Metastatic Complications Research Articles

Redefining readmissions in gynecologic cancer: readmissions resulting in hospital-to-hospice transitions may represent high value care

Objectives: Hospital readmissions are used as a marker of quality of care, with unplanned admissions identified as low value care. Hospice is a marker of high value care and a readmission resulting in discharge to hospice may indicate value in readmission. The primary objective of this study was to describe readmissions that resulted in discharge to hospice. Methods: We performed a retrospective cohort study of women with a diagnosis of gynecologic cancer who were readmitted within 30 days to a single urban academic hospital between July 2017 and April 2020. Patient demographics, oncology data, admission cost, discharge status, length of admission and length of hospice admission were collected from the electronic medical record. Length of hospice admission ≥3 days was defined as high value care. Descriptive statistics were performed to identify factors associated with discharge to hospice. Results: We identified 98 patients readmitted during the study period. 36.7% (n=36) had uterine cancer, 49.0% (n=48) had ovarian cancer, 12.2% (n=12) had cervical cancer and 2.0% (n=2) had vulvar cancer. 47% (n=46) had recurrent disease. 11.2% (n=11) of patients readmitted had a previous outpatient palliative care consult prior to the index admission and 28.6% (n=28) had an inpatient palliative care consult during the index admission. Patients were readmitted from the Emergency Department (n=50, 51.0%), ambulatory visit (n=31, 31.6%) or hospital transfer (n=17, 17.3%). The most common categories of reason for readmission were gastrointestinal (n=20, 20.4%), complication of metastases (n=15, 15.3%), and primary malignancy (n=12, 12.2%). The median time to readmission was 10 days (IQR 5-16 days) and the median length of readmission was 5 days (IQR 3-9 days). 23.5% (n=23) of patients had multiple readmissions, with a median of 2 readmissions (range 2-4). One-third of patients (n=36, 36.7%) received a palliative care consult and hospice was discussed with 21.4% (n=21) during readmission. 17.3% of patients (n=17) were discharged to hospice from a hospital readmission, with a median length of hospice admission, prior to death, of 7 days (IQR 2-14 days). 81% of patients with whom hospice was discussed were discharged to hospice. 70.6% of patients (n=12) had a length of hospice admission ≥3 days. There was a significant association of repeat readmission and discharge to hospice (p Conclusions: Hospital readmissions in gynecologic cancer patients resulted in a hospital-to-hospice transition in 17.3% of all patients, and 81% of patients with whom hospice was discussed. Multiple readmissions may precipitate a decision to enroll in hospice. Readmissions may not indicate substandard care and instead potentially demonstrate an opportunity to deliver high value care to patients, as both enrollment in hospice at end of life and hospice enrollment for ≥3 days are considered optimal quality oncology metrics.

Staphylococcus aureus Bacteremia Among Patients Receiving Maintenance Hemodialysis: Trends in Clinical Characteristics and Outcomes

Staphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations with clinical outcomes with SAB in this population over a 21-year period. Prospective cohort study. 453 hospitalized, non-neutropenic adults receiving maintenance HD who developed monomicrobial SAB between 1995 and2015. Clinical characteristics and bacterial genotype. All-cause and SAB-attributable mortality, persistent bacteremia, and metastatic complications. Proportions of participants experiencing each outcome were calculated overall and by calendar year. Secular trends were estimated using binomial risk regression, a generalized linear model with the log link function for a binomial outcome. Associations with outcomes were estimated using logistic regression. Over the 21-year study period, patients receiving maintenance HD experienced significant increases in age- and diabetes-adjusted SAB-attributable mortality (0.45% [95% CI, 0.36%-0.46%] per year), persistent bacteremia (0.86% [95% CI, 0.14%-1.55%] per year), metastatic complications (0.84% [95% CI, 0.11%-1.56%] per year), and infection with the virulent Saureus clone USA300 (1.47% [95% CI, 0.33%-2.52%] per year). Over time, the suspected source of SAB was less likely to be a central venous catheter (-1.32% [95% CI,-2.05 to-0.56%] per year) or arteriovenous graft (-1.08% [95% CI,-1.54 to-0.56] per year), and more likely to be a nonvascular access source (1.89% [95% CI, 1.29%-2.43%] per year). Patients with a nonvascular access suspected source of infection were more likely to die as a result of their S aureus infection (OR, 3.20 [95% CI, 1.36-7.55]). The increase in USA300 infections may have contributed to the observed increase in persistent bacteremia (OR, 2.96 [95% CI, 1.12-7.83]) but did not explain the observed increases in SAB-attributable mortality (OR, 0.83 [95% CI, 0.19-3.61]) or metastatic complications (OR, 1.34 [95% CI, 0.53-3.41]). Single-center, inpatient cohort. The clinical and molecular epidemiology of SAB in patients receiving maintenance HD has changed over time, with an increase in SAB-attributable mortality and morbidity despite a decline in catheter-related infections.

Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus.

Angiogenesis, as a process occurring under the regulation of a variety of factors, is one of the important ways of vascular development. It coexists in a variety of pathological and physiological processes. Now a large number of studies have proved that tumor growth, metastasis, and various vascular complications of diabetes are closely related to angiogenesis, and an increasing number of studies have shown that there are many common factors between the two. But angiogenesis is the opposite of the two: it is enhanced in tumors and suppressed in diabetes. Therefore, this review discusses the causes of the phenomenon from the expression of various factors affecting angiogenesis in these two diseases and their effects on angiogenesis in the relevant microenvironment, as well as the application status of these factors or cells as therapeutic targets in the treatment of these two diseases.

Survival Analysis and Prognostic Factors for Prostate Cancer Patients at Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur

Prostate cancer is the third commonest type of cancer in Malaysian men with the incidence of 1,807 in 2018 compared to 1,186 cases reported in 2014. Prostate cancer is also known to cause disease, economic burden and lead to significant financial implications for the healthcare system. This study aimed to measure the rate of survival and to determine the prognostic factors for prostate cancer patients at Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur. This was a retrospective study design involving prostate cancer patients who had been diagnosed and had sought treatment at Universiti Kebangsaan Malaysia Medical Centre from 2008 to 2017. Data were obtained from the patients’ medical records based on TRUS biopsy. The study period was from July 2017 to December 2018. Survival probabilities were estimated using Kaplan-Meier, and differences were compared using the log-rank test. The adjusted hazard ratio (HR) for variables was estimated after fitting the Cox proportion hazard model. Patients' death status due to prostate cancer was the endpoint of the survival analysis. A total of 283 patients’ data were analysed. Total five-year and ten-year survival rates of prostate cancer patients were 77.8 and 65.5%, respectively, regardless of the stage and treatment. The predictor factors for survival age were ≥75 years (HR = 8.49, 95% C.I: 1.16-62.13), Gleason score ≥8 (HR = 2.36, 95% C.I: 1.18-4.73) and cancer metastasis complications (HR = 5.26, 95% C.I: 2.88-9.63). Survival rates and prognostic factors of prostate cancer in the study were almost similar to those in nearby countries in the region. Preventive actions such as prostate cancer screening, early detection of cancer and early treatment should be empowered to improve the survival rate of prostate cancer patients in this hospital.

Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling.

Osteolysis resulting from osteoclast overactivation is one of the severe complications of breast cancer metastasis to the bone. Previous studies reported that the anti-cancer agent DZNep induces cancer cell apoptosis by activating Akt signaling. However, the effect of DZNep on breast cancer bone metastasis is unknown. We previously found that DZNep enhances osteoclast differentiation by activating Akt. Therefore, we explored the use of the anti-cancer agent AZD3463 (an Akt inhibitor) along with DZNep, as AZD3463 can act as an anti-cancer agent and can also potentially ameliorate bone erosion. We evaluated osteoclast and breast cancer cell phenotypes and Akt signaling in vitro by treating cells with DZNep and AZD3463. Furthermore, we developed a breast cancer bone metastasis animal model in mouse tibiae to further determine their combined effects in vivo. Treatment of osteoclast precursor cells with DZNep alone increased osteoclast differentiation, bone resorption, and expression of osteoclast-specific genes. These effects were ameliorated by AZD3463. The combination of DZNep and AZD3463 inhibited breast cancer cell proliferation, colony formation, migration, and invasion. Finally, intraperitoneal injection of DZNep and AZD3463 ameliorated tumor progression and protected against bone loss. In summary, DZNep combined with AZD3463 prevented skeletal complications and inhibited breast cancer progression by suppressing Akt signaling.

