Refractory Nausea Research Articles

DDEL-05. IMPRESSIVE RESPONSE TO IDH-INHIBITOR THERAPY IN IDH-MUTANT, H3K27M INTACT BRAINSTEM GLIOMAS

Abstract IDH-mutated brainstem gliomas in adults are a rare entity, with only a handful of cases reported in the literature. Diagnosis and treatment of these gliomas remain challenging. There is significant morbidity associated with a surgical biopsy, thus biopsies are often deferred, and tumors of the brainstem are treated presumptively with radiation and temozolomide. However, in the presence of new targeted therapies, confirming pathology for these patients is becoming increasingly important. We present two cases of IDH-mutant grade 2 astrocytomas of the brainstem that revealed both clinical and radiographic responses to IDH-inhibitor therapy. Interestingly, both patients had the same non-canonical IDH mutation, IDH-R132C, towards which ivosedinib is known to have activity. One patient had tumor progression following radiation therapy and 8 cycles of temozolomide and had subsequently exhibited a dramatic radiographic improvement, including resolution of enhancing disease following initiation of ivosidenib therapy. Clinically, this patient improved from a KPS 50 to KPS 100 after 2.5 years of ivosedinib. The other patient also had an impressive clinical improvement after only 3 months of ivosedinib treatment, with radiographic stability, improvement in balance, and resolution of his previous refractory nausea. These case reports suggest that consideration should be given to brainstem biopsy in adults specifically to evaluate for the presence of a targetable IDH mutation.

Mirtazapine: An Antidepressant for Treating Chronic, Refractory Nausea and Vomiting in a Patient With Metastatic Sarcoma Receiving Palliative Care: A Case Report

ABSTRACTManaging chronic, refractory nausea and vomiting in advanced cancer patients is challenging, especially when unrelated to cancer treatment. Mirtazapine, a tetracyclic antidepressant, effectively alleviates these symptoms, improving quality of life. It offers a promising palliative care alternative, addressing multiple symptoms and reducing polypharmacy, thereby enhancing patient satisfaction.

A nationwide double-blind phase III randomized clinical trial (RCT) of olanzapine vs. prochlorperazine for the treatment of refractory nausea in patients receiving moderately or highly emetogenic chemotherapy among NCI Community Oncology Research Program (NCORP) practices.

185 Background: Despite advances in antiemetics given during chemotherapy, nausea remains a clinically significant issue and greatly impairs quality of life (QOL). Current ASCO guidelines recommend olanzapine or prochlorperazine for refractory chemotherapy-induced nausea. However, there is a lack of direct empirical comparisons to establish their relative efficacy. Methods: The URCC NCORP Research Base and 21 NCORP practices enrolled 1,363 chemotherapy-naïve patients with breast cancer starting a high/moderate emetogenic chemotherapy regimen to this Phase III RCT (NCT03367572). Antiemetics were prescribed per ASCO guidelines. Screening occurred during Cycle 1, followed by randomization for Cycle 2. Those with ≥ moderate nausea (≥3 on a 1-7 scale) in Cycle 1 and willing to continue were randomized (1:1:1 ratio) into 3 arms (n=310): 1) ASCO regimen plus olanzapine (OLZ), 2) ASCO regimen plus prochlorperazine (PC), or 3) ASCO regimen plus placebo. Nausea was evaluated using a four-day home diary (4x daily), with the primary outcomes being changes in average (avg) and maximum (max) nausea. FACT-G measured QOL. Intent-to-treat primary analyses (ANOVA and Cohen’s Δ effect size) evaluated whether OLZ or PC improved nausea, testing between-arm differences in nausea change from Cycle 1 to 2 compared to placebo at a p=0.025 significance level corrected for 3 arms. Results: The median age was 50.7y, with 80.7% White/12.3% Black/5.8% Asian/4.2% Latino, and evenly distributed across groups. The change in avg nausea score was statistically significant for the OLZ (avg change = −1.07: Cohen’s Δ = 0.49) and PC arms (avg change = −0.94: Cohen’s Δ = 0.38) compared to the placebo (avg change = −0.50; p <0.001 vs OLZ, p = 0.01 vs PC). Similar but larger changes were noted for change in max nausea score in the OLZ (max change = −2.57: Cohen’s Δ = 0.86) and PC arms (max change = −2.01: Cohen’s Δ = 0.47) against the placebo (max change = −1.30; p <0.001 vs OLZ, p <0.01 vs PC). The OLZ arm had a clinically significant change in overall QOL from pre-chemo to Cycle 2 vs placebo (FACT-G mean difference = +4.91; p = 0.006) but the PC arm vs placebo did not (FACT-G mean difference = −0.87; p = 0.61). OLZ exhibited superiority over PC in terms of changes in max nausea (mean difference = −0.56; p = 0.023) and QOL (FACT-G mean difference = +5.80; p = 0.006), but not for avg nausea (mean difference = −0.13; p = 0.418). Conclusions: OLZ and PC, when added to ASCO guidelines, each significantly reduces refractory nausea. OLZ demonstrates superior max nausea control with clinically and statistically significant improvements in QOL. This study fills the gap in empirical comparisons and solidifies OLZ's position as a promising intervention for refractory nausea. Clinical trial information: NCT03367572 .

