The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation.

Background: The proliferation and apoptosis of cancer cells play important roles in breast carcinomas. However, to date, there have been few reports on the correlation between the expression of PTEN and AKT phosphorylation in breast cancer. This present study investigated the effects of the phosphatase and tensin homology deleted from chromosome 10 (PTEN) gene on the proliferation and apoptosis of breast cancer cells through protein kinase B (AKT) phosphorylation. Methods: Human breast cancer MDA-MB-231 cells were transfected with the pcDNA3.0 control vector or the pcDNA3.0-PTEN vector for 48 hours. The Cell Counting Kit 8 (CCK-8) was used to detect cell survival rates, double staining was performed to detect apoptosis, and Western blot (WB) analysis was conducted to detect protein expression. The effects of PTEN expression on the cell cycle and apoptosis of human breast cancer cell line MDA-MB-231, and on the levels of phosphorylated AKT protein were further analyzed. Moreover, the relationship between the PTEN gene and clinical features were also analyzed. Results: The cell survival rate of cells transfected with pcDNA3.0-PTEN was significantly lower than that of cells transfected with the control pcDNA3.0 vector (55.65%±12.18% vs. 97.32%±12.45%, P=0.004). Compared with the pcDNA3.0 group, the apoptosis rate of the pcDNA3.0-PTEN group was significantly increased (20.65±2.18 vs. 2.32±0.45, P=0.001). The expression of PTEN protein in pcDNA3.0-PTEN group was higher than that in the pcDNA3.0 group, and the expression of the AKT and mTOR proteins was significantly lower than that in pcDNA3.0 group (P<0.05). The expression of PTEN in the lymph node metastasis positive group was significantly higher than that in the lymph node metastasis negative group (P<0.05). The expression of the AKT protein in breast cancer was higher than that in normal breast tissue, and the difference was statistically significant (P<0.01). Conclusions: Overexpression of the PTEN gene can promote AKT phosphorylation, increase the apoptotic index of breast cancer cells, and reduce the proliferative activity of breast cancer cells. This provided a new direction for the next treatment of breast cancer, but further clinical research is needed.

Outcomes of adjuvant radiation therapy after chemotherapy in resected extrahepatic cholangiocarcinoma: A National Cancer Database analysis.

BACKGROUND: Adjuvant capecitabine is considered a standard of care for resected cholangiocarcinoma per the BILCAP trial. The role of adjuvant radiation therapy in that trial was not addressed. This study was designed to examine the outcomes of adjuvant radiation in patients who received chemotherapy for resected cholangiocarcinoma. METHODS: Using the National Cancer Database, the authors identified high-risk patients with resected extrahepatic cholangiocarcinoma with either positive nodes (N+) or margins (R1) who received adjuvant chemotherapy between 2006 and 2014. Overall survival (OS) was determined with the Kaplan-Meier method. Propensity score matching (PSM) and multivariate analysis (MVA) were performed to identify prognostic factors for survival. RESULTS: The authors identified 1478 patients after PSM who were included in the analysis. There was no difference in OS between patients receiving single-agent chemotherapy and patients receiving multiagent chemotherapy (p = .69). There was a significant OS benefit associated with radiation therapy. The median OS and the 5-year OS rate for radiated patients versus nonradiated patients were 34 months and 33% versus 27 months and 24% (p < .001) for the whole group, 30 months and 29% versus 24 months and 19% (p = .007) for the N+ subgroup, and 25 months and 23% versus 20 months and 12% (p = .03) for the R1 subgroup. MVA demonstrated that age, N stage, T stage, R1, and grade were associated with increased mortality, whereas adjuvant radiation was associated with decreased mortality (p < .001). CONCLUSIONS: This is the first study showing that adjuvant radiation therapy after chemotherapy resulted in a significant OS benefit for patients with resected high-risk extrahepatic cholangiocarcinoma. Trials are needed to address the role of radiation therapy in this population.

Comparative Perioperative Outcomes by Esophagectomy Surgical Technique.

INTRODUCTION: Surgical resection is vital in the curative management of patients with esophageal cancer. However, a myriad of surgical procedures exists based on surgeon preference and training. We report on the perioperative outcomes based on esophagectomy surgical technique. METHODS: A prospectively managed esophagectomy database was queried for patients undergoing esophagectomy from 1996 and 2016. Basic demographics, tumor characteristics, operative details, and post-operative outcomes were recorded and analyzed by comparison of transhiatal vs Ivor-lewis and minimally invasive (MIE) vs open procedures. RESULTS: We identified 856 patients who underwent esophagectomy. Neoadjuvant therapy was administered in 543 patients (63.4%). There were 504 (58.8%) open esophagectomies and 302 (35.2%) MIE. There were 13 (1.5%) mortalities and this did not differ among techniques (p = 0.6). While there was no difference in overall complications between MIE and open, complications occurred less frequently in patients undergoing RAIL and MIE IVL compared to other techniques (p = 0.003). Pulmonary complications also occurred less frequently in RAIL and MIE IVL (p < 0.001). Anastomotic leaks were less common in patients who underwent IVL compared to trans-hiatal approaches (p = 0.03). MIE patients were more likely to receive neoadjuvant therapy (p = 0.001), have lower blood loss (p < 0.001), have longer operations (p < 0.001), and higher lymph node harvests (p < 0.001) compared to open patients. CONCLUSION: Minimally invasive and robotic Ivor Lewis techniques demonstrated substantial benefits in post-operative complications. Oncologic outcomes similarly favor MIE IVL and RAIL.

