Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22.

PURPOSE: Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes. METHODS: We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA). RESULTS: The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1-5, 6, and 7-10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain. CONCLUSION: Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1-5 as mild pain, 6 as moderate pain, and 7-10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.

Minimal clinically important differences in the EORTC QLQ-BM22 and EORTC QLQ-C15-PAL modules in patients with bone metastases undergoing palliative radiotherapy.

PURPOSE: Validated tools for evaluating quality of life (QOL) in patients with bone metastases include the EORTC QLQ-BM22 and QLQ-C15-PAL modules. A statistically significant difference in metric scores may not be clinically significant. To aid in their interpretation, we performed analyses to determine the minimal clinically important differences (MCID) for these QOL instruments. METHODS: Both anchor-based and distribution-based methods were used to determine the MCID among patients with bone metastases enrolled in a randomized phase III trial. For the anchor-based approach, overall QOL as measured by the QLQ-C15-PAL module was used as the anchor and only the subscales with moderate or better correlation were used for subsequent MCID analysis. In the anchor-based approach, patients were classified as improved, stable or deteriorated by the change in the overall QOL score from baseline to follow-up after 42 days. The MCID and confidence interval was then calculated for all subscales. In the distribution-based approach, the MCID was expressed as a proportion of the standard deviation and standard error measurement from the subscale score distribution. RESULTS: A total of 204 patients completed the questionnaires at baseline and follow-up. Only the dyspnea and insomnia subscales did not have at least moderate correlation with the overall QOL anchor. Using the anchor-based approach, 10/11 subscales had an MCID score significantly different than 0 for improvement and 3/11 subscales had a significant MCID score for deterioration. The magnitude of MCID scores was higher for improvement in comparison with deterioration. For improvement, the anchor-based approach showed good agreement with the distribution-based approach when using 0.5 SD as the MCID. However, there was greater lack of agreement between these approaches for deterioration. CONCLUSION: We present the MCID scores for the EORTC QLQ-BM22 and QLQ-C15-PAL QOL instruments. The results of this study can guide clinicians in the interpretation of these instruments. CLINICAL TRIALS REGISTRY: NCT01248585.

Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial.

BACKGROUND: Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare. METHODS: In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed. FINDINGS: Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence bound 0·0, one-sided p=0·05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 [41%] of 147 vs 68 [48%] of 143), fatigue (58 [39%] of 147 vs 49 [34%] of 143), constipation (47 [32%] of 147 vs 37 [26%] of 143), and nausea (34 [23%] of 147 vs 34 [24%] of 143), most of which were mild grade 1 or 2. INTERPRETATION: Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases. FUNDING: The NCIC CTG's programmatic grant from the Canadian Cancer Society Research Institute.

Geographical disparities of rectal cancer local recurrence and outcomes: a population-based analysis.

BACKGROUND: Challenges exist in providing high-quality cancer treatments to populations spread over large geographical areas. Local recurrence of rectal cancer is a complicated clinical problem associated with high morbidity and mortality. OBJECTIVES: objectives of this study were to evaluate population-based rates and predictors of local recurrence of rectal cancer in the Province of Manitoba, Canada, with emphasis on the effects of geography. DESIGN: : This was a population-based retrospective analysis. Administrative data from the Manitoba Cancer Registry and individual patient charts were reviewed. SETTINGS: Patients with stages I to III rectal cancer who underwent surgery with curative intent in Manitoba between 2004 and 2006 were included. MAIN OUTCOME MEASURES: The primary outcome was the development of local recurrence after surgical resection. RESULTS: Three hundred seventy patients with a mean age of 67 years were identified. The 5-year local recurrence rate was 17.4%. In multivariate analysis, relative to Winnipeg residents, rural residents, regardless of where they underwent surgery, had an increased risk of local recurrence (HR, 3.47; 95% CI, 1.74-6.92 for surgery in Winnipeg; HR, 2.98; 95% CI, 1.59-5.57 for surgery in rural Manitoba). The absence of both neoadjuvant radiotherapy and adjuvant chemotherapy was associated with a higher risk of local recurrence. Higher risk of mortality was noted for rural patients (HR, 1.90; 95% CI, 1.24-2.89) and for those who developed local recurrence (HR, 2.01; 95% CI, 1.27-3.19). CONCLUSION: Local recurrence rates for rectal cancer are high in Manitoba. Geography is an important variable, because rural status is associated with higher local recurrence rates and decreased survival. The use of neoadjuvant radiotherapy was an important predictor of lower local recurrence rates. Further initiatives are imperative to identify why rural patients experience differences in outcomes in Manitoba.