Predictors of early removal of intragastric balloon due to intolerance: Insights from a multiethnic Asian cohort.

Intolerance frequently limits the use of intragastric balloons (IGBs) in the treatment of obesity. This includes refractory nausea, vomiting and abdominal discomfort. Our study aims to identify predictors of balloon intolerance and early removal, which will help to guide patient selection for this intervention and peri-procedure care. We conducted a retrospective cohort study of 54 consecutive patients who underwent IGB insertion from July 2017 to July 2022 in a single tertiary institution in Singapore. Forty-seven (87.0%) patients completed therapy, while 7 patients (13.0%) had early removal of the balloon due to intolerance. Characteristics of both groups were compared. Multivariate analysis revealed significant associations between early balloon removal and both depression (P=0.012) and anxiety (P=0.001) after adjusting for age, sex, ethnicity, height, nulliparity, balloon type and volume. Univariate analysis revealed that anxiety was the main risk factor (P=0.004, odds ratio 9.111, 95% confidence interval 1.624-51.124), while depression was no longer a significant predictor. Identifying predictors of balloon intolerance and early removal can enhance patient selection and improve peri-procedural care. In patients with a history of depression or anxiety, it is important to ensure adequate counselling and preparation prior to balloon insertion.

Oral Cannabis Extract for Secondary Prevention of Chemotherapy-Induced Nausea and Vomiting: Final Results of a Randomized, Placebo-Controlled, Phase II/III Trial.

The aim of this randomized, placebo-controlled, two-stage, phase II/III trial was to determine the efficacy of an oral cannabis extract in adults with refractory nausea and/or vomiting during moderately or highly emetogenic, intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Here, we report results of the prespecified combined analysis including the initial phase II and subsequent phase III components. Study treatment consisted of oral capsules containing either tetrahydrocannabinol 2.5 mg plus cannabidiol 2.5 mg capsules (THC:CBD) or matching placebo, taken three times a day from days -1 to 5, in addition to guideline-consistent antiemetics. The primary measure of effect was the difference in the proportions of participants with no vomiting or retching and no use of rescue medications (a complete response) during hours 0-120 after the first cycle of chemotherapy on study (cycle A). We recruited 147 evaluable of a planned 250 participants from 2016 to 2022. Background antiemetic prophylaxis included a corticosteroid and 5-hydroxytryptamine antagonist in 97%, a neurokinin-1 antagonist in 80%, and olanzapine in 10%. THC:CBD compared with placebo improved the complete response rate from 8% to 24% (absolute difference 16%, 95% CI, 4 to 28, P = .01), with similar effects for absence of significant nausea, use of rescue medications, daily vomits, and the nausea scale on the Functional Living Index-Emesis quality-of-life questionnaire. More frequent bothersome adverse events of special interest included sedation (18% v 7%), dizziness (10% v 0%), and transient anxiety (4% v 1%). There were no serious adverse events attributed to THC:CBD. THC:CBD is an effective adjunct for chemotherapy-induced nausea and vomiting despite standard antiemetic prophylaxis, but was associated with additional adverse events. Drug availability, cultural attitudes, legal status, and preferences may affect implementation. Future analyses will evaluate the cost-effectiveness of THC:CBD.

