The PrEDICT-DGE score as a simple preoperative screening tool identifies patients at increased risk for delayed gastric emptying after pancreaticoduodenectomy.

BACKGROUND: Morbidity after Pancreaticoduodenectomy (PD) has remained unchanged over the past decade. Delayed Gastric Emptying (DGE) is a major contributor with significant impact on healthcare-costs, quality of life and, for malignancies, even survival. We sought to develop a scoring system to aid in easy preoperative identification of patients at risk for DGE. METHODS: The ACS-NSQIP dataset from 2014 to 2018 was queried for patients undergoing PD with Whipple or pylorus preserving reconstruction. 15,154 patients were analyzed using multivariable logistic regression to identify risk factors for DGE, which were incorporated into a prediction model. Subgroup analysis of patients without SSI or fistula (primary DGE) was performed. RESULTS: We identified 9 factors independently associated with DGE to compile the PrEDICT-DGE score: Procedures (Concurrent adhesiolysis, feeding jejunostomy, vascular reconstruction with vein graft), Elderly (Age>70), Ductal stent (Lack of biliary stent), Invagination (Pancreatic reconstruction technique), COPD, Tobacco use, Disease, systemic (ASA>2), Gender (Male) and Erythrocytes (preoperative RBC-transfusion). PrEDICT-DGE scoring strongly correlated with actual DGE rates (R2 = 0.95) and predicted patients at low, intermediate, and high risk. Subgroup analysis of patients with primary DGE, retained all predictive factors, except for age>70 (p = 0.07) and ASA(p = 0.30). CONCLUSION: PrEDICT-DGE scoring accurately identifies patients at high risk for DGE and can help guide perioperative management.

Impact of preoperative biliary drainage on 30 Day outcomes of patients undergoing pancreaticoduodenectomy for malignancy.

BACKGROUND: Preoperative biliary drainage (PBD) has been advocated to address the plethora of physiologic derangements associated with cholestasis. However, available literature reports mixed outcomes and is based on largely outdated and/or single-institution studies. METHODS: Patients undergoing PBD prior to pancreaticoduodenectomy (PD) for periampullary malignancy between 2014-2018 were identified in the ACS-NSQIP pancreatectomy dataset. Patients with PBD were propensity-score-matched to those without PBD and 30-day outcomes compared. RESULTS: 8,970 patients met our inclusion criteria. 4,473 with obstruction and PBD were matched to 829 with no preoperative drainage procedure. In the non-jaundiced cohort, 711 stented patients were matched to 2,957 without prior intervention. PBD did not influence 30-day mortality (2.2% versus 2.4%) or major morbidity (19.8% versus 20%) in patients with obstructive jaundice. Superficial surgical site infections (SSIs) were more common with PBD (6.8% versus 9.2%), however, no differences in deep or organ-space SSIs were found. Patients without obstruction prior to PBD exhibited a 3-fold increase in wound dehiscence (0.5% versus 1.5%) additionally to increased superficial SSIs. CONCLUSION: PBD was not associated with an increase in 30-day mortality or major morbidity but increased superficial SSIs. PBD should be limited to symptomatic, profoundly jaundiced patients or those with a delay prior to PD.

Travel patterns of cancer surgery patients in a regionalized system.

BACKGROUND: Regionalization of complex surgeries has increased patient travel distances possibly leaving a substantial burden on those at risk for poorer surgical outcomes. To date, little is known about travel patterns of cancer surgery patients in regionalized settings. To inform this issue, we sought to assess travel patterns of those undergoing a major cancer surgery within a regionalized system. MATERIALS AND METHODS: We identified 4733 patients who underwent lung, esophageal, gastric, liver, pancreatic, and colorectal resections from 2002-2014 within a multihospital system in the Mid-Atlantic region of the United States. Patient age, race and/or ethnicity, and insurance status were extracted from electronic health records. We used Geographical Information System capabilities in R software to estimate travel distance and map patient addresses based on cancer surgery type and these characteristics. We used visual inspection, analysis of variance, and interaction analyses to assess the distribution of travel distances between patient populations. RESULTS: A total of 48.2% of patients were non-white, 49.9% were aged >65 y, and 54.9% had private insurance. Increased travel distance was associated with decreasing age and those undergoing pancreatic and esophageal resections. Also, black patients tend to travel shorter distances than other racial and/or ethnic groups. CONCLUSIONS: These maps offer a preliminary understanding into variations of geospatial travel patterns among patients receiving major cancer surgery in a Mid-Atlantic regionalized setting. Future research should focus on the impact of regionalization on timely delivery of surgical care and other quality metrics.

