Cecal bascule, initially described in 1899 by Treves, is the rarest form of cecal volvulus and re... more Cecal bascule, initially described in 1899 by Treves, is the rarest form of cecal volvulus and represents a phenomenon when a redundant and distended cecum folds anteriorly over the ascending colon causing an intestinal obstruction. Patients with cerebral palsy are at increased risk for this condition. We present a 28-year-old male with cerebral palsy, fully functionally dependent in activities of daily living, who presented to the emergency department with a large loop ileostomy prolapse which was the result of an inverted prolapsed cecum due to a cecal bascule. What differentiated this patient from others is that the prolapsed portion was the efferent limb of the ileostomy with the intussuscepted cecum and the entire right colon. To correct this, he underwent a right hemicolectomy with end ileostomy and transverse mucous fistula creation through the previous ostomy site. He progressed well appropriately postoperatively and was discharged home.This report highlights the rare phenom...
Additional file 8: Table S4. List of pathways associated with gene/proteins significantly increas... more Additional file 8: Table S4. List of pathways associated with gene/proteins significantly increased in HCC explant samples that exhibited post-transplant recurrence. Table S5. List of pathways associated with genes/proteins significantly decreased in HCC explant samples that exhibited post-transplant recurrence. Table S6. Clinical characteristics of the 29 patients transplanted for HCC beyond Milan criteria with versus without recurrence post-transplant. Median values are reported, and the 95% confidence intervals are displayed in the brackets.
Additional file 7: Table S3. Significantly enriched pathways among proteins differentially expres... more Additional file 7: Table S3. Significantly enriched pathways among proteins differentially expressed between HCC samples developing recurrence compared to non-recurrent ones. Pathways are determined using pathDIP, and those with adjusted p-value
Additional file 3: Figure S3. Kaplan–Meier survival plots for: (A) ALDH1A1 gene and protein; (B) ... more Additional file 3: Figure S3. Kaplan–Meier survival plots for: (A) ALDH1A1 gene and protein; (B) LGALS3 gene and protein; (C) LGALS3BP gene and protein in HCC patients. The levels of the gene/protein were grouped by mean. For ALDH1A1 gene: low level
BACKGROUND In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting... more BACKGROUND In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. METHODS Using OPTN/UNOS data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post- DAAs introduction. We categorized these patients into two eras: Pre-DAA (2008-2012 [pre-DAA era]) and Post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. RESULTS 17,215 LT recipients were eligible for this study (HCV/HIV [n = 160]; HIV mono-infection [n = 188]; HCV mono-infection [n = 16,867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of one- and three-year graft loss Post-DAA, compared Pre-DAA (one-year: adjusted hazard ratio [aHR] 0.29, 95% CI 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; three-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95%CI 0.58-0.70, respectively). The hazards of one- and three-year graft loss Post-DAA in HIV mono-infection were comparable to those in Pre-DAA. HCV/HIV coinfection had significantly lower patient mortality Post-DAA, compared to Pre-DAA (one-year: aHR 0.30, 95% CI 0.17-0.55; three-year: aHR 0.31, 95% CI 0.15-0.63). CONCLUSIONS Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection. This article is protected by copyright. All rights reserved.