Cannabis Hyperemesis Syndrome: An Underrecognized Cause of Nausea and Vomiting in Pregnancy

Introduction: Cannabis Hyperemesis Syndrome (CHS) is characterized by refractory and recurrent nausea and vomiting in birthing people with chronic cannabis use and is emerging as an increasingly common diagnosis in patients who present to the emergency department. The objective of this retrospective case series was to describe presentation, management and outcomes of CHS during pregnancy. Methods: Patients were identified by the investigator at two tertiary care centers in Kansas City from January 2019 to October 2021. Patients were included if (1) intrauterine pregnancy (2) refractory and recurrent nausea and vomiting without acute cause, and (3) documented chronic cannabis use which preceded symptom onset were noted. The study was approved by the UMKC IRB (#308059). Results: Twelve patients were identified who met inclusion criteria, ranging in age from 17 to 32 years (mean 23.2 ± 4.5). Eleven patients reported daily cannabis use. The mean number of emergency department visits during pregnancy for nausea and vomiting was 8.9 (± 7.1). Patients presented at a wide range of gestational ages, between 4 and 37 weeks (mean 19.6 ± 9.8). Compulsive hot water bathing for symptom relief was documented in 33% of cases (4 of 12). The rate of fetal growth restriction in this series was 44% (4 of 9). Despite counseling, only one patient successfully discontinued cannabis use. Conclusions: CHS should be considered in the differential diagnosis of nausea and vomiting in pregnancy. Patients who meet criteria should be counseled about cannabis cessation as part of treatment recommendations.

Cost-effectiveness of an oral THC: CBD cannabis extract for secondary prevention of refractory, chemotherapy-induced nausea and vomiting.

TPS11188 Background: The CannabisCINV trial showed the incorporation of a THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract in addition to usual, guideline-recommended antiemetic prophylaxis, reduced the incidence of refractory chemotherapy-induced nausea and vomiting. The aim of this within-trial cost-effectiveness analysis was toassess the incremental costs and benefits of oral THC: CBD versus placebo, for preventing chemotherapy-induced nausea and vomiting. Methods: The analysis was performed from a health system perspective, using prospectively collected data from the CannabisCINV trial and linked Medicare data. The evaluation focused on the costs and benefits associated with oral THC: CBD cannabis extract versus placebo in addition to usual care, on complete response: defined as no emesis and no use of rescue medications during the overall treatment phase (0-120 h, cycle 1). The primary economic outcome was an incremental cost-effectiveness ratio (ICER) of achieving a complete response. One-way sensitivity analyses and non-parametric bootstrapping (with 1,000 replications) were conducted to assess the robustness of results. Results: Of 147 participants randomized, 60 of 73 assigned THC:CBD and 66 of 74 assigned placebo consented to Medicare data linkage. The incidence of complete response was higher for THC:CBD than placebo (24% vs 5%, absolute difference 19%, 95%CI 13 to 26%). The mean cost (AUD) of hospitalisation was $580 (SD $7,831) for the intervention group and $1,873 (SD $7,235) for placebo. The mean healthcare costs (AUD) were $1,464 (SD $4,667) for THC:CBD group and $2,725 (SD $9,237) for the placebo. The THC:CBD group had a mean total healthcare cost saving of $1,261 per patient (95% CI -$3,550 to $1029) compared with the placebo group. THC:CBD was less expensive and more effective than placebo (i.e. dominant), in the primary analysis, and over the range of pre-specified sensitivity analyses. Conclusions: This within-trial analysis indicates oral THC: CBD is cost-effective for the treatment of refractory, chemotherapy-induced nausea and vomiting from a health system perspective and supports reimbursement in this setting. The trial and economic evaluation were prospectively registered in the Australian and New Zealand. Clinical trial information: ACTRN12616001036404.

