Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 23
Filter
2.
Surg Endosc ; 38(5): 2602-2610, 2024 May.
Article in English | MEDLINE | ID: mdl-38498210

ABSTRACT

INTRODUCTION: Minimally invasive Pancreatoduodenectomy (MIPD), or the Whipple procedure, is increasingly utilized. No study has compared laparoscopic (LPD) and robotic (RPD) approaches, and the impact of the learning curve on oncologic, technical, and post-operative outcomes remains relatively understudied. METHODS: The National Cancer Database was queried for patients undergoing LPD or RPD from 2010 to 2020 with a diagnosis of pancreatic cancer. Outcomes were compared between approaches using propensity-score matching (PSM); the impact of annual center-level volume of MIPD was also assessed by dividing volume into quartiles. RESULTS: A total of 3,342 patients were included. Most (n = 2,716, 81.3%) underwent LPD versus RPD (n = 626, 18.7%). There was a high rate (20.2%, n = 719) of positive margins. Mean length-of-stay (LOS) was 10.4 ± 8.9 days. Thirty-day mortality was 2.8% (n = 92) and ninety-day mortality was 5.7% (n = 189). PSM matched 625 pairs of patients receiving LPD or RPD. After PSM, there was no differences between groups based on age, sex, race, CCI, T-stage, neoadjuvant chemo/radiotherapy, or type of PD. After PSM, there was a higher rate of conversion to open (HR = 0.68, 95%CI = 0.50-0.92)., but there was no difference in LOS (HR = 1.00, 95%CI = 0.92-1.11), 30-day readmission (HR = 1.08, 95% CI = 0.68-1.71), 30-day (HR = 0.78, 95% CI = 0.39-1.56) or 90-day mortality (HR = 0.70, 95% CI = 0.42-1.16), ability to receive adjuvant therapy (HR = 1.15, 95% CI = 0.92-1.44), nodal harvest (HR = 1.01, 95%CI = 0.94-1.09) or positive margins (HR = 1.19, 95% CI = 0.89-1.59). Centers in lower quartiles of annual volume of MIPD demonstrated reduced nodal harvest (p = 0.005) and a higher rate of conversion to open (p = 0.038). Higher-volume centers had a shorter LOS (p = 0.012), higher rate of initiation of adjuvant therapy (p = 0.042), and, most strikingly, a reduction in 90-day mortality (p = 0.033). CONCLUSION: LPD and RPD have similar surgical and oncologic outcomes, with a lower rate of conversion to open in the robotic cohort. The robotic technique does not appear to eliminate the "learning curve", with higher volume centers demonstrating improved outcomes, especially seen at minimum annual volume of 5 cases.


Subject(s)
Laparoscopy , Pancreatic Neoplasms , Pancreaticoduodenectomy , Propensity Score , Robotic Surgical Procedures , Humans , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy/statistics & numerical data , Robotic Surgical Procedures/statistics & numerical data , Robotic Surgical Procedures/methods , Male , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Female , Laparoscopy/methods , Laparoscopy/statistics & numerical data , Aged , Middle Aged , Treatment Outcome , Length of Stay/statistics & numerical data , Postoperative Complications/epidemiology , Retrospective Studies , Margins of Excision , Learning Curve
3.
Pancreatology ; 24(3): 489-492, 2024 May.
Article in English | MEDLINE | ID: mdl-38443232

ABSTRACT

OBJECTIVE: Serous cystic neoplasms (SCN) are benign pancreatic cystic neoplasms that may require resection based on local complications and rate of growth. We aimed to develop a predictive model for the growth curve of SCNs to aid in the clinical decision making of determining need for surgical resection. METHODS: Utilizing a prospectively maintained pancreatic cyst database from a single institution, patients with SCNs were identified. Diagnosis confirmation included imaging, cyst aspiration, pathology, or expert opinion. Cyst size diameter was measured by radiology or surgery. Patients with interval imaging ≥3 months from diagnosis were included. Flexible restricted cubic splines were utilized for modeling of non-linearities in time and previous measurements. Model fitting and analysis were performed using R (V3.50, Vienna, Austria) with the rms package. RESULTS: Among 203 eligible patients from 1998 to 2021, the mean initial cyst size was 31 mm (range 5-160 mm), with a mean follow-up of 72 months (range 3-266 months). The model effectively captured the non-linear relationship between cyst size and time, with both time and previous cyst size (not initial cyst size) significantly predicting current cyst growth (p < 0.01). The root mean square error for overall prediction was 10.74. Validation through bootstrapping demonstrated consistent performance, particularly for shorter follow-up intervals. CONCLUSION: SCNs typically have a similar growth rate regardless of initial size. An accurate predictive model can be used to identify rapidly growing outliers that may warrant surgical intervention, and this free model (https://riskcalc.org/SerousCystadenomaSize/) can be incorporated in the electronic medical record.