Organotin compounds as effective antimetastatic substances in the treatment of epidermoid lung carcinoma Lewis (LLC) in an experiment.

e15054 Background: Lung cancer occupies one of the first places in the structure of oncological diseases in the world. Reducing the life expectancy of patients, as a rule, occurs as a result of metastatic complications, so the search for new antimetastatic agents is an urgent task for experimental pharmacology and oncology. The aim of our study is to assess the severity of metastatic lesion in the Lewis lung epidermoid carcinoma (LLC) model in the presence of an organotin compound. Methods: The study was conducted on experimental C57BL/6 mice (n = 24, each group contained 12 mice) with LLC (subcutaneous transplantation) in the presence of the cytotoxic organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio]phenol (Me5). All manipulations were carried out in accordance with the European Convention for the Protection of Vertebrates Used for Experimental and Other Scientific Purposes (ETS 123). Female mice (8 weeks of age, weighing 21-22 g) were intraperitoneally injected with a 1% aqueous gelatin solution of organotin Me5 daily for 5 days. The most effective total dose of Me5 was 250 mg / kg. The animals of the control group received saline solution in similar modes and volumes. In the experimental and control groups, the degree of metastatic lesion was assessed on the 21-day post-grafting period according to the scale proposed by D. Tarin and J. E. Price, which allows us to differentiate the severity of the lesion depending on the number of metastases and their size. The experiment describes three degrees of lesion: LCP-1 (metastases less than 10 pcs. with a diameter not exceeding 1 mm); LCP-2 (metastases from 10 to 30 pieces, some of them larger than 1 mm) and HCP-3 (metastases larger than 30 pieces of different sizes, but no drain). The pathohistological structure was studied by the light-optical method with hematoxylin and eosin staining. Results: When administered intraperitoneal to mice, Me5 did not inhibit the growth of the primary tumor site in the experimental group, but significantly reduced the severity of metastatic lesions in the lungs. In the control group, 75 % of mice with LLC had LCP - 2 (low colonization potential) and in 25% of HCP-3 (high colonization potential) metastatic lesions, in the experimental group only mild lesions were noted in all animals: 58% of mice had LCP – 1, 42% - LCP-2. Conclusions: It is concluded that the overall result of this study clearly demonstrates that the organotin compound 2,6-bis (1,1-dimethylethyl) - 4 - [(triphenylstannyl)thio] phenol (Me5) is an effective antimetastatic agent in the Lewis lung epidermoid carcinoma (LLC) model at a total dose of 250 mg/kg.

Could lymphocyte to C-reactive protein ratio predict the prognosis in patients with gastric cancer?

Development or progression of inflammation in neoplastic diseases is known to be part of the disease. Lymphocyte to C-reactive protein ratio (LCR) is a new indicator showing the inflammatory state. The aim of this study is to show the clinical importance of the relationship between the preoperative LCR and the prognosis of patients with gastric cancer. We evaluated gastric cancer patients, who underwent surgery between 2010 and 2015. LCR and neutrophil-to-lymphocyte ratio (NLR) were calculated from pre-treatment of complete blood counts. Both ratios were compared to the perioperative outcomes and median survival times. Association between LCR and postoperative tumour stage was studied by using multivariate analysis with other clinicopathological variables. A total of 123 patients were included. The mean age of the patients was 65.36± 10.08. Preoperative low LCR value was associated with advanced tumour stage, adjacent organ invasion, lymph node metastasis and postoperative early complications. The receiver operating characteristic analysis results showed that LCR and NLR parameters were significant (CI 0.718-0.886; 95%); P < 0.001, CI 0.534-0.732; 95%). Cut-off value being 193, the mean survival of patients who had LCR values of overcut-off value was found to be significantly higher compared with the patients with lower LCR values (P < 0.001). LCR, a simple calculated ratio of values obtained from easy and widely available serum indicators could be an effective prognostic marker with gastric cancer.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia- A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Jaw Metastasis from a Prostate Adenocarcinoma Associated with Numb Chin Syndrome: Case Report

AbstractNumb chin syndrome is an uncommon maxillofacial manifestation involving mental neuropathic complications of mandibular bone metastasis with prostate adenocarcinoma. We report a case of a male, 68 years, with a history of bone tibia and spinal metastatic prostate cancer, undergoing bilateral orchiectomy for hormonal blockade and chemotherapy; disease progression was confirmed by bone scintigraphy which noted no critical points but an increase in alkaline phosphatase; therapy with abiraterone and zoledronic acid quarterly was introduced 1 year after diagnosis. The patient attended a dental appointment after 10 months of bisphosphonate use, complaining of a “tingling” sensation in the right chin mental region, 6 months after tooth extraction, with diagnostic hypothesis of medication-related jaw osteonecrosis. Intra-oral exam showed edema in the right mandibular body region extending to the painless, hardened chin, with exudate drainage as compression. An incisional biopsy was performed and anatomopathological and immunohistochemical analysis showed positive staining for cytokines and NKX3, confirming the diagnosis of adenocarcinoma metastasis. The patient was referred to continue treatment with radiotherapy and, subsequently, Xofigo and zoledronic acid to improve symptomatology and control of the adenocarcinoma. Facial numbness should alert clinicians to the potential of metastatic disease in any patient who presents with chin or jaw numbness and has no other obvious cause for their complaint, and early differential diagnosis between jaw osteonecrosis and bone metastasis in the jaw is important for immediate management and improvement in treatment and quality of life.