Improving Clinician Confidence in Insulin Prescriptions at Discharge for Individuals With Newly Diagnosed Type 1 Diabetes.

Background In a questionnaire, we found that pediatric clinicians at Basildon and Thurrock University Hospital (BTUH) have low confidence levels in prescribing multiple daily injections (MDI) for newly diagnosed pediatric patients with type 1 diabetes mellitus. We designed and evaluated locally tailored prescription guidance to improve confidence in MDI discharge prescriptions for pediatric doctors of all grades. Methods We designed a prescription guidance tool by adapting existing local guidelines to improve clinician familiarity with MDI prescriptions and prevent prescription errors. The intervention was delivered in a single pediatric unit to doctors of all levels. Feedback was collected, and the clinicians' confidence in their MDI prescriptions was evaluated before and after the intervention. Questionnaires were distributed to all pediatric doctors within the unit to assess their confidence in prescribing MDIs using a five-point Likert Scale. Furthermore, the questionnaires aimed to determine whether clinicians regularly consulted the existing local guidelines. Local guidelines were adapted in consultation with the local pediatric diabetic multidisciplinary team (MDT) and with reference to the East of England Pediatric Diabetes Network to present MDI guidance in a more concise format, which includes an example MDI discharge medication checklist. Following approval by the local guidelines management group, additional changes were made to enhance the practicality and accessibility of the discharge prescription guidance for clinicians. These guidelines were distributed to the pediatric MDT via email and displayed in visible areas of the department. Results Out of the 13 doctors surveyed, 10 provided pre- and post-intervention feedback (77%). Statistical significance was calculated using unpaired t-tests. Ninety percent of pediatric doctors routinely refer to local guidelines for guidance on MDI prescriptions. However, 50% of respondents felt that existing local guidelines were not easily accessible, given the time and effort required to locate them. The mean confidence score for completing MDI prescriptions at discharge before the intervention was 1.9 (SD: 0.83). After the intervention, it increased to 4 (SD: 0.63) (95% CI: 2.79-1.41, p<0.0001). Ninety percent of pediatric doctors felt that the design and display of the MDI guidelines optimized patient care. Conclusions Following the presentation of the project at a local audit and quality improvement (QI) meeting, the adapted guidelines were included in the junior doctor induction program at BTUH and made accessible on the local intranet. The production of locally tailored prescription guidance for MDI prescriptions at discharge has led to an increase in the confidence of pediatric doctors when writing their prescriptions. We aimed to continue updating this guidance as necessary and making further developments to enhance clinician confidence.

Metformin for Prevention of Anthropometric and Metabolic Complications of Androgen Deprivation Therapy in Prostate Cancer Patients Receiving Radical Radiotherapy: A Phase II Randomized Controlled Trial.

