Ernest L. Rosato

Impact of obesity on perioperative morbidity and mortality after pancreaticoduodenectomy.

BACKGROUND Obesity has been implicated as a risk factor for perioperative and postoperative complications. The aim of this study was to determine the impact of obesity on morbidity and mortality in patients undergoing pancreaticoduodenectomy (PD). STUDY DESIGN Between January 2000 and July 2007, 262 patients underwent PD at Thomas Jefferson University Hospital, of whom 240 had complete data, including body mass index (BMI; calculated as kg/m(2)) for analysis. Data on BMI, preoperative parameters, operative details, and postoperative course were collected. Patients were categorized as obese (BMI >or= 30), overweight (BMI >or= 25 and < 30), or normal weight (BMI < 25). Complications were graded according to previously published scales. Other end points included length of postoperative hospital stay, blood loss, and operative duration. Analyses were performed using univariate and multivariable models. RESULTS There were 103 (42.9%) normal-weight, 71 (29.6%) overweight, and 66 (27.5%) obese patients. There were 5 perioperative deaths (2.1%), with no differences across BMI categories. A significant difference in median operative duration and blood loss between obese and normal-weight patients was identified (439 versus 362.5 minutes, p = 0.0004; 650 versus 500 mL, p = 0.0139). In addition, median length of stay was significantly longer for BMI (9.5 versus 8 days, p = 0.095). Although there were no significant differences in superficial wound infections, obese patients did have an increased rate of serious complications compared with normal-weight patients (24.2% versus 13.6%, respectively; p = 0.10). CONCLUSIONS Obese patients undergoing PD have a substantially increased blood loss and longer operative time but do not have a substantially increased length of postoperative hospital stay or rate of serious complications. These findings should be considered when assessing patients for operation and when counseling patients about operative risk, but they do not preclude obese individuals from undergoing definitive pancreatic operations.

Robot-assisted minimally invasive esophagectomy is equivalent to thoracoscopic minimally invasive esophagectomy

The use of the surgical robot has been increasing in thoracic surgery. Its three-dimensional view and instruments with surgical wrists may provide advantages over traditional thoracoscopic techniques. Our initial experience with thoracoscopic robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer was compared with our traditional thoracoscopic minimally invasive esophagectomy (MIE) approach for esophageal cancer. A retrospective review of a prospective database was performed. From July 2008 to October 2009, 43 patients underwent MIE resection. Patients who had benign disease and intrathoracic anastomosis were excluded. Results are presented as mean ± SD. Significance was set as P < 0.05. Eleven patients who underwent RAMIE and 26 who underwent MIE were included in the cohort. No differences in age, sex, race, body mass index, or preoperative radiotherapy or chemotherapy between the groups were observed. No significant differences in operative time, blood loss, number of resected lymph nodes, postoperative complications, days of mechanical ventilation, length of intensive care unit stay, or length of hospital stay were also observed. In this short-term study, RAMIE was found to be equivalent to thoracoscopic MIE and did not offer clear advantages.

Oncologic Efficacy Is Not Compromised, and May Be Improved with Minimally Invasive Esophagectomy