Electrocoagulation for liver metastases.

Primary liver tumours and liver metastases from colorectal carcinoma are two of the most common malignant tumours to affect the liver. The liver is second only to the lymph nodes as the most common site for metastatic disease. More than half of the people with metastatic liver disease will die from metastatic complications. Electrocoagulation by diathermy is a method used to destroy tumour tissue, using a high-frequency electriccurrent generating high temperatures, applied locally with an electrode (needle, blade, or ball). The objective of this method is to destroy the tumour completely, if possible, in a single session. With the time, electrocoagulation by diathermy has been replaced by other techniques, but the evidence is unclear. To assess the beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention,versus no intervention, other ablation methods, or systemic treatments in people with liver metastases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, CINAHL,ClinicalTrials.gov, ICTRP, and FDA to October 2020. We consideredall randomised trials that assessed beneficial and harmful effects of electrocoagulation by diathermy, administered alone or with another intervention, versus comparators, in people with liver metastases, regardless of the location of the primary tumour. We used standard methodological procedures expected by Cochrane. We assessed risk of bias of the included trialusing predefined risk of bias domains, and presented the review results incorporating the certainty of the evidence using GRADE. We included one randomised clinical trial with 306 participants (175 males;131 females) who had undergone resection of the sigmoid colon, and who had five or more visible andpalpable hepatic metastases. The diagnosis was confirmed by histological assessment (biopsy) and by carcinoembryonic antigen (CEA) level. The trial was conducted in Iraq. The age of participants ranged between 38 and 79 years. The participants wererandomised to four different study groups. The liver metastases were biopsied and treated (only once) in three of the groups: 75 received electrocoagulation by diathermy alone, 76 received electrocoagulation plus allopurinol, 78 received electrocoagulation plus dimethyl sulphoxide. In the fourth intervention group, 77 participants functioning as controls received a vehicle solution of allopurinol 5 mL 4 x a dayby mouth; the metastases were left untouched. The status of theliver and lungs wasfollowed by ultrasound investigations, without the use of a contrast agent. Participants were followed for five years. The analyses are based on per-protocol data only analysing 223 participants. We judged the trial to be at high risk of bias.After excluding 'nonevaluable patients', the groups seemed comparable for baseline characteristics. Mortality due to disease spread at five-yearfollow-up was98% in the electrocoagulation group (57/58 evaluable people); 87% in the electrocoagulation plus allopurinol group (46/53 evaluable people); 86% in the electrocoagulation plus dimethyl sulphoxide group (49/57 evaluable people); and 100% in the control group (55/55 evaluable people). We observedno difference in mortality between the electrocoagulation alone group versus the control group (risk ratio (RR) 0.98, 95%confidence interval (CI) 0.94 to 1.03; 113 participants; very low-certaintyevidence). We observedlower mortality in the electrocoagulation combined with allopurinol or dimethyl sulphoxide group versus the control group (RR0.87, 95% CI0.80 to 0.95; 165 participants; low-certainty evidence). We are very uncertainregarding post-operative deaths betweenthe electrocoagulation alone group versusthe control group(RR1.03, 95% CI 0.07 to 16.12; 152 participants; very low-certainty evidence)andbetween the electrocoagulation combined with allopurinol or dimethyl sulphoxidegroups versusthe control group(RR1.00, 95%CI0.09 to 10.86; 231 participants; very low-certainty evidence). The trial authors did not report data on number of participants with other adverse events and complications, recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life.Data on failure to clear liver metastaseswere not provided for the control group. There was no information on funding or conflict of interest. We identified no ongoing trials. The evidence on the beneficial and harmful effects of electrocoagulation alone or in combination with allopurinol or dimethyl sulphoxide in people with liver metastases is insufficient, as it is based on one randomised clinical trial at low to very low certainty. It is very uncertain if there is a difference in all-cause mortality and post-operative mortality between electrocoagulation alone versus control. It is also uncertain if electrocoagulation in combination with allopurinol ordimethyl sulphoxidemay result in a slight reduction of all-cause mortality in comparison with a vehicle solution of allopurinol (control).It is very uncertain if there is a difference in post-operative mortality between the electrocoagulation combined with allopurinol or dimethyl sulphoxidegroup versuscontrol.Data on other adverse events and complications, failure to clear liver metastases or recurrence of liver metastases, time to progression of liver metastases, tumour response measures, and health-related quality of life were most lacking or insufficiently reported for analysis. Electrocoagulation by diathermy is no longer used in the described way, and this may explain the lack of further trials.