Subject(s)
Cystadenoma, Serous , Neoplasms, Cystic, Mucinous, and Serous , Pancreatic Cyst , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Pancreatic Cyst/surgery , Cystadenoma, Serous/surgery
4.
J Surg Oncol ; 129(4): 793-801, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38151831

ABSTRACT

INTRODUCTION: Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS: Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS: Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively.  Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION: Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Follow-Up Studies , Hepatectomy , Colorectal Neoplasms/pathology , Blood Transfusion, Autologous , Retrospective Studies , Liver Neoplasms/secondary , Neoplasm Recurrence, Local/pathology , Prognosis
5.
JCO Clin Cancer Inform ; 7: e2300111, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37820293

ABSTRACT

PURPOSE: Liver metastases occur in about 50% of colorectal cancer cases and drive patient outcomes. Circulating tumor DNA (ctDNA) is emerging as a diagnostic, surveillance, and tumor mutational information tool. METHODS: Patients with colorectal cancer liver metastasis (CCLM) seen in a multidisciplinary liver tumor clinic from January to August 2022 received ctDNA testing on each visit. ctDNA was obtained using the Guardant360 platform. Tumor mutational burden (TMB) is defined as the number of identified mutations per megabase of genome analyzed. RESULTS: Fifty-two patients had available ctDNA, with 34 (65%) tested preoperatively and 18 (35%) postoperatively; nine patients had sequential pre- and postoperative testing. The median time to test result was 12 days (IQR, 10-13.5). There were a greater number of somatic mutations identified preoperatively (n = 29 v n = 11) and a greater genomic heterogeneity (P = .0069). The mean TMB score was 12.77 in those without pathologic response to cytotoxic therapy and 6.0 in those with pathologic response (P = .10). All nine patients with sequential testing were positive preoperatively, compared with just three (33.3%) postoperatively (P = .0090). Positive postoperative ctDNA was associated with the increased likelihood of disease recurrence after resection (57%) versus negative ctDNA (0%, P = .0419). CONCLUSION: Routine ctDNA screening in patients with CCLM is logistically feasible. Liver resection and/or transplant may be associated with clearance of detectable ctDNA and a reduction in TMB or genomic heterogeneity. Persistence of ctDNA alterations postresection appears predictive of disease recurrence. Further studies are necessary to confirm these findings, and longitudinal ctDNA testing is needed to monitor changing tumor biology.


Subject(s)
Circulating Tumor DNA , Colorectal Neoplasms , Liver Neoplasms , Humans , Circulating Tumor DNA/genetics , Neoplasm Recurrence, Local/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/surgery , Colorectal Neoplasms/diagnosis
6.
J Gastrointest Surg ; 27(11): 2676-2683, 2023 11.
Article in English | MEDLINE | ID: mdl-37653152

ABSTRACT

INTRODUCTION: Drain amylase on day 1 (DA-D1) after pancreaticoduodendectomy (PD) to predict occurrence of postoperative pancreatic fistula (POPF) is controversial. In this study, we evaluate the optimal DA-D1 level to predict clinically relevant POPF (CR-POPF). METHODS: The 2014-2020 NSQIP pancreatectomy-targeted database was queried for patients who underwent elective PD. Perioperative data was extracted to determine development of POPF and CR-POPF per International Study Group of Pancreatic Fistula guidelines. Receiver operative curve (ROC) and Youden's index were used to assess the performance and optimal cutoff for DA-D1 to predict CR-POPF. The DA-D1 value was confirmed with a multivariable logistic regression to determine hazard ratios (HR) for CR-POPF and conditional logistic regression by modified fistula risk score (mFRS) subgroups. RESULTS: A total of 6,087 patients with complete perioperative data were included. Mean DA-D1 was 2,897 ± 8,636 U/L; median drain duration was 5 days. CR-POPF was documented in 544 (8.9%) patients. DA-D1 ROC for CR-POPF had area under the curve of 0.779 (95%CI 0.759-0.798). Youden's index for the CR-POPF ROC coordinates had 77.6% sensitivity and 66.3% specificity, corresponding to DA-D1 values ≥ 720U/L as an optimal cutoff. CR-POPF was higher for patients with DA-D1 ≥ 720U/L (HR 4.6; p = 0.001). Patients DA-D1 < 720U/L with a negligible, low, intermediate, and high mFRS had respectively 1%, 3%, 4%, and 7% rate of CR-POPF. CONCLUSION: DA-D1 < 720U/L after elective PD is a clinically useful predictor of CR-POPF. For patients with negligible to intermediate FRS, surgeons should consider utilizing DA-D1 < 720 U/L for removal of a drain on the first postoperative day.


Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreatic Fistula/surgery , Amylases , Pancreas/surgery , Pancreatectomy/adverse effects , Risk Factors , Drainage , Postoperative Complications/epidemiology , Retrospective Studies
7.
J Gastrointest Surg ; 27(11): 2424-2433, 2023 11.
Article in English | MEDLINE | ID: mdl-37620660

ABSTRACT

INTRODUCTION: Cirrhotic patients with primary liver cancer may undergo curative-intent resection when selected appropriately. Patients with T1 tumors and low-MELD are generally referred for resection. We aim to evaluate whether minimally invasive hepatectomy (MIH) is associated with improved outcomes versus open hepatectomy (OH). METHODS: NSQIP hepatectomy database 2014-2021 was used to select patients with T1 Hepatocellular Carcinoma (HCC) or Intra-hepatic Cholangiocarcionoma (IHCC) and low-MELD cirrhosis (MELD ≤ 10) who underwent partial hepatectomy. Propensity score matching was applied between OH and MIH patients, and 30-day postoperative outcomes were compared. Multivariable regression was used to identify predictors of post-hepatectomy liver failure (PHLF) in the selected population. RESULTS: There were 922 patients: 494 (53.6%) OH, 372 (40.3%) MIH, and 56 (6.1%) began MIH converted to OH (analyzed with the OH cohort). We matched 354 pairs of patients with an adequate balance between the groups. MIH was associated with lower rates of bile leak (HR 0.37 [0.19-0.72)], PHLF (HR 0.36 [0.15-0.86]), collections requiring drainage (HR 0.30 [0.15-0.63]), postoperative transfusion (HR 0.36 [0.21-0.61]), major (HR 0.45 [0.27-0.77]), and overall morbidity (HR 0.44 [0.31-0.63]), and a two-day shorter median hospitalization (3 vs. 5 days; HR 0.61 [0.45-0.82]). No difference was noted in operative time, wound, respiratory, and septic complications, or mortality. Regression analysis identified ascites, prior portal vein embolization (PVE), additional hepatectomies, Pringle's maneuver, and OH (vs. MIH) as independent predictors of PHLF. CONCLUSION: MIH for early-stage HCC/IHCC in low-MELD cirrhotic patients was associated with improved postoperative outcomes over OH. These findings suggest that MIH should be considered an acceptable approach in this population of patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Failure , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Hepatectomy/adverse effects , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Liver Failure/etiology , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery
8.
HPB (Oxford) ; 25(10): 1213-1222, 2023 10.
Article in English | MEDLINE | ID: mdl-37357114

ABSTRACT

BACKGROUND: In distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC), we hypothesize that minimally invasive DP (MIDP) carries short-term benefits over ODP (ODP) in the absence of postoperative pancreatic fistula (POPF). METHODS: NSQIP database was queried to select patients who underwent DP for PDAC with available report on POPF. The population was divided into No-POPF vs. POPF groups. In each group, propensity-score matching was applied to compare 30-day outcomes of ODP vs. MIDP. RESULTS: There were 2,824 patients; 2,332 (82%) had No-POPF and 492 (21%) had POPF. In No-POPF patients, 921 pairs were matched between ODP and MIDP. MIDP patients had slightly longer operations (227 vs. 205 minutes; p < 0.001), but lower rates of surgical site complications (1% vs. 2.9%; p = 0.002), postoperative transfusion (7.1% vs. 11.0%; p = 0.003), overall morbidity (21.1% vs. 26.3%; p = 0.009), and one-day shorter median length of stay (LOS) (5 vs. 6 days; p = 0.001). In the POPF group, 172 pairs were matched. There was no difference in morbidity, mortality, reoperation, LOS, and home discharge. Similar conclusions were drawn in the intention-to-treat and per-protocol analyses. CONCLUSION: POPF is common following DP for PDAC. In the absence of POPF, MIDP is associated with fewer postoperative morbidities and shorter LOS.


Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Laparoscopy , Pancreatic Neoplasms , Robotic Surgical Procedures , Humans , Pancreatic Neoplasms/pathology , Adenocarcinoma/surgery , Adenocarcinoma/complications , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Laparoscopy/adverse effects , Carcinoma, Pancreatic Ductal/pathology , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Fistula/surgery , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Pancreatic Neoplasms
9.
HPB (Oxford) ; 25(10): 1187-1194, 2023 10.
Article in English | MEDLINE | ID: mdl-37211463

ABSTRACT

INTRODUCTION: Idiopathic acute pancreatitis (IAP) is a diagnosis of exclusion; systematic work-up is challenging but essential. Recent advances suggest IAP results from micro-choledocholithiasis, and that laparoscopic cholecystectomy (LC) or endoscopic sphincterotomy (ES) may prevent recurrence. METHODS: Patients diagnosed with IAP from 2015-21 were identified from discharge billing records. Acute pancreatitis was defined by the 2012 Atlanta classification. Complete workup was defined per Dutch and Japanese guidelines. RESULTS: A total of 1499 patients were diagnosed with IAP; 455 screened positive for pancreatitis. Most (N = 256, 56.2%) were screened for hypertriglyceridemia, 182 (40.0%) for IgG-4, and 18 (4.0%) MRCP or EUS, leaving 434 (29.0%) patients with potentially idiopathic pancreatitis. Only 61 (14.0%) received LC and 16 (3.7%) ES. Overall, 40% (N = 172) had recurrent pancreatitis versus 46% (N = 28/61) following LC and 19% (N = 3/16) following ES. Forty-three percent had stones on pathology after LC; none developed recurrence. CONCLUSION: Complete workup for IAP is necessary but was performed in <5% of cases. Patients who potentially had IAP and received LC were definitively treated 60% of the time. The high rate of stones on pathology further supports empiric LC in this population. A systematic approach to IAP is lacking. Interventions aimed at biliary-lithiasis to prevent recurrent IAP have merit.


Subject(s)
Cholecystectomy, Laparoscopic , Choledocholithiasis , Pancreatitis, Chronic , Humans , Acute Disease , Choledocholithiasis/diagnosis , Pancreatitis, Chronic/surgery , Sphincterotomy, Endoscopic , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods
11.
Biochem J ; 477(8): 1541-1564, 2020 04 30.
Article in English | MEDLINE | ID: mdl-32348475

ABSTRACT

Protein glycosylation represents a nearly ubiquitous post-translational modification, and altered glycosylation can result in clinically significant pathological consequences. Here we focus on O-glycosylation in tumor cells of mice and humans. O-glycans are those linked to serine and threonine (Ser/Thr) residues via N-acetylgalactosamine (GalNAc), which are oligosaccharides that occur widely in glycoproteins, such as those expressed on the surfaces and in secretions of all cell types. The structure and expression of O-glycans are dependent on the cell type and disease state of the cells. There is a great interest in O-glycosylation of tumor cells, as they typically express many altered types of O-glycans compared with untransformed cells. Such altered expression of glycans, quantitatively and/or qualitatively on different glycoproteins, is used as circulating tumor biomarkers, such as CA19-9 and CA-125. Other tumor-associated carbohydrate antigens (TACAs), such as the Tn antigen and sialyl-Tn antigen (STn), are truncated O-glycans commonly expressed by carcinomas on multiple glycoproteins; they contribute to tumor development and serve as potential biomarkers for tumor presence and stage, both in immunohistochemistry and in serum diagnostics. Here we discuss O-glycosylation in murine and human cells with a focus on colorectal, breast, and pancreatic cancers, centering on the structure, function and recognition of O-glycans. There are enormous opportunities to exploit our knowledge of O-glycosylation in tumor cells to develop new diagnostics and therapeutics.


