Olugbenga Olowokure

Factors associated with recidivism following pancreaticoduodenectomy

OBJECTIVES Factors related to readmission after pancreaticoduodenectomy (PD) may include postoperative morbidity and the functional status of the patient. This study aimed to retrospectively review our institutions experience of readmission of patients who had undergone Whipple procedure PD. METHODS Recidivism was defined as readmission to the primary or a secondary hospital within, respectively, 30 days, 30-90 days or 90 days postoperatively. Associations between recidivism, perioperative factors and patient characteristics were evaluated. RESULTS During the past 5 years, 30-day, 30-90-day and 90-day recidivism rates were 14.5%, 18.5% and 27.4%, respectively. The most common reasons for readmission included dehydration and/or malnutrition (37.5% of readmissions) and pain (12.5%). Patients who underwent PD for chronic pancreatitis were more likely to be readmitted within 90 days of surgery than patients who underwent PD for malignancy (P < 0.01). Intraoperative transfusion was also associated with 30-90-day and 90-day recidivism (P < 0.01). Preoperative comorbidities, including Charlson Comorbidity Index score, number of pre-discharge complications, type of Whipple reconstruction, preoperative biliary stenting, need for vascular reconstruction and patient body mass index were not associated with recidivism. CONCLUSIONS Our data confirm previous reports indicating high rates of readmission after PD. To our knowledge, this report is the first to demonstrate chronic pancreatitis as an independent risk factor for readmission.

Pulmonary metastases in pancreatic cancer, is there a survival influence?

Pancreatic cancer is known to be one of the most lethal cancers. The majority of patients present with advanced stage disease, making curative approach unachievable. In untreated patients, the median survival does not exceed 6 months in metastatic disease and 10 months in locally advanced disease. Furthermore, the 5-year survival rate remains poor even in patients with early stage disease who are surgical candidates. The detrimental outcome is related to the high potency of developing metastasis which can be detected at diagnosis, when the disease progresses or relapses after surgery. Although the liver is the most common site of pancreatic cancer metastases, the cancer can escape the liver in some cases and metastasize to the lung or other distant organs. The involvement of some sites not others might reflect subgroups of this cancer with different molecular backgrounds. Identifying these groups may have utility in determining prognosis and stratifying treatment for patients.

Pancreatic cancer: current standards, working towards a new therapeutic approach.

Pancreatic cancer is the fourth leading cause of cancer deaths with a 5-year survival of 4–6%. Clinical challenges remain to be addressed, since few promising approaches to treat pancreatic cancer have been reported. Here we discuss the potential of a new biotherapeutic agent composed of a lysosomal protein (Saposin C, SapC) and an acidic phospholipid (dioleoylphosphatidylserine, DOPS) which can be assembled into stable nanovesicles (SapC-DOPS) for tackling pancreatic cancer. Phosphatidylserine (PS) is a lipid biomarker on membrane surface of pancreatic cancer cells and can be effectively targeted by SapC-DOPS nanovesicles for cancer-selective therapy. SapC-DOPS nanovesicles have shown excellent pre-clinical therapeutic and safety profiles. Safety profiles which suggests that this new approach is potentially a viable option for pancreatic cancer therapy that is worthy of further clinical development.

Gemcitabine plus Nab-Paclitaxel with chemoradiation in locally advanced pancreatic cancer (LAPC)

Gemcitabine (GEM) is a cytotoxic agent that is potent against pancreatic adenocarcinoma. Nab-paclitaxel (nab-P), an albumin-bound formulation of paclitaxel, appears to decrease levels of cytidine deaminase, which is the primary gemcitabine catabolic enzyme, this likely increases sensitivity to GEM when these agents are combined. Here we present a case of a 52 year old female with locally advanced pancreatic cancer with elevated CA19-9 at diagnosis who received GEM + nab-P followed by GEM based chemoradiation who underwent surgical resection despite persistent stable disease on radiographic studies and was found to have complete pathologic response.

Does radiologic response correlate to pathologic response in patients undergoing neoadjuvant therapy for borderline resectable pancreatic malignancy

In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT.