Heterogeneity of antigenic constellation in human hepatocellular carcinoma.

Hepatocellular carcinoma is one of the primary liver malignancies responsible for over a million deaths per year worldwide (approximately 10% of all deaths in the adult age range). The diagnosis of HCC can be difficult and often requires the use of more than one microscopic technique. A retrospective study was performed on a study batch of 42 cases that died of HCC due to metastasis or other secondary complications. Tissue samples were taken in order to investigate the tumour antigenic constellation by means of IHC method using a large variety of antibodies. In situ hybridization was also performed for albumin mRNA to assess the albumin expression in some selected cases. Telomerase activity was investigated using IHC method for the hTERT catalytic subunit. A cocktail of hepatic cytokeratins (CK8, 18) combined with Hep Par-1 and associated to albumin proved to be more powerful than albumin alone in differentiating HCC and increased the value of tumour diagnosis. hTERT expression was proportionally reverse to the tumour degree of differentiation, but was independent from the expression of tumour-proliferating indexes. The heterogeneity of the antigenic constellation in hepatocellular carcinoma suggests an antigenic mosaicism, which can be expressed a synchronous or metachronous manner, depending on the tumour degree of differentiation.

Multi-omic molecular profiling reveals potentially targetable abnormalities shared across multiple histologies of brain metastasis.

The deadly complication of brain metastasis (BM) is largely confined to a relatively narrow cross-section of systemic malignancies, suggesting a fundamental role for biological mechanisms shared across commonly brain metastatic tumor types. To identify and characterize such mechanisms, we performed genomic, transcriptional, and proteomic profiling using whole-exome sequencing, mRNA-seq, and reverse-phase protein array analysis in a cohort of the lung, breast, and renal cell carcinomas consisting of BM and patient-matched primary or extracranial metastatic tissues. While no specific genomic alterations were associated with BM, correlations with impaired cellular immunity, upregulated oxidative phosphorylation (OXPHOS), and canonical oncogenic signaling pathways including phosphoinositide 3-kinase (PI3K) signaling, were apparent across multiple tumor histologies. Multiplexed immunofluorescence analysis confirmed significant T cell depletion in BM, indicative of a fundamentally altered immune microenvironment. Moreover, functional studies using in vitro and in vivo modeling demonstrated heightened oxidative metabolism in BM along with sensitivity to OXPHOS inhibition in murine BM models and brain metastatic derivatives relative to isogenic parentals. These findings demonstrate that pathophysiological rewiring of oncogenic signaling, cellular metabolism, and immune microenvironment broadly characterizes BM. Further clarification of this biology will likely reveal promising targets for therapeutic development against BM arising from a broad variety of systemic cancers.

NCMP-02. CEREBRAL SPINAL FLUID (CSF) PREDICTORS OF DEVELOPING DISSEMINATED NECROTIZING LEUKOENCEPHALOPATHY IN LEPTOMENINGEAL CARCINOMATOSIS (LMC): A SINGLE INSTITUTIONAL REVIEW

Abstract BACKGROUND LMC is a rare complication of systemic cancer metastasis to the leptomeninges. Although first described in 1870 treatment options remain few for this rapidly fatal condition commonly excluded from clinical trials and disease site guideline updates. Whole brain radiation therapy (WBRT) and intrathecal (IT) chemotherapy are commonly employed and there is growing evidence for systemic therapies that cross the blood brain barrier. Disseminated necrotizing leukoencephalopathy (DNL) is a self-limited rare treatment-related radiographic finding variably associated with clinical decline and often misdiagnosed as progression or infection. DNL has been reported in patients exposed to IT chemotherapy and CNS irradiation. Our lab recently published improved LMC control with extended survival after standardization of Ommaya clinic IT treatment regimens, although with increased incidence of DNL. METHODS We retrospectively analyzed patients with LMC treated with IT chemotherapy after WBRT between 2017 – 2020. We reviewed sequential brain imaging over the treatment course to determine if there were predictive CSF markers associated with the development of DNL. RESULTS Of the 41 patients evaluated, 24% (n=10) developed DNL at a median 24-weeks after start of IT chemotherapy and WBRT. Of the patients with radiographically assessed DNL, 80% (n=8) experienced elevated CSF protein and 40% (n=4) had elevated white blood cells within 8-weeks prior to radiographic determination of DNL. Cytology remained benign and glucose was not significantly changed prior to DNL development. CONCLUSION Given the poor outcome of LMC, there is a need for treatment standardization and better understanding of treatment-associated radiographic changes. Evaluation of CSF markers to predict impending development of DNL in this treatment population might limit radiographic misdiagnoses and patient clinical decline as well as offer a potential window of opportunity for treatment de-escalation.

