Clifford S. Cho

A Multicenter Analysis of Distal Pancreatectomy for Adenocarcinoma: Is Laparoscopic Resection Appropriate?

BACKGROUND As compared with open distal pancreatectomy (ODP), laparoscopic distal pancreatectomy (LDP) affords improved perioperative outcomes. The role of LDP for patients with pancreatic ductal adenocarcinoma (PDAC) is not defined. STUDY DESIGN Records from patients undergoing distal pancreatectomy (DP) for PDAC from 2000 to 2008 from 9 academic medical centers were reviewed. Short-term (node harvest and margin status) and long-term (survival) cancer outcomes were assessed. A 3:1 matched analysis was performed for ODP and LDP cases using age, American Society of Anesthesiologists (ASA) class, and tumor size. RESULTS There were 212 patients who underwent DP for PDAC; 23 (11%) of these were approached laparoscopically. For all 212 patients, 56 (26%) had positive margins. The mean number of nodes (+/- SD) examined was 12.6 +/-8.4 and 114 patients (54%) had at least 1 positive node. Median overall survival was 16 months. In the matched analysis there were no significant differences in positive margin rates, number of nodes examined, number of patients with at least 1 positive node, or overall survival. Logistic regression for all 212 patients demonstrated that advanced age, larger tumors, positive margins, and node positive disease were independently associated with worse survival; however, method of resection (ODP vs. LDP) was not. Hospital stay was 2 days shorter in the matched comparison, which approached significance (LDP, 7.4 days vs. ODP, 9.4 days, p = 0.06). CONCLUSIONS LDP provides similar short- and long-term oncologic outcomes as compared with OD, with potentially shorter hospital stay. These results suggest that LDP is an acceptable approach for resection of PDAC of the left pancreas in selected patients.

Hilar Cholangiocarcinoma: Current Management

Objective:To review the literature with regard to outcome of surgical management for hilar cholangiocarcinoma (Klatskin tumor). Background:Hilar cholangiocarcinoma is a rare tumor with a poor prognosis. Surgical resection provides the only possibility for cure. Advances in hepatobiliary imaging and surgical strategies to treat this disease have resulted in improved postoperative outcomes. Methods:We performed a review of the English literature on hilar cholangiocarcinoma from 1990 to 2007. This review included preoperative evaluation, surgical techniques, issues and controversies in management, prognostic variables, and considerations for future directions. Results:Complete resection remains the most effective and only potentially curative therapy for hilar cholangiocarcinoma. Negative resection margins are associated with improved outcomes, and major hepatic resections have enhanced the likelihood of R0 resection. Portal vein embolization may be indicated in selected patients before extensive hepatic resection. Staging laparoscopy should be considered to detect occult metastatic disease. Orthotopic liver transplantation might be applicable for a highly selected subgroup. Conclusions:Surgical resection including major hepatic resection remains the mainstay of treatment of hilar cholangiocarcinoma. Additional evidence is needed to fully define the role of orthotopic liver transplantation. Improvements in adjuvant therapy are essential for improving long-term outcome.

Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients.

Objective and Background:Morbidity, mortality, and length of hospital stay after pancreaticoduodenectomy (PD) have significantly decreased over recent decades. Despite this progress, early readmission rates after PD have been reported as high as 50%. Few reports have delineated factors associated with readmission after PD. Methods:The medical records of 6 high-volume institutions were reviewed for patients who underwent PD between 2005 and 2010. Data collection included patient characteristics, medical comorbidities, and perioperative factors. Analysis included readmissions up to 90 days after PD. Results:A total of 1302 patients underwent PD across all institutions. The 30-day and 90-day readmission rates were 15% and 19%, respectively. The most common reasons for 30-day readmission included infectious complications (n = 65) and delayed gastric emptying (n = 29). The most common reasons for readmission after 90 days included wound infections and intra-abdominal abscess (n = 75) and failure to thrive (n = 38). On multivariate analysis, factors associated with higher readmission rates included a preoperative diagnosis of chronic pancreatitis, higher transfusion requirements, and postoperative complications including intra-abdominal abscess and pancreatic fistula (all P < 0.02). Factors not associated with higher readmission rates included advanced age, body mass index, cardiovascular/pulmonary comorbidities, diabetes, steroid use, Whipple type (standard vs pylorus preserving PD), preoperative endobiliary stenting, and vascular reconstruction. Conclusions:These multi-institutional data represent a large experience of PD without the biases typically of single center studies. Factors related to infection, nutritional status, and delayed gastric emptying were the most common reasons for readmission after PD. Postoperative complications including pancreatic fistula predicted higher rates of readmission.

Resection of hilar cholangiocarcinoma: concomitant liver resection decreases hepatic recurrence.