BACKGROUND: Patients with prostate cancer undergoing treatment with radical radiation therapy (RT) plus androgen deprivation therapy (ADT) experience a constellation of deleterious metabolic and anthropometric changes related to hypogonadism that are associated with increased morbidity and mortality. We assessed the effect of metformin versus placebo to blunt the adverse effects of ADT on body weight, waist circumference, and other metabolic parameters. METHODS AND MATERIALS: This phase 2, multicenter, randomized controlled trial (RCT) randomized normoglycemic men with locally advanced prostate cancer receiving radical RT and ADT (18-36 months) in a 1:1 ratio to receive metformin 500 mg by mouth 3 times a day (for 30-36 months) versus identical placebo. RESULTS: From December 2015 to October 2019, 83 men were randomized with median follow-up of 23 months. Baseline mean body mass Index (BMI) of the cohort was 30.2 (range 22.2-52.5). Change in mean weight relative to baseline was lower among men who received metformin compared with placebo at 5 months (-1.80 kg, P = .038), but was not significant with longer follow-up (1 year: +0.16 kg, P = .874). Although participants on ADT had increases in waist circumference in both study arms, metformin did not significantly reduce these changes (1 year: +2.79 cm (placebo) versus +1.46 cm (metformin), P = .336). Low-density lipoprotein (LDL) cholesterol was lower in the metformin arm (-0.32 mmol/L) compared with the placebo arm (-0.03 mmol/L) at 5 months (P = .022), but these differences were not significant with longer follow-up (1 year: -0.17 mmol/L vs -0.19 mmol/L, P = .896). There were no differences in HbA1C, triglyceride, high-density lipoprotein (HDL) cholesterol, and total cholesterol by study arm. CONCLUSIONS: Men receiving radical RT and ADT gained weight and had increases in waist circumference over time that metformin did not significantly mitigate. Although this study did not observe any preventive effect of metformin on the anthropometric and metabolic complications of ADT, metformin continues to be studied in phase 3 RCTs in this patient population to assess its potential antineoplastic effects.

The Feasibility of Quality Assurance in the TOPGEAR International Phase 3 Clinical Trial of Neoadjuvant Chemoradiation Therapy for Gastric Cancer (an Intergroup Trial of the AGITG/TROG/NHMRC CTC/EORTC/CCTG).

PURPOSE: The TOPGEAR phase 3 trial hypothesized that adding preoperative chemoradiation therapy (CRT) to perioperative chemotherapy will improve survival in patients with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. Our objective is to describe the RTQA methods and outcomes. METHODS AND MATERIALS: RTQA was undertaken in real time before treatment for the first 5 patients randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one-third of subsequent cases. RTQA consisted of evaluating (1) clinical target volume and organ-at-risk contouring and (2) radiation therapy planning parameters. Protocol violations between high- (20+ patients enrolled) and low-volume centers were compared using the Fisher exact test. RESULTS: TOPGEAR enrolled 574 patients, of whom 286 were randomized to receive preoperative CRT and 203 (71%) were included for RTQA. Of these, 67 (33%) and 136 (67%) patients were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72%. In total, 28% of cases required resubmission. In total, 200 of 203 cases (99%) passed RTQA before treatment. Cases from low-volume centers required resubmission more often (44/136 [33%] vs 13/67 [18%]; P = .078). There was no change in the proportion of cases requiring resubmission over time. Most cases requiring resubmission had multiple protocol violations. At least 1 aspect of the clinical target volume had to be adjusted in all cases. Inadequate coverage of the duodenum was most common (53% major violation, 25% minor violation). For the remaining cases, the resubmission process was triggered secondary to poor contour/plan quality. CONCLUSIONS: In a large multicenter trial, RTQA is feasible and effective in achieving high-quality treatment plans. Ongoing education should be performed to ensure consistent quality during the entire study period.

Evaluation of the ITV-margin and variables affecting bladder and mesorectal deformation during long course neoadjuvant radiotherapy for rectal cancer.

