No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer.

BACKGROUND/PURPOSE: Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. METHODS: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. RESULTS: 586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). CONCLUSION: CA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

The use of angiotensin system inhibitors correlates with longer survival in resected pancreatic adenocarcinoma patients.

BACKGROUND: Activities and inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) may affect the survival of resected pancreatic ductal adenocarcinoma (PDAC) patients METHOD: A single-institution retrospective analysis of resected PDAC patients between 2010 and 2019. To estimate the effect of angiotensin system inhibitors (ASIs) on patient survival, we performed Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse probability weighting (IPW) analysis. RESULTS: 742 patients were included in the analysis. The average age was 67.0 years, with a median follow-up of 24.1 months. The use of ASI was associated with significantly longer overall survival in univariate (p = 0.004) and multivariable (HR = 0.70 [0.56-0.88],p = 0.003) adjusted analysis. In a propensity score-matched cohort of 400 patients, ASI use was again associated with longer overall survival (p = 0.039). Lastly, inverse probability weighting (IPW) analysis suggested that the use of ASI was associated with an average treatment effect on the treated (ATT) of HR = 0.68 [0.53-0.86],p = 0.002) for overall survival. CONCLUSION: In this single-institution retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival in multiple statistical models. Prospective clinical trials are needed before routine clinical implementation of ASI as an adjuvant to existing therapy can be recommended.

Septal Thickness Does Not Impact Outcome After Hypertrophic Obstructive Cardiomyopathy Surgery (Septal Myectomy and Subvalvular Mitral Apparatus Remodeling): A 15-Years of Experience.

Background: The aim of this study was to assess the impact of septal thickness on long-term outcomes of surgical treatment for hypertrophic obstructive cardiomyopathy (HOCM) and correction of mitral subvalvular anomalies. Methods: Sixty-six consecutive patients (58 ± 12 years, 56% female) undergoing extended septal myectomy and subvalvular mitral apparatus remodeling from 2007 to 2021 were retrospectively reviewed. Patients were divided into 2 groups according to septal thickness: moderate [< 18 mm, 29 patients (44%)] and severe [≥ 18 mm, 37 patients (56%)]. End points included survival, symptom improvement, reduction of left ventricle outflow tract (LVOT) gradient, resolution of mitral regurgitation (MR), and reoperation. Results: The mean interventricular septal thickness was 19 ± 3 mm, 15.8 ± 0.8 mm in patients with moderate and 21.4 ± 3.2 mm in those with severe hypertrophy. Preoperative data, intraoperative variables, postoperative complication rates, pre-discharge echocardiographic and clinical parameters did not differ between the two study groups [except for procedures involving the posterior mitral leaflet (p = 0.033) and septal thickness after myectomy (p = 0.0001)]. Subvalvular apparatus remodeling (secondary chordae of mitral valve resection and papillary muscle and muscularis trabecula procedures including resection, splitting, and elongation) was invariably added to septal myectomy (100%). Four (6%) procedures involved the posterior mitral leaflets. Mitral valve replacement was carried out in two patients (3%, p = 0.4). Reoperation for persistent MR was necessary in one patient (1%, p = 0.4). Neither iatrogenic ventricular septal defect nor in-hospital mortality occurred. During follow-up (mean 4.8 ± 3.8 years), two deaths occurred. NYHA class was reduced from 2.9 ± 0.7 to 1.6 ± 0.6 (p < 0.0001), the LVOT gradient from 89.7 ± 34.5 to 16.3 ± 8.8 mmHg (p < 0.0001), mitral valve regurgitation grade from 2.5 ± 1 to 1.2 ± 0.5 (p < 0.0001), and septal thickness from 18.9 ± 3.7 to 13.9 ± 2.7 mm (p < 0.0001). Conclusions: Regardless of septal thickness, subvalvular apparatus remodeling with concomitant septal myectomy can provide satisfactory long-term outcomes in terms of symptom improvement, LVOT obstruction relief, and MR resolution (without mitral valve replacement in most cases) in patients with HOCM.

