Blood-Based Multi-Cancer Detection Using a Novel Variant Calling Assay (DEEPGENTM): Early Clinical Results.

This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.

Totally robotic vs hybrid abdominoperineal resection: A retrospective multicenter analysis.

INTRODUCTION: Laparoscopic abdominoperineal resection (APR) for low rectal cancers is technically demanding. Robotic assistance may be of help and can be hybrid (HAPR) or totally robotic (RAPR). The present study describes outcomes of robotic APR and compares both approaches. MATERIAL AND METHODS: A multicentric retrospective analysis of rectal cancer patients undergoing either HAPR or RAPR was conducted. Patients' demographics, surgeons' experience, oncologic results, and intraoperative and postoperative outcomes were collected. RESULTS: One hundred twenty-five patients were included, 48 in HAPR group and 77 in RAPR group. Demographics and comorbidities were comparable. Operative time was reduced in RAPR group (266.9 ± 107.8 min vs 318.9 ± 75.1 min, P = .001). RAPR patients were discharged home more frequently (91.18% vs 66.67%, P = .001), and experienced fewer parastomal hernias (3.71% vs 9.86%, P = .001). CONCLUSION: RAPR is safe and feasible with appropriate oncologic outcomes. Totally robotic approach reduces operative time and may improve functional outcomes.

Novel technique of robotic extralevator abdominoperineal resection with gracilis flap closure.

BACKGROUND: The purpose of this paper is to introduce a robotic assisted approach to extralevator abdominoperineal excision in the modified Lloyd-Davis position with reconstruction of the perineum using pedicled gracilis flaps, and to discuss outcomes in a cohort of six patients. METHODS: Data was collected by chart review on six patients who underwent extralevator excision with gracilis flap reconstruction from 10/2013 to 06/2015. Technical details, operative data, oncologic outcomes, and wound healing complications were evaluated. RESULTS: There were no instances of intraoperative perforation or positive circumferential resection margin, and one case of locoregional recurrence. Two patients experienced flap venous congestion and one patient developed a perineal abscess. All patients went on to complete healing. CONCLUSIONS: The combination of a minimally invasive robotic assisted extralevator abdominoperineal excision performed in the modified Lloyd-Davis position with reconstruction of the perineum with pedicled gracilis flaps has excellent oncologic outcomes and acceptable wound healing complications. Copyright © 2016 John Wiley & Sons, Ltd. StartCopTextCopyright © 2016 John Wiley & Sons, Ltd.

Robotic Rectal Cancer Resection: A Retrospective Multicenter Analysis.

BACKGROUND: Conventional laparoscopy has been applied to colorectal resections for more than 2 decades. However, laparoscopic rectal resection is technically demanding, especially when performing a tumor-specific mesorectal excision in a difficult pelvis. Robotic surgery is uniquely designed to overcome most of these technical limitations. The aim of this study was to confirm the feasibility of robotic rectal cancer surgery in a large multicenter study. METHODS: Retrospective data of 425 patients who underwent robotic tumor-specific mesorectal excision for rectal lesions at seven institutions were collected. Outcome data were analyzed for the overall cohort and were stratified according to obese versus non-obese and low versus ultra-low resection patients. RESULTS: Mean age was 60.9 years, and 57.9 % of patients were male. Overall, 51.3 % of patients underwent neoadjuvant therapy, while operative time was 240 min, mean blood loss 119 ml, and intraoperative complication rate 4.5 %. Mean number of lymph nodes was 17.4, with a positive circumferential margin rate of 0.9 %. Conversion rate to open was 5.9 %, anastomotic leak rate was 8.7 %, with a mean length of stay of 5.7 days. Operative times were significantly longer and re-admission rate higher for the obese population, with all other parameters comparable. Ultra-low resections also had longer operative times. CONCLUSION: Robotic-assisted minimally invasive surgery for the treatment of rectal cancer is safe and can be performed according to current oncologic principles. BMI seems to play a minor role in influencing outcomes. Thus, robotics might be an excellent treatment option for the challenging patient undergoing resection for rectal cancer.