BACKGROUND: Stomas are common surgical procedures with predictable outcome. When the operation is... more BACKGROUND: Stomas are common surgical procedures with predictable outcome. When the operation is done properly there can still be a spectrum of morbidities from poor appliance fitting to chronic skin breakdown. Irregularities in parastomal skin contour secondary to scarring, wound contraction, and change in weight and body habitus are major culprits. In cases where revising the stoma of relocating it are not options, other solutions are necessary. We report our experience with six patients who underwent recontouring of the parastomal soft tissue with fat grafting for improved skin contour and ostomy care.intervention:Patients were evaluated for contour deformities that were the primary cause for stoma/appliance disfunction. Deformities including skin folds, contracted scars, fat necrosis, tissue atrophy were identified for fat grafting. Areas of soft tissue prominence and fullness were highlighted for lipectomy via liposuction. In the operating room the appliances removed, topography and deformities marked in sitting and supine positions. Subcision, fat grafting and liposuction performed as necessary to the different areas of the abdomen. The goal of the surgery was a 3 cm wide uniform ring around the stoma in the superficial subcutaneous plane. Volumes for the fat grafting and lipectomy varied by patient. Photographs and interviewing performed before and after surgery. We frequently over-corrected the parastomal depressions to account for the 30% anticipated loss of the fat grafted over time. Medical records were reviewed to assess the improvement of postoperative stoma care. Outcome: Six patients underwent parastomal fat grafting from February 2017 to June 2018. Three patients had an end-ileostomy, one had a loop ileostomy, one with a chronic enterocutaneous fistula with ostomy appliance, and one patient had a urostomy. An average of 192.5 mL lipoaspirate was harvested (range: 120 - 350 mL), and 108 mL of filtrated and washed fat was grafted (range: 58-230 mL). Lipectomy via liposuction to the target area was performed in 2 patients. Average fat aspiration was 85 mL (75 ml and 110 ml). One patient had near complete resolution of leaks after the surgery and no major issues were reported after one year from the procedure. Two patients had major improvement of appliance seal with short-term follow up. Three patients had partial improvement in seal when compared to continuous leakage preoperatively. No complications were related to the procedure. CONCLUSIONS: Fat grafting is a novel and safe technique that could provide a solution for difficult stoma. partial improvements can have a significant positive impact on lifestyle. The procedure can be repeated if necessary. This is especially useful when patients have prohibitive risks to have further transabdominal procedures. Larger sample size and long-term follow up will be needed for further assessment of the outcomes.https://scholarlycommons.henryford.com/merf2019caserpt/1071/thumbnail.jp
Background: Pancreatic acinar cell carcinoma is a rare exocrine malignancy that is distinct from ... more Background: Pancreatic acinar cell carcinoma is a rare exocrine malignancy that is distinct from pancreatic ductal adenocarcinoma. We sought to describe its changing incidence, compare its natural history to that of pancreatic ductal adenocarcinoma, and evaluate impact of treatment modalities using the National Cancer Data Base, and Surveillance Epidemiology and End Results datasets. Methods: Patients with histologically confirmed diagnosis were identified from the National Cancer Data Base and Surveillance Epidemiology and End Results. Parametric univariate analyses were performed to compare patient characteristics, tumor types and outcomes. Incidence trends were calculated using Surveillance Epidemiology and End Results data and unadjusted Kaplan-Meier Survival analysis was performed using data from the National Cancer Data Base. Results: Incidence of acinar cell carcinoma significantly increased by 73% over the study period compared to only 22% for ductal adenocarcinoma (P<0.01). Unadjusted and adjusted stage-specific survival was substantially superior for acinar cell carcinoma versus ductal adenocarcinoma in all stages. Pancreatic acinar cell carcinoma demonstrated lower age at diagnosis, larger and lower grade tumors, was less likely to demonstrate histopathologic lymphovascular invasion, and more likely to undergo curative-intent resection with lower positive margins compared to ductal adenocarcinoma. Amongst resected patients, ductal carcinoma histology remained the strongest independent predictor of increased mortality hazard compared to pancreatic acinar cell carcinoma. Conclusions: Acinar cell carcinoma is a less aggressive malignancy with a significantly rising incidence of unknown etiology and better overall survival in both unadjusted analysis and after adjustment for clinically relevant predictors of mortality.