Internal target volume (ITV) margins were estimated by evaluating the movement of mesorectum and bladder during neoadjuvant long-course radiation therapy (RT) for rectal cancer. In this prospective study, 23 patients with rectal cancer had planning CT (pCT) and weekly cone beam CT (CBCT) in supine position during preoperative long-course RT. Mesorectal wall motion was analyzed based on the coordinates of the most anterior, posterior, left and right points on the pCT and CBCT. Overlap volume (OV) between the pCT bladder and CBCT mesorectum was generated. Variables that might affect relative bladder volume (ratio of CBCT to pCT bladder volumes), anterior mesorectal wall position, and OV were studied. ITV margins were also calculated. In females, smaller OV and less movement of the upper anterior mesorectal wall were identified, suggesting smaller ITV margins might be required compared to males. The relative bladder volume did not change significantly over time and was correlated with OV: the larger the relative bladder volume, the less the OV. ITV margin of 0.8 to 1.1 cm in right-left direction is satisfactory. Posteriorly, only 8 to 9 mm margin is required for upper and mid rectal regions but double of this is required for inferior third. Anteriorly, 1.3 cm margin is adequate for lower and mid rectal regions and 2.4 cm is required superiorly. An anisotropic ITV expansion of clinical target volume (CTV) for rectal cancer radiotherapy contouring provides a robust method to encompass the deformation of bladder and mesorectum. The ITV margin should take into account sex and distance from the anal verge.

Current Role of Immunotherapy in Gastric, Esophageal and Gastro-Esophageal Junction Cancers-A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference.

Gastric, esophageal and gastro-esophageal junction cancers are associated with inferior outcomes. For early-stage disease, perioperative chemotherapy or chemoradiation followed by surgery is the standard treatment. For most patients with advanced upper gastrointestinal tract cancers, platinum-based chemotherapy remains a standard treatment. Recently, several randomized clinical trials have demonstrated the benefit of immunotherapy involving checkpoint inhibitors alone or in combination with chemotherapy in patients with gastro-esophageal cancer and have changed the treatment landscape. The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC), involving experts from four Western Canadian provinces, convened virtually on 16 June 2021 and developed the recommendations on the role of immunotherapy in patients with gastro-esophageal cancer.

Report from the Western Canadian Gastrointestinal Consensus Cancer Conference-Management of Total Neoadjuvant Therapy in Rectal Cancer.

An educational session related to the Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held virtually on 14 October 2020. The WCGCCC is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba), who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists, radiologists, and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of total neoadjuvant therapy in rectal cancer.

Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference.

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.

Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats treated with theophylline and caffeine.

Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine (5-HT) acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine (m-CPP) at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine (a component of coffee and tea) or theophylline (a component of tea) as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed.

Gastrointestinal and genitourinary toxicity profiles of metformin versus placebo in men with prostate cancer receiving prostate radiotherapy: interim toxicity results of a double-blinded, multicenter, phase II randomized controlled trial.

Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Report from the Western Canadian Gastrointestinal Cancer Consensus Conference Virtual Education Series-Transition from Local to System Therapy and Optimal Sequencing of Systemic Therapy for HCC.

The Western Canadian Gastrointestinal Cancer Consensus Conference (WC-5) convened virtually on 10 February 2021. The WC-5 is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular cancer (HCC). Recommendations have been made for the transition from local to systemic therapy and the optimal sequencing of systemic regimens in the management of HCC.

Report from the 21st Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; 20-21 September 2019.

The 21st annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Calgary, Alberta, 20-21 September 2019. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists, pathologists, radiologists, and allied health care professionals such as dietitians and nurses participated in presentation and discussion sessions to develop the recommendations presented here. This consensus statement addresses current issues in the management of hepato-pancreato-biliary (HPB) cancers.

Toxic effects of multiple anticancer drugs on skin.

In this study, cutaneous toxicities associated with the administration of chemotherapy in combination are discussed. Rapidly growing cells are the targets of chemotherapy, so the skin, hair follicles, and nail matrix are frequently affected by chemotherapy. Chemotherapy skin reactions are more likely toxic than allergic reactions. There are numerous chemotherapy-induced cutaneous reactions that have been described in the literature. In addition to a variety of miscellaneous reactions, 19 major cutaneous reactions were discussed in current study. This study was designed to evaluate the clinical spectrum of all cutaneous toxicities over two years in hospitalized and ambulatory patients in the Department of Pediatric oncology and to establish probable relationship between the reaction and suspected anticancer protocol with the help of WHO (World Health Organization) Common Toxicity Criteria by Grade. The data on the cutaneous toxicities were analyzed by percentile and ranking method. The minimal (0.8%) cutaneous adverse effects monitored during the study were Petechiae, photosensitivity, pruritus, urticaria, wound-infection, erythema multiforme, hand-foot skin reaction, injection site reaction, dry skin. Alopecia was the single most common (64.3%) adverse effect observed during the study, where as the pigmentary changes were the second most common (18.2%) adverse effect monitored. While these side effects are generally not life threatening, they can be a source of significant distress to patients, especially alopecia.

