Metastatic and Malignant Phyllodes Tumors of the Breast: An Update for Current Management.

Metastatic, malignant phyllodes tumor (PT) of the breast is a rare and aggressive neoplasm. Currently, there is no agreed upon consensus as to best management practices. A systematic review of literature was conducted investigating surgical, chemotherapeutic, and radiotherapeutic management for metastatic PT. Databases employed to identify articles included Embase, PubMed, and SAGE Journals. Diagnosis of metastatic PT has been of significant difficulty to radiologists as it is often confused with fibroadenomas. Surgically, metastatectomy has been correlated with increased overall survival (of 25.9 versus 9.9 months; P = .01). Radiotherapy has often been associated with palliation and pain control in metastatic, malignant neoplasia. However, one study showed that in malignant PT, radiation was associated with significantly lower rates of local recurrence (OR: 0.048 versus 0.209). Anthracycline containing chemotherapy regimens has been associated with improved overall survival (22.4 months versus 13.2 months; P = .040). Further research must be conducted into this rare malignancy to elucidate accurate diagnosis and care for patients with advanced metastatic or malignant phyllodes tumors.

Small Cell Carcinoma of the Rectum-An Unexpected Diagnosis: Current Treatment Options for a Rare and Aggressive Entity.

Rectal small cell carcinoma is a rare and aggressive cancer subtype for which a consensus of optimal treatment has not yet been reached. This cancer presents a difficult surgical problem, and thus, the mainstay of treatment tends to mirror that of small cell carcinoma of the lung (chemotherapy, radiation therapy, and immune modulators). This brief report highlights current treatment options available for this rare and difficult entity. There is a significant need for large-center clinical trials and prospective studies to help determine the best treatment regimen to effectively care for patients with small cell carcinoma of the rectum.

Novel treatment strategy of targeting epigenetic dysregulation in pancreatic neuroendocrine tumors.

BACKGROUND: Epigenetic dysregulation is an integral step in the progression of pancreatic neuroendocrine tumors. We hypothesized that tumor suppressor repression by DNA methyltransferase 1 in pancreatic neuroendocrine tumors could be targeted with epigenetic treatment. METHODS: Resected pancreatic neuroendocrine tumors from 32 patients were stained for DNA methyltransferase 1 and scored. Human (BON1) and murine (STC) pancreatic neuroendocrine tumor cells were treated with DNA methyltransferase 1 inhibitor 5-azacytidine and chemotherapeutic agents 5-fluorouracil and temozolomide. Cell proliferation assay and tumor suppressor gene analysis were performed with qRT-PCR and Clarion S microarray. Tumor measurements were compared in a murine treatment model. RESULTS: High DNA methyltransferase scores were associated with high Ki-67 (6.7% vs 70.6% P < .01), mitotic rate (0.0% vs 31.3%), and grade (20.0% vs 80.4%, P < .01). Treatment with 5-azacytidine and chemotherapy resulted in a reduction of cell proliferation compared to chemotherapy alone in BON1 (77.3% vs 53.1%, P < .001) and STC (73.4% vs 34.2%, P < .001). Treatment with 5-azacytidine and chemotherapy resulted in upregulation of tumor suppressors CDKN1A (7.6 rel. fold, P < .001), BRCA2 (4.3 rel. fold, P < .001), and CDH1 (6.0 rel. fold, P = .026) in BON1 and CDKN1a (14.5 rel. fold, P < .001) and CDH (17.5 rel. fold, P < .001) in STC. In microarray, 5-azacytidine drove global genetic changes in combination treatment. In vivo tumors treated with chemotherapy measured 88.6 ± 19.54 mm3 vs 52.89 ± 10.51 mm3 in those treated with combination therapy (P = .009). CONCLUSION: Epigenetic dysregulation with DNA methyltransferase 1 is associated with pancreatic neuroendocrine tumors and is a potential targetable strategy. 5-azacytidine and chemotherapy in combination can reduce cell proliferation, upregulate silenced tumor suppressor genes, and decrease in vivo tumors in pancreatic neuroendocrine tumors.

Trauma Incidence During the New Jersey COVID-19 Stay-At-Home Order: A Multicenter Study.