The case describes a 39 year old male that presented with epigastric pain, nausea and constipatio... more The case describes a 39 year old male that presented with epigastric pain, nausea and constipation. A computed tomography revealed a 2 x 3 cm lesion in the head of the pancreas. The patient was referred to our institution and a high contrast computed tomography showed the lesion to have grown to 5 x 5 cm within a period of 15 days. Biopsies were obtained from the pancreatic mass. However, a few days later the patient went into circulatory shock and was transported to the intensive care unit where he was treated for acute onset liver and kidney failure. The patient’s condition progressively worsened and despite all efforts of resuscitation, he passed away. Final immunohistochemical analysis revealed a poorly differentiated pancreatic adenosquamous carcinoma with sarcomatoid characteristics. pancreatic adenosquamous carcinoma is a rare exocrine pancreatic tumor demonstrated to have a more aggressive disease course than ductal adenocarcinoma. The additional sarcomatoid component in the...
Gastric cancer requires 5 cm margins when surgical resection is feasible. Only distal gastric can... more Gastric cancer requires 5 cm margins when surgical resection is feasible. Only distal gastric cancers can be treated with a subtotal gastrectomy. Lymph node dissection is essential for staging and risk stratification. While there is controversy between the stations of lymph nodes that need to be removed, the present chapter describes a D2 lymphadenectomy.
The first reports on pancreatic cancer resections were published after operations performed by Fr... more The first reports on pancreatic cancer resections were published after operations performed by Friedrich Trendelenburg (Bonn) in 1882, Theodor Billroth (Wien) in 1884, Alessandro Codivilla (Imola/Bologna) and William S Halsted (Baltimore) in 1898, Walter Kausch (Berlin) in 1912, Georg Hirschel (Heidelberg) in 1914, and Alexander Brunschwig (Chicago) in 1937. Presumably, the majority of these operations were performed for cancers of the papilla of Vater rather than for exocrine pancreatic cancer. It wasn’t until the publication by Allan Oldfather Whipple (New York) with two co-workers in 1935 [1] and subsequently his own article on “The rationale of radical surgery for cancer of the pancreas and ampullary region” in 1941 [2] that highlighted to surgical societies that pancreatic head cancer was technically resectable.
BACKGROUND The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after l... more BACKGROUND The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC. METHODS Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders. RESULTS Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71-1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71-1.54, p = 0.83). CONCLUSION Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.
Importance Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after li... more Importance Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. Objective To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. Design, Setting, and Participants A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. Main Outcomes and Measures The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. Results Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. Conclusions and Relevance This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.
Background: Patient-derived xenografts (PDXs) allow for patient cancer tissue amplification and d... more Background: Patient-derived xenografts (PDXs) allow for patient cancer tissue amplification and downstream in vivo research applications. A majority of PDXs derive from treatment naïve (TN) tumors. We aimed to generate PDXs from surgically resected TN and neoadjuvant (NA) pancreatic (PDAC) cancers to compare engraftment outcomes and create modern agent chemoresistant models. Methods: We maintain a prospective GI cancer PDX program. With informed consent and IRB approval, resected PDAC tissue is implanted into immunocompromised mice. Tumor growth is monitored, viable tumor is passed into subsequent generations, and pathologists confirm PDX histopatholgy to original patient tumor. MatePair sequencing characterized generated PDXs. Outcomes include 1) ischemic time (IT-time from retrieval to implantation, and 2) engraftment (ER-% of successful engraftment). Patient clinical, pathologic, and follow-up data were abstracted. Grade III treatment response was considered chemoresistant. Results: During 1/2013-8/2017, 139 patients with histologically confirmed PDAC were implanted (48 naïve and 91 neoadjuvant) with successful PDX ER in 70 (51%) tumors that was higher for TN tumors. Mate-pair analysis demonstrated highly correlative genomic signatures to primary patient tumor and PDX. Median IT did not differ between treatment groups Table. In NA tumors successful PDX ER varied by therapy type: FOLFIRINOX (FFX) 51%, gemcitabine/nab-paclitaxel (GA) 62%, and combined FFX/GA 22%. Table compares clinicopathologic features and patient outcomes between therapy type and PDX ER. Patients with successful PDX ER had significantly worse clinical RFS and OS regardless of treatment status. In total, we generated 19 FFX, 6 GA, and 1 FFX/GA resistant PDX models for future work. Conclusion: PDX generation after NA therapy is feasible and allows for creation of chemoresistant models for future drug development. Engraftment is successful in patients with minimal treatment response. PDX growth correlates with outcomes and is a valuable translational model for any patient. These PDXs will accommodate and assess differential responses to current therapies and elucidate predictive markers of response or resistance
Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular car... more Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Re...
