Search

Major depressive disorder (MDD) is a common and severe psychiatric disease, which does not only lead to variety of neuropsychiatric symptoms, but unfortunately in a relatively large proportion of cases also to suicide. The pathogenesis of MDD still requires definition. We have previously shown that ceramide is increased in the blood plasma of patients with MDD. In mouse models of MDD, which are induced by treatment with corticosterone or application of chronic unpredictable stress, increased blood plasma ceramide also increased and caused an inhibition of phospholipase D in endothelial cells of the hippocampus and reduced phosphatidic acid levels in the hippocampus. Here, we demonstrated that corticosterone treatment of PC12 cells resulted in reduced cellular autophagy, which is corrected by treatment with phosphatidic acid. In vivo, treatment of mice with corticosterone or chronic unpredictable stress also reduced autophagy in hippocampus neurons. Autophagy was normalized upon i.v. injection of phosphatidic acid in these mouse models of MDD. In an attempt to identify targets of phosphatidic acid in neurons, we demonstrated that corticosterone reduced levels of the ganglioside GM1 in PC-12 cells and the hippocampus of mice, which were normalized by treatment of cells or i.v. injection of mice with phosphatidic acid. GM1 application also normalized autophagy in cultured neurons. Phosphatidic acid and GM1 corrected stress-induced alterations in behavior, i.e., mainly anxiety and anhedonia, in experimental MDD in mice. Our data suggest that phosphatidic acid may regulate via GM1 autophagy in neurons. [ABSTRACT FROM AUTHOR]

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer. Key messages: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine. Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization. Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase. Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. Patients and Methods: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1–49) or high (50–100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). Results: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13–4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61–3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01–1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01–6.53; P < 0.0001) were associated with worse OS. Conclusions: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies. [ABSTRACT FROM AUTHOR]

Background: The AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival. Methods: A 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS. Results: Among 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only. Conclusions: AJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PDAC) is one of the most common cancers worldwide. Unfortunately, the prognosis of PDAC is rather poor, and for instance, in the USA, over 47,000 people die because of pancreatic cancer annually. Here, we demonstrate that high expression of acid sphingomyelinase in PDAC strongly correlates with long-term survival of patients, as revealed by the analysis of two independent data sources. The positive effects of acid sphingomyelinase expression on long-term survival of PDAC patients were independent of patient demographics as well as tumor grade, lymph node involvement, perineural invasion, tumor stage, lymphovascular invasion, and adjuvant therapy. We also demonstrate that genetic deficiency or pharmacological inhibition of the acid sphingomyelinase promotes tumor growth in an orthotopic mouse model of PDAC. This is mirrored by a poorer pathologic response, as defined by the College of American Pathologists (CAP) score for pancreatic cancer, to neoadjuvant therapy of patients co-treated with functional inhibitors of the acid sphingomyelinase, in particular tricyclic antidepressants and selective serotonin reuptake inhibitors, in a retrospective analysis. Our data indicate expression of the acid sphingomyelinase in PDAC as a prognostic marker for tumor progression. They further suggest that the use of functional inhibitors of the acid sphingomyelinase, at least of tricyclic antidepressants and selective serotonin reuptake inhibitors in patients with PDAC, is contra-indicated. Finally, our data also suggest a potential novel treatment of PDAC patients with recombinant acid sphingomyelinase. Key messages: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. Expression of acid sphingomyelinase (ASM) determines outcome of PDAC. Genetic deficiency or pharmacologic inhibition of ASM promotes tumor growth in a mouse model. Inhibition of ASM during neoadjuvant treatment for PDAC correlates with worse pathology. ASM expression is a prognostic marker and potential target in PDAC. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. Methods: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. Results: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. Conclusions: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting. [ABSTRACT FROM AUTHOR]

Introduction: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. Patients and Methods: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan–Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. Results: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. Conclusion: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies. [ABSTRACT FROM AUTHOR]