INTRODUCTION: Given the early surge of COVID-19 in New Jersey (NJ), a statewide executive order (EO) to stay-at-home was instituted on March 22, 2020. We hypothesized that the EO would result in a decreased number of trauma admissions, length of stay, and resources utilized in trauma patients at NJ trauma centers. METHODS: In an institutional review board-approved, retrospective, multicenter study, trauma registries at three level one trauma centers in NJ were queried from March 22 to June 14 in 2020 and compared to the same timeframe the year prior. Epidemiological and clinical data were obtained including demographics, select preexisting conditions, mechanism of injury, injury severity score, resources utilized, and outcomes. RESULTS: 1859 trauma patients were evaluated during the EO versus 2201 the year prior. During the EO, trauma patients were less likely to be transferred from another hospital (21% versus 29% P < 0.05), more likely to have a penetrating mechanism (16% versus 12% P < 0.05), were equally likely to require a procedure (P = 0.44) and had similar injury severity score (5 [interquartile range [IQR] 1-9] versus 5 [IQR 1-9], P = 0.73). There was no significant difference in ventilator days (0 [IQR 0-1] versus 0 [IQR 0-2] P = 0.08), intensive care unit days (2 [IQR 0-4] versus 2 [IQR 0-3] P = 0.99), or length of stay (2 [IQR 1-5] versus 2 [IQR 1-6] P = 0.73). Patients were more likely to be sent home than to rehabilitation or long-term acute care hospital during the EO (81% versus 78%, P = 0.02). CONCLUSIONS: The 2020 COVID-19 EO was associated with a significantly different epidemiology with a higher rate of penetrating injury during the EO, and similar volume of injured patients evaluated.

Gastric Neuroendocrine Tumor Treatment and Survival Outcome Depends on Facility Type.

BACKGROUND: Gastric neuroendocrine tumors (gNETs) are rare cancers for which surgery may improve survival. We aim to determine if facility type affects treatment and survival outcomes. METHODS: The NCDB was queried for patients with gNET from 2004-2016 and stratified into Academic/Research Program (ARP), Community Cancer Program (CCP), Comprehensive Community Cancer Program (CCCP), or Integrated Network Cancer Program (INCP). Overall survival along with clinical and demographic features was compared. RESULTS: Median survival was improved in patients treated at an academic program: 137.3 months versus 88.0, 96.3, and 100.2 for CCP, CCCP, INCP, respectively (P < .0001). Patients treated at academic centers were more likely to have surgery (64.2% vs 59.1%, 57.5%, 51.4%, P < .0001). After propensity matching for age, race, grade, stage, insurance status, and comorbidity score, survival benefit from treatment at an academic center remained (P = .03), particularly for patients undergoing surgery (P < .0001) and chemotherapy (P = .04). CONCLUSION: Patients with gNET treated at an academic hospital had improved median survival after propensity matching and may benefit from treatment at academic rather than community medical centers.

Tyrosine kinase inhibitors versus radiation therapy in unresectable dermatofibrosarcoma protuberans (DFSP): A narrative systematic review.

BACKGROUND: In unresectable dermatofibrosarcoma protuberans (DFSP), no clear guideline exists regarding the use of tyrosine kinase inhibitors (TKI) versus radiotherapy. This study reviews current literature regarding TKI and radiotherapy in unresectable DFSP. METHODS: Following PROSPERO registration (CRD42021232508), a systematic literature search was performed including all studies reporting clinical results of TKI and/or radiotherapy in the treatment of unresectable DFSP. A narrative synthesis was used to compare patient characteristics, outcomes, and adverse effects. RESULTS: Of 1345 screened studies, 14 were included for review. Patient age ranged 18-77 years and 55% were male. Radiotherapy patients exhibited lower grade disease than TKI patients. Overall clinical benefit following TKI ranged from 70% to 96%. Radiotherapy patients exhibited control or resolution on last follow-up in 90% of cases. Radiotherapy adverse effects were mild, while TKI adverse effects were more severe and managed with dose reduction. CONCLUSION: TKI may be employed in unresectable DFSP of all histology types whereas radiation alone may be limited to low-grade and classic-type DFSP. TKI may cause more severe adverse effects compared to radiation alone.

Treatment of Abdominal Aortic Aneurysm Utilizing Adipose-Derived Mesenchymal Stem Cells in a Porcine Model.

INTRODUCTION: The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation. MATERIALS AND METHODS: Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 106 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann-Whitney U-tests. RESULTS: All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P < 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 µm versus 643.55 IQR 560.91-733.88 µm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals. CONCLUSIONS: Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.

Hyperamylasemia grade versus drain fluid amylase: which better predicts pancreatectomy outcomes?

