There is substantial interest in liquid biopsy approaches for cancer early detection among subjects at risk, using multi-marker panels. CA19-9 is an established circulating biomarker for pancreatic ...cancer; however, its relevance for pancreatic cancer early detection or for monitoring subjects at risk has not been established.
CA19-9 levels were assessed in blinded sera from 175 subjects collected up to 5 years before diagnosis of pancreatic cancer and from 875 matched controls from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. For comparison of performance, CA19-9 was assayed in blinded independent sets of samples collected at diagnosis from 129 subjects with resectable pancreatic cancer and 275 controls (100 healthy subjects; 50 with chronic pancreatitis; and 125 with noncancerous pancreatic cysts). The complementary value of 2 additional protein markers, TIMP1 and LRG1, was determined.
In the PLCO cohort, levels of CA19-9 increased exponentially starting at 2 years before diagnosis with sensitivities reaching 60% at 99% specificity within 0 to 6 months before diagnosis for all cases and 50% at 99% specificity for cases diagnosed with early-stage disease. Performance was comparable for distinguishing newly diagnosed cases with resectable pancreatic cancer from healthy controls (64% sensitivity at 99% specificity). Comparison of resectable pancreatic cancer cases to subjects with chronic pancreatitis yielded 46% sensitivity at 99% specificity and for subjects with noncancerous cysts, 30% sensitivity at 99% specificity. For prediagnostic cases below cutoff value for CA19-9, the combination with LRG1 and TIMP1 yielded an increment of 13.2% in sensitivity at 99% specificity (P = .031) in identifying cases diagnosed within 1 year of blood collection.
CA19-9 can serve as an anchor marker for pancreatic cancer early detection applications.
Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has
attempts at expression-based molecular classification. The goal of this work is to profile ...purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples.
We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts.
Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes.
Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.
Background
Large centralized databases are used with increasing frequency for reporting hospital-specific and nationwide trends and outcomes after various surgical procedures in order to improve ...quality of surgical care. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a risk-adjusted, case-weighted complication tracking initiative that reports 30-day outcomes from more than 400 academic and community institutions in the US. However, the accuracy of event reporting specific to pancreatic surgery has never been examined in depth.
Methods
We retrospectively reviewed medical records of patients, the information on whose postoperative course was originally reported through ACS-NSQIP between 2006 and 2010. Preoperative characteristics, operative data, and postoperative events were recorded after review of electronic medical records including physician and nursing notes, operative room records and anesthesiologist reports. Fidelity of reported clinical events was assessed. Accuracy, sensitivity, and specificity were calculated for each variable of interest.
Results
Two hundred and forty-nine pancreatectomies were reviewed, including 145 (58.2 %) Whipple procedures, 19 (7.6 %) total pancreatectomies, 65 (26.1 %) distal pancreatectomies, and 15 (6.0 %) central or partial resections. Median age was 65.7, males comprised 41.5 % of the group, and 74.3 % of patients were Caucasian. The overall rate of complications reported by NSQIP was 44.0 %, compared with 45.0 % in our review, however discordance was observed in 27.3 % of the time, including 34 cases of reporting a complication where there was not one, and 34 cases of missed complication. The most frequently reported event was postoperative bleeding requiring transfusion, however this was also the event most commonly misclassified. Additionally, three procedures unrelated to the index operation were recorded as reoperation events. While a pancreas-specific module does not yet exist, ACS-NSQIP reports a 7.6 % rate of organ-space surgical site infections; when compared with our institutional rate of Grades B and C postoperative fistula (10.4 %), we observed discordance 4.4 % of the time. Delayed gastric emptying, a common post-pancreatectomy morbidity, was not captured at all. Additionally, there were significant inaccuracies in reporting urinary tract infections, postoperative pneumonia, wound complications, and postoperative sepsis, with discordance rates of 4.4, 3.2, 3.6, and 6.8 %, respectively.
Conclusions
ACS-NSQIP data are an important and valuable tool for evaluating quality of surgical care, however pancreatectomy-specific postoperative events are often misclassified, underscoring the need for a hepatopancreatobiliary-specific module to better capture key outcomes in this complex and unique patient population.
Purpose
We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies ...with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).
Methods
A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100 %), chemotherapy (61 %), and hepatic chemoembolization (50 %). Patients received capecitabine at 600 mg/m
2
orally twice daily on days 1–14 (maximum 1,000 mg orally twice daily) and TMZ 150–200 mg/m
2
divided into two doses daily on days 10–14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle.
Results
Using RECIST parameters, 1 patient (5.5 %) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5 %) achieved a partial response (PR), and 4 patients (22.2 %) had stable disease (SD). Total response rate was 61 %, and clinical benefit (responders and SD) was 83.2 %. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3–18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28–140 months). The only grade 3 toxicity was thrombocytopenia (11 %). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths.
Conclusions
CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.