Colloid Carcinoma of the Pancreas: A Rare Initial Presentation of Lynch Syndrome.

Patients with Lynch syndrome, most commonly associated with colorectal cancer, have an increased risk of developing other tumors including pancreatic ductal adenocarcinoma and precursor lesions, such as intraductal papillary mucinous neoplasms. Here, we present a case of a man in his early 20s who presented with a retroperitoneal mass involving the head of the pancreas. Following a pancreaticoduodenectomy combined with para-aortic lymphadenectomy, a pathologic diagnosis of colloid carcinoma, also known as mucinous noncystic carcinoma, of the pancreas was reported. Further testing established the diagnosis of Lynch syndrome. This case is unique because colloid carcinoma of the pancreas is rare and has never been reported as an initial presentation of Lynch syndrome.

Outcomes of liver transplant recipients with hepatitis C and human immunodeficiency virus coinfection.

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

Loss of transforming growth factor ß adaptor protein ß-2 spectrin leads to delayed liver regeneration in mice.

UNLABELLED: Liver regeneration, following partial hepatectomy (PHx), occurs through precisely controlled and synchronized cell proliferation, in which quiescent hepatocytes undergo one to two rounds of replication, with restoration of liver mass and function. We previously demonstrated that loss of the Smad3/4 adaptor protein ß-2 spectrin (ß2SP) is associated with faster entry into S phase, and hepatocellular cancer formation. These observations led us to further pursue the role of ß2SP in cell cycle progression in vivo. Liver regeneration studies with PHx in ß2SP(+/-) mice reveal a surprising and significant decrease in liver/body weight ratio at 48 hours after PHx in ß2SP(+/-) mice in comparison to wildtype mice. At 48 hours after PHx we also observe decreased levels of cyclin E (2.4-fold, P < 0.05), Cdk1 (7.2-fold, P < 0.05), cyclin A, pRb (Ser249/Thr252), proliferative cell nuclear antigen (PCNA), cyclin D1 with elevated levels of pCdk1 (Thr14) (3.6-fold, P < 0.05). Strikingly, at 24 hours elevated levels of p53 (4-fold, P < 0.05), phospho-p53 (ser15 and ser20), and p21 (200-fold, P < 0.05) persisting to 48 hours after PHx further correlated with raised expression of the DNA damage markers pChk2 (Thr68) and γH2AX (S139). However, compromised cell cycle progression with loss of ß2SP is not rescued by inhibiting p53 function, and that G(2) /M phase arrest observed is independent and upstream of p53. CONCLUSION: ß2SP deficiency results in dysfunctional hepatocyte cell cycle progression and delayed liver regeneration at 48 hours after PHx, which is p53-independent. ß2SP loss may increase susceptibility to DNA damage, impair cell cycle progression, and ultimately lead to hepatocellular cancer.

Persistent disparities in liver transplantation for patients with hepatocellular carcinoma in the United States, 1998 through 2007.

BACKGROUND: Prior studies have demonstrated that among patients with hepatocellular carcinoma (HCC), African Americans (AAs) and Asian/Pacific Islanders (APIs) are substantially less likely to undergo liver transplantation (LT) compared with whites. The authors examined whether disparities in the receipt of LT among LT-eligible HCC patients changed over a 10-year time period, and whether the disparities might be explained by sociodemographic or clinical factors. METHODS: The National Cancer Data Base, a national hospital-based cancer registry, was used to study 7707 adults with small (≤ 5 cm), nonmetastatic HCC diagnosed between 1998 and 2007. Racial/ethnic patterns in the use of LT were compared during 2 periods of 5 years each: 1998 through 2002 (n = 2412 patients) and 2003 through 2007 (n = 5295 patients). Data regarding comorbid medical conditions were only available during the later time period. RESULTS: Large and persistent racial/ethnic differences in the probability of receiving LT were observed. Compared with whites, hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for receiving LT from 1998 through 2002 were 0.64 (95% CI, 0.46-0.89) for AA patients, 1.01 (95% CI, 0.79-1.29) for Hispanic patients, and 0.52 (95% CI, 0.39-0.68) for API patients. Analogous results for 2003 through 2007 were 0.64 (95% CI, 0.54-0.76) for AA patients, 0.86 (95% CI, 0.75-0.99) for Hispanic patients, and 0.58 (95% CI, 0.49-0.69) for API patients. AA patients were less likely than whites to undergo any form of surgery, and API patients were more likely than whites to undergo surgical resection. Adjustment for sociodemographic and clinical factors produced only small changes in these HRs. CONCLUSIONS: Between 1998 and 2007, there were large and persistent racial/ethnic disparities noted in the receipt of LT among patients with HCC. These disparities were not explained by sociodemographic or clinical factors.