Cannabinoid hyperemesis syndrome: a case report and literature review

IntroductionCannabis is the most used recreational drug worldwide. Cannabinoids have long been known for their anti-emetic properties. Paradoxically, chronic cannabis consumption has been linked to inducing refractory nausea and vomiting, a condition called cannabinoid hyperemesis syndrome (CHS). CHS remains inadequately acknowledged by clinicians.ObjectivesReport a CHS case and discuss this syndrome’s diagnosis, pathophysiology, and management.MethodsCollection of clinical information and review of the literature.ResultsWe share the case of a 38-year-old male who repeatedly recured to the emergency department (ED) due to persistent vomiting, nausea, and abdominal pain. The patient had experienced similar intermittent episodes over the past 12 years. Interestingly, the use of hot showers provided symptomatic relief. Urine drug tests consistently showed positive results for cannabinoids. During acute phases, he required supportive treatment involving fluid therapy. Long-term treatment included cannabis abstinence. CHS is defined by episodic vomiting, following prolonged excessive cannabis consumption, which is alleviated by sustained cessation of cannabis. During the acute phase of the condition, patients often find relief using hot baths and showers, which is a common behavior observed. CHS-related complications encompass acute kidney injury and severe electrolyte disturbances. CHS can result in multiple ED visits, frequent hospitalizations, extensive diagnostic evaluations, and elevated healthcare expenditures. Although the exact pathophysiology of CHS remains unclear, some mechanisms have been proposed. These include reduced gastric motility by gastrointestinal cannabinoid receptors 1 (CB1) overriding, cannabinoid lipid buildup, endocannabinoid system dysregulation, dysregulated stress response, changes in thermoregulation, modifications in the transient receptor potential vanilloid system and genetic polymorphisms in the P450 system. In the acute phase, the foremost concern is providing supportive care including intravenous hydration and electrolyte corrections. The most effective treatment for CHS is cannabis cessation. Nevertheless, there are alternative treatments that have shown promise in alleviating symptoms, such as hot water hydrotherapy, topical capsaicin, haloperidol, benzodiazepines, propranolol and aprepitant.ConclusionsAs cannabis usage becomes increasingly prevalent, it becomes imperative for healthcare providers to acknowledge the long-term effects of cannabinoids, specifically regarding CHS. This diagnosis should be contemplated when evaluating patients who experience recurrent and incoercible vomiting coupled with a history of cannabis consumption. The compulsion to take hot baths or showers can serve as a noteworthy indicator for diagnosing CHS.Disclosure of InterestNone Declared

A Multidisciplinary Minimally Invasive Approach Is Necessary for the Contemporary Management of Esophageal Diverticula.

Background: Esophageal diverticula were traditionally treated with open surgery, which is associated with significant morbidity and mortality rates. Management has shifted to minimally invasive approaches with several advantages. We examine outcomes in patients with esophageal diverticula treated with minimally invasive techniques by a multidisciplinary surgical team at a single center. Materials and Methods: A retrospective review of a prospectively maintained database was performed for patients who underwent minimally invasive surgery for esophageal diverticula at our institution from June 2010 to December 2022. Primary outcomes were 30-day morbidity and mortality rates. Secondary outcomes were symptom resolution, length of stay (LOS), readmission, and need for reintervention. Results: A total of 28 patients were identified. Twelve patients had pharyngeal diverticula, 7 patients had midesophageal diverticula, and 9 patients had epiphrenic diverticula. Thirty-day morbidity and readmission rates were 10.7% (3 patients), 1 pharyngeal (sepsis), 1 midesophageal (refractory nausea), and 1 epiphrenic (poor oral intake). There were no esophageal leaks. Average LOS was 2.3 days, with the pharyngeal group experiencing a significantly shorter LOS (1.3 days versus 3.4 days for midesophageal, P < .01 versus 2.8 days for epiphrenic, P < .05). Symptom resolution after initial operation was 78.6%. Reintervention rate was 17.9%, and symptom resolution after reintervention was 100%. There were no mortalities. Conclusion: This study demonstrates that esophageal diverticula can be repaired safely and efficiently when performed by a multidisciplinary team utilizing advanced minimally invasive endoscopic and robotic surgical techniques. We advocate for the management of this rare condition at a high-volume center with extensive experience in foregut surgery.