Review of Contemporary Invasive Treatment Approaches and Critical Appraisal of Guidelines on Hypertrophic Obstructive Cardiomyopathy: State-of-the-Art Review.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a heterogeneous disease with different clinical presentations, albeit producing similar dismal long-term outcomes if left untreated. Several approaches are available for the treatment of HOCM; e.g., alcohol septal ablation (ASA) and surgical myectomy (SM). The objectives of the current review were to (1) discuss the place of the standard invasive treatment modalities (ASA and SM) for HOCM; (2) summarize and compare novel techniques for the management of HOCM; (3) analyze current guidelines addressing HOCM management; and (4) offer suggestions for the treatment of complex HOCM presentations. METHODS: We searched the literature and attempted to gather the most relevant and impactful available evidence on ASA, SM, and other invasive means of treatment of HOCM. The literature search yielded thousands of results, and 103 significant publications were ultimately included. RESULTS: We critically analyzed available guidelines and provided context in the setting of patient selection for standard and novel treatment modalities. This review offers the most comprehensive analysis to-date of available invasive treatments for HOCM. These include the standard treatments, SM and ASA, as well as novel treatments such as dual-chamber pacing and radiofrequency catheter ablation. We also account for complex pathoanatomic presentations and current guidelines to offer suggestions for tailored care of patients with HOCM. Finally, we consider promising future therapies for HOCM. CONCLUSIONS: HOCM is a heterogeneous disease associated with poor outcomes if left untreated. Several strategies for treatment of HOCM are available but patient selection for the procedure is crucial.

Pancreatic-Portal Vein Fistula: a Rare Diagnosis with Wide-Ranging Complications-13-Year Experience of a Pancreas Center of Excellence.

PURPOSE: To determine factors affecting mortality, and long-term patency of portal vein, in patients with pancreatic-portal vein fistula (PPVF). METHODS: Consecutive cases of PPVF at the University of Pittsburgh Medical Center from 2008 to 2020 were retrospectively identified. Clinical history, imaging studies, management strategies, complications, and long-term outcomes were analyzed. RESULTS: Fourteen patients, representing the largest PPVF cohort reported to date (mean age 58.6 years, 64.3% women, median follow-up 10 months [1-98 months]) were identified. Underlying chronic pancreatitis was seen in 9 (64.3%) patients, while 5 (35.7%) developed PPVF with first attack of acute pancreatitis. PPVF involved proximal main portal vein (MPV) in 10 (78.6%) patients. Of the 5 patients (35.7%) who died, all had occlusive (n=4) or near-occlusive (n=1) PPVF-associated filling defect (FD) in the MPV. Conversely, 7 of 9 survivors (87.5%) had subocclusive FD and patent MPV. In patients with sepsis (n=5), 1 underwent surgical necrosectomy and survived, while 3 of 4 (75%) patients without debridement died. CONCLUSION: Occlusive/near-occlusive PPVF-associated MPV FD, and sepsis, are associated with high mortality rates, while subocclusive MPV FD is associated with survival and long-term MPV patency. PPVF is a potentially life-threatening, and possibly under-diagnosed, entity that warrants early clinical suspicion for timely diagnosis, to facilitate optimal management.

COVID-19 and Extracorporeal Membrane Oxygenation.

INTRODUCTION: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently and rapidly emerged and developed into a global pandemic. In SARS-CoV-2 patients with refractory respiratory failure, there may be a role for veno-venous extracorporeal membrane oxygenation (V-V ECMO) as a life-saving rescue intervention. METHODS: This review summarizes the evidence gathered until June 12, 2020; electronic databases were screened for pertinent reports on coronavirus and V-V ECMO. Search was conducted by two independent investigators; keywords used were SARS-CoV-2, COVID-19, ECMO, and extracorporeal life support (ECLS). RESULTS: Many patients with COVID-19 experience moderate symptoms and a relatively quick recovery, but others must be admitted into the intensive care unit due to severe respiratory failure and often must be mechanically ventilated. Further deterioration may require institution of extracorporeal oxygenation. Infection mechanisms may trigger "cytokine storm," an inflammatory disorder notable for multi-organ system failure; together with other metabolic and hematological changes, these amplify the changes pertinent to ECMO therapy, often exaggerating blood coagulation disorders. Thirty-two studies were found describing experiences with ECMO in the treatment of COVID-19. Of 4,912 COVID-19 patients, 2,119 (43%) developed ARDS and 2,086 (42%) were transferred to the ICU; 1,015 patients (21%) were treated with ECMO. While in an overall cohort, observed mortality was 640 (13%), the mortality within ECMO subgroups reached up to 34.6% (range 0-100%). CONCLUSION: The efficacy of ECMO treatment for COVID-19 is largely dependent on the expertise of the center in ECLS due to the interplay between the changes in hematological and inflammatory modulators associated with both COVID-19 and ECMO. In order to support gas exchange during early infection with SARS-CoV-2, ECMO has a strong rationale for the treatment of the most critically ill patients. Due to the limited resources during a global pandemic, ECMO should be reserved for only the most severe cases of COVID-19.