Role of transforming growth factor beta signaling and expansion of progenitor cells in regenerating liver.

UNLABELLED: Adult hepatic progenitor cells are activated during regeneration when hepatocytes and bile duct epithelium are damaged or unable to proliferate. On the basis of its role as a tumor suppressor and in the potential malignant transformation of stem cells in hepatocellular carcinoma, we investigated the role of key transforming growth factor beta (TGF-beta) signaling components, including the Smad3 adaptor protein beta2-Spectrin (beta2SP), in liver regeneration. We demonstrate a streaming hepatocyte-specific dedifferentiation process in regenerating adult human liver less than 6 weeks following living donor transplantation. We then demonstrate a spatial and temporal expansion of TGF-beta signaling components, especially beta2SP, from the periportal to the pericentral zone as regeneration nears termination via immunohistochemical analysis. This expansion is associated with an expanded remaining pool of octamer 3/4 (Oct3/4)-positive progenitor cells localized to the portal tract in adult human liver from more than 6 weeks posttransplant. Furthermore, disruption of TGF-beta signaling as in the beta2SP (beta2SP+/-) knockout mouse demonstrated a striking 2 to 4-fold (P < 0.05) expanded population of Oct3/4-positive cells with activated Wnt signaling occupying an alpha-fetoprotein (AFP)+/cytokeratin-19 (CK-19)-positive progenitor cell niche following two-thirds partial hepatectomy. CONCLUSION: TGF-beta signaling, particularly beta2SP, plays a critical role in hepatocyte proliferation and transitional phenotype and its loss is associated with activation of hepatic progenitor cells secondary to delayed mitogenesis and activated Wnt signaling.

Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling.

Cancer stem cells (CSCs) are critical for the initiation, propagation, and treatment resistance of multiple cancers. Yet functional interactions between specific signaling pathways in solid organ "cancer stem cells," such as those of the liver, remain elusive. We report that in regenerating human liver, two to four cells per 30,000-50,000 cells express stem cell proteins Stat3, Oct4, and Nanog, along with the prodifferentiation proteins TGF-beta-receptor type II (TBRII) and embryonic liver fodrin (ELF). Examination of human hepatocellular cancer (HCC) reveals cells that label with stem cell markers that have unexpectedly lost TBRII and ELF. elf(+/-) mice spontaneously develop HCC; expression analysis of these tumors highlighted the marked activation of the genes involved in the IL-6 signaling pathway, including IL-6 and Stat3, suggesting that HCC could arise from an IL-6-driven transformed stem cell with inactivated TGF-beta signaling. Similarly, suppression of IL-6 signaling, through the generation of mouse knockouts involving a positive regulator of IL-6, Inter-alpha-trypsin inhibitor-heavy chain-4 (ITIH4), resulted in reduction in HCC in elf(+/-) mice. This study reveals an unexpected functional link between IL-6, a major stem cell signaling pathway, and the TGF-beta signaling pathway in the modulation of mammalian HCC, a lethal cancer of the foregut. These experiments suggest an important therapeutic role for targeting IL-6 in HCCs lacking a functional TGF-beta pathway.

Liver stem cells and hepatocellular carcinoma.

Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression. However, many details about hepatocellular cancer stem cells that are important for early detection remain poorly understood, including the precise cell(s) of origin, molecular genetics, and the mechanisms responsible for the highly aggressive clinical picture of hepatocellular carcinoma (HCC). Exploration of the difference between CSCs from normal stem cells is crucial not only for the understanding of tumor biology but also for the development of specific therapies that effectively target these cells in patients. These ideas have drawn attention to control of stem cell proliferation by the transforming growth factor beta (TGF-beta), Notch, Wnt, and Hedgehog pathways. Recent evidence also suggests a key role for the TGF-beta signaling pathway in both hepatocellular cancer suppression and endoderm formation, suggesting a dual role for this pathway in tumor suppression as well as progression of differentiation from a stem or progenitor stage. This review provides a rationale for detecting and analyzing tumor stem cells as one of the most effective ways to treat cancers such as HCC.