Perioperative use of low dose haloperidol safely reduces episodes of postoperative nausea/vomiting and length of stay following elective minimally invasive bariatric surgery.

While total intravenous anesthesia (TIVA) protocols include Dexamethasone and Ondansetron prophylaxis, bariatric patients continue to be considered at particularly high risk for postoperative nausea/vomiting (PONV). A multimodal approach for prophylaxis is recommended by the Bariatric Enhanced Recovery After Surgery (ERAS) Society however, there remains a lack of consensus on the optimal strategy to manage PONV in these patients. Haloperidol has been shown at low doses to have a therapeutic effect in treatment of refractory nausea and in PONV prophylaxis in other high risk surgical populations. We sought to investigate its efficacy as a prophylactic medication for PONV in the bariatric population andto identify which perioperative strategies were most effective at reducing episodes of PONV. An institutional bariatric database was created by retrospectively reviewing patients undergoing elective minimally invasive bariatric procedures from 2018 to 2022. Demographic data reviewed included age, gender, preoperative body mass index (BMI), ethnicity, and primary language. Primary endpoints included patient reported episodes of PONV, total doses of Ondansetron administered, need for a second antiemetic (rescue medication), complication rate (most commonly readmission within 30days), and length of stay. Fisher's exact test, Mann-Whitney test, and ANOVA were used to evaluate the effect of perioperative management on various endpoints. A total of 475 patients were analyzed with Haloperidol being utilized in 15.8% of all patients. Patients receiving Haloperidol were less likely to require Ondansetron outside of the immediate perioperative period (34.7% vs. 49.8%, p = 0.02), experienced less PONV (41.3% vs. 64.3%, p = 0.01) and also had a decreased median length of stay (27.3 vs. 35.8h, p < 0.0001). Addition of low dose Haloperidol to Bariatric ERAS protocols decreases incidence of PONV and the need for additional antiemetic coverage resulting in a significantly shorter length of stay, increasing the likelihood of safe discharge on postoperative day 1.

THU673 Unusual Metastasis Of Differentiated Thyroid Carcinoma

Abstract Disclosure: M. Aiad: None. O.A. Aluko: None. B. Bhatt: None. Background: Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid malignancy. Distant metastasis of PTC are rare and usually occur in the bones, lungs, and lymph nodes of the neck. Retinal and skin metastases are extremely rare. We present a case of PTC with metastasis to the distal extremity with sites including retina, skin and breasts. Clinical Case: A 40-year-old Caucasian female with a past medical history of papillary thyroid cancer at age 16 status post total thyroidectomy followed by two radioactive iodine treatments, who is incidentally found to have recurrent metastatic disease to lungs, retina, subcutaneous soft tissue and bones. After having an accident, trauma CT revealed pulmonary nodules and around the time patient started to notice subcutaneous lumps on the chest and gradually worsening blurry vision indicating further imaging as well as ophthalmological evaluation. The biopsy of the right lower lung nodules showed metastatic differentiated follicular variant papillary thyroid cancer, positive for RET mutation. TSH was appropriately suppressed at 0.128uIU/mL on levothyroxine 100 mcg daily, with elevated thyroglobulin level 47ng/mL and antibody 1.7IU/mL. The molecular testing was positive for RET gene mutation; thus she started targeted therapy with selpercatinib 120 mg twice daily. Shortly after starting therapy, she presented to the ER with complaints of headaches and refractory nausea. Imaging done showed evidence of intracranial metastases, bilateral intraocular lesions in the posterior globe as well as intraventricular hemorrhage. She received IV steroids, selpercatinib was held due to the possibility of exacerbating intraventricular hemorrhage. Following multidisciplinary discussion between neuro-oncology and radiation oncology, she started stereotactic radiotherapy (SRT) to choroidal plexus lesions with a plan to restart systemic therapy once SRT is completed. Conclusion: The epidemiological aspects of thyroid metastases in rare sites are likely unknown and could significantly impact patient management. Most cases of uncommon metastasis have been reported after several years of diagnosis such as in our patient who developed multiple metastasis to rare sites including skin, retina, breast and choroid plexus. Presentation: Thursday, June 15, 2023

Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients.

Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders. Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders. At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists. Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.

Gastric electrical stimulation is safe during pregnancy and delivery: Results from a French cohort.

Gastric electrical stimulation (GES) is an effective therapy in medically refractory chronic nausea and vomiting. GES is assumed to be a contraindication for pregnancy. We examined the safety of GES during pregnancy and its clinical impact on vomiting symptoms. A retrospective study was performed in two tertiary centers including all female patients of childbearing age implanted with GES. Patients without pregnancy while on GES were asked about their desire and concerns about pregnancy. Patients who were pregnant while on GES therapy were interviewed about the course of the pregnancy and labor, as well as the health of the children. Among 91 patients implanted at childbearing age, 54 patients without pregnancy answered the questionnaire. Nine patients (16.7%) reported a desire for pregnancy and five patients (7.4%) reported worries about the safety of GES during pregnancy. Sixteen pregnancies were reported in 10 patients. All pregnancies ended in a live birth with premature birth in 12 pregnancies (75.0%). No health concern was currently noted in these children. No severe GES-related complications occurred during pregnancy with only pain at the implantation site reported during 3 pregnancies (18.8%). The severity and frequency of nausea and vomiting significantly increased during the first trimester (p = 0.04 and p = 0.005, respectively) and decreased after the delivery, becoming lower than before the pregnancy (p = 0.044 and p = 0.011, respectively). Patients are concerned regarding pregnancy while being treated with GES. No serious maternal or fetal complications related to GES were noted in our cohort.

Upper gastro intestinal endoscopy in pregnancy: A single centre experience

Introdction: Upper gastro intestinal (GI) endoscopy is advisable to perform when strongly indicated during pregnancy. This study was to evaluate the outcomes of upper GI endoscopy during pregnancy. Methods: A single centre retrospective study was carried out. Randomly selected 500 medical records of the pregnant mothers who were referred as out patients and hospitalized from 2012 to 2022 were retrieved. Inclusion criteria for retrieving data of the patients who underwent upper GI endoscopy were; Major or continued bleeding, severe or refractory nausea and vomiting or abdominal pain, dysphagia or odynophagia. Endoscopic findings were recorded in a computer based database. Ethical approval was obtained from the Ethical Review Committee of Nawaloka Hospitals of Sri Lanka. No conflict of interest. Results: A total of 16 records of patients underwent upper GI endoscopy were retrieved during 2012 to 2022. The mean age of the patients was 25.48 ± 6.5 years. Ten patients (62.5%:10/16) were primigravida. During the first, second and third trimester of pregnancy, number of patients who underwent upper GI endoscopy were 8 (50%), 4 (25%), and 4 (25%) respectively. The major indication was persistence epigastric pain (75%: 12/16) followed by dysphagia (18.7%:3/16) and hematemesis in one patient. All patients had undergone conservative treatment without any therapeutic upper GI endoscopy. There were no records that were found to have ERCP, capsular endoscopy or enteroscopy during pregnancy among our patients. No records were found of having endoscopy related adverse effects on mothers or foetuses. Conclusion: The upper GI endoscopy especially oesophago-gastro-dudenoscopy (OGD) may be performed without a major risk to the mother and the baby. However, further prospective multicentre research studies are strongly recommended.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Possible Effect of Blonanserin Transdermal Patch on Antiemetic Control in Patients with Terminal Cancer with Refractory Nausea.

