall Following Mastectomy for Breast Cancer.

Rosai-Dorfman disease (RDD) is a rare benign proliferative histiocytic disorder generally affecting the cervical lymph nodes as sinus histiocytosis with massive lymphadenopathy. We present a unique case of multifocal soft tissue RDD originating from previous mastectomy site and retroperitoneum. The patient is a 62-year-old African American female with a prior history of bilateral breast invasive ductal adenocarcinoma. 2 years following completion of therapy, our patient re-presented with an abdominal wall mass. The core biopsy was discordant, and the mass had rapid growth prompting excision. After the excision of the abdominal wall mass pathology confirmed RDD. A PET confirmed a solitary mass behind the left kidney this mass was biopsied and confirmed that it was RDD in the retroperitoneum. Due to the slow growth of this mass observation was deemed reasonable. We present this case to highlight the need for further research to improve treatment guidelines and expectations.

Late Diagnosis of Metastatic Leiomyosarcoma Originating in the Ureter.

This case report highlights a patient with a leiomyosarcoma originating in the ureter. A chart review was performed on a single patient who presented with a malignant retroperitoneal mass measuring 11.5 × 8.2 × 6.5 cm with subsequent metastasis sites to the breast, pancreas, liver, and lungs. The diagnosis of a leiomyosarcoma is uncommon, accounting for 0.1-0.4% of all cancer diagnoses in the United States. The diagnosis of a leiomyosarcoma originating from the ureter is extremely rare with fewer than 20 reported cases to date. Lack of typical urinary tract cancer signs and symptoms prevented an early presentation, allowing for considerable tumor growth and making complete surgical resection unlikely. We present this case as an example of a rare presentation of a very rare disease and to emphasize the necessity for further research of leiomyosarcoma and early diagnosis.

Multiple Intraabdominal and Pelvic Cystadenomas From Ovarian Remnant Syndrome.

Serous cystadenomas are benign epithelial neoplasms of the ovary, and they typically have an average size of around 10 cm. Our patient is a 68-year-old female who originally presented with abdominal page. Our patient's prior surgical history includes a bilateral salpingo-oophorectomy. Computed tomography scans showed five abdominal and pelvic masses of significant size. Our patient elected to undergo exploratory laparotomy and mass excision, and all five masses were able to be removed successfully. Final pathology confirmed the diagnosis of serous cystadenomas consistent with ovarian origin despite our patient undergoing a previous bilateral salpingo-oophorectomy. Our patient presented with a rare syndrome known as ovarian remnant syndrome that is thought to be caused by difficult hysterectomy procedures and prior abdominal surgeries that can unknowingly leave ovarian remnants. Second, the patient was found to have 5 abdominal and pelvic masses, and most of the masses were a very large size.

Poorly Differentiated Metastatic Carcinoma of Possible Eccrine Sweat Gland Origin.

Sweat gland carcinomas are a rare group of cancer, representing less than .01% of all diagnosed skin malignancies. We report the case of a 32-year-old male who presented with a fungating lesion on the posterolateral side of his left knee. Immunohistochemical results were positive for cytokeratin 5/6 and cytokeratin 7, consistent with possible eccrine gland origin. Our patient underwent wide local excision of the mass with lymph node dissection. Pathology confirmed the diagnosis of poorly differentiated carcinoma of possible adnexal, eccrine gland origin. He completed taxol/cisplatin-based chemotherapy and radiation. Surveillance imaging showed bilateral lung nodules, a right pleural effusion, and peritoneal carcinomatosis, which were diagnostic of metastatic carcinoma. He started carboplatin and epirubicin chemotherapy and has been doing well. Because standard of care treatment options for metastatic eccrine carcinoma have not been developed, it is imperative to report these cases to better understand these complex tumors and their treatment.

Expression of trefoil factor 3 is decreased in colorectal cancer.

In colorectal cancer (CRC), high expression of trefoil factor 3 (TFF3) is associated with tumor progression and reduced patient survival; however, bioinformatics analyses of public 'omics' databases show low TFF3 expression in CRCs as compared to normal tissues. Thus, we examined TFF3 expression in CRCs and matching normal tissues to evaluate its role in CRC progression. TFF3 gene expression was characterized using the bioinformatics portal UALCAN (http://ualcan.path.uab.edu). Tissue microarrays (TMAs) of archival CRC specimens (n=96) were immunostained with anti­human TFF3 antibodies. Immunohistochemical (IHC) staining intensity was semi­quantitatively scored. For this cohort, the median follow­up was 5.4 years. Associations between clinical and pathological variables were determined using Chi­square or Fisher's exact tests. Univariate disease­free survival was estimated by the Kaplan­Meier method. Omics data analyses by UALCAN showed downregulation of TFF3 expression in CRC relative to normal tissue at protein (χ2, P<0.0001) levels. There was a similar decreasing trend of TFF3 expression in the pathologic stages of the CRCs (RNA, χ2, P=0.88 and protein, χ2 P<0.0001). UALCAN data analysis showed that TFF3 exhibited 27% lower mRNA expression in tumors with mutant TP53 (P=0.007). Confirming the findings of omics analyses, IHC analysis of TMAs exhibited lower TFF3 expression in 95.6% (65 of 68) of the available normal­tumor matching pairs (χ2, P<0.0001). There was no statistically significant association of tumor TFF3 expression with patient sex, race/ethnicity, tumor location within the colorectum, Tumor, Node, Metastasis (TNM) stage, lymph node metastasis, or surgical margins. However, low TFF3 IHC staining in tumor tissue was associated with histological grade (P=0.026). Kaplan­Meier survival analysis showed no prognostic value of low TFF3 expression relative to those with high expression (log­rank, P=0.605). Our findings demonstrate low expression of TFF3 in CRCs. Association between low TFF3 and histopathological features suggests involvement of this molecule in progression of CRC.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study.

BACKGROUND: Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. METHODS: Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. KEY RESULTS: A total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%). CONCLUSIONS & INFERENCES: In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.

The relationship between complaints of night-time heartburn and sleep-related gastroesophageal reflux.

This study investigated whether the complaint of night-time heartburn (NHB) as opposed to daytime heartburn (DHB) is a reliable reflection of actual sleep-related reflux events. Three groups of individuals were studied: individuals with complaints of NHB at least twice per week (n = 24), individuals with complaints of DHB (n = 23), and normal participants without any complaints of regular heartburn during the day or night (n = 25). All three groups were studied on one occasion with combined pH monitoring and polysomnography, and subjective questionnaires about sleep disturbance and sleep quality were given to all participants. The NHB group had significantly more sleep-related reflux events compared with both DHB and control groups (P < 0.01). DHB subjects had significantly (P < 0.05) more sleep-related reflux events than normal controls. Total acid contact time (ACT) was significantly (P < 0.05) elevated in the NHB group compared with both the DHB and control group. Sleep-related ACT was also significantly (P < 0.05) elevated in the NHB group compared with the other two groups, while upright (daytime) ACT was not significantly different. The NHB group was significantly (P < 0.05) worse regarding measures of both objective and subjective sleep quality. Subjects with exclusively DHB do have sleep-related reflux that is greater than normal controls. Subjects with NHB have significantly more sleep-related reflux, and both objective and subjective sleep abnormalities compared with normal controls. Complaints of NHB reflect sleep-related reflux events and may be indicative of a more clinically significant condition.