BACKGROUND Liver transplant (LT) listing criteria for hepatocellular carcinoma (HCC) remain contr... more BACKGROUND Liver transplant (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate post-transplant HCC recurrence prediction calculator. METHODS HCC patients listed for LT from 2000-2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and post-transplant outcomes. We compared the CoxNet (regularized Cox regression), Survival Random Forest, Survival Support Vector Machine (SVM), and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it to other currently available recurrence risk algorithms on a held-out test set (AFP, MORAL, and HALT-HCC score). RESULTS The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% CI 0.64 - 0.84). In comparison, the recalibrated risk algorithms' concordance scores were: AFP score 0.64 (outperformed by the CoxNet model, one-sided 95% CI >0.006; p=0.04) and MORAL score 0.64 (outperformed by the CoxNet model one-sided 95% CI >0.015; p=0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI 0.63-0.81) and was not significantly outperformed (one-sided 95% CI >-0.05; p=0.29). CONCLUSIONS Developing a comprehensive post-transplant HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.
Background Despite high waiting list mortality rates, concern still exists on the appropriateness... more Background Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. Methods Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008–2011 and 2012–2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. Results A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipient...
Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes.... more Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Patient-derived xenografts preserve the unique histology and genetic characteristics of the original patient tumor. Successful engraftment is an independent predictor for worse recurrence-free patient survival. Patients with tumors containing tetraploid genomes had worse overall survival. Lay summary Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.
Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 re... more Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination. The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed. A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased lon...
Cecal bascule, initially described in 1899 by Treves, is the rarest form of cecal volvulus and re... more Cecal bascule, initially described in 1899 by Treves, is the rarest form of cecal volvulus and represents a phenomenon when a redundant and distended cecum folds anteriorly over the ascending colon causing an intestinal obstruction. Patients with cerebral palsy are at increased risk for this condition. We present a 28-year-old male with cerebral palsy, fully functionally dependent in activities of daily living, who presented to the emergency department with a large loop ileostomy prolapse which was the result of an inverted prolapsed cecum due to a cecal bascule. What differentiated this patient from others is that the prolapsed portion was the efferent limb of the ileostomy with the intussuscepted cecum and the entire right colon. To correct this, he underwent a right hemicolectomy with end ileostomy and transverse mucous fistula creation through the previous ostomy site. He progressed well appropriately postoperatively and was discharged home.This report highlights the rare phenom...
Additional file 8: Table S4. List of pathways associated with gene/proteins significantly increas... more Additional file 8: Table S4. List of pathways associated with gene/proteins significantly increased in HCC explant samples that exhibited post-transplant recurrence. Table S5. List of pathways associated with genes/proteins significantly decreased in HCC explant samples that exhibited post-transplant recurrence. Table S6. Clinical characteristics of the 29 patients transplanted for HCC beyond Milan criteria with versus without recurrence post-transplant. Median values are reported, and the 95% confidence intervals are displayed in the brackets.