Medicaid Expansion and Disparity Reduction in Surgical Cancer Care at High-Quality Hospitals.

BACKGROUND: The Affordable Care Act's Medicaid expansion has been heavily debated due to skepticism about Medicaid's ability to provide high-quality care. Particularly, little is known about whether Medicaid expansion improves access to surgical cancer care at high-quality hospitals. To address this question, we examined the effects of the 2001 New York Medicaid expansion, the largest in the pre-Affordable Care Act era, on this disparity measure. STUDY DESIGN: We identified 67,685 nonelderly adults from the New York State Inpatient Database who underwent select cancer resections. High-quality hospitals were defined as high-volume or low-mortality hospitals. Disparity was defined as model-adjusted difference in percentage of patients receiving operations at high-quality hospitals by insurance type (Medicaid/uninsured vs privately insured) or by race (African American vs white). Levels of disparity were calculated quarterly for each comparison pair and then analyzed using interrupted time series to evaluate the impact of Medicaid expansion. RESULTS: Disparity in access to high-volume hospitals by insurance type was reduced by 0.97 percentage points per quarter after Medicaid expansion (p < 0.0001). Medicaid/uninsured beneficiaries had similar access to low-mortality hospitals as the privately insured; no significant change was detected around expansion. Conversely, racial disparity increased by 0.87 percentage points per quarter (p < 0.0001) in access to high-volume hospitals and by 0.48 percentage points per quarter (p = 0.005) in access to low-mortality hospitals after Medicaid expansion. CONCLUSIONS: Pre-Affordable Care Act Medicaid expansion reduced the disparity in access to surgical cancer care at high-volume hospitals by payer. However, it was associated with increased racial disparity in access to high-quality hospitals. Addressing racial barriers in access to high-quality hospitals should be prioritized.

The Affordable Care Act's Medicaid expansion and utilization of discretionary vs. non-discretionary inpatient surgery.

BACKGROUND: While pre-Affordable Care Act expansions in Medicaid eligibility led to increased utilization of elective inpatient procedures, the impact of the Affordable Care Act on such preference-sensitive procedures (also known as discretionary procedures) versus time-sensitive non-discretionary procedures remains unknown. As such, we performed a hospital-level quasi-experimental evaluation to measure the differential effects of the Affordable Care Act's Medicaid expansion on utilization of discretionary procedures versus non-discretionary procedures. METHODS: The State Inpatient Database (2012-2014) yielded 476 hospitals providing selected discretionary procedures or non-discretionary procedures performed on 288,446 non-elderly, adult patients across 3 expansion states and 2 non-expansion control states. Discretionary procedures included non-emergent total knee and hip arthroplasty, while non-discretionary procedures included nine cancer surgeries. Mixed Poisson interrupted time series analyses were performed to determine the impact of the Affordable Care Act's Medicaid expansion on the number of discretionary procedures versus non-discretionary procedures provided among non-privately insured patients (Medicaid and uninsured patients) and privately insured patients. RESULTS: Analysis of the number of non-privately insured procedures showed an increase in discretionary procedures of +15.1% (IRR 1.15, 95% CI:1.11-1.19) vs -4.0% (IRR 0.96, 95% CI:0.94-0.99) and non-discretionary procedures of +4.1% (IRR 1.04, 95% CI:1.0-1.1) vs -5.3% (IRR 0.95, 95% CI:0.93-0.97) in expansion states compared to non-expansion states, respectively. Analysis of privately insured procedures showed no statistically meaningful change in discretionary procedures or non-discretionary procedures in either expansion or non-expansion states. CONCLUSION: In this multi-state evaluation, the Affordable Care Act's Medicaid expansion preferentially increased utilization of discretionary procedures versus non-discretionary procedures in expansion states compared to non-expansion states among non-privately insured patients. These preliminary findings suggest that increased Medicaid coverage may have contributed to the increased use of inpatient surgery for discretionary procedures.

Primary mucosa-associated lymphoid tissue lymphoma of the liver: A report of two cases and review of the literature.