Ferrous Sulfate-Induced Esophageal Injury Leading to Esophagitis Dissecans Superficialis.

Medication-induced esophagitis is a well-known but relatively rare clinical diagnosis, most common in patients with preexisting esophageal dysmotility, obstruction, or altered anatomy. Esophagitis dissecans superficialis (EDS) is a rare endoscopic finding characterized by sloughing of large fragments of the esophageal mucosal lining. The causes of EDS include prior trauma, heavy smoking history, ingestion of alcoholic and hot beverages, and immunosuppression. We present a unique case of EDS secondary to ferrous sulfate-induced pill esophagitis. The patient was a 94-year-old male who presented with dysphagia to solids, odynophagia, and weight loss. Esophagogastroduodenoscopy (EGD) revealed EDS. Biopsies demonstrated vacuolar degeneration at the midlevel of the epithelium with overlying hyperkeratosis and parakeratosis, with noted black/brown pigment present at the level of the split in the epithelium. The patient was started on a liquid diet with no oral administration of pills. EGD was repeated and showed a significant improvement in esophageal mucosa and resolution of strictures. Although medication-induced esophagitis is not classically associated with EDS, specific circumstances that are associated with pill esophagitis may lead to progression to EDS. In the case of our patient, prolonged contact of ferrous sulfate to the esophageal mucosa is thought be a result of an enlarged left atrium and pulmonary arteries secondary to longstanding coronary artery disease and an enlarged left bronchus secondary to chronic obstructive pulmonary disease and right pneumonectomy. These anatomical changes likely led to an extended duration of contact and are believed to have led to erosion of the superficial esophageal mucosa, eventually progressing to EDS.

A Rare Presentation of Poorly Differentiated Lung Carcinoma with Duodenal Metastasis and Literature Review.

Lung cancer is a common malignancy which is frequently found to metastasize to distant sites including bone, liver, and adrenal glands. There are rare reports of metastases to the gastrointestinal (GI) tract, with the duodenum being the most uncommon. We present a rare case of a poorly differentiated lung carcinoma metastasizing to the duodenum. This case enhances the medical literature as it provides additional distinct features to the clinical and histological presentation of metastatic lung carcinoma to the GI tract. A 61-year-old male with a history of poorly differentiated lung carcinoma presented with worsening dizziness, fatigue, and early satiety. He had extensive workup done in the past for hemoptysis including a computerized tomography scan of the chest which showed a new lobulated, apical lesion and hilar lymphadenopathy. He ultimately had a transthoracic fine-needle aspiration (FNA) of the mass and was later diagnosed with poorly differentiated lung carcinoma. On examination, the patient was noted to be pale, tachycardic, and hypotensive. The patient was noted to have an acute drop in his hemoglobin requiring fluid resuscitation, multiple blood transfusions, and evaluation with an esophagogastroduodenoscopy. He was found to have an oozing ulcer in the third portion of the duodenum whose biopsies showed poorly differentiated carcinoma with areas of neuroendocrine differentiation, similar to his lung biopsy results, which was consistent with metastatic lung carcinoma.

Working in the dark: Interaction with a sub clinical COVID-19 subject and lessons learned.

Subclinical COVID-19 subjects pose a significant challenge. We present a very close clinical interaction with a subclinical COVID-19 subject that met the "standard screening criteria" and is unique in several ways. Learning from our experience, we suggest close attention should be paid to any unexpected findings such as groundglass opacity on CT as it could help early identification of subclinical COVID-19 infection.