New perspectives on robotic pancreaticoduodenectomy: An analysis of the National Cancer Database.

BACKGROUND: Pancreatic ductal adenocarcinoma is a common malignancy. Despite all advancements, the prognosis remains, poor with an overall 5-year survival of only 10.8%. Recently, a robotic platform has become an attractive tool for treating pancreatic cancer (PC). While recent studies indicated improved lymph node (LN) harvest during robotic pancreaticoduodenectomy (PD), data on long-term outcomes are insufficient. AIM: To evaluate absolute LN harvest during PD. Secondary outcomes included evaluating the association between LN harvest and short- and long-term oncological outcomes for three different surgical approaches. METHODS: We conducted an analysis of the National Cancer Database, including patients diagnosed with PC who underwent open, laparoscopic, or robotic PD in 2010-2018. One-way analysis of variance was used to compare continuous variables, chi-square test - for categorical. Overall survival was defined as the time between surgery and death. Median survival time was estimated with the Kaplan-Meier method, and groups were compared with the Wilcoxon test. A Cox proportional hazards model was used to assess the association of covariates with survival after controlling for patient characteristics and procedure type. RESULTS: 17169 patients were included, 8859 (52%) males; mean age 65; 14509 (85%) white. 13816 (80.5%) patients had an open PD, 2677 (15.6%) and 676 (3.9%) - laparoscopic and robotic PD respectively. Mean comorbidity index (Charlson-Deyo Score) 0.50. On average, 18.84 LNs were harvested. Mean LN harvest during open, laparoscopic and robotic PD was 18.59, 19.65 and 20.70 respectively (P < 0.001). On average 2.49 LNs were positive for cancer and did not differ by the procedure type (P = 0.26). Vascular invasion was noted in 42.6% of LNs and did differ by the approach: 42.1% for open, 44.0% for laparoscopic and 47.2% for robotic PD (P = 0.015). Median survival for open PD was 26.1 mo, laparoscopic - 27.2 mo, robotic - 29.1 mo (P = 0.064). Survival was associated with higher LN harvest, while higher number of positive LNs was associated with higher mortality. CONCLUSION: Our study suggests that robotic PD is associated with increased intraoperative LN harvest and has comparable short-term oncological outcomes and survival compared to open and laparoscopic approaches.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

Assessing the effect of human dental pulp mesenchymal stem cell secretome on human oral, breast, and melanoma cancer cell lines.

BACKGROUND: The secretome of the dental pulp mesenchymal stem cells (DPMSCS-S) have an array of regenerative potential and could aid in the rehabilitation of cancer patients post-therapeutic interventions, although caution is required as DPMSC-S have shown to augment prostate cancer cells. Thus, it is vital to assess if these pro-carcinogenic effects extend to other cancer types. OBJECTIVE: To assess if DPMSC-S has any pro-carcinogenic effect on oral cancer, breast cancer, and melanoma cell lines. MATERIALS AND METHODS: Conditioned media obtained from the isolated and characterized DPMSC (DPMSC-CM) were profiled using bead-based multiplex assay. AW13515 (oral cancer), MDA-MB-231 (breast cancer), and A-375 (melanoma) cell lines were exposed to 20%, 50%, and 100% DPMSC-CM for 24, 48, and 72 h. DPMSC-CM effect on the cancer cell properties and secretome were assessed. RESULTS: DPMSC-CM augmented invasion, adhesion, multi-drug resistance, DNA repair, and mitochondrial repair in AW13516 through upregulation of growth factors Ang-2, EGF, M-CSF, PDGF-AA, PDGF-BB, pro-inflammatory cytokines TNF-α, IL-2, downregulation of anti-inflammatory cytokine TGF-ß1, and pro-inflammatory cytokine IL-4. In MDA-MB-231, invasion, and multi-drug resistance were augmented through upregulation of growth factors EGF, EPO, G-CSF, HGF, M-CSF, PDGF-AA, and pro-inflammatory cytokine TNF-α, CXCL10, IL-12p70. EMT, invasion, migration, and adhesion were augmented in A-375 through upregulation of growth factors Ang-2, EGF, PDGF-BB, TGF-α, pro-inflammatory cytokines TNF-α, and IL-17A. CONCLUSION: DPMSC-CM can augment the carcinogenic properties of oral cancer, breast cancer, and melanoma cells, further animal model studies are required to validate our in-vitro findings.