Subject(s)
Neoplasms/metabolism , Polysaccharides/metabolism , Animals , Antigens, Tumor-Associated, Carbohydrate/genetics , Antigens, Tumor-Associated, Carbohydrate/metabolism , Glycosylation , Humans , Neoplasms/genetics
12.
HPB (Oxford) ; 22(4): 563-569, 2020 04.
Article in English | MEDLINE | ID: mdl-31537457

ABSTRACT

BACKGROUND: Standard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration. METHODS: Single institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration. Short-term, long-term, and lifetime risk of biliary occlusion and survival were compared after adjustment for stage and comprehensive complication index (CCI). RESULTS: Baseline demographics and tumor characteristics were equivalent between cohorts. Short-term complications were more frequent after OSBB, whereas late complications were greater after SEMS. The cumulative incidence of recurrent biliary obstruction was greater after SEMS, but lifetime complication burden and median survival were equivalent. CONCLUSION: OSBB was associated with longer hospital stays and more short-term complications, and SEMS was associated with a higher risk of recurrent biliary obstruction among surgical patients with unresectable PDAC. Patient preference should be defined pre-operatively in the case the unresectable disease is encountered during attempted resection.


Subject(s)
Adenocarcinoma/pathology , Cholestasis/surgery , Palliative Care , Pancreatic Neoplasms/pathology , Postoperative Complications/epidemiology , Self Expandable Metallic Stents , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Aged , Cholestasis/etiology , Cholestasis/mortality , Female , Humans , Length of Stay , Male , Middle Aged , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Retrospective Studies , Survival Rate , Treatment Outcome
13.
J Thorac Cardiovasc Surg ; 159(4): 1451-1461.e7, 2020 04.
Article in English | MEDLINE | ID: mdl-31740116

ABSTRACT

OBJECTIVE: The study objective was to describe the surgical pathway progression through adolescence of an inception cohort of neonates with aortic valve atresia managed initially with surgical palliation or primary transplantation, comparing survival and self-reported health-related quality of life. METHODS: From 1994 to 2000, 565 neonates with aortic atresia were admitted to 26 Congenital Heart Surgeons' Society hospitals and followed annually for vital status. Initial management included surgical palliation (n = 453) and primary cardiac transplantation (n = 68). PedsQL health-related quality of life questionnaires were sent cross-sectionally to a subgroup of 198 patients alive at previous follow-up, with 80 responses. RESULTS: Risk of death was initially high for both treatment strategies. However, compared with initial surgical palliation, survival with primary transplantation, including wait-list mortality, was greater and persisted long-term (65% vs 40% at 15 years; P = .002). Survival after secondary transplantation (48% at 9 years) was lower than after primary transplantation (74%). Health-related quality of life total score was lower overall than that of the general adolescent population (71 ± 16 vs 84 ± 13; P = .0001; normal = 100), but similar to that of adolescents with chronic diseases. It was similar in the surgical palliation and primary transplantation groups (70 ± 16 vs 75 ± 15; P = .3). Patients who received surgical palliation reported more symptoms (76 ± 15 vs 63 ± 18; P = .02). CONCLUSIONS: Patients receiving primary heart transplantation for aortic atresia in 1994 to 2000 experienced better survival, fewer symptoms, and equivalent quality of life compared with those undergoing initial surgical palliation. Notwithstanding the limited availability of neonatal and infant donor hearts, primary transplantation may be considered for those neonates with risk factors predictive of exceptionally poor survival after surgical palliation.


Subject(s)
Aortic Valve , Heart Transplantation , Heart Valve Diseases/surgery , Palliative Care , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Heart Valve Diseases/mortality , Heart Valve Prosthesis Implantation , Humans , Infant , Infant, Newborn , Male , Norwood Procedures , Quality of Life , Survival Rate , Treatment Outcome
14.
Glycobiology ; 30(5): 282-300, 2020 04 20.
Article in English | MEDLINE | ID: mdl-31742337