Background We sought to further elucidate the increased risk for breast cancer among survivors of thyroid cancer. Methods Using the Surveillance, Epidemiology, and End Results-9 database, we ...conducted a retrospective cohort analysis on women ≥18 years of age with breast and thyroid cancer from 1973 to 2011. Results A total of 707,678 breast cancer patients and 53,853 thyroid cancer patients were included; 1,750 patients developed breast cancer after a preceding diagnosis of thyroid cancer (T1B). Age-specific risk for breast cancer was greater among thyroid cancer survivors. Incidence trends showed a significant age-time interaction and suggested a difference in thyroid cancer biology as well as a treatment effect. Compared with patients with thyroid cancer only, T1B patients were older with smaller cancers, had more follicular thyroid cancers, and fewer patients received radioactive iodine. T1B patients developed breast cancer earlier than the general population, had more estrogen receptor/progesterone receptor-positive and mixed invasive tumor histology, but smaller tumors, and there is no significant difference in the number of lymph nodes involved or radiation therapy. Conclusion Thyroid cancer survivors are at greater risk for developing breast cancer than the general population. These patients develop breast cancer early, have more estrogen receptor/progesterone receptor-positive tumors, and have a greater incidence of mixed invasive cancer. Recognition of this association between thyroid and breast cancer should prompt vigilant screening in thyroid cancer survivors and further investigation into the relationship of these 2 diseases.
Background Traditional resections for benign and low-grade malignant neoplasms of the mid pancreas result in loss of normal parenchyma that can cause pancreatic endocrine and exocrine insufficiency. ...Central pancreatectomy (CP) is a parenchyma-sparing option for such lesions. This study evaluates a single institution’s experience with CP and compares outcomes with distal pancreatectomy (DP). Methods We retrospectively collected data on CP patients from 1997 through 2009 and evaluated outcomes. In a subset of 50 patients, we performed a matched-pairs analysis to directly compare the short- and long-term outcomes of CP and DP. Results Seventy-three patients underwent CP with a median operating room time of 254 minutes. Overall morbidity was 41.1% with pancreatic fistula in 20.5%. Mortality was 0%. There were no differences in fistula, morbidity, and mortality rates between the CP and DP groups. The CP group had resected for smaller lesions. CP patients had a lower rate of new-onset and worsening diabetes than DP patients (14% vs 46%; P = .003). Of new-onset and worsening diabetics, only 1 CP patient required insulin compared with 14 DP patients ( P = .002). Conclusion CP is safe and effective for select neoplasms of the mid pancreas. Patients undergoing CP have markedly decreased insulin requirements compared with DP patients.
Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk.
Patients at high risk of ...pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk.
Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening.
Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective.
Background
Irreversible electroporation (IRE) for treatment of locally advanced pancreatic tumors is garnering increasing attention. This study was conducted to determine perioperative morbidity and ...mortality for locally advanced pancreatic cancer.
Methods
Prospective data of 50 consecutive patients receiving IRE for T4 lesions at a single tertiary center were analyzed. The primary end point was Clavien–Dindo complications at 90 days, and the secondary outcomes were survival and recurrence.
Results
A total of 50 patients underwent 53 IRE procedures for primary treatment (
n
= 29) or margin extension (
n
= 24), and 47 patients had adenocarcinoma. Six patients died within 90 days after the procedure (5 in the primary control group). Mortality occurred a median of 26 days (range, 8–42 days) after the procedure. Five patients in both the margin-extension and primary control groups experienced grade 3 or 4 morbidity (
p
= 0.739). The incidences of grades 3 to 5 complications did not differ significantly based on the adjustable parameters of IRE, tumor size, or primary treatment versus margin extension. After a median follow-up period of 8.69 months interquartile range (IQR), 0.26–16.26 months, the median overall survival period for the primary control group was 7.71 months 95 % confidence interval (CI), 6.03–12.0 months) and was not reached in the margin-extension group (
p
= 0.01, log-rank).
Conclusions
At the authors’ center, the mortality rate after IRE was higher than reported in other series, with the majority occurring in the primary control group. Major morbidity trended around upper gastrointestinal bleeding, visceral ulcerations/perforations, and portal vein thromboses. This favors further investigation of the safety and efficacy of IRE.
Background
Retroperitoneal laparoscopic adrenalectomy is gaining traction as a minimally invasive technique. One of the purported relative contraindications is BMI given the smaller working space. We ...hypothesize that other anthropometric measurements may be better predictors of operative time.
Methods
An IRB-approved, single-institution, retrospective study of 83 patients who underwent laparoscopic retroperitoneal adrenalectomy evaluated the association of anthropometric measurements taken from cross-sectional imaging and the primary outcome of operative time. Descriptive statistics were performed with Wilcoxon rank-sum test for continuous variables (median; IQR) and Chi-square (
n
; %) for categorical variables. A linear random effects model was used to model operative time.
Results
The majority of the patients were white (40; 48.2%) women (46; 55.4%) with a median age of 54 with interquartile range (IQR) of 43–63 and a median BMI of 27.8 (IQR 21.2–38.6). On univariable analysis, factors that led to longer operative time included right-sided operation (
p
= 0.04), male gender (
p
< 0.01), clinical diagnosis (
p
< 0.01), waist area (
p
< 0.01), waist/hip ratio (
p
< 0.01), periadrenal volume (
p
< 0.01), posterior adiposity index (PAI) (
p
< 0.01) and BMI (
p
< 0.01). Only side, order of operation, and periadrenal fat volume (
p
< 0.01,
p
= 0.02 and
p
< 0.01, respectively) remained independent predictors of increased operative time on multivariable analysis.
Conclusion
This study demonstrates that anthropometric measurements, specifically periadrenal fat volume, and side of operation, are better predictors for increased operative time in laparoscopic retroperitoneal adrenalectomies than BMI. This information can help facilitate appropriate patient selection for this operative approach.
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