Additional file 7: Table S3. Significantly enriched pathways among proteins differentially expres... more Additional file 7: Table S3. Significantly enriched pathways among proteins differentially expressed between HCC samples developing recurrence compared to non-recurrent ones. Pathways are determined using pathDIP, and those with adjusted p-value
Additional file 3: Figure S3. Kaplan–Meier survival plots for: (A) ALDH1A1 gene and protein; (B) ... more Additional file 3: Figure S3. Kaplan–Meier survival plots for: (A) ALDH1A1 gene and protein; (B) LGALS3 gene and protein; (C) LGALS3BP gene and protein in HCC patients. The levels of the gene/protein were grouped by mean. For ALDH1A1 gene: low level
BACKGROUND In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting... more BACKGROUND In recipients with HCV/HIV coinfection, the impact that the wider use of direct-acting antivirals (DAAs) has had on post-liver transplant (LT) outcomes has not been evaluated. We investigated the impact of DAAs introduction on post-LT outcome in patients with HCV/HIV coinfection. METHODS Using OPTN/UNOS data, we compared post-LT outcomes in patients with HCV and/or HIV pre- and post- DAAs introduction. We categorized these patients into two eras: Pre-DAA (2008-2012 [pre-DAA era]) and Post-DAA (2014-2019 [post-DAA era]). To study the impact of DAAs introduction, inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. RESULTS 17,215 LT recipients were eligible for this study (HCV/HIV [n = 160]; HIV mono-infection [n = 188]; HCV mono-infection [n = 16,867]). HCV/HIV coinfection and HCV mono-infection had a significantly lower hazard of one- and three-year graft loss Post-DAA, compared Pre-DAA (one-year: adjusted hazard ratio [aHR] 0.29, 95% CI 0.16-0.53 in HIV/HCV, aHR 0.58, 95% CI 0.54-0.63, respectively; three-year: aHR 0.30, 95% CI 0.14-0.61, aHR 0.64, 95%CI 0.58-0.70, respectively). The hazards of one- and three-year graft loss Post-DAA in HIV mono-infection were comparable to those in Pre-DAA. HCV/HIV coinfection had significantly lower patient mortality Post-DAA, compared to Pre-DAA (one-year: aHR 0.30, 95% CI 0.17-0.55; three-year: aHR 0.31, 95% CI 0.15-0.63). CONCLUSIONS Post-LT outcomes in patients with coinfection significantly improved and became comparable to those with HCV mono-infection after introducing DAA therapy. The introduction of DAAs supports the use of LT in the setting of HCV/HIV coinfection. This article is protected by copyright. All rights reserved.
BACKGROUND: Stomas are common surgical procedures with predictable outcome. When the operation is... more BACKGROUND: Stomas are common surgical procedures with predictable outcome. When the operation is done properly there can still be a spectrum of morbidities from poor appliance fitting to chronic skin breakdown. Irregularities in parastomal skin contour secondary to scarring, wound contraction, and change in weight and body habitus are major culprits. In cases where revising the stoma of relocating it are not options, other solutions are necessary. We report our experience with six patients who underwent recontouring of the parastomal soft tissue with fat grafting for improved skin contour and ostomy care.intervention:Patients were evaluated for contour deformities that were the primary cause for stoma/appliance disfunction. Deformities including skin folds, contracted scars, fat necrosis, tissue atrophy were identified for fat grafting. Areas of soft tissue prominence and fullness were highlighted for lipectomy via liposuction. In the operating room the appliances removed, topography and deformities marked in sitting and supine positions. Subcision, fat grafting and liposuction performed as necessary to the different areas of the abdomen. The goal of the surgery was a 3 cm wide uniform ring around the stoma in the superficial subcutaneous plane. Volumes for the fat grafting and lipectomy varied by patient. Photographs and interviewing performed before and after surgery. We frequently over-corrected the parastomal depressions to account for the 30% anticipated loss of the fat grafted over time. Medical records were reviewed to assess the improvement of postoperative stoma care. Outcome: Six patients underwent parastomal fat grafting from February 2017 to June 2018. Three patients had an end-ileostomy, one had a loop ileostomy, one with a chronic enterocutaneous fistula with ostomy appliance, and one patient had a urostomy. An average of 192.5 mL lipoaspirate was harvested (range: 120 - 350 mL), and 108 mL of filtrated and