S2820 Perforated Ulcer as a Complication of Duodenal Neuroendocrine Tumor

INTRODUCTION: The incidence of duodenal neuroendocrine tumors (D-NETs) is only 0.19 per 100,000 in the US. Very little is known about the various patient presentations, and therefore every case is valuable. We present a patient found to have a duodenal NET and duodenal peptic ulcer disease complicated by sudden perforation. CASE DESCRIPTION/METHODS: A 54 year old female with lupus, antiphospholipid syndrome, cerebrovascular accident, heart failure, and left ventricular thrombus on warfarin, presented with melena, non bloody non bilious vomiting and a hemoglobin of 6. EGD revealed a duodenal 4 mm nodule consistent with well differentiated NET on histopathology and multiple 2 mm clean base ulcers. The patient was transfused blood and treated with PPI therapy. Serotonin and gastrin levels were < 20 and 60 respectively. Chromogranin A level was elevated at 1486. She was scheduled for EUS guided endoscopic resection of her NET. She later developed acute abdominal pain and coffee ground emesis. CT Angiography was negative for mesenteric ischemia but revealed pneumoperitoneum and hemorrhagic ascites. She underwent emergency exploratory laparotomy with repair of perforation of duodenal wall but decompensated and expired. DISCUSSION: The WHO classifies NETs based on mitotic activity, G1 to G3. D-NET can also be classified as gastrinomas (50–60%), somatostatinomas (15%), nonfunctional tumors (19-27%), paragangliomas (< 2%) and poorly differentiated carcinomas (< 3%). Diagnosis is usually incidental during EGD evaluation and is based on histological analysis for chromogranin and synaptophysin. Our patient was on anticoagulation and presented with peptic ulcer disease and NET in the duodenum. Gastrin level was only 60, ruling out a functional gastrinoma and Zollinger Ellison Syndrome. 80% of NETs tend to have elevated serum chromogranin. Only 3% of patients develop carcinoid syndrome, a complication of metastasis to the liver. For our patient, CT did not reveal any metastasis and serotonin levels were normal. Local nonfunctional < 1 cm NET can be endoscopically resected. Our patient was planned for EUS guided resection, but she did not make it to her procedure. EGD showed clean based ulcers, which have the lowest risk for ulcer complications. It is reasonable to speculate that her NET may have contributed to mucosal fragmentation and ulcer perforation. Unusual presentations of rare diseases such as D-NETs should be reported and is an area that requires further research.

LEMIERRE'S SYNDROME: A FORGOTTEN DISEASE

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Lemierre’s Syndrome is a largely forgotten disease in the era of antibiotics, with an incidence of 1 in 1 million per year. It is characterized by thrombophlebitis of the internal jugular (IJ) vein and bacteraemia of oral cavity anaerobes, in a young otherwise healthy adult. It was highly prevalent and often fatal prior to the introduction of antibiotics; however cases have since declined significantly, with a recent resurgence (1). CASE PRESENTATION: A 21-year-old female with no previous history presented with high grade fevers and progressive shortness of breath for 2 days. She reported a recent sore throat that failed to improve with oral Azithromycin. She denied any intravenous (IV) drug use or recent dental work. She was febrile at 103 F, with a HR: 128bpm, RR: 28 bpm & oxygen saturation: 86% on room air, requiring supplemental oxygen. Oropharyngeal exam was normal with a central uvula without any erythema, tonsillar exudates, or palpable cervical adenopathy. Labs were normal except for a leucocytosis of 13 k/mm3 and thrombocytopenia of 31 k/mm3. CT chest showed bilateral lung nodules with basilar, sub-pleural predominance & early cavitation consistent with septic emboli (Fig 1). CT neck showed a venous thrombus extending from the right palatine tonsillar vein into the right IJ vein, consistent with Lemierre's syndrome (Fig 2). Blood cultures grew Prevotella intermedia after 4 days of inoculation. She was started on broad spectrum antibiotics with de-escalation to oral amoxicillin/clavulanic acid and metronidazole for 6 weeks. Therapeutic anticoagulation was stopped after development of a haemothorax. DISCUSSION: Lemierre's syndrome is a triad of oropharyngeal infection with bacteremia, thrombophlebitis of IJ vein and distant metastatic abscesses, typically preceded by a sore throat which results in deep tissue invasion by highly thrombogenic oral anaerobes. The most frequent metastatic site is the lungs, but any organ may be involved (2). Most common pathogen responsible is Fusobacterium, an obligate anaerobic, gram-negative bacilli, but very limited literature is published regarding Provetella spec. associated Lemierre's syndrome (2). Incidence has significantly declined after the introduction of Penicillin, however, there has been a resurge, presumably due to a trend against prescribing antibiotics for sore throat (2-3). Diagnosis is usually clinical with supporting radiological evidence and growth of a typical causative organism, usually from blood. It is often mistakenly diagnosed as primary bacteremia from an infected organ or tonsillitis. Treatment consists of prolonged antibiotics and management of its complications. CONCLUSIONS: Lemierre's syndrome should be considered in any patient with unrelenting sore throat and anaerobic bacteremia. Prompt initiation of targeted antibiotics would prevent metastatic complications and thus reduce overall healthcare costs. Reference #1: Bilateral Lemierre's syndrome: a case report and literature review. Moore BA Et al. Ear Nose Throat J. 2002 Apr;81(4):234-6, 238-40, 242 passim. Reference #2: Lemierre’s syndrome: forgotten, but not absent. Bahall M, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2017-221203 Reference #3: Lemierre’s syndrome: current perspectives on diagnosis and management. Katrine M Johannesen et al. Infection and Drug Resistance 2016:9 221–227 DISCLOSURES: No relevant relationships by Nelson Agudelo Higuita, source=Web Response No relevant relationships by Maham Khan, source=Web Response No relevant relationships by Miranda McGhee, source=Web Response No relevant relationships by Aejaz Ul Haq, source=Web Response