Background: Haloperidol is widely used for antiemetic control in advanced cancer. However, due to its limited administration methods (oral or injection), its management is frequently challenging in palliative home care. Recently, a blonanserin transdermal patch was developed as the first antipsychotic percutaneous agent. Objectives: This study aimed to evaluate its effectiveness and safety for refractory nausea. Methods: We conducted an observational study of 21 terminal cancer patients who had been initiated for refractory nausea in their homes. Results: After its initiation, none of the patients experienced aggravated nausea, and the number of patients with severe nausea decreased dramatically (52.4% vs. 9.5%, p = 0.008). Of 16 patients without ascites, 12.5% had not improved their nausea, which was lower than in patients with ascites (80.0%). Conclusions: Blonanserin transdermal patch has a possible effect on antiemetic control in cancer patients, and its efficacy might be particularly prominent in patients without ascites.

Gastric Electrical Stimulation as a New Treatment Modality for Refractory Nausea and Vomiting with Normal Gastric Emptying.

Nausea and vomiting are cardinal symptoms affecting many patients with delayed or normal gastric emptying. The current therapies are very limited and less than optimal. Therefore, gastrointestinal symptoms persist despite using all the standard approaches for gastroparesis, functional dyspepsia, or unexplained nausea and vomiting. It is well established that gastric electrical stimulation (GES) is effective in reducing nausea and vomiting in gastroparesis, but there are essentially no data available that detail the efficacy of GES in symptomatic patients without gastroparesis. We present a unique case of a female patient diagnosed with functional dyspepsia, whose nausea and vomiting which were refractory to all standard therapies were successfully addressed with the implantation of a GES system.

A CASE OF ANAPHYLAXIS TO FOSAPREPITANT

<h3>Introduction</h3> Fosaprepitant is a small molecule, intravenously administered antiemetic drug that is a selective NK-1 receptor antagonist. Systemic hypersensitivity reactions to fosaprepitant are rare. <h3>Case Description</h3> A 42-year-old male with Shwachman-Diamond syndrome presents with newly diagnosed myelodysplastic syndrome. He was initiated on chemotherapy with azacitidine and venetoclax. He developed neutropenic fever from a perianal abscess and fistula. Chemotherapy was paused, and cefepime/metronidazole was started. When chemotherapy was restarted, he was pretreated with fosaprepitant 150mg for refractory nausea. Fosaprepitant was administered over 7 minutes. Symptoms of shortness of breath and epigastric pain began during the infusion. Hypoxia developed 17 minutes after the infusion with O2 84% and a new 4L oxygen requirement. Notable signs included wheezing, periorbital/perioral edema, tachypnea, and tachycardia. He received 0.3mg IM epinephrine, nebulized epinephrine, 50mg IV Benadryl, and 125mg IV methylprednisolone. He required intubation for worsening upper lip/tongue edema and recrudescence of wheezing as well as an epinephrine IV infusion for hypotension. A tryptase level was drawn 3 hours after symptom onset and was elevated to 13.2 mcg/L (baseline 6.7 mcg/L). <h3>Discussion</h3> Fosaprepitant is an unusual cause of systemic hypersensitivity reactions with <1% incidence reported in the literature. Our patient represents an unexpected case of anaphylaxis on first exposure to fosaprepitant with the likely mechanism being non-IgE mediated mast cell activation. Chemotherapy and antibiotics were reintroduced without complication. Increased awareness of hypersensitivity reactions to fosaprepitant is critical given the growing use of this antiemetic drug for cases of refractory nausea.