Transgender surgery - Knowledge gap among physicians impacting patient care.

Transgender surgeries are increasingly performed across the globe and in the United States. Although comprehensive centers exist, which are well equipped to cater and tailor to the needs of this population subset, quite often their resultant complications are handled at a different institution owing to the acuity of the condition. However, interestingly the psychosocial needs, medical pathophysiology, available surgical procedures, and their resultant complications are still not a part of the regular medical curriculum. This translates into inadequate care when physicians from vast majority of institutions that do not routinely perform transgender surgery encounter these patients with complications from gender-affirming surgeries. We present a case of a patient who underwent complex multiple gender-affirming surgeries, presenting to our emergency department with an acute abdomen; this resulted in a diagnostic and management dilemma and review of brief pertinent literature. We recommend that transgender medicine and its basics needs should be exposed to currently practicing physicians by continuing medical education, trainees and medical students alike via incorporation into their curriculum, to decrease health disparities among the lesbian, gay, bisexual, transgender, and queer community.

Preoperative versus intraoperative diagnosis of hiatal hernia in bariatric population.

BACKGROUND: Hiatal hernia is frequently encountered intraoperatively during bariatric surgery. There is scarce research pertaining to the diagnostic accuracy of a preoperative diagnostic modality in comparison to intraoperative diagnosis, along with patient characteristics and related factors contributing to hiatal hernia. OBJECTIVE: To identify the prevalence and associations of hiatal hernia in the bariatric patient population, we compared the diagnostic accuracy of upper gastrointestinal series and esophagogastroduodenoscopy with the intraoperative findings across various patient characteristics. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, Teaching Hospital, New York, USA. METHODS: Retrospective study of patients from 2015 to 2018 who met National Institutes of Health criteria for bariatric surgery. RESULTS: There were 1094 patients included (135 males, 959 females), with an age range of 18 to 74 years. The diagnostic accuracy was determined by a sensitivity of 64.71% (95% confidence interval [CI] .55-.70), specificity of 74.38% (95% CI .71-.70), positive predictive value of 29.86% (95% CI .24-.30), negative predictive value of 92.59% (95%CI .89-90), likelihood ratio of 2.526, and P value < .0001 for esophagogastroduodenoscopy; a sensitivity of 14.02% (95% CI .08-0), specificity of 98.23% (95% CI .96-.90), positive predictive value of 71.43% (95% CI .50-.80), negative predictive value of 78.35% (95% CI .74-.80), likelihood ratio 7.921, and P value < .0001 were used for upper gastrointestinal series. Hiatal hernia with age <60 years was 17.09% versus 48.44% at >60 years (P < .0001). Hiatal hernia incidence was 17% in Hispanics, 22.5% in Caucasians, and 23.10% in blacks. CONCLUSION: The prevalence of hiatal hernia is 18.92%. There is strong association between hiatal hernia and age and ethnicity and no association based on sex and body mass index. The diagnostic accuracy of upper gastrointestinal series is very low compared with that of esophagogastroduodenoscopy for hiatal hernia. Preoperative diagnosis of hiatal hernia in the bariatric population is not required based on our study. Not only does it lessen the economic burden, patient wait time, and discomfort of an additional study, but preoperative diagnosis does not change, alter, or aid in the intraoperative management of hiatal hernia considering the suboptimal accuracy of preoperative diagnostics, thus deeming them unwarranted.

Omental Infarction with Acute Appendicitis in an Overweight Young Female: A Rare Presentation.