Background:Hilar cholangiocarcinoma is an uncommon tumor with a poor prognosis. We sought to evaluate recurrence patterns and prognostic factors for disease-specific and disease-free survival in patients with surgically resected hilar cholangiocarcinoma in a single institution over the last 21 years. Methods:From 1985 to 2006, all patients with hilar cholangiocarcinoma referred to a tertiary surgical clinic were evaluated. Demographic data, tumor characteristics, and outcome were analyzed retrospectively. Outcome was compared in patients treated in a recent era (1995–2006) compared with an earlier era (1985–1994). Results:Of 91 patients evaluated, 22 patients (24%) had unresectable disease at presentation. Of the 69 patients submitted to laparotomy, resection was possible in 55% and the curative (R0) resection rate was 63%. In patients submitted to exploration, the operative (60 day) morbidity and mortality rates were 26% and 3%. Median disease-specific (DSS) and disease-free survival (DFS) were 29 and 20 months, respectively (median FU, 29 months.). In patients undergoing R0 resection, the median survival was prolonged (65 months). In the more recent era, resectability rates improved (69% vs. 17%; P = 0.0002), and this was associated with an improvement in median survival (30 vs. 4 months; P < 0.001). Factors predictive of improved disease-specific and disease-free survival included negative histologic margins, concomitant hepatic lobectomy, lack of nodal disease, well-differentiated histology, and an earlier tumor stage (P < 0.05). Concomitant liver resection was associated with a higher R0 resection rate (P = 0.006) and improved DSS and DFS (P = 0.005). In addition, concomitant liver resection was associated with a decreased incidence of initial recurrence in liver (P = 0.031). Conclusions:In patients with hilar cholangiocarcinoma, concomitant hepatic resection is associated with improved DFS, DSS, and decreased hepatic recurrence. Therefore, hepatectomy combined with bile duct resection should be considered standard treatment.

Preoperative Radiographic Assessment of Hepatic Steatosis with Histologic Correlation

BACKGROUND The adverse impact of hepatic steatosis on perioperative outcomes after liver resection is gaining recognition. But the accuracy of preoperative radiologic assessment of fatty liver disease remains unclear. The objective of this study was to correlate preoperative radiologic estimation with postoperative histologic measurement of steatosis. STUDY DESIGN Patients who underwent partial hepatectomy between 1997 and 2001, with complete preoperative radiographic imaging and postoperative pathologic assessment of steatosis, were retrospectively analyzed. The presence of steatosis was assessed radiographically using noncontrast-enhanced CT (NCCT), contrast-enhanced CT (CCT), or MRI, using standard quantitative radiologic criteria. Repeat histologic analysis was used to quantify the extent of hepatic steatosis. RESULTS One hundred thirty-one patients were studied. The overall sensitivity and specificity for all imaging modalities in detecting pathologically confirmed hepatic steatosis were 56% and 82%, respectively. Sensitivity and specificity for NCCT, CCT, and MRI using standard quantitative criteria were 33% and 100%, 50% and 83%, and 88%, and 63%, respectively. Increasing body mass indices adversely affected the accuracy of NCCT (p=0.002). Preoperative chemotherapy did not notably affect radiologic accuracy. CONCLUSIONS The presence of a fatty-appearing liver on NCCT scans indicates clinically significant steatosis, but steatosis cannot be excluded based on a normal NCCT scan, particularly in obese patients. Conversely, normal MRI helps to exclude hepatic steatosis, but abnormal MRI is not a reliable indicator of fatty change. CCT is not an effective means of identifying steatosis. We conclude that, when used alone, conventional cross-sectional imaging does not consistently permit accurate identification of hepatic steatosis.

Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms.

The behavior of neuroendocrine neoplasms is poorly defined, and predictors of outcome after surgical resection have yet to be identified. Consequently, guidelines for treatment remain unclear. Current pathologic classification systems do not permit meaningful discrimination of hepatic neuroendocrine neoplasms.

Importance of Low Preoperative Platelet Count in Selecting Patients for Resection of Hepatocellular Carcinoma: A Multi-Institutional Analysis

BACKGROUND Low platelet count is a marker of portal hypertension but is not routinely included in the standard preoperative evaluation of patients with hepatocellular carcinoma (HCC) because it pertains to liver function (Child/model for end-stage liver disease [MELD] score) and tumor burden (Milan criteria). We hypothesized that low platelet count would be independently associated with increased perioperative morbidity and mortality after resection. STUDY DESIGN Patients treated with liver resection for HCC between January 2000 and January 2010 at 3 institutions were eligible. Preoperative platelet count, Child/MELD score, and tumor extent were recorded. Low preoperative platelet count (LPPC) was defined as <150 × 10(3)/μL. Postoperative liver insufficiency (PLI) was defined as peak bilirubin >7 mg/dL or development of ascites. Univariate and multivariate regression was performed for predictors of major complications, PLI, and 60-day mortality. RESULTS A total of 231 patients underwent resection, of whom 196 (85%) were classified as Child A and 35 (15%) as Child B; median MELD score was 8. Overall, 168 (71%) had tumors that exceeded Milan criteria and 134 (58%) had major hepatectomy (≥3 Couinaud segments). Overall and major complication rates were 55% and 17%, respectively. PLI occurred in 25 patients (11%), and 21 (9%) died within 60 days of surgery. Patients with LPPC (n = 50) had a significantly increased number of major complications (28% versus 14%, p = 0.031), PLI (30% versus 6%, p = 0.001), and 60-day mortality (22% versus 6%, p = 0.001). When adjusted for Child/MELD score and tumor burden, LPPC remained independently associated with increased number of major complications (odds ratio [OR] 2.8, 95% confidence intervals [CI] 1.1 to 6.8, p = 0.026), PLI (OR 4.0, 95% CI 1.4 to 11.1, p = 0.008), and 60-day mortality (OR 4.6, 95% CI 1.5 to 14.6, p = 0.009). CONCLUSIONS LPPC is independently associated with increased major complications, PLI, and mortality after resection of HCC, even when accounting for standard criteria, such as Child/MELD score and tumor extent, used to select patients for resection. Patients with LPPC may be better served with transplantation or liver-directed therapy.