washed fat was grafted (range: 58-230 mL). Lipectomy via liposuction to the target area was performed in 2 patients. Average fat aspiration was 85 mL (75 ml and 110 ml). One patient had near complete resolution of leaks after the surgery and no major issues were reported after one year from the procedure. Two patients had major improvement of appliance seal with short-term follow up. Three patients had partial improvement in seal when compared to continuous leakage preoperatively. No complications were related to the procedure. CONCLUSIONS: Fat grafting is a novel and safe technique that could provide a solution for difficult stoma. partial improvements can have a significant positive impact on lifestyle. The procedure can be repeated if necessary. This is especially useful when patients have prohibitive risks to have further transabdominal procedures. Larger sample size and long-term follow up will be needed for further assessment of the outcomes.https://scholarlycommons.henryford.com/merf2019caserpt/1071/thumbnail.jp
Background: Pancreatic acinar cell carcinoma is a rare exocrine malignancy that is distinct from ... more Background: Pancreatic acinar cell carcinoma is a rare exocrine malignancy that is distinct from pancreatic ductal adenocarcinoma. We sought to describe its changing incidence, compare its natural history to that of pancreatic ductal adenocarcinoma, and evaluate impact of treatment modalities using the National Cancer Data Base, and Surveillance Epidemiology and End Results datasets. Methods: Patients with histologically confirmed diagnosis were identified from the National Cancer Data Base and Surveillance Epidemiology and End Results. Parametric univariate analyses were performed to compare patient characteristics, tumor types and outcomes. Incidence trends were calculated using Surveillance Epidemiology and End Results data and unadjusted Kaplan-Meier Survival analysis was performed using data from the National Cancer Data Base. Results: Incidence of acinar cell carcinoma significantly increased by 73% over the study period compared to only 22% for ductal adenocarcinoma (P<0.01). Unadjusted and adjusted stage-specific survival was substantially superior for acinar cell carcinoma versus ductal adenocarcinoma in all stages. Pancreatic acinar cell carcinoma demonstrated lower age at diagnosis, larger and lower grade tumors, was less likely to demonstrate histopathologic lymphovascular invasion, and more likely to undergo curative-intent resection with lower positive margins compared to ductal adenocarcinoma. Amongst resected patients, ductal carcinoma histology remained the strongest independent predictor of increased mortality hazard compared to pancreatic acinar cell carcinoma. Conclusions: Acinar cell carcinoma is a less aggressive malignancy with a significantly rising incidence of unknown etiology and better overall survival in both unadjusted analysis and after adjustment for clinically relevant predictors of mortality.
The case describes a 39 year old male that presented with epigastric pain, nausea and constipatio... more The case describes a 39 year old male that presented with epigastric pain, nausea and constipation. A computed tomography revealed a 2 x 3 cm lesion in the head of the pancreas. The patient was referred to our institution and a high contrast computed tomography showed the lesion to have grown to 5 x 5 cm within a period of 15 days. Biopsies were obtained from the pancreatic mass. However, a few days later the patient went into circulatory shock and was transported to the intensive care unit where he was treated for acute onset liver and kidney failure. The patient’s condition progressively worsened and despite all efforts of resuscitation, he passed away. Final immunohistochemical analysis revealed a poorly differentiated pancreatic adenosquamous carcinoma with sarcomatoid characteristics. pancreatic adenosquamous carcinoma is a rare exocrine pancreatic tumor demonstrated to have a more aggressive disease course than ductal adenocarcinoma. The additional sarcomatoid component in the...
Gastric cancer requires 5 cm margins when surgical resection is feasible. Only distal gastric can... more Gastric cancer requires 5 cm margins when surgical resection is feasible. Only distal gastric cancers can be treated with a subtotal gastrectomy. Lymph node dissection is essential for staging and risk stratification. While there is controversy between the stations of lymph nodes that need to be removed, the present chapter describes a D2 lymphadenectomy.