BACKGROUND: The clinical importance of postoperative hyperamylasemia (POHA) grade is unknown. Our objectives were to evaluate the association of POHA grade with clinically relevant postoperative pancreatic fistula (CR-POPF) and compare its prognostic utility against postoperative day 1 drain fluid amylase (DFA-1). METHODS: Patients who underwent pancreatectomy from January 2019 through March 2020 were identified in the ACS NSQIP pancreatectomy-targeted dataset. POHA grade was assigned using post-operative serum amylase and clinical sequelae. The primary outcome was CR-POPF within 30 days. The association of POHA grade with CR-POPF was assessed using multivariable logistic regression, and c-statistics were used to compare POHA grade versus DFA-1. RESULTS: POHA occurred in 520 patients at 98 hospitals, including 261 (50.2%) with grade A, 234 (45.0%) with grade B, and 25 (4.8%) with grade C POHA. CR-POPFs were increased among patients with grade B (66.2%, OR 9.28 [5.84-14.73]) and C (68.0%, OR 10.50 [3.77-29.26]) versus grade A POHA (19.2%). POHA-inclusive models better predicted CR-POPF than those with DFA-1 alone (p < 0.002) and models with both predictors outperformed POHA alone (p = 0.039). CONCLUSION: POHA grade represents a measure of post-pancreatectomy outcomes that predicts CR-POPF and outperforms DFA-1 but must be aligned with new international definitions.

What to do When Decompressive Gastrostomies and Jejunostomies are not Options? A Scoping Review of Transesophageal Gastrostomy Tubes for Advanced Malignancies.

BACKGROUND: In advanced malignant bowel obstruction, decompressive gastrostomy tubes (GTs) may not be feasible due to ascites, peritoneal carcinomatosis, and altered gastric anatomy. Whereas nasogastric tubes (NGTs) allow temporary decompression, percutaneous transesophageal gastrostomy tubes (PTEGs) are an alternative method for long-term palliative decompression. This study performed a scoping review to determine outcomes with PTEG in advanced malignancies. METHODS: A systematic literature search was performed to include all studies that reported the clinical results of PTEGs for malignancy. No language, national, or publication status restrictions were used. RESULTS: The analysis included 14 relevant studies with a total of 340 patients. In 11 studies, standard PTEGs were inserted with a rupture-free balloon's placement into the mouth or nose and esophageal puncture under fluoroscopy or ultrasound, followed by a guidewire into the stomach with placement of a single-lumen tube. Of 340 patients, 65 (19.1%) had minor complications, and 5 (2.1%) had significant complications, including bleeding and severe aspiration pneumonia. Of 171 patients, 169 with PTEGs (98.8%) reported relief of nasal discomfort from NGT and alleviation of obstructive symptoms. The one randomized controlled trial reported a significantly higher quality of life with PTEGs than with NGTs. CONCLUSIONS: When decompression for advanced malignancy is technically not feasible with a gastrostomy tube, the PTEG is a viable, safe option for palliation. The PTEG is associated with lower significant complication rates than the gastrostomy tube and significantly higher patient-derived outcomes than the NGT.

Effects of radiation and chemotherapy on adipose stem cells: Implications for use in fat grafting in cancer patients.

Autologous fat transplantation is a versatile tool in reconstructive surgery. Adipose-derived stem cells (ASCs) increase survival of fat grafts and thus are increasingly used for breast reconstruction in breast cancer patients. However, radiation and/or chemotherapy have been proposed to inhibit soft tissue regeneration in wound healing thus suggesting alteration in stem cell pathways. Therefore, elucidating effects of radiation and chemotherapy on ASCs is critical if one desires to enhance the survival of fat grafts in patients. This review outlines our work evaluating the function and recoverability of ASCs from radiation or chemotherapy patients, focusing specifically on their availability as a source of autologous stem cells for fat grafting and breast reconstruction in cancer patients. Even though evidence suggests radiation and chemotherapy negatively influence ASCs at the cellular level, the efficiency of the isolation and differentiation capacity did not appear influenced in patients after receiving chemotherapy treatment, although fat from radiated patients exhibited significantly altered ASC differentiation into endothelial-like cells. Further, the in vitro growth rates of patient's ASCs do not differ significantly before or after treatment. Taken together, these studies suggest ASCs as an important new tool for grafting and reconstruction even when radiation and chemotherapy treatment are involved.

Simple Versus Radical Resection for Duodenal Adenocarcinoma: A Propensity Score Matched Analysis of National Cancer Database.

BACKGROUND: Duodenal adenocarcinoma treatment consists of either simple or radical surgical resection. Existing evidence suggests similar survival outcomes between the two but is limited by small numbers and single-institution analysis. We aim to compare survival after partial versus radical resection for duodenal adenocarcinoma using the National Cancer Database (NCDB). METHODS: Using NCDB results from 2004 to 2014, we compared patients with duodenal adenocarcinoma undergoing partial resection (n = 1247) and radical resection (n = 1240) by age, sex, facility type, facility location, cancer stage, cancer grade, lymph node sampling, node status, tumor size, margin status, neoadjuvant therapy, and adjuvant therapy using chi-square analysis. Survival was compared using propensity matching. RESULTS: Patients undergoing partial resection had overall earlier cancer stage, more favorable tumor grade, and were less likely to undergo lymph node sampling and neoadjuvant therapy. When overall survival was compared between the 2 propensity-matched groups, the median survival was 46.7 months after partial resection and 43.2 months after radical resection (P = .329), and overall survival was similar between the 2 groups (P = .894). The use of adjuvant therapy demonstrated improved survival over either surgery alone (P < .0001, P = .0037). CONCLUSION: Partial resection did not demonstrate worse survival outcomes than radical resection for duodenal adenocarcinoma. The use of adjuvant therapy in addition to surgery demonstrated improved survival regardless of surgery type and played a larger role in survival than the type of surgery. Our findings provide evidence to support the continued use of both partial and radical surgical resections to treat duodenal malignancy.