BACKGROUND Major morbidity and mortality rates continue to be high in large series of transthoracic esophagectomies. Minimally invasive approaches are being increasingly used. We compare our growing series of minimally invasive (combined thoracoscopic and laparoscopic) esophagectomies (MIEs) with a series of open transthoracic esophagectomies. STUDY DESIGN We identified 65 patients who underwent an MIE with thoracoscopy/laparotomy (n = 11), Ivor Lewis (n = 2), or 3-hole approach (n = 52). These patients were compared with 53 patients who underwent open Ivor-Lewis esophagectomy (n = 15) or 3-hole esophagectomy (n = 38) over the past 10 years. RESULTS The MIE and open groups were similar regarding gender and average age. The majority of patients in the open group underwent neoadjuvant chemoradiation therapy (81%); a significantly smaller (43%) number of patients in the MIE group underwent neoadjuvant therapy (p < 0.0001). Regarding oncologic efficacy, 97% and 94% of patients in both groups underwent R0 resections. Patients undergoing MIE had a significant increase in the number of harvested lymph nodes (median 20 vs 9; p < 0.0001). Length of stay was significantly decreased in patients who underwent MIE (8.5 days vs 16 days; p = 0.002). Finally, there were significantly fewer serious complications (grades 3-5) in the MIE group (19% vs 48%; p = 0.0008). CONCLUSIONS In this initial report of a single-institution series of MIE, we demonstrate that oncologic efficacy is not compromised and may actually be improved with a significantly increased number of harvested LNs. We also demonstrate that this approach is associated with fewer serious complications and a significant decrease in the length of postoperative hospital stay.

Positive microscopic margins alter outcome in lymph node-negative cholangiocarcinoma when resection is combined with adjuvant radiotherapy.

Purpose:The purpose of this study was to evaluate the prognostic significance of positive microscopic margins in hilar cholangiocarcinoma in patients treated with resection and adjuvant radiotherapy. Materials and Methods:Between January 1983 and December 1997, 65 patients were definitively diagnosed with hilar cholangiocarcinoma and treated at our institution. Twenty-eight patients underwent curative resection. Of these patients, 23 received adjuvant radiotherapy with an average dose of 53 Gy (both external beam radiotherapy and low-dose rate brachytherapy). Portals included the preoperative primary tumor bed site with a 3- to 5-cm margin, the porta hepatis, and celiac lymph nodes. The patients with lymph node-negative pathologic specimens were reviewed, and an analysis of microscopic margins and subsequent impact on survival was determined with the Kaplan-Meier method and Wilcoxon test. Results:There were 16 patients who met inclusion criteria. There was no perioperative mortality. Seven patients had negative margins and 9 patients had positive microscopic margins. Median follow up was 55 months, and median survival was 24.5 months for the entire group. Median and 5-year survival were 21.5 months and 18.4% in the margin-negative group and 26 months and 15% in patients with positive margins (P = 0.45). These survival differences were not statistically significant. Discussion:Positive microscopic margins in lymph node-negative, resected hilar cholangiocarcinoma may not represent a negative prognostic factor when resection is combined with postoperative radiotherapy in this cohort. Further prospective, randomized studies are required to fully elucidate the benefits of adjuvant radiotherapy.

Cholangiocarcinoma: The Impact of Tumor Location and Treatment Strategy on Outcome

The purpose of this study was to evaluate how the outcome of patients with extrahepatic cholangiocarcinoma (EHBC) may have been influenced by tumor location and treatment selection. The primary endpoint of this study is overall survival (OS). Between January 1983 and December 1997, 221 patients with biliary tumors were evaluated at Thomas Jefferson University Hospital. Of these, 118 fit the inclusion criteria for this study. The extent of disease was assessed by computed tomography, percutaneous transhepatic cholangiography or endoscopic retrograde cholangiopancreatography, magnetic resonance imaging, and ultrasonography. All patients had histologic confirmation of malignancy. Roux-en Y, hepaticojejunostomy, or choledochojejunostomy followed surgical resection of the primary tumor. Palliative measure (PS) included biliary catheter placement without brachytherapy or external beam irradiation (RT). RT was delivered via high-energy photons. Intraluminal brachytherapy was performed via percutaneous biliary catheterization with iridium-192 ribbon sources. Chemotherapy consisted of either intravenous 5-fluorouracil alone or in combination with doxorubicin, mitomycin C, or paclitaxel. PS consisted of metal bile duct stent placement. Median follow-up time for the entire group was 102 months and 43 months for patients who were still alive at the conclusion of the study period. Patients with proximal tumors underwent resection (n = 5), surgery and RT (n = 23), RT only (n = 31), chemotherapy only (n = 6), or PS (n = 12). Patients with distal tumors were treated with surgical resection (n = 17) or a combination of surgery and RT (n = 13), RT only (n = 6), or PS (n = 4). Median survival time (MST) for all 118 patients was 22 months. The MST for patients with distal tumors was 47 months versus 17 months for those with proximal tumors. The MST has not been reached for patients with distal EHBC treated with surgical resection and postoperative RT, whereas the median survival for those treated with surgery alone is 62.5 months. However, 4 of 17 of these patients had in situ carcinoma. Six patients had distal tumors treated with RT only with a MST of 6 months. Patients with proximal tumors treated with surgery and RT had a superior OS at 5 years compared to patients treated with RT alone (24 vs. 13 months; p = 0.007). There was an improved OS in patients with proximal tumors treated with surgical resection and RT compared to surgery alone (p = 0.023). There is no discernable influence of chemotherapy on outcome in patients with proximal EHBC. The MST for patients treated with PS was 3.5 months. Surgery and postoperative RT appear to be better than either surgery or RT alone in patients with proximal EHBC. In patients with distal EHBC, the addition of resection and RT appears to offer an advantage, which is increasingly apparent with longer follow-up time. The prognosis remains dismal for patients treated with palliative intent.