Safety assessment of metarrestin in dogs: A clinical candidate targeting a subnuclear structure unique to metastatic cancer cells

Pancreatic cancer is a leading cause of cancer-related deaths in the U.S. Ninety percent of patients with stage IV pancreatic cancer die within one year of diagnosis due to complications of metastasis. A metastatic potential of cancer cells has been shown to be closely associated with formation of perinucleolar compartment (PNC). Metarrestin, a first-in-class PNC inhibitor, was evaluated for its toxicity, toxicokinetics, and safety pharmacology in beagle dogs following every other day oral (capsule) administration for 28 days to support its introduction into clinical trials. The study consisted of four dose groups: vehicle; 0.25, 0.75 and 1.50 mg/kg/dose. Metarrestin reached its maximum concentration in blood at 3 h (overall median Tmax) across all doses with a mean t1/2 over 168 h of 55.5 h. Dose dependent increase in systemic exposure (Cmax and AUClast) with no sex difference was observed on days 1 and 27. Metarrestin accumulated from Day 1 to Day 27 at all dose levels and in both sexes by an overall factor of about 2.34. No mortality occurred during the dosing period; however, treatment-related clinical signs of toxicity consisting of hypoactivity, shaking/shivering, thinness, irritability, salivation, abnormal gait, tremors, ataxia and intermittent seizure-like activity were seen in both sexes at mid and high dose groups. Treatment-related effects on body weight and food consumption were seen at the mid and high dose levels. Safety pharmacology study showed no treatment-related effects on blood pressure, heart rate, corrected QT, PR, RR, or QRS intervals, or respiratory function parameters (respiratory rate, tidal volume, minute volume). There were no histopathological changes observed, with the exception of transient thymic atrophy which was considered to be non-adverse. Based primarily on clinical signs of toxicity, the No Observed Adverse Effect Level (NOAEL) in dogs was considered to be 0.25 mg/kg metarrestin after every other day dosing for 28 days with a mean of male and female Cmax = 82.5 ng/mL and AUClast = 2521 h*ng/mL, on Day 27.

Management of conjunctival melanoma with local excision and adjuvant brachytherapy.

To evaluate the management of conjunctival melanoma with local excision and adjuvant brachytherapy. Data of all patients who received local excision and adjuvant brachytherapy for conjunctival melanoma between 1999 and 2016 in a Dutch national referral centre were reviewed. A protocol with Sr-90 was used until 2012, a protocol with Ru-106 was used hereafter. Local recurrence, metastasis, survival, visual acuity and treatment complications were assessed. A total of 58 patients was identified: 32 patients were treated with Sr-90 and 26 with Ru-106. Mean follow-up time was 97.3 months (143.1 months after Sr-90, and 40.2 months after Ru-106). All lesions were epibulbar, the median tumour thickness was 0.9 mm. Local recurrence occurred in 13/58 cases (22%), with a 5-year recurrence rate of 21%. Local recurrence occurred equally often in both protocols, with 5-year recurrence rates of 19% (Sr-90) versus 23% (Ru-106) (p = 0.68). Metastasis developed in 3/58 cases (5%), with 2 cases after Sr-90, and 1 after Ru-106 (p = 1.00). The most reported complications were pain (29%), dry eyes (21%), symblepharon (9%), ptosis (12%) and cataract (9%). No severe corneal or scleral complications were observed. Median visual acuity was 1.00 pre-surgery, at the end of follow-up this was 1.00(Sr-90) and 0.95 (Ru-106). Local excision with adjuvant brachytherapy provides good tumour control with excellent visual outcome and mild side effects in patients with limited conjunctival melanoma. Results after Sr-90 or Ru-106 were comparable; a choice for either treatment may be based on experience of the clinician and availability of materials.