ABSTRACT

The Tn antigen is a neoantigen abnormally expressed in many human carcinomas and expression correlates with metastasis and poor survival. To explore its biomarker potential, new antibodies are needed that specifically recognize this antigen in tumors. Here we generated two recombinant antibodies to the Tn antigen, Remab6 as a chimeric human IgG1 antibody and ReBaGs6 as a murine IgM antibody and characterized their specificities using multiple biochemical and biological approaches. Both Remab6 and ReBaGs6 recognize clustered Tn structures, but most importantly do not recognize glycoforms of human IgA1 that contain potential cross-reactive Tn antigen structures. In flow cytometry and immunofluorescence analyses, Remab6 recognizes human cancer cell lines expressing the Tn antigen, but not their Tn-negative counterparts. In immunohistochemistry (IHC), Remab6 stains many human cancers in tissue array format but rarely stains normal tissues and then mostly intracellularly. We used these antibodies to identify several unique Tn-containing glycoproteins in Tn-positive Colo205 cells, indicating their utility for glycoproteomics in future biomarker studies. Thus, recombinant Remab6 and ReBaGs6 are useful for biochemical characterization of cancer cells and IHC of tumors and represent promising tools for Tn biomarker discovery independently of recognition of IgA1.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/analysis , Biomarkers, Tumor/analysis , Carcinoma/diagnosis , Glycoproteins/analysis , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Antigens, Tumor-Associated, Carbohydrate/genetics , Antigens, Tumor-Associated, Carbohydrate/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Carcinoma/genetics , Carcinoma/immunology , Female , Glycoproteins/genetics , Glycoproteins/immunology , Humans , Infant , Male , Mice , Middle Aged , Recombinant Proteins/immunology , Tumor Cells, Cultured , Young Adult
15.
HPB (Oxford) ; 21(11): 1585-1591, 2019 11.
Article in English | MEDLINE | ID: mdl-31076257

ABSTRACT

BACKGROUND: Enucleation of low-grade pancreatic tumors achieves oncological outcomes equivalent to resection but conserves parenchyma. Given strict selection criteria, we hypothesized that minimally-invasive (MI) enucleation is associated with decreased composite major morbidity (CMM) compared to open. METHODS: Pancreas-targeted ACS NSQIP (2014 -2016) was queried for enucleation (CPT code: 48120) and analyzed by intended surgical approach regardless of conversion. The primary outcome was CMM, a validated 30-day composite metric of adverse events. RESULTS: Enucleation was performed using an open (n = 71; 62.3%) or MI (n = 43; 37.7%) approach with 7 conversions (16.2%). Both cohorts had interchangeable baseline characteristics. No selection factors governing MI were identified. MI-enucleation reduced median length of stay (4 vs. 5 days; p = 0.003), whereas rates of CMM after open (24; 34%) and MIenucleation (12; 28%) were equivalent (p = 0.541). Multivariable analysis demonstrated an association between CMM and prolonged operative time (OR 2.7, 95% CI 1.14 -6.74), female sex (OR 0.38, 95% CI 0.16 -0.94), and ASA score <3 (OR 0.39, 95% CI 0.16 -0.96) but not surgical approach. CONCLUSION: MI-enucleation was not associated with reduced 30-day CMM compared to open, whereas prolonged operating time and unmodifiable patient factors were correlated with adverse outcomes.


Subject(s)
Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Neoplasm Grading , Pancreatic Neoplasms/pathology , Retrospective Studies
16.
Respir Med ; 150: 126-130, 2019 04.
Article in English | MEDLINE | ID: mdl-30961938

ABSTRACT

BACKGROUND: The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined. METHODS: A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH). RESULTS: Mean age (±standard deviation) of LD-PH patients was 64 ±â€¯10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ±â€¯10 vs 56 ±â€¯18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02). CONCLUSIONS: Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.


Subject(s)
Familial Primary Pulmonary Hypertension/mortality , Hypertension, Pulmonary/mortality , Lung/blood supply , Vascular Resistance/physiology , Adult , Aged , Cardiac Catheterization/methods , Echocardiography/methods , Familial Primary Pulmonary Hypertension/epidemiology , Familial Primary Pulmonary Hypertension/physiopathology , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Hemodynamics/physiology , Humans , Hypertension, Pulmonary/epidemiology , Hypertension, Pulmonary/physiopathology , Lung/physiopathology , Lung Diseases, Interstitial/epidemiology , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/physiopathology , Lung Diseases, Obstructive/epidemiology , Lung Diseases, Obstructive/mortality , Lung Diseases, Obstructive/physiopathology , Male , Middle Aged , Prospective Studies , Pulmonary Artery/physiopathology , Survival Analysis , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/epidemiology
17.
HPB (Oxford) ; 21(8): 1039-1045, 2019 08.
Article in English | MEDLINE | ID: mdl-30723060