The first reports on pancreatic cancer resections were published after operations performed by Fr... more The first reports on pancreatic cancer resections were published after operations performed by Friedrich Trendelenburg (Bonn) in 1882, Theodor Billroth (Wien) in 1884, Alessandro Codivilla (Imola/Bologna) and William S Halsted (Baltimore) in 1898, Walter Kausch (Berlin) in 1912, Georg Hirschel (Heidelberg) in 1914, and Alexander Brunschwig (Chicago) in 1937. Presumably, the majority of these operations were performed for cancers of the papilla of Vater rather than for exocrine pancreatic cancer. It wasn’t until the publication by Allan Oldfather Whipple (New York) with two co-workers in 1935 [1] and subsequently his own article on “The rationale of radical surgery for cancer of the pancreas and ampullary region” in 1941 [2] that highlighted to surgical societies that pancreatic head cancer was technically resectable.
BACKGROUND The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after l... more BACKGROUND The impact of packed Red Blood Cell (pRBC) transfusion on oncological outcomes after liver transplantation (LT) for Hepatocellular Carcinoma (HCC) remains controversial. We evaluated the impact of pRBC transfusion on HCC recurrence and overall survival (OS) after LT for HCC. METHODS Patients with HCC transplanted between 2000 and 2018 were included and stratified by receipt of pRBC transfusion. Outcomes were HCC recurrence and OS. Propensity score matching was performed to account for confounders. RESULTS Of the 795 patients, 234 (29.4%) did not receive pRBC transfusion. After matching the 1-, 3-, and 5-year cumulative incidence of recurrence was 6.6%, 12.5% and 14.8% for no-pRBC transfusion, and 8.6%, 18.8% and 21.3% (p = 0.61) for pRBC transfusion. The OS at 1-, 3-, 5-year was 93.0%, 84.6% and 75.8% vs 92.0%, 79.7% and 73.5% (p = 0.83) for no-pRBC transfusion and pRBC transfusion, respectively. There were no differences in recurrence (HR 1.13, 95%CI 0.71-1.78, p = 0.61) or OS (HR 1.04, 95%CI 0.71-1.54, p = 0.83). CONCLUSION Perioperative administration of pRBC in liver transplant recipients for HCC resulted in a nonsignificant increase of HCC recurrence and death after accounting for confounder. Surgeons should continue to exercise cation and optimize patients iron stores medically preoperatively.
Importance Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after li... more Importance Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. Objective To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. Design, Setting, and Participants A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. Main Outcomes and Measures The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. Results Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. Conclusions and Relevance This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.
Background: Patient-derived xenografts (PDXs) allow for patient cancer tissue amplification and d... more Background: Patient-derived xenografts (PDXs) allow for patient cancer tissue amplification and downstream in vivo research applications. A majority of PDXs derive from treatment naïve (TN) tumors. We aimed to generate PDXs from surgically resected TN and neoadjuvant (NA) pancreatic (PDAC) cancers to compare engraftment outcomes and create modern agent chemoresistant models. Methods: We maintain a prospective GI cancer PDX program. With informed consent and IRB approval, resected PDAC tissue is implanted into immunocompromised mice. Tumor growth is monitored, viable tumor is passed into subsequent generations, and pathologists confirm PDX histopatholgy to original patient tumor. MatePair sequencing characterized generated PDXs. Outcomes include 1) ischemic time (IT-time from retrieval to implantation, and 2) engraftment (ER-% of successful engraftment). Patient clinical, pathologic, and follow-up data were abstracted. Grade III treatment response was considered chemoresistant. Results: During 1/2013-8/2017, 139 patients with histologically confirmed PDAC were implanted (48 naïve and 91 neoadjuvant) with successful PDX ER in 70 (51%) tumors that was higher for TN tumors. Mate-pair analysis demonstrated highly correlative genomic signatures to primary patient tumor and PDX. Median IT did not differ between treatment groups Table. In NA tumors successful PDX ER varied by therapy type: FOLFIRINOX (FFX) 51%, gemcitabine/nab-paclitaxel (GA) 62%, and combined FFX/GA 22%. Table compares clinicopathologic features and patient outcomes between therapy type and PDX ER. Patients with successful PDX ER had significantly worse clinical RFS and OS regardless of treatment status. In total, we generated 19 FFX, 6 GA, and 1 FFX/GA resistant PDX models for future work. Conclusion: PDX generation after NA therapy is feasible and allows for creation of chemoresistant models for future drug development. Engraftment is successful in patients with minimal treatment response. PDX growth correlates with outcomes and is a valuable translational model for any patient. These PDXs will accommodate and assess differential responses to current therapies and elucidate predictive markers of response or resistance
Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular car... more Background and aims Liver transplantation (LT) can be offered to patients with Hepatocellular carcinoma (HCC) beyond Milan criteria. However, there are currently limited molecular markers on HCC explant histology to predict recurrence, which arises in up to 20% of LT recipients. The goal of our study was to derive a combined proteomic/transcriptomic signature on HCC explant predictive of recurrence post-transplant using unbiased, high-throughput approaches. Methods Patients who received a LT for HCC beyond Milan criteria in the context of hepatitis B cirrhosis were identified. Tumor explants from patients with post-transplant HCC recurrence (N = 7) versus those without recurrence (N = 4) were analyzed by mass spectrometry and gene expression array. Univariate analysis was used to generate a combined proteomic/transcriptomic signature linked to recurrence. Significantly predictive genes and proteins were verified and internally validated by immunoblotting and immunohistochemistry. Re...
BACKGROUND Liver transplant (LT) listing criteria for hepatocellular carcinoma (HCC) remain contr... more BACKGROUND Liver transplant (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate post-transplant HCC recurrence prediction calculator. METHODS HCC patients listed for LT from 2000-2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and post-transplant outcomes. We compared the CoxNet (regularized Cox regression), Survival Random Forest, Survival Support Vector Machine (SVM), and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it to other currently available recurrence risk algorithms on a held-out test set (AFP, MORAL, and HALT-HCC score). RESULTS The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% CI 0.64 - 0.84). In comparison, the recalibrated risk algorithms' concordance scores were: AFP score 0.64 (outperformed by the CoxNet model, one-sided 95% CI >0.006; p=0.04) and MORAL score 0.64 (outperformed by the CoxNet model one-sided 95% CI >0.015; p=0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI 0.63-0.81) and was not significantly outperformed (one-sided 95% CI >-0.05; p=0.29). CONCLUSIONS Developing a comprehensive post-transplant HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting.
Background Despite high waiting list mortality rates, concern still exists on the appropriateness... more Background Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. Methods Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008–2011 and 2012–2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. Results A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipient...
Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes.... more Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Patient-derived xenografts preserve the unique histology and genetic characteristics of the original patient tumor. Successful engraftment is an independent predictor for worse recurrence-free patient survival. Patients with tumors containing tetraploid genomes had worse overall survival. Lay summary Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.
Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 re... more Optimal management of patients with intrahepatic cholangiocarcinoma (ICCA) and elevated CA19-9 remains undefined. We hypothesized CA19-9 elevation above normal indicates aggressive biology and that inclusion of CA19-9 would improve staging discrimination. The National Cancer Data Base (NCDB-2010-2012) was reviewed for patients with ICCA and reported CA19-9. Patients were stratified by CA19-9 above/below normal reference range. Unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis of overall survival (OS) were performed. A total of 2,816 patients were included: 938 (33.3%) normal; 1,878 (66.7%) elevated CA19-9 levels. Demographic/pathologic and chemotherapy/radiation were similar between groups, but patients with elevated CA19-9 had more nodal metastases and less likely to undergo resection. Among elevated-CA19-9 patients, stage-specific survival was decreased in all stages. Resected patients with CA19-9 elevation had similar peri-operative outcomes but decreased lon...
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