Background: Major pathologic response (MPR) following neoadjuvant therapy (NAT) in pancreatic ductal adenocarcinoma (PDAC) patients undergoing resection is associated with improved survival. We sought to determine whether racial disparities exist in MPR rates following NAT in patients with PDAC undergoing resection. Methods: Patients with potentially operable PDAC receiving at least 2 cycles of neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ± radiation followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Self-reported race was dichotomized as Black and non-Black, and multivariable models evaluated the association between race and MPR (i.e., pathologic complete response [pCR] or near-pCR). Cox regression evaluated the association between race and disease-free (DFS) and overall survival (OS). Results: Results of 486 patients who underwent resection following NAT (mFOLFIRINOX 56%, gemcitabine/nab-paclitaxel 25%, radiation 29%), 67 (13.8%) patients were Black. Black patients had lower CA19-9 at diagnosis (median 67 vs. 204 U/mL; P = 0.003) and were more likely to undergo mild/moderate chemotherapy dose modification (40 vs. 20%; P = 0.005) versus non-Black patients. Black patients had significantly lower rates of MPR compared with non-Black patients (13.4 vs. 25.8%; P = 0.039). Black race was independently associated with worse MPR (OR 0.26, 95% confidence interval [CI] 0.10-0.69) while controlling for NAT duration, CA19-9 dynamics, and chemotherapy modifications. There was no significant difference in DFS or OS between Black and non-Black cohorts. Conclusions: Black patients undergoing pancreatectomy appear less likely to experience MPR following NAT. The contribution of biologic and nonbiologic factors to reduced chemosensitivity in Black patients warrants further investigation. [ABSTRACT FROM AUTHOR]

Pancreas ductal adenocarcinoma (PDAC) remains a malignant tumor with very poor prognosis and low 5-year overall survival. Here, we aimed to simultaneously target mitochondria and lysosomes as a new treatment paradigm of malignant pancreas cancer in vitro and in vivo. We demonstrate that the clinically used sphingosine analog FTY-720 together with PAPTP, an inhibitor of mitochondrial Kv1.3, induce death of pancreas cancer cells in vitro and in vivo. The combination of both drugs results in a marked inhibition of the acid sphingomyelinase and accumulation of cellular sphingomyelin in vitro and in vivo in orthotopic and flank pancreas cancers. Mechanistically, PAPTP and FTY-720 cause a disruption of both mitochondria and lysosomes, an alteration of mitochondrial bioenergetics and accumulation of cytoplasmic Ca2+, events that collectively mediate cell death. Our findings point to an unexpected cross-talk between lysosomes and mitochondria mediated by sphingolipid metabolism. We show that the combination of PAPTP and FTY-720 induces massive death of pancreas cancer cells, thereby leading to a substantially delayed and reduced PDAC growth in vivo. Key messages: FTY-720 inhibits acid sphingomyelinase in pancreas cancer cells (PDAC). FTY-720 induces sphingomyelin accumulation and lysosomal dysfunction. The mitochondrial Kv1.3 inhibitor PAPTP disrupts mitochondrial functions. PAPTP and FTY-720 synergistically kill PDAC in vitro. The combination of FTY-720 and PAPTP greatly delays PDAC growth in vivo. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a very common, severe disease with a lifetime prevalence of ~ 10%. The pathogenesis of MDD is unknown and, unfortunately, therapy is often insufficient. We have previously reported that ceramide levels are increased in the blood plasma of patients with MDD and in mice with experimental MDD. Here, we demonstrate that ceramide-enriched exosomes in the blood plasma are increased in mice with stress-induced MDD. Genetic studies reveal that neutral sphingomyelinase 2 is required for the formation of ceramide-enriched exosomes in the blood plasma. Accordingly, induced deficiency of neutral sphingomyelinase 2 prevented mice from the development of stress-induced MDD. Intravenous injection of microparticles from mice with MDD or injection of ceramide-loaded exosomes induced MDD-like behavior in untreated mice, which was abrogated by ex vivo pre-incubation of purified exosomes with anti-ceramide antibodies or ceramidase. Mechanistically, injection of exosomes from mice with MDD or injection of ex vivo ceramide-loaded microparticles inhibited phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus, which has been previously shown to mediate MDD by plasma ceramide. In summary, our data indicate that ceramide-enriched exosomes are released by neutral sphingomyelinase 2 into the blood plasma upon stress and mediate stress-induced MDD. Key messages: Stress induces ceramide-enriched exosomes in the blood plasma. Ceramide-enriched exosomes mediate major depressive disorder (MDD). Deficiency of neutral sphingomyelinase 2 protects from stress-induced MDD. Neutralization or digestion of ceramide in exosomes prevents stress-induced MDD. Ceramide-enriched exosomes inhibit endothelial phospholipase D in the hippocampus. [ABSTRACT FROM AUTHOR]

Background: T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors. Methods: The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement. Results: The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). On multivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17–1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28–1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03–1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62–2.58; p < 0.01). Conclusions: Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC. [ABSTRACT FROM AUTHOR]

Background: The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease. Methods: The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality. Results: Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months, p < 0.01). Subset analyses based on individual "good" prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months, p < 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months, p = 0.19) and those with all "good" prognostic features (95.9 months vs 90.6 months, p = 0.15), AC was not associated with improved survival. Conclusions: In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC. [ABSTRACT FROM AUTHOR]

Background: Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even if they do, the impact of reduced dose density (DD) on survival is not known. Patients and Methods: A single institutional prospective database was queried for patients with PDAC who underwent curative resection between 2009 and 2018. The primary outcome was DD, defined as the percentage of total planned chemotherapy actually received and associated survival. Results: Of the 126 patients included, 38.9% underwent a neoadjuvant approach, which was associated with a greater median number of completed chemotherapy cycles (5 cycles versus 4 cycles, p < 0.01) and a higher median total DD (93.0% versus 65.0%, p < 0.01), compared with an adjuvant treatment approach. In both groups, adjuvant chemotherapy completion rates were low, with only 55 patients completing all adjuvant cycles. After sequential survival analysis, patients who received a DD ≥ 80% had improved median overall survival (OS) (27.1 months versus 18.6 months, p = 0.01), compared with patients who achieved a DD < 80%. On multivariate Cox proportional-hazards modeling, only the presence of lymphovascular invasion (HR: 1.77, 95% CI: 1.04–2.99, p = 0.04) and DD < 80% (HR: 1.91, 95% CI: 1.23–3.00, p = 0.01) were associated with decreased OS. Conclusions: In this cohort study, patients who received ≥ 80% DD had significantly better OS. DD should be considered an important prognostic metric in pancreatic cancer, and strategies are needed to improve chemotherapy tolerance to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. Methods: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan–Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. Results: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). Conclusion: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes. [ABSTRACT FROM AUTHOR]

Background: Hepatic angiosarcoma is a rare primary liver tumor. The aim of this current study was to evaluate the presentation and treatment outcomes in a modern cohort.Methods: This was a retrospective, multi-institutional, observational study of patients with histopathologic diagnoses of primary hepatic angiosarcoma from four institutions. Clinicopathologic characteristics, treatments, and patient outcomes were examined.Results: Forty-four patients with hepatic angiosarcoma were identified. Patients were predominantly Caucasian and presented at a median age of 63.7 years; 81.4% of patients had bilobar disease and 37.2% had metastatic disease at the time of presentation. Only 10 patients underwent surgical resection. Median overall survival for the entire cohort was 5.8 months (interquartile range 1.9-16.4), and 1-, 3-, and 5-year actual survival was 30.0%, 8.1%, and 5.6%, respectively. There were only two 5-year survivors, both of whom presented with localized disease and underwent curative resection.Conclusion: The prognosis for hepatic angiosarcoma remains quite poor. Surgical resection for localized disease results in the best outcomes. Unfortunately, current imaging modalities are often non- diagnostic, and most patients are unresectable at the time of presentation. [ABSTRACT FROM AUTHOR]