Hospital-based, acute care encounters after radiofrequency ablation of hepatic tumours.

BACKGROUND: The use of radiofrequency ablation (RFA) for cancer is increasing; however, post-discharge outcomes have not been well described. The aim of the present study was to determine rates of hospital-based, acute care utilization within 30 days of discharge after RFA. METHODS: Using state-level data from California, patients were identified who were at least 40 years of age who underwent RFA of hepatic tumours without a concurrent liver resection from 2007-2011. Our primary outcome was hospital readmissions or emergency department visits within 30 days of discharge. A multivariable regression model was constructed to identify patient factors associated with these events. RESULTS: The final sample included 1764 patients treated at 100 centres. Hospital readmissions (11.3/100 discharges), emergency department visits (6.0/100 discharges) and overall acute care utilization (17.3/100 discharges) were common. Most encounters occurred within 10 days of discharge for diagnoses related to the procedure. Patients with renal failure [adjusted odds ratio (AOR) = 1.98 (1.11-3.53)], obesity [AOR = 1.69 (1.03-2.77)], drug abuse [AOR = 2.95 (1.40-6.21)] or those experiencing a complication [AOR = 1.52 (1.07-2.15)] were more likely to have a hospital-based acute care encounter within 30 days of discharge. CONCLUSIONS: Hospital-based acute care after RFA is common. Patients should be counselled regarding the potential for acute care utilization and interventions targeted to high-risk populations.

Short-term outcomes of ablation therapy for hepatic tumors: evidence from the 2006-2009 nationwide inpatient sample.

BACKGROUND: Radiofrequency ablation (RFA) for the treatment of hepatic tumors has been increasingly used across the United States. Whether treatment-related morbidity has remained low with broader adoption is unclear. We conducted this study to describe in-hospital morbidity associated with RFA for hepatic tumors and to identify predictors of adverse events in a nationally representative database. METHODS: Using the 2006-2009 Nationwide Inpatient Sample, we evaluated all patients aged ≥40 years who underwent an elective RFA for primary or metastatic liver tumors (N = 1298). Outcomes included in-hospital procedure-specific and postoperative complications. Multivariable logistic regression analyses were performed to identify patient and facility predictors of complications. RESULTS: Most patients underwent a percutaneous (39.9 %) or laparoscopic (22.0 %) procedure for metastatic liver tumors (57.5 %). Procedure-specific complications were frequent (18.2 %), with transfusion requirements (10.7 %), intraoperative bleeding (4.3 %), and hepatic failure (2.8 %) being the most common. Arrhythmias [adjusted odds ratio (AOR) = 1.93 (1.23-3.04)], coagulopathy [AOR = 4.65 (2.95-7.34)], and an open surgical approach [AOR = 2.77 (1.75-4.36)] were associated with an increased likelihood of procedure-specific complications, whereas hospital RFA volume ≥16/year was associated with a reduced likelihood [AOR = 0.59 (0.38-0.91)]. Postoperative complications were also common (12.0 %), with arrhythmias, heart failure, coagulopathy, and open surgical approach acting as significant predictors. CONCLUSIONS: In-hospital morbidity is common after RFA for hepatic tumors. While several patient factors are associated with more frequent procedure-specific complications, treatment at hospitals with an annual volume ≥16 cases/year was associated with a 41 % reduction in the odds of procedure-specific complications.

Open versus laparoscopic liver resection: looking beyond the immediate postoperative period.

BACKGROUND: Laparoscopic liver resection for malignant disease has shown short-term benefit. This study aimed to compare in-house, 30-day, and 1-year morbidity between laparoscopic and open liver resections. METHODS: The charts for all patients who underwent liver resection for malignant disease between April 2006 and October 2009 were reviewed. Patient, operative, and outcomes data at 30 days and 1 year were collected. RESULTS: For 76 patients, 49 open and 27 laparoscopic resections were performed. The two groups were similar in terms of age, gender, body mass index (BMI), extent of liver resection, use of ablation therapy, and tumor pathology (P > 0.05). The laparoscopic group had less blood loss (P = 0.004) and shorter hospital stays (P = 0.002). During their hospital stay, patients treated laparoscopically had fewer complications, but the difference was not significant. Home disposition was similar in the laparoscopic (96%) and open (90%) groups. More patients were readmitted at 30 days (2 vs. 9; P = 0.31) and 1 year (4 vs. 19; P = 0.04) in the open group. The all-cause 1-year mortality rates were similar between the laparoscopic and open groups (14.8% vs. 10.2%). CONCLUSION: The benefits of laparoscopic liver resection may extend beyond the initial postoperative period, with fewer readmissions despite shorter hospital stays. This also may suggest lower long-term hospital costs.