Omental infarction is an uncommon cause of acute abdomen but one that clinically mimics more serious and common causes of acute abdomen like appendicitis and cholecystitis. Historically, it was diagnosed only intraoperatively during surgery for presumed appendicitis or other causes of acute abdomen. But with the increase in the use of imaging, especially abdominal computed tomography (CT) scan in the work-up for acute abdomen, more cases of omental infarction are being diagnosed preoperatively. This has also led to the observation that omental infarction is a self-limiting condition which can be managed conservatively. Currently, conservative management and surgery are the only treatment options for omental infarction with no consensus as to the best treatment modality. Having a patient with both acute appendicitis and omental infarction simultaneously is extremely rare with only two reported cases in the literature thus far. Here, we present a 10-year-old obese female who presented to our hospital with acute abdomen and was found to have acute appendicitis and omental infarction. The patient underwent laparoscopic appendectomy and resection of the infarcted omentum and had uneventful recovery and was discharged on the second postoperative day. In this report, we present a review of current literature on omental infarction and highlight the importance of imaging especially abdominal CT scan in the nonoperative diagnosis and treatment of omental infarction.

Incidental Finding of Urethral Diverticulum in a Woman with History of Recurrent Urinary Tract Infections.

We present an incidental finding and management of a urethral diverticulum containing mixed composition of struvite and ammonium urate stones. Status post sleeve gastrectomy, patient presented to our bariatric clinic with epigastric pain associated with nausea and vomiting. A computed tomography scan was performed to rule out any complications of the procedure in which urethral stones were reported contained within a diverticulum. This finding, in retrospect, correlated with patient's past history of recurrent urinary tract infections. Over all, urethral diverticulum with struvite stones is a rare entity with few reported cases in literature thus a high index of suspicion is needed in patients with related symptoms. Here a case presentation and treatment rationale are described along with a brief review of existing literature.

ReShape Intragastric Balloon Complicated by Gastric Perforation and Peritonitis.

BACKGROUND: Obesity is a growing global epidemic with tremendous financial burden and health care costs worldwide. Restrictive surgery has emerged as the definitive treatment option to combat morbid obesity and its associated comorbidities. The advent of endoscopy has new grounds in obesity with the introduction of inflatable balloon placed in the stomach that decreases satiety by volume restriction. MATERIALS AND METHODS: We report a first case of gastric perforation with peritonitis after ReShape intragastric balloon placement that needed emergent surgical intervention. Decision was made to proceed with exploratory laparotomy, device deflation, and removal with subsequent gastric defect repair. RESULTS: Postoperative period was uneventful, drain was removed on postoperative day 2, and patient tolerated diet and was discharged home subsequently. Biopsy of the perforation site demonstrated mild non-specific chronic gastritis. CONCLUSION: In the modern era of minimal invasiveness, any new approach would roar popularity among patients and hence is of utmost importance for clinicians to be constantly educated on scientific research and innovations in their field.

Retroperitoneal Pseudoaneurysm Mimicking Ureteral Calculus: Pitfalls in Diagnosis.

Arterial aneurysms (AA) can be classified as true aneurysms, characterized by the persistence of all three layers of the arterial wall with progressive dilation and wall thinning; arterial pseudoaneurysms (APAs) are characterized by a tear in the vessel wall and a periarterial hematoma formation. They could occur due to a visceral, retroperitoneal, or peripheral origin. Most AA/APA are usually found incidentally, and it is imperative to be vigilant in order to diagnose and manage them due to their potentially life-threatening complications. We present a case of a 35-year-old woman presenting with right-sided abdominal pain mimicking renal colic with an initial misdiagnosis of ureteral calculus. Post-cystoscopy, a misdiagnosis was confirmed, and subsequently, the patient had a right retroperitoneal mass excision. The histopathology report concluded the calcified retroperitoneal mass to be pseudoaneurysm. Such pitfalls in diagnosis are essential to be shared with the larger medical community for increased vigilance and optimal management of pseudoaneurysms.

Acute Pancreatitis with Splenic Infarction as Early Postoperative Complication following Laparoscopic Sleeve Gastrectomy.

Obesity is becoming a global health burden along with its comorbidities. It imposes tremendous financial burden and health costs worldwide. Surgery has emerged as the definitive treatment option for morbidly obese patients with comorbidities. Laparoscopic sleeve gastrectomy is performed now more than ever making it imperative for physicians and surgeons to recognize both the common and the uncommon risks and complications associated with it. In this report we describe a rare early life-threatening postoperative complication following laparoscopic sleeve gastrectomy. From our extensive review of literature, there is no existing report of acute pancreatitis with splenic infarction postsleeve gastrectomy to this date.

Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance.

The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA). Dectin 1 ligation accelerated the progression of PDA in mice, whereas deletion of Clec7a-the gene encoding dectin 1-or blockade of dectin 1 downstream signaling was protective. We found that dectin 1 can ligate the lectin galectin 9 in mouse and human PDA, which results in tolerogenic macrophage programming and adaptive immune suppression. Upon disruption of the dectin 1-galectin 9 axis, CD4+ and CD8+ T cells, which are dispensable for PDA progression in hosts with an intact signaling axis, become reprogrammed into indispensable mediators of anti-tumor immunity. These data suggest that targeting dectin 1 signaling is an attractive strategy for developing an immunotherapy for PDA.

NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4+ T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8+ T cell activation. The suppressive effects of NLRP3 signaling were IL-10 dependent. Pharmacological inhibition or deletion of NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD complex), or caspase-1 protected against PDA and was associated with immunogenic reprogramming of innate and adaptive immunity within the TME. Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA.

Case Report of Ectopic Liver on Gallbladder Serosa with a Brief Review of the Literature.

This case describes an intraoperative incidental finding and surgical removal of ectopic liver tissue attached to the gallbladder during a standard laparoscopic cholecystectomy for acute cholecystitis. These anomalies are rare, with interesting associations and possible clinically relevant complications. The details of the case, along with a brief literature review of embryology, common ectopic sites, and associations/complications, are presented in this paper. Since laparoscopic cholecystectomy is a very common procedure, it is important to increase vigilance of ectopic liver tissues during surgeries to minimize complications and provide optimal management.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. METHODS: We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. RESULTS: Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. CONCLUSIONS: Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses. MCSF blockade negates this effect, allowing radiation to have increased efficacy in slowing tumor growth.

Minimally invasive surgical technique integrating multiple procedures with large specimen extraction via inguinal hernia orifice.

While laparoscopic surgery can be performed using small skin incisions, any resected specimen must still be able to fit through these opening. For procedures, such as cholecystectomies and appendectomies, this is not usually a problem; however, for large specimens such as bowel or large tumors, this becomes problematic. Currently, the standard technique is to attempt piecemeal removal of the specimen or enlarge one of the laparoscopic incisions, effectively creating a mini laparotomy. Creating a larger incision adds many of the drawbacks of open laparotomy and should be avoided whenever possible. In this article, we present a new technique of combining the repair of an inguinal hernia, umbilical hernia with a duodenal tumor resection in order to extract the specimen through the inguinal hernia orifice.

A Rare Case of Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical condition with only about 100 cases reported in the literature. It is characterized by primary hyperplasia of pulmonary neuroendocrine cells (PNECs) which are specialized epithelial cells located throughout the entire respiratory tract, from the trachea to the terminal airways. DIPNECH appears in various forms that include diffuse proliferation of scattered neuroendocrine cells, small nodules, or a linear proliferation. It is usually seen in middle-aged, nonsmoking women with symptoms of cough, dyspnea, and wheezing. We present a 45-year-old, nonsmoking woman who presented with symptoms of DIPNECH associated with bilateral pulmonary nodules and left hilar adenopathy. Of interest, DIPNECH in our patient was associated with metastatic pulmonary carcinoids, papillary carcinoma of the left breast, oncocytoma and angiomyolipoma of her left kidney, and cortical nodules suggestive of tuberous sclerosis. She had video assisted thoracoscopic surgery (VATS), modified radical mastectomy with reconstruction, and radical nephrectomy. She is currently symptom-free most of the time with over two years of follow-up.

Surgical resection of a giant primary liposarcoma of the anterior mediastinum.

This case describes the incidental finding and surgical removal of an 1.8-kg liposarcoma in the anterior mediastinum. These tumors are very rare and would normally present with symptoms of intrathoracic compression; however, this patient was completely asymptomatic. The case presentation and treatment rationale are described along with a brief review of existing literature.