Impact of Diabetes Mellitus on the Outcome of Pancreatic Cancer

Introduction Diabetes mellitus (DM) has the potential to impact the pathogenesis, treatment, and outcome of pancreatic cancer. This study evaluates the impact of DM on pancreatic cancer survival. Methods We conducted a retrospective cohort study from the Veterans Affairs (VA) Central Cancer Registry (VACCR) for pancreatic cancer cases between 1995 and 2008. DM and no-DM cases were identified from comorbidity data. Univariate and multivariable analysis was performed. Multiple imputation method was employed to account for missing variables. Results Of 8,466 cases of pancreatic cancer DM status was known in 4728 cases that comprised this analysis. Males accounted for 97.7% cases, and 78% were white. Overall survival was 4.2 months in DM group and 3.6 months in the no-DM group. In multivariable analysis, DM had a HR = 0.91 (0.849–0.974). This finding persisted after accounting for missing variables using multiple imputations method with the HR in DM group of 0.93 (0.867–0.997). Conclusions Our data suggest DM is associated with a reduction in risk of death in pancreatic cancer. Future studies should be directed towards examining this association, specifically impact of DM medications on cancer outcome.

Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

BACKGROUND Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). METHODS In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done. Kaplan Meyer method was used to calculate progression free survival (PFS), and overall survival (OS). Cox model was used to test the association between baseline variables and OS/PFS, adjusting for gender and age at diagnosis. Patients were identified using ICD code for BT tumors, 26 patients met inclusion criteria: histologically proven advanced BTC that received GC as their initial chemotherapy. GC was given as per ABC-02 protocol with appropriate modifications until disease progression or unacceptable toxicities. RESULTS Median age at diagnosis was 62 years (range, 31-81 years). Eighteen (69%) were IHC, 5 EHC, 3 GBC, 61% male, 73% whites. Performance status (PS): 0-1: 69%, PS 2: 31%. Baseline CA19-9 data was available for 21 patients, (range 1 to 69,543), and abnormal CA19-9 was seen in 14 patients (54%). PFS was 4.5 months (95% CI: 3.1-8.9 months) and OS was 10.5 months (95% CI: 7.9-18.8 months). OS at 6 and 12 months was 69% (18/26) and 42% (11/26). Thirty-eight percent (10/26) received 2nd line chemotherapy, of these 9/10 received 5FU based chemotherapy. Eleven percent (3/26) received 3rd line chemotherapy. Increase in baseline carcinoembryonic antigen (CEA), alanine aminotransferase, alkaline phosphatase (ALP) and total bilirubin was associated with increased risk of death while increase in baseline CEA and ALP was associated with increased risk of progression (P valve <0.05). In the group of patients who had all three major risk factors (PS ≥2, CEA >3, and stage IVb), the median survival was 2.9 months (95% CI: 2.6-9.3 months), which was significantly worse compared to rest of the population [median 18 months (95% CI: 5.4-19.5 months), P<0.01]. CONCLUSIONS Our data supports the use of GC as a first line regimen for advance BTC in a non-clinical trial setting. Results are comparable to those reported in ABC-02 trial, despite inclusion of PS 2 patients whom constituted 31% of our population. In the patient population studied, baseline CEA and liver function test appeared able to predict response to GC in advanced BTC. Patients with all three high risk factors (PS ≥2, CEA >3, and stage IVb) did poorly and may need careful selection prior to initiating chemotherapy.

Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease

Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory patterns of LDF have probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria

Background. Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single‐center experience with tumor downstaging and its effects on post–orthotopic liver transplantation outcomes. Methods. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha‐fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post‐transplant mortality. Results. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow‐up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high‐risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha‐fetoprotein <400 ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high‐risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow‐up period of 17 months. Downstaged high‐risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log‐rank P > .05). Conclusions. In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post‐transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for transplantation.

Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies

Taxane–gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15–20 mg/m2) before (part 1a) or after (part 1b) gemcitabine (700–1000 mg/m2) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m2 cabazitaxel plus 1000 mg/m2 gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3–4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation.