Ching Wei D. Tzeng

Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer

OBJECTIVES The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT). METHODS This study included all patients with borderline resectable pancreatic cancer, a serum CA 19-9 level of ≥40 U/ml and bilirubin of ≤2 mg/dl, in whom NT was initiated at one institution between 2001 and 2010. The study evaluated the associations between pre- and post-NT CA 19-9, resection and overall survival. RESULTS Among 141 eligible patients, CA 19-9 declined during NT in 116. Following NT, 84 of 141 (60%) patients underwent resection. For post-NT resection, the positive predictive value of a decline and the negative predictive value of an increase in CA 19-9 were 70% and 88%, respectively. The normalization of CA 19-9 (post-NT <40 U/ml) was associated with longer median overall survival among both non-resected (15 months versus 11 months; P = 0.022) and resected (38 months versus 26 months; P = 0.020) patients. Factors independently associated with shorter overall survival were no resection [hazard ratio (HR) 3.86, P < 0.001] and failure to normalize CA 19-9 (HR 2.13, P = 0.001). CONCLUSIONS The serum CA 19-9 level represents a dynamic preoperative marker of tumour biology and response to NT, and provides prognostic information in both non-resected and resected patients with borderline resectable pancreatic cancer.

Predictors of morbidity and mortality after hepatectomy in elderly patients: analysis of 7621 NSQIP patients

OBJECTIVES Increasingly, surgeons are performing hepatectomies in older patients. This study was designed to analyse the incidences of and risk factors for post-hepatectomy morbidity and mortality in elderly patients. METHODS All elective hepatectomies for the period 2005-2010 recorded in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were evaluated. Factors associated with 30-day rates of morbidity and mortality were compared between patients aged ≥75 years and those aged <75 years. RESULTS Elderly patients accounted for 894 of 7621 (11.7%) hepatectomies. These patients more frequently had comorbidities (diabetes, cardiovascular or lung disease, lower albumin, elevated creatinine, anaesthesia risk; all P < 0.05) and were more likely to undergo partial or left rather than right or extended hepatectomies (P = 0.013). Despite the lesser surgical magnitude of these procedures, elderly patients experienced higher rates of severe complications (23.9% versus 18.4%; P < 0.001) and overall postoperative mortality (4.8% versus 2.0%; P < 0.001). The occurrence of any severe complication was associated with a mortality rate of 20.1% in elderly patients and 10.8% in non-elderly patients (P < 0.001). This disparity in mortality was more pronounced in patients with two or more (31.7% versus 20.2%; P < 0.001) and three or more (46.3% versus 31.1%; P < 0.001) severe complications. Independent risk factors for severe complications and/or mortality included an albumin level of < 4 g/dl, lung disease, intraoperative transfusion, a concurrent intra-abdominal operation, and an operative time of >240 min (all P < 0.05). CONCLUSIONS Given their lower physiologic reserve, elderly patients are at much greater risk for mortality after severe complications. To improve outcomes, surgeons should balance age and preoperative comorbidities with magnitude of hepatectomy.

Risk of venous thromboembolism outweighs post-hepatectomy bleeding complications: analysis of 5651 National Surgical Quality Improvement Program patients

BACKGROUND Historically, liver surgeons have withheld venous thromboembolism (VTE) chemoprophylaxis due to perceived postoperative bleeding risk and theorized protective anticoagulation effects of a hepatectomy. The relationships between extent of hepatectomy, postoperative VTE and bleeding events were evaluated using the National Surgical Quality Improvement Program (NSQIP) database. METHODS From 2005 to 2009, all elective open hepatectomies were identified. Factors associated with 30-day rates of VTE, postoperative transfusions and returns to the operating room (ROR), were analysed. RESULTS The analysis included 5651 hepatectomies with 3376 (59.7%) partial, 585 (10.4%) left, 1134 (20.1%) right, and 556 (9.8%) extended. Complications included deep vein thrombosis (DVT) (1.93%), pulmonary embolism (PE) (1.31%), venous thromboembolism (VTE) (2.88%), postoperative transfusion (0.76%) and ROR with transfusion (0.44%). VTE increased with magnitude of hepatectomy (partial 2.13%, left 2.05%, right 4.15%, extended 5.76%; P < 0.001) and outnumbered bleeding events (P < 0.001). Other factors independently associated with VTE were aspartate aminotransferase (AST) ≥27 (P= 0.022), American Society of Anesthesiologists (ASA) class ≥3 (P < 0.001), operative time >222 min (P= 0.043), organ space infection (P < 0.001) and length of hospital stay ≥7 days (P= 0.004). VTE resulted in 30-day mortality of 7.4% vs. 2.3% with no VTE (P= 0.001). CONCLUSIONS Contrary to the belief that transient postoperative liver insufficiency is protective, VTE increases with extent of hepatectomy. VTE exceeds major bleeding events and is strongly associated with mortality. These data support routine post-hepatectomy VTE chemoprophylaxis.

Yield of clinical and radiographic surveillance in patients with resected pancreatic adenocarcinoma following multimodal therapy

BACKGROUND Following potentially curative resection at this centre, patients with pancreatic adenocarcinoma (PAC) are routinely enrolled in a programme of clinical and radiographic surveillance. This study sought to evaluate its diagnostic yield. METHODS All patients who underwent pancreaticoduodenectomy for PAC at this institution during 1998-2008 were identified. Patients with asymptomatic recurrence were compared with those with symptomatic recurrence. Factors associated with survival following the detection of recurrence were compared. RESULTS A total of 216 of 327 (66.1%) resected patients developed recurrence. Asymptomatic recurrence was detected in 118 (54.6%) patients. Symptomatic recurrence was associated with multifocal disease or carcinomatosis, poor performance status and less frequent subsequent therapy. Median time to recurrence did not differ between groups, but survival after detection was shorter in symptomatic patients (5.1 months vs. 13.0 months; P < 0.001). Treatment was administered more frequently to asymptomatic patients (91.2% vs. 61.4%; P < 0.001). At recurrence, a preserved performance status score of ≤ 1, further therapy, low CA 19-9, and an isolated site of recurrence were independently associated with longer post-recurrence survival (P < 0.001). CONCLUSIONS Overall, 54.6% of cases of recurrent PAC were detected prior to the onset of symptoms using a standardized clinical and radiographic surveillance strategy. Although this retrospective analysis limits definitive conclusions associating this strategy with survival, these results suggest the need for further studies of postoperative surveillance.

Systematic Use of an Intraoperative Air Leak Test at the Time of Major Liver Resection Reduces the Rate of Postoperative Biliary Complications

BACKGROUND After hepatectomy, bile leaks remain a major cause of morbidity, cost, and disability. This study was designed to determine if a novel intraoperative air leak test (ALT) would reduce the incidence of post-hepatectomy biliary complications. STUDY DESIGN Rates of postoperative biliary complications were compared among 103 patients who underwent ALT and 120 matched patients operated on before ALT was used. All study patients underwent major hepatectomy without bile duct resection at 3 high-volume hepatobiliary centers between 2008 and 2012. The ALT was performed by placement of a transcystic cholangiogram catheter to inject air into the biliary tree, the upper abdomen was filled with saline, and the distal common bile duct was manually occluded. Uncontrolled bile ducts were identified by localization of air bubbles at the transection surface and were directly repaired. RESULTS The 2 groups were similar in diagnosis, chemotherapy use, tumor number and size, resection extent, surgery duration, and blood loss (all, p > 0.05). Single or multiple uncontrolled bile ducts were intraoperatively detected and repaired in 62.1% of ALT vs 8.3% of non-ALT patients (p < 0.001). This resulted in a lower rate of postoperative bile leaks in ALT (1.9%) vs non-ALT patients (10.8%; p = 0.008). Independent risk factors for postoperative bile leaks included extended hepatectomy (p = 0.031), caudate resection (p = 0.02), and not performing ALT (p = 0.002) (odds ratio = 3.8; 95% CI, 1.3-11.8; odds ratio = 4.0; 95% CI, 1.1-14.3; and odds ratio = 11.8; 95% CI, 2.4-58.8, respectively). CONCLUSIONS The ALT is an easily reproducible test that is highly effective for intraoperative detection and repair of open bile ducts, reducing the rate of postoperative bile leaks.

Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: Ten-year institutional experience

We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC).

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database

BACKGROUND Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). METHODS Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. RESULTS We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). DISCUSSION Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma

Importance We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. Objective To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Design, Setting, and Participants Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015. Exposures Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%). Main Outcomes and Measures Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Results Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Conclusions and Relevance Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.

Open Pancreaticoduodenectomy Case Volume Predicts Outcome of Laparoscopic Approach: A Population-based Analysis

Objective: To determine if laparoscopic pancreaticoduodenectomy (LPD) is safe and offers benefits over open pancreaticoduodenectomy (OPD) at institutions with lower pancreaticoduodenectomy (PD) volume. Background: Although a hospital-based case volume-outcome relationship for morbidity, mortality, and oncologic quality has been reported for OPD, comparative trends for LPD have yet to be investigated. Methods: A total of 4739 patients with complete data were identified in National Cancer Data Base between 2010 and 2011; 4309 patients had OPD and 430 patients had LPD. Institutions were categorized into quartiles based on PD case volume. For the entire cohort and within each quartile, LPD and OPD were compared for 30-day and 90-day mortality, length of hospital stay, 30-day unplanned readmission rate, and margin status. Binary logistic regression, linear regression, and propensity score matching was performed. Results: Hospitals with low PD case volume (⩽25 PDs per year; 91% of all hospitals in the US and 25% of cases) had the highest 30- and 90-day mortality, highest margin positivity rates, and lowest lymph node counts. These trends were more pronounced in the LPD group. Only in the highest-volume hospitals was LPD associated with shorter hospital stay and lower readmission compared with OPD. Conclusions: These findings confirm that risks of postoperative mortality and suboptimal oncologic surgical quality following PD are higher in low-volume hospitals. Furthermore, these risks are more profound with LPD compared with OPD. These data suggest that the putative benefits of LPD are unlikely to be observed in institutions performing ⩽25 PDs per year.

Identifying Esophagectomy Patients at Risk for Predischarge Versus Postdischarge Venous Thromboembolism

BACKGROUND Current guidelines recommend postoperative venous thromboembolism (VTE) chemoprophylaxis for moderate-risk patients (3% rate or greater) and extended-duration chemoprophylaxis for high-risk patients (6% or greater). Large-scale studies of and recommendations for esophagectomy patients are lacking. This study was designed to evaluate the timing, rates, and predictors of postesophagectomy VTE. METHODS Patients undergoing esophagectomies for cancer were identified from the 2005 to 2012 American College of Surgeons National Surgical Quality Improvement database. Timing and rates of VTE (deep venous thrombosis or pulmonary embolism, or both) were calculated. Events were stratified as predischarge or postdischarge. Perioperative factors associated with 30-day rates of predischarge and postdischarge VTE were analyzed. RESULTS Of 3,208 patients analyzed, the surgical approach was Ivor-Lewis (n = 1,131, 35.3%), transhiatal (n = 945, 29.5%), three-field (n = 587, 18.3%), thoracoabdominal (n = 364, 11.3%), and nongastric conduit reconstruction (n = 181, 5.6%). Rates were 2.0% pulmonary embolism, 3.7% deep venous thrombosis, and 5.1% VTE. Overall median length of stay was 11 days (versus 19 days, p < 0.001, if predischarge VTE). Predischarge VTE occurred on median day 9, whereas postdischarge VTE occurred on day 19 (p < 0.001). Only 17% of VTE occurred after discharge. Multivariate analysis identified being male (odds ratio [OR] 2.09, p = 0.018), white race (OR 1.93, p = 0.004), prolonged ventilation (OR 3.24, p < 0.001), and other major complications (OR 1.90, p = 0.005) as independent predictors of predischarge VTE. Older age (OR 1.06 per year, p = 0.006) and major complications (OR 3.14, p = 0.004) were independently associated with postdischarge VTE. CONCLUSIONS Postesophagectomy VTE occurs in a clinically significant proportion of esophageal cancer patients with identifiable risk factors for predischarge and postdischarge events. Elderly patients and patients with major complications are most likely to benefit from extended-duration chemoprophylaxis.