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer

BACKGROUND Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. METHODS Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. RESULTS Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. CONCLUSIONS The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

High basic fibroblast growth factor levels in nipple aspirate fluid are correlated with breast cancer

PURPOSEThe angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor are important in malignant breast epithelial growth. Nipple aspirate fluid (NAF) is a physiologic fluid collected noninvasively that contains proteins secreted by the breast ductal epithelium and may contain markers of breast cancer. The purpose of this study was to determine whether high concentrations of bFGF and vascular endothelial growth factor in NAF would be associated with in situ and invasive breast cancer, and whether prostate-specific antigen, a marker in NAF associated with breast cancer, would improve our ability to determine which subjects had the disease. METHODSBoth bivariate and multivariate analyses were performed to determine the effects of race, menopausal status, bFGF concentration, and prostate-specific antigen on cancer risk. Bivariate analysis was also performed to determine the relationship between vascular endothelial growth factor concentration and cancer risk. RESULTSMean NAF bFGF levels were higher in women with breast cancer than in those without (19.2 vs 1.74 ng/g). Vascular endothelial growth factor was not associated with breast cancer. Race and menopausal status did not significantly affect the relationship between bFGF and cancer risk. bFGF, race, and menopausal status were each independent predictors of breast cancer, with bFGF being the most important. With knowledge of all three variables, the model was 89.9% sensitive and 69.0% specific in predicting which women had breast cancer. Adding prostate-specific antigen increased the sensitivity to 90.9% and the specificity to 83.3%. In subjects with NAF bFGF > 150 ng/g and prostate-specific antigen < 100 ng/g, 94.1% (32/34) of subjects had cancer. For women with NAF prostate-specific antigen > 100 ng/ g and bFGF < 150 ng/g, 90.5% were cancer free. CONCLUSIONSbFGF concentration in NAF is directly associated with breast cancer, regardless of race and menopausal status. NAF bFGF may prove helpful in the early detection of breast cancer.

The HYSLAR trial: a prospective randomized controlled trial of the use of a restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in patients undergoing pancreaticoduodenectomy.