S3556 Unique Approach to Refractory Nausea With Ketamine Infusion

Introduction: Functional refractory nausea is defined as nausea that persists for more than 4 weeks. Nausea can result from complex interactions between afferent and efferent pathways of the central nervous system and gastrointestinal tract. Management of refractory nausea, especially if it is associated with migraines, can be difficult to treat as conventional therapies such antiemetic and prokinetics are ineffective. We present a case of functional refractory nausea that was incidentally treated successfully with ketamine infusion. Case Description/Methods: A 37-year-old male with a history of pancreatic insufficiency, migraines, and chronic refractory nausea since 2016 with recurrent ED visits presented this time with headache and nausea for 7 days. He had tried multiple prophylactic medications at home including triptans and muscle relaxers without relief. For his nausea he tried ondansetron but it only provided temporary relief for 15-20 minutes. In the ED, the patient received prochlorperazine, diphenhydramine, and ketorolac for his headache and nausea. He continued to complain of his symptoms and was subsequentially given 20.4 milligram of ketamine infusion over 1 hour with resolution of his headache as expected. Surprisingly, the patient’s nausea concomitantly resolved with the ketamine infusion. After discharge, he was followed in GI clinic after one week and 3 months where he stated he was completely free of nausea without the use of his prophylactic medications. Discussion: Functional refractory nausea has been associated with decreased quality of life for patients. This presents as an economic burden in terms of health care costs and resources with recurrent admissions and ED visits. Conventional treatments for nausea include the use of antiemetics and prokinetics to name a few. The use of ketamine infusion has only been reported in one other case study for abortive and prophylactic therapy for nausea. Ketamine is a noncompetitive antagonist to N-methyl-d-aspartate receptor. The mechanism by which it helps with refractory nausea is still unclear but it is believed to be related to reduction of neural transmissions by ketamine. Ketamine is a generic medication that is cost effective. Side effects of ketamine are dose dependent and include cystitis and liver toxicity, which is unlikely with the doses given for nausea treatment. This case represents incidental resolution of nausea with ketamine administration and more studies are required for its role in abortive and prophylactic therapy.

S2518 Rare Gastrointestinal Manifestations of Metastatic Breast Cancer

Introduction: Breast cancer is the most common cancer and a leading cause of mortality among women. Breast cancer commonly metastasizes to the lung, liver, bones, and adrenal glands. However, there are rare instances where breast cancer can metastasize to the GI tract, most commonly the stomach. We present a case of a 65-year-old woman diagnosed with breast cancer in 1997 and found to have metastases to the stomach and cecum 19 and 21 years later, respectively. Case Description/Methods: A 65-year-old female with a past medical history of infiltrating lobular breast carcinoma (ER-positive) status post resection and chemotherapy and PUD presented 19 years later with refractory nausea. EGD showed localized moderate inflammation characterized by congestion, erythema, and friability in the stomach. Pathology (IHC staining) revealed tumor cells that were ER- and CAM5.2-positive and PR-negative. These findings were consistent with metastatic carcinoma with a breast primary. The patient had a subsequent PET scan that was positive for metastasis to the bone, spine, and pelvis and was restarted on hormonal-based chemotherapy. Two years later the patient presented with nausea, vomiting, and loss of appetite. CT of the abdomen with contrast showed a new finding of a 1.2 cm metastasis to the cecum. Colonoscopy showed altered vascular, atrophic, ulcerated mucosa in the cecum and thickening of mucosal folds in the proximal ascending colon. Pathology (IHC staining) revealed neoplastic cells positive for GATA-3 and negative for CDX-2, which support the diagnosis of infiltrating carcinoma from breast primary. The patient was continued on several different lines of chemotherapy. Discussion: Metastatic disease of the breast to the GI tract is a relatively rare presentation. It can be difficult to detect due to recognition of GI symptoms that are attributed to chemotherapy or a primary GI disease/malignancy. This can lead to delays in diagnosis and treatment. Due to this patient’s initial nausea, an EGD was conducted which revealed gastritis. Biopsies were positive for metastatic carcinoma in the stomach consistent with a primary breast cancer. Subsequent colonoscopy revealed metastatic disease to the cecum and ascending colon. Previously reported cases have shown that metastatic breast cancer to the GI tract can be diagnosed up to 30 years later. This highlights the importance of including primary breast cancer metastasis in the differential of ambiguous gastrointestinal symptoms.