Senescence-associated gene YPEL3 is downregulated in human colon tumors.

BACKGROUND: Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3. METHODS: We collected colon tumor samples with matched normal control samples and analyzed them for YPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116(-/-) p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A. RESULTS: Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3 expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce YPEL3 expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in YPEL3 regulation in colon cancer. CONCLUSIONS: YPEL3 is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of YPEL3 downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of YPEL3 in colon adenocarcinomas. Future investigation of YPEL3 and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.

Tumors at the aortoiliac/inferior vena cava bifurcation: preoperative, anesthetic, and intraoperative considerations.

Primary and recurrent retroperitoneal tumors can involve the aortoiliac vasculature. They are often considered inoperable or incurable because of the locally advanced nature of the disease or the technical aspects involved in safely resecting the lesion. Safe resection of these lesions requires experience and extensive preoperative planning for success. A retrospective database review of 76 patients with retroperitoneal tumors identified tumors involving major vascular structures in the abdomen and pelvis undergoing resection of tumor en bloc with the aortoiliac vasculature. Preoperative planning and intraoperative technical maneuvers are reviewed. Patients were followed until time of this report. Four patients with retroperitoneal tumors involving the aortoiliac vessels underwent surgery: two patients with sarcoma (one primary and one recurrent), one with metastatic renal cell carcinoma, and one with a paraganglioma. All patients had resection of the aorta and vena cava or the iliac artery and vein. Arterial reconstruction (anatomic or extra-anatomic) was performed in all cases. The patient with renal cell carcinoma also required venous reconstruction to support a renal autotransplant. Veno-venous bypass was required in one patient. Local control was achieved in 3 of 4 cases. Surgery for retroperitoneal tumors involving major vascular structures is technically feasible with appropriate planning and technique. Multiple disciplines are required, including general surgical oncology, vascular surgery, and possibly, cardiothoracic surgery.

Colorectal cancer metastasis presenting as a testicular mass: case report and review of the literature.

Metastatic lesions to the testicle are uncommon. The authors report a testicular mass as the initial manifestation of distant metastasis from colorectal cancer. This case describes a 51-year-old white man who presented with an enlarged right testicle 9 months after undergoing a right hemicolectomy for a stage IIIC colon adenocarcinoma. The diagnostic and management strategy is discussed. In addition, the literature is reviewed to characterize this uncommon entity further. Although rare, testicular metastasis must be considered in patients with previously resected colorectal carcinoma.

Pancreaticoduodenectomy after neoadjuvant therapy in a Jehovah's witness with locally advanced pancreatic cancer: case report and approach to avoid transfusion.

Although the morbidity and mortality rates associated with pancreaticoduodenectomy (PD) have been improving over the past several decades, perioperative transfusions are often needed. Here, we review the preoperative planning and overall management of a Jehovah's Witness patient with locally advanced pancreatic cancer who would not accept blood transfusion. Management of this case is reviewed, along with the relevant literature regarding major surgery in the Jehovah's Witness population. The use of neoadjuvant chemoradiation was used successfully in locally advanced disease, allowing surgical resection. In addition, we outline a cogent strategy using pre-, intra-, and postoperative techniques to minimize blood loss and maintain hemoglobin at acceptable levels thereby preventing the need for transfusion. These strategies, once in place, may be able to reduce transfusions in all patients having major resections for malignancy.

The physiologic effects of laparoscopy: applications in oncology.