Objective:This study was designed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes. Background:Three percent hypertonic saline (HYS) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period. Methods:Between May 2011 and November 2013, patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board–approved, single-center, prospective, parallel, randomized controlled trial (NCT 01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2 mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation, 1 mL/kg/hr HYS postoperation). Results:A total of 264 patients were randomized. Demographic variables between groups were similar. The HYS patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P = 0.02). The overall complication rate was reduced in the HYS group (43% vs 54%), with a relative risk of 0.79 [95% confidence interval (CI), 0.62–1.02; P = 0.073], factoring stratification for pancreas texture. After adjustment for age and weight, the relative risk was 0.75 [95% CI (0.58–0.96); P = 0.023]. The total number of complications was significantly reduced in the HYS group (93 vs 123), with an incidence rate ratio of 0.74 [95% CI (0.56–0.97); P = 0.027]. After adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52–0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day mortality were similar between groups. Conclusions:A moderately restrictive fluid regimen with HYS resulted in a statistically significant 25% reduction in complications when adjusted for age, weight, and pancreatic texture.

Minimally Invasive Esophagectomy Provides Significant Survival Advantage Compared with Open or Hybrid Esophagectomy for Patients with Cancers of the Esophagus and Gastroesophageal Junction

BACKGROUND Minimally invasive esophagectomy (MIE) is increasingly being used to treat patients with cancer of the esophagus and gastroesophageal junction. We previously reported that oncologic efficacy may be improved with MIE compared with open or hybrid esophagectomy (OHE). We compared survival of patients undergoing MIE and OHE. STUDY DESIGN Our contemporary series of patients who underwent MIE (2008 to 2013) was compared with a cohort undergoing OHE (3-hole [n = 39], Ivor Lewis [n = 16], hybrid [n = 13], 2000 to 2013). Summary statistics were calculated by operation type; Kaplan-Meier methods were used to compare survival. Cox regression was used to assess the impact of operation type (MIE vs OHE) on mortality, adjusting for age, sex, total lymph nodes, lymph node ratio (LNR), neoadjuvant chemoradiotherapy (CRT), and stage. RESULTS The MIE (n = 104) and OHE (n = 68) groups were similar with respect to age and sex. The MIE group tended to have higher BMI, earlier stage disease, and was less likely to receive CRT. The MIE group experienced lower operative mortality (3.9% vs 8.8%, p = 0.35) and significantly fewer major complications. Five-year survival between groups was significantly different (MIE, 64%, OHE, 35%, p < 0.001). Multivariate analysis demonstrated that patients undergoing OHE had a significantly worse survival compared with MIE independent of age, LNR, CRT, and pathologic stage (hazard ratio 2.00, p = 0.019). CONCLUSIONS This study supports MIE for EC as a superior procedure with respect to overall survival, perioperative mortality, and severity of postoperative complications. Several biases may have affected these results: earlier stage in the MIE group and disparity in timing of the procedures. These results will need to be confirmed in future prospective studies with longer follow-up.

Reoperative completion pancreatectomy for suspected malignant disease of the pancreas.

BACKGROUND Completion pancreatectomy (CP) is a reoperative procedure to excise remnant pancreatic tissue after a prior pancreatic resection. In this study, we document our institutions experience with CP for recurrent malignant disease of the pancreas, describing indications for surgery, procedures performed, and patient outcomes. METHODS We performed a retrospective review of 861 patients from the pancreatic surgery database in the Department of Surgery of Thomas Jefferson University from October 2005 to December 2010 to identify all cases of CP performed for suspected malignant disease. RESULTS Eleven patients underwent reoperative CP at our institution from 2005 to 2010. The median time interval between the initial operation and CP was 32 mo. A combination of clinical symptoms, elevated tumor markers, and imaging studies were used for diagnosis of recurrent disease. Pancreatic ductal adenocarcinoma was the most common pathology, found in six patients. The postoperative complication rate was 18% and the median postoperative hospital length of stay was 6 d. There were no 30-d readmissions and no perioperative deaths. The 1-y survival rate following CP was 71% with an overall median survival of 17.5 mo. CONCLUSIONS CP is a safe and effective option for a highly selected group of patients with suspected recurrent malignant disease of the remnant pancreas. Morbidity and mortality rates are within acceptable limits and similar to initial pancreatic resection. Eligibility depends heavily upon the absence of distant metastatic disease, technical factors for resection, and patient performance status.