Role of metastasectomy for liver metastasis in stage IV anal cancer.

INTRODUCTION: There is a paucity of data on the role of metastasectomy for metastatic anal cancer on survival outcomes. We aim to define the role of metastasectomy in stage IV anal cancer. METHODS: National Cancer Database (NCDB) from 2004 to 2014 was accessed to include patients with metastatic anal cancer, excluding adenocarcinoma, neuroendocrine, and 'other' histologies. We compared patients undergoing metastasectomy (n = 165) to those who did not have metastasectomy (n = 2093) by age, sex, cancer grade, and site of metastasis, including metastasis to bone, liver, and lung, using chi-square analysis. The primary outcome was overall survival. RESULTS: Patients had equal distribution of metastatic sites between those who underwent metastasectomy versus no metastasectomy: bone (7.64% vs 4.85%, p = 0.22), brain (0.24% vs 0%, p = 1.0), liver (23.22% vs 29.70%, p = 0.07), and lung (11.85% vs 9.09%, p = 0.38). Survival following metastasectomy was increased at one year (71% vs. 61%, p = 0.016), two years (50% vs. 38%, p = 0.014), and five years (30% vs. 19%, p = 0.025). Median overall survival was increased (23 months vs. 16 months; p = 0.015) for patients with metastasectomy. Survival increases were demonstrated only in the group with liver metastasis undergoing metastasectomy. When stratifying for liver metastases only, median overall survival time was further increased (34 months vs. 16 months; p < 0.0001) following metastasectomy. CONCLUSION: These results demonstrate a survival benefit for hepatic metastasectomy in stage IV anal cancer. Our findings demonstrate a potential survival benefit in highly select patients with metastatic anal cancer to the liver. These findings support further investigation in a randomized clinical trial to delineate these findings.

Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment Strategies for an Incurable Disease.

INTRODUCTION: Recurrence of gastrointestinal stromal tumors (GISTs) after surgical resection and imatinib mesylate (IM) adjuvant therapy poses a significant treatment challenge. We present the case of a patient who underwent surgical resection after recurrence and review the current literature regarding treatment. CASE PRESENTATION: A 58-year-old man with a large intra-abdominal jejunal GIST was treated with complete surgical resection followed by IM. The patient experienced disease recurrence 3.5 years later and underwent IM dose escalation and reresection. CONCLUSION: Current strategies to treat recurrent GIST include dose escalation, modifying adjuvant tyrosine kinase inhibitor therapy, and surgery. High-level evidence will be required to better define the combinatory roles of tyrosine kinase inhibitor therapy, guided by molecular profiling, and surgery in the management of recurrent GIST.

Baseline predictors of efavirenz-containing antiretroviral regimen adverse experiences.

PURPOSE: We aimed to identify modifiable, routinely available patient characteristics associated with adverse experiences potentially attributable to efavirenz-based regimens in patients in Botswana. METHODS: HIV-infected treatment naïve individuals starting a standard antiretroviral regimen including two nucleoside analog reverse transcriptase inhibitors and efavirenz in Botswana were enrolled in a prospective cohort. Adverse experiences were measured at 1 and 6 months using the efavirenz checklist, a 35-item instrument developed by the AIDS Clinical Trials Group. RESULTS: We enrolled 232 patients from 11 March 2010 to 17 March 2011. One hundred ninety-six were included in the month 1 analyses. Of the 196 included in the month 1 analyses, 157 (80%) completed the 6-month follow-up. Median efavirenz checklist score was 6 (interquartile range (IQR): 2-15) at month 1 and 1 (IQR: 0-5) at month 6. The median change in efavirenz checklist score from month 1-6 was -4 (IQR: -11 to -1), representing an improvement. Depressive symptoms, low CD4 count and less alcohol use were associated with improvement in adverse experiences over time. Low weight was associated with increased extent of adverse experiences at month 1 and 6. There was no confounding or effect modification. CONCLUSIONS: Clinicians may want to consider more intensive and tailored adverse experience education and management in patients based on depressive symptoms, CD4 count, and weight. Further assessment of the mechanism of the effect of alcohol use on adverse experiences, including analysis of CYP2B6 genotype and plasma efavirenz concentrations, is warranted.