ABSTRACT

BACKGROUND: Minimizing pain and disability are key postoperative objectives of robot-assisted distal pancreatectomy (RADP). This study tested effects of bupivacaine transversus abdominis plane (TAP) block on opioid consumption and pain after RADP. METHODS: Retrospective case-control study (June 2012 -Oct 2017) evaluating bilateral intraoperative bupivacaine TAP block as an interrupted time series. Linear regression evaluated opioid consumption in terms of intravenous (IV) morphine milligram equivalents (MME) and controlled for preoperative morbidity. Secondary outcomes included numerical rating scale (NRS) pain scores. RESULTS: 81 RADP patients met eligibility, 48 before and 33 after implementation of TAP. Baseline characteristics were equivalent with a trend toward higher age, Charlson comorbidity, and ASA score among the TAP cohort. TAP patients consumed on average 4.52 fewer IV MME than controls during the first six postoperative hours (p = 0.032) and reported lower mean NRS scores at six (p = 0.009) and 12 h (p = 0.006) but not at 24 h (p = 0.129). Postoperative morbidity and lengths of stay (LOS) were equivalent (5 vs. 6 days, p = 0.428). CONCLUSION: Bupivacaine TAP block was associated with significant reductions in opioid consumption and pain after RADP but did not shorten hospital LOS consistent with bupivacaine's limited half-life.


Subject(s)
Abdominal Muscles/drug effects , Analgesics, Opioid/administration & dosage , Nerve Block/methods , Pain, Postoperative/therapy , Pancreatectomy/adverse effects , Robotic Surgical Procedures/adverse effects , Abdominal Muscles/physiopathology , Aged , Bupivacaine/therapeutic use , Case-Control Studies , Chi-Square Distribution , Databases, Factual , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Pain Management , Pain Measurement , Pain, Postoperative/diagnosis , Pancreatectomy/methods , Reference Values , Retrospective Studies , Robotic Surgical Procedures/methods , Statistics, Nonparametric , Treatment Outcome
18.
Am J Cardiol ; 122(3): 505-510, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30201113

ABSTRACT

Septostomy reduces right ventricular (RV) workload at the expense of hypoxemia in patients with advanced pulmonary hypertension (PH). A patent foramen ovale (PFO) may serve as a "natural" septostomy, but the incidence and impact of a PFO in PH remains uncertain. We prospectively examined echocardiograms in 404 PH patients referred for initial hemodynamic assessment. Patients included had saline bubble injection and if negative repeatinjection after Valsalva maneuver. Echocardiographic and hemodynamic data were examined. Survival was modeled using Kaplan-Meier method. Eisenmenger syndrome or known atrial shunts other than PFO were excluded: 292 patients met entry criteria. A PFO was identified in 16.8% of the entire cohort, 22.9% of pulmonary arterial hypertension (PAH) patients, and 8.6% of Dana Point group 2 PH patients. Right atrial to pulmonary capillary wedge pressure difference was lowest in the latter group (-7.9 ± 7.1 vs -1.7 ± 5.5 mm Hg for all others, p <0.01). Patients with a PFO were younger (53.9 vs 58.6 years, p = 0.02). A PFO was more often present with moderately or severely dilated (p = 0.01) or dysfunctional (p = 0.03) RVs. Six year survival was unchanged by PFO presence for all patients, including those with PAH. Proportional hazards analysis found only age and functional class independently predicted survival (p <0.01). A PFO is identified less often in Dana Point group 2 PH, likely due to inability of Valsalva maneuver to overcome right atrial to pulmonary capillary wedge pressure difference. In conclusion, the incidence of a PFO in the PH population increases with more dilated and dysfunctional RVs, suggesting that the PFO may be stretched open rather than congenital. The presence of a PFO does not impact survival in PH or PAH.