The effectiveness of prophylactic ipsilateral central neck dissection in selected patients who underwent total thyroidectomy for clinically node-negative unilateral papillary thyroid carcinoma.

BackgroundProphylactic central neck dissection (CND) in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) remains controversial. The purpose of this study was to evaluate the benefits of prophylactic ipsilateral CND compared with bilateral CND in total thyroidectomy for cN0 unilateral PTC.MethodsWe retrospectively enrolled 174 patients who underwent total thyroidectomies with prophylactic CND for cN0 unilateral PTC between January 2009 and May 2010. The prophylactic CND patients were divided into group 1, the ipsilateral CND group (n=74), and group 2, the bilateral CND group (n=100). The incidence of central lymph node metastasis (CLNM) and postoperative complications, such as hypoparathyroidism, recurrent laryngeal nerve injury, and recurrence were assessed.ResultsCLNM was found in 22 (29.8%) in group 1 and 69 (69%) in group 2. The incidence of postoperative severe hypocalcemia less than 7.0 was also significantly different (six patients [8.1%] in group 1 and 23 [23%] in group 2; p=0.009). Permanent hypoparathyroidism was significantly more frequent in group 2 (4.1% vs. 19%; p=0.005). However, the incidence of transient hypoparathyroidism, recurrence, and recurrent laryngeal nerve injury was not significantly different.ConclusionProphylactic ipsilateral CND has advantage not only to reduce incidence of some complications but also to have similar recurrence rate compared with bilateral CND. We suggest that prophylactic ipsilateral CND may be safe and effective for selected patients undergoing total thyroidectomy for cN0 unilateral PTC.

Ex vivo interaction between blood components and hormone-dependent breast cancer cells induces alterations associated with epithelial-mesenchymal transition and thrombosis

ABSTRACT The prevalence of breast cancer is steadily increasing with metastasis and thromboembolic complications identified as the most common causes of death. The acquisition of an aggressive phenotype by hormone-dependent breast cancers is mediated by Transforming Growth Factor Beta 1 (TGF-β1) expression and is associated with epithelial-mesenchymal transition (EMT) and, potentially, increased propensity for thrombosis. We investigated this phenomenon by assessing the effect of platelet-rich plasma (PRP) and whole blood (WB) on parameters of EMT and hypercoagulation in vitro. MCF-7 breast cancer cells were cultured under standard conditions, followed by co-culture with PRP or WB. Cells were processed for real-time PCR (TGF-β1 and vimentin), electron microscopy or immunocytochemistry (TGF-β1). Micrographs were qualitatively assessed, and real-time PCR data analyzed with PAST Statistical Software. The addition of blood components heightened TGF-β1 immunolocalization and significantly increased corresponding gene expression. Both PRP and WB significantly increased vimentin expression and induced a shape change from a typical epithelial phenotype to a spindle-shape morphology, indicative of EMT. Fibrin fiber, network and plaque formation indicated a hypercoagulatory environment. The results thus show that in preparation for hematogenous metastasis, hormone-dependent breast cancer cells assume an aggressive phenotype associated with EMT, simultaneously increasing the propensity for the formation of thrombo-emboli.

Acral Lentiginous Melanoma on the Palm: Unusual Site with a Fatal Outcome

Introduction: Melanoma is more common in the western countries than among darker pigmented individuals, but acral lentiginous is the most frequently encountered subtype among Indians. Case Presentation: An Indian male presented with a progressively increasing blackish ulcerated nodule on left palm overlying a heterogeneously hyperpigmented macule present since 6 months. A diagnosis of acral lentiginous melanoma was made and a wide local excision with left axillary dissection was done. The patient missed the initial sessions of chemotherapy and succumbed three months later due to metastatic complications. Conclusions: Melanoma may present with varied morphologies which may resemble benign dermatoses at initial presentation causing a delay in diagnosis. Occurrence of acral lentiginous melanoma on the palm is unusual and may go unnoticed due to its innocuous appearance. The survival rates drop drastically as the tumor metastasizes. Thus, a high index of suspicion is warranted to make a timely diagnosis in an attempt to improve patient outcome.