The use of laparoscopic approaches to surgical disease continues to advance quickly. Laparoscopy applied to oncologic surgery continues to be debated. We review the experience of laparoscopy as it relates to surgery for tumors. Specifically, we discuss the physiologic changes and tumor response to laparoscopy, as well as the current concepts explaining port site recurrence.

Evaluation of Charlson-Age Comorbidity Index as predictor of morbidity and mortality in patients with colorectal carcinoma.

The Charlson-Age Comorbidity Index (CACI) is a validated tool used to predict patient outcome based on comorbid medical conditions. We wanted to determine if the CACI would predict morbidity and mortality outcomes in patients undergoing surgery for colorectal carcinoma. Records of 279 consecutive colorectal cancer patients who underwent laparotomy by a single surgical group between 1997 and 2001 were reviewed in a retrospective fashion for patient demographics, stage at diagnosis, operation, surgeon, perioperative complications, tumor characteristics, comorbid diseases, performance status, length of stay (LOS), disposition, and mortality. Using the preoperative history and physical, all patients were assigned a score for the CACI. Perioperative morbidity and mortality were recorded and graded to account for severity. The University Statistical Consulting Center and SPSS software were used to analyze the results. The patients were primarily white (97.1%) with a male-to-female ratio of 1:1.2 and a median age of 72 years. AJCC stage at presentation was stage 0 (3.2%), stage I (28.3%), stage II (24.4%), stage III (24.4%), or stage IV (19.7%). Median LOS was 7.0 days. Perioperative mortality was 17 of 279 (6.1%), and overall mortality was 32.6% at a median follow-up of 18.5 months. Higher CACI scores and AJCC stage at presentation correlated with longer LOS and overall mortality. Only the CACI correlated with perioperative mortality and disposition. No correlation was observed with location of tumor, type of surgery, or surgeon. Patients with higher cumulative number of weighted comorbid conditions as indicated by the CACI are at higher risk for perioperative and overall mortality. This simple scoring system is also a significant predictor of disposition (home versus extended care facility) and LOS. The CACI can be a useful preoperative tool to assess and counsel patients undergoing surgery for colorectal carcinoma.

Axillary lymph node metastasis following resection of abdominal wall laparoscopic port site recurrence of gallbladder cancer.

Abdominal wall port site recurrence of gallbladder cancer is well described in the literature in patients that have undergone laparoscopic cholecystectomy with the incidental finding of a gallbladder cancer. The etiology and consequences of this type of metastatic recurrence are unclear. This report describes two cases with the unique sequelae of the interval development of nodal metastases to the axillary lymph nodes following resection of an abdominal wall laparoscopic port site recurrence of gallbladder cancer. The first case involves a patient who developed an isolated left axillary lymph node metastasis approximately 10 months after undergoing resection of a left-sided abdominal wall port site recurrence for a T2 gallbladder cancer. The original tumor had been found at laparoscopic cholecystectomy and definitively treated surgically approximately 3 years earlier. The second case involves a patient who developed isolated nodal metastases to the right axillary lymph nodes approximately 4 months after undergoing resection of right-sided abdominal wall port site recurrence, segment 4/5 hepatic resection, and portal lymphadenectomy for a T2 gallbladder cancer. This tumor had originally been found at laparoscopic cholecystectomy approximately 1 year earlier. These unique sequelae of the interval development of nodal metastases to the axillary lymph nodes demonstrated in both cases has not been previously reported.

Merkel cell carcinoma metastatic to the head of the pancreas.

CONTEXT: Merkel cell carcinoma is an aggressive cutaneous tumor without clearly defined treatment and high propensity for metastasis. CASE REPORT: This case describes a sixty four year old presenting with obstructive jaundice approximately two years after having a Merkel cell carcinoma resected from his finger. He underwent a successful pancreaticoduodenectomy with pathology confirming metastatic Merkel cell carcinoma. This report reviews the history, presentation, and current treatment recommendations for Merkel cell carcinoma. CONCLUSIONS: We propose that resection of metastases from Merkel cell carcinoma may confer a survival advantage and should be strongly considered, particularly if isolated.