Mucosa-associated lymphoid tissue (MALT) lymphoma of the liver is a very rare condition and thus the diagnosis may be challenging. The clinical presentation is usually variable, ranging from minimal clinical symptoms to severe end stage liver disease. In this paper, we describe the clinicopathologic findings in two cases of primary hepatic MALT lymphoma. One case is an 80-year-old female with no underlying chronic liver disease and the second case is a 30-year-old female with autoimmune hepatitis complicated by MALT lymphoma. In both specimens, there was diffuse infiltration of atypical B-lymphocytes that were positive for CD20 and CD79a, but negative for CD5, CD43 and CD10. There were occasional lymphoepithelial lesions involving the hepatocytes or bile ducts. Polymerase chain reaction analysis showed monoclonal immunoglobulin heavy chain gene rearrangement in both cases. The first case was treated with surgery but developed pulmonary recurrence a year after complete resection but went into remission following treatment with rituximab. A second recurrence occurred in the right parotid gland 7 years later, which was treated with idelalisib. The second case was effectively treated with rituximab. To our knowledge, the second case is the first reported case linked to autoimmune hepatitis.

Primary Epidermoid Cyst of Biliary Duct Presenting as Choledochal Cyst.

Choledochal cyst is a cystic dilation of the biliary tree that can increase the risk of malignancy in bile ducts and the gallbladder. These are usually lined by bile duct epithelium, which may undergo intestinal and squamous metaplasia. This is the first report of clinically diagnosed type II choledochal cyst that is entirely lined by metaplastic stratified squamous epithelium, unlike most other cysts, which are histologically lined by bile duct epithelium. This observation can potentially explain the underlying pathogenic mechanism of rare reports of squamous cell carcinomas arising in bile duct systems.

Foreign body entrapment during thoracic surgery-time for closed loop communication.

OBJECTIVES: During general thoracic surgery procedures, devices are often placed in the airway and oesophagus. This creates an opportunity for foreign body entrapment (FBE) during pulmonary and foregut surgery. Like retained foreign bodies (RFB), FBE is an entirely preventable event. Unlike RFB, there is minimal literature on FBE, thus little is known about its occurrence, risk factors, and prevention. METHODS: A survey was distributed to 215 surgeons of the General Thoracic Surgical Club. The survey included questions about socio-demographics, procedural volume, occurrence of FBE and factors leading to FBE. RESULTS: There were 110 responses (51%, 110/215). The majority of respondents worked in academic hospitals (75%, 82/110), in urban environments (63%, 69/110), and were male (85%, 94/110). One hundred and four respondents performed pulmonary resections and 92 performed foregut surgeries. In the pulmonary group, 40% (42/104) reported FBE with 67% (23/42) in open procedures. In the foregut group 38% (35/92) reported FBE with 69% (24/35) in open procedures. With both groups combined, 54.5% (60/110) of respondents reported FBE at least once and 29% (24/110) reported more than one FBE in their career. The most frequently reported contributing factor was communication errors between the surgical and anaesthesia teams. CONCLUSIONS: FBE during general thoracic procedures occurs in both minimally invasive and open pulmonary and foregut procedures. The greatest risk factor is communication error. Specific routine closed loop communication with the anaesthesia team prior to stapling/suturing the airway or oesophagus would minimize the risk of FBE.

Why Do Long-Distance Travelers Have Improved Pancreatectomy Outcomes?

BACKGROUND: Centralization of complex surgical care has led patients to travel longer distances. Emerging evidence suggested a negative association between increased travel distance and mortality after pancreatectomy. However, the reason for this association remains largely unknown. We sought to unravel the relationships among travel distance, receiving pancreatectomy at high-volume hospitals, delayed surgery, and operative outcomes. STUDY DESIGN: We identified 44,476 patients who underwent pancreatectomy for neoplasms between 2004 and 2013 at the reporting facility from the National Cancer Database. Multivariable analyses were performed to examine the independent relationships between increments in travel distance mortality (30-day and long-term survival) after adjusting for patient demographics, comorbidity, cancer stage, and time trend. We then examined how additional adjustment of procedure volume affected this relationship overall and among rural patients. RESULTS: Median travel distance to undergo pancreatectomy increased from 16.5 to 18.7 miles (p for trend < 0.001). Although longer travel distance was associated with delayed pancreatectomy, it was also related to higher odds of receiving pancreatectomy at a high-volume hospital and lower postoperative mortality. In multivariable analysis, difference in mortality among patients with varying travel distance was attenuated by adjustment for procedure volume. However, longest travel distance was still associated with a 77% lower 30-day mortality rate than shortest travel among rural patients, even when accounting for procedure volume. CONCLUSIONS: Our large national study found that the beneficial effect of longer travel distance on mortality after pancreatectomy is mainly attributable to increase in procedure volume. However, it can have additional benefits on rural patients that are not explained by volume. Distance can represent a surrogate for rural populations.