Laparoscopic versus open left pancreatectomy: can preoperative factors indicate the safer technique?

Background: Laparoscopic left pancreatectomy (LLP) is associated with favorable outcomes compared with open left pancreatectomy (OLP). However, it is unclear if the risk factors associated with operative morbidity differ between these two techniques. Guidelines for determining which patients should undergo OLP versus LLP do not exist. Methods: A multi-institutional analysis of OLP and LLP performed in 9 academic medical centers was undertaken. LLP cases were defined in an intent-to-treat manner. Perioperative variables were analyzed to identify factors associated with complications and pancreatic fistulae after OLP and LLP. In addition, complication and fistula rates for patients undergoing OLP and LLP were compared in matched cohorts to determine if one approach resulted in superior outcomes over the other. Results: Six hundred and ninety-three left pancreatectomy cases (439 OLP, 254 LLP) were analyzed. OLP and LLP cases were similar with respect to patient age and American Society of Anesthesiologists score. Body mass index (BMI) was higher in patients undergoing LLP. OLP was more often performed for adenocarcinoma and larger tumors, resulted in longer resected specimen lengths, and more commonly involved concomitant splenectomy. Estimated blood loss was higher and operative times were longer during OLP. On multivariate analysis, variables associated with major complications and clinically significant fistulae differed between OLP and LLP. Patients with body mass index ⩽27, without adenocarcinoma, and with pancreatic specimen length ⩽8.5 cm had significantly higher rates of significant fistulae after OLP than after LLP; in contrast, no preoperatively evaluable variables were associated with a higher likelihood of significant fistula after LLP versus OLP. Conclusions: Risk factors for complications and pancreatic fistulae after left pancreatectomy differ when open versus laparoscopic techniques are employed. Preoperative characteristics may identify cohorts of patients who will benefit more from LLP, and no patient cohorts had higher postoperative complication rates after LLP than OLP. These observations suggest that LLP may be the operative procedure of choice for most patients with left-sided pancreatic lesions; a more definitive prospective and randomized comparison may be warranted.

Tolerance and near-tolerance strategies in monkeys and their application to human renal transplantation

Summary: Studies in non‐human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non‐human primates are T‐cell depletion by anti‐CD3 immunotoxin and co‐stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non‐human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non‐human primates. However, there has not been a one‐to‐one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non‐human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non‐human primates.

Successful conversion from conventional immunosuppression to anti-CD154 monoclonal antibody costimulatory molecule blockade in rhesus renal allograft recipients.

BACKGROUND Several conventional forms of immunosuppression have been shown to antagonize the efficacy of anti-CD154 monoclonal antibody- (mAb) based costimulatory molecule blockade immunotherapy. Our objective was to determine if allograft recipients treated with a conventional immunosuppressive regimen could be sequentially converted to anti-CD154 mAb monotherapy without compromising graft survival. METHODS Outbred juvenile rhesus monkeys underwent renal allotransplantation from MHC-disparate donors. After a 60-day course of triple therapy immunosuppression with steroids, cyclosporine, and mycophenolate mofetil, monkeys were treated with: (1) cessation of all immunosuppression (control); (2) seven monthly doses of 20 mg/kg hu5C8 (maintenance), or; (3) 20 mg/kg hu5C8 on posttransplant days 60, 61, 64, 71, 79, and 88 followed by five monthly doses (induction+maintenance). Graft rejection was defined by elevation in serum creatinine>1.5 mg/dl combined with histologic evidence of rejection. RESULTS Graft survival for the three groups were as follows: group 1 (control): 70, 75, >279 days; group 2 (maintenance): 83, 349, >293 days, and; group 3 (induction+maintenance): 355, >377, >314 days. Acute rejection developing in two of four monkeys after treatment with conventional immunosuppression was successfully reversed with intensive hu5C8 monotherapy. CONCLUSIONS Renal allograft recipients can be successfully converted to CD154 blockade monotherapy after 60 days of conventional immunosuppression. An induction phase of anti-CD154 mAb appears to be necessary for optimal conversion. Therefore, although concurrent administration of conventional immunosuppressive agents including steroids and calcineurin inhibitors has been shown to inhibit the efficacy of CD154 blockade, sequential conversion from these agents to CD154 blockade appears to be effective.