Subject(s)
Foramen Ovale, Patent/complications , Heart Ventricles/physiopathology , Hypertension, Pulmonary/etiology , Pulmonary Wedge Pressure/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Cardiac Surgical Procedures/methods , Echocardiography, Transesophageal , Female , Follow-Up Studies , Foramen Ovale, Patent/diagnosis , Foramen Ovale, Patent/surgery , Heart Ventricles/diagnostic imaging , Humans , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate/trends , United States/epidemiology , Valsalva Maneuver , Young Adult
19.
Am J Manag Care ; 23(8): 474-480, 2017 Aug.
Article in English | MEDLINE | ID: mdl-29087147

ABSTRACT

OBJECTIVES: Pulmonary hypertension portends a poorer prognosis for blacks versus white populations, but the underlying reasons are poorly understood. We investigated associations of disease characteristics, insurance status, and race with clinical outcomes. STUDY DESIGN: Retrospective cohort study of patients presenting for initial pulmonary hypertension evaluation at 2 academic referral centers. METHODS: We recorded insurance status (Medicare, Medicaid, private, self-pay), echocardiographic, and hemodynamics data from 261 patients (79% whites, 17% blacks) with a new diagnosis of pulmonary hypertension. Subjects were followed for 2.3 years for survival. Adjustment for covariates was performed with Cox proportional hazards modeling. RESULTS: Compared with white patients, blacks were younger (50 ± 15 vs 53 ± 12 years; P = .04), with females representing a majority of patients in both groups (80% vs 66%; P = .08) and similar functional class distribution (class 2/3/4: 30%/52%/16% blacks vs 33%/48%/14% whites; P = .69). Blacks diagnosed with incident pulmonary hypertension were more frequently covered by Medicaid (12.5% vs 0.7%) and had less private insurance (50% vs 61%; P = .007) than whites. At presentation, blacks had more right ventricular dysfunction (P = .04), but similar mean pulmonary arterial pressure (46 vs 45 mm Hg, respectively; P = .66). After adjusting for age and functional class, blacks had greater mortality risk (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.18-3.44), which did not differ by race after additional adjustment for insurance status (HR, 1.74; 95% CI, 0.84-3.32; P =.13). CONCLUSIONS: In a large cohort of patients with incident pulmonary hypertension, black patients had poorer right-side heart function and survival rates than white patients. However, adjustment for insurance status in our cohort removed differences in survival by race.


Subject(s)
Black or African American/statistics & numerical data , Hypertension, Pulmonary/ethnology , Hypertension, Pulmonary/therapy , Insurance Coverage/statistics & numerical data , Insurance, Health/statistics & numerical data , Academic Medical Centers , Adult , Age Factors , Aged , Comorbidity , Female , Healthcare Disparities/ethnology , Humans , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index , Sex Factors , Socioeconomic Factors
20.
Pulm Circ ; 5(1): 117-23, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25992276

ABSTRACT

Diabetes complicates management in a number of disease states and adversely impacts survival; how diabetes affects patients with pulmonary hypertension (PH) has not been well characterized. With insulin resistance having recently been demonstrated in PH, we sought to examine the impact of diabetes in these patients. Demographic characteristics, echo data, and invasive hemodynamic data were prospectively collected for 261 patients with PH referred for initial hemodynamic assessment. Diabetes was defined as documented insulin resistance or treatment with antidiabetic medications. Fifty-five patients (21%) had diabetes, and compared with nondiabetic patients, they were older (mean years ± SD, 61 ± 13 vs. 56 ± 16; [Formula: see text]), more likely to be black (29% vs. 14%; [Formula: see text]) and hypertensive (71% vs. 30%; [Formula: see text]), and had higher mean (±SD) serum creatinine levels (1.1 ± 0.5 vs. 1.0 ± 0.4; [Formula: see text]). Diabetic patients had similar World Health Organization functional class at presentation but were more likely to have pulmonary venous etiology of PH (24% vs. 10%; [Formula: see text]). Echo findings, including biventricular function, tricuspid regurgitation, and pressure estimates were similar. Invasive pulmonary pressures and cardiac output were similar, but right atrial pressure was appreciably higher (14 ± 8 mmHg vs. 10 ± 5 mmHg; [Formula: see text]). Despite similar management, survival was markedly worse and remained so after statistical adjustment. In summary, diabetic patients referred for assessment of PH were more likely to have pulmonary venous disease than nondiabetic patients with PH, with hemodynamics suggesting greater right-sided diastolic dysfunction. The markedly worse survival in these patients merits further study.

SELECTION OF CITATIONS
SEARCH DETAIL
...