Neoadjuvant therapy and pancreatic cancer: a national cancer database analysis.

BACKGROUND: We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent or multiagent chemotherapy, and neoadjuvant chemoradiation (NCRT) on survival in pancreatic cancer. METHODS: Utilizing the National Cancer Database, we identified patients who underwent pancreatic resection for adenocarcinoma (2006 to 2013). Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. RESULTS: We identified 26,563 patients who underwent pancreatic resection: UFS =23,877, NCRT =1,482, and NCT =1,204. Multiagent chemotherapy was utilized in 77% of NCT and 42% of NCRT. There was improved R0 resections associated with neoadjuvant therapy compared to UFS, however, there was no difference between NCT and NCRT. In addition, the was improved R0 with MA-NCT (P<0.001) but not for single agent NCT (P=0.26). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001), and 23.6, 23.9, 31.6, 25.9, and 26.6 months in R0 patients (P=0.03), respectively. There was no difference in OS in patients with R1/2 resection. MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. CONCLUSIONS: There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy.

Accuracy of endoscopic ultrasound staging for T2N0 esophageal cancer: a National Cancer Database analysis.

BACKGROUND: To determine accuracy of clinical staging of T2N0 esophageal cancer from the National Cancer Database (NCDB). METHODS: The NCDB was accessed to identify patients with T2N0M0 esophageal cancer (adenocarcinoma or squamous cell carcinoma) treated between 2004-2013 that underwent esophagectomy. Pathologic staging was compared to clinical stage. Univariate (UVA) and multivariate analysis (MVA) was performed to identify factors related to pathologic upstaging using Cox proportional hazard ratio. RESULTS: We identified 1,840 patients with T2N0 esophageal cancer who underwent esophagectomy as first line therapy. The median age was 67 years. The vast majority of patients were male and had distal adenocarcinomas. Clinical staging in was accurate pathologically in 30.7% of patients. While there was a trend for worse accuracy with increasing year of diagnosis, there rate of pT0-2N0 was stable. Tumor length >3 cm was significantly associated with tumor upstaging, while poor differentiation was significantly associated with nodal upstaging. UVA and MVA identified younger age, tumor length >3 cm, and poor differentiation were significantly associated with overall upstaging. Gender, tumor location, and tumor histology were not prognostic. CONCLUSIONS: Clinical staging for T2N0M0 esophageal cancer continues to remain highly inaccurate, however, rates of pT0-2N0 have steadily remained over 50%. Tumor length >3 cm and poor differentiation are strongly associated with pathologic upstaging.

Anastomotic leak and neoadjuvant chemoradiotherapy in esophageal cancer.

BACKGROUND: Anastomotic leaks (AL) cause significant morbidity after esophagectomy. Most patients receive neoadjuvant chemoradiation (NCR) prior to esophagectomy which has been associated with increase perioperative complications and mortality. We report on a comparison of AL rates in upfront surgical (UFS) and NCR patients. METHODS: An esophagectomy database was queried for UFS and NCR patients treated between 1996 and 2015. Predictors of AL rate were identified using univariate and multivariate (MVA) analysis and propensity score matching (PSM). RESULTS: We identified 820 patients (UFS, 288; NCR, 532). Overall AL rate was 5.4%. Decreased AL rate was observed in NCR patients on MVA (8.0% vs. 4.1%; P=0.02) but no difference was seen after PSM (7.7% vs. 4.2%; P=0.14). MVA of factors associated with decreased AL in UFS patients included distal esophageal tumors and body mass index (BMI) >25. Age, gender, year of surgery, histology, anastomotic location, and diabetes were not prognostic. Before PSM, MVA of NCR patients of factors associated with decreased AL revealed that only thoracic anastomosis was prognostic. However, this was not observed after PSM. MVA of factors associated with decreased AL in all patients revealed thoracic anastomosis, NCR, and BMI 25-30. After PSM, only distal esophageal tumors and thoracic anastomosis were prognostic for decreased AL. CONCLUSIONS: There is no difference in the AL rate between UFS and NCR patients. Decreased AL rate was observed in patients with distal esophageal tumors and thoracic anastomosis.

Adjuvant radiation provides survival benefit for resected pancreatic adenocarcinomas of the tail.

BACKGROUND: The appropriate adjuvant treatment for resected pancreatic cancer remains a controversy. We sought to determine the effect of adjuvant treatment on overall survival (OS) in patients with pancreatic tail adenocarcinoma. METHODS: Retrospective review of patients with upfront surgically resected pancreatic tail cancer treated at our institution between 2000-2012 was performed to determine outcomes of patients treated with and without adjuvant radiation therapy (RT). Survival curves were calculated according to the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the Cox proportional hazards model. RESULTS: Thirty-four patients met inclusion criteria. 79% received adjuvant chemotherapy, either concurrent with RT or alone. The groups were well matched, with the only significant difference being patient sex. On both UVA and MVA there was significantly worse survival in patients with a post-op CA19-9 >90 [hazard ratio (HR) 5.55; 95% confidence interval (CI): 1.20-25.7, P=0.03] and improved survival in patients treated with adjuvant RT (HR 0.15; 95% CI: 0.04-0.58, P=0.006). The median and 2-year OS were 21.6 months and 47% for patients treated with adjuvant RT compared with 11.3 months and 21% for those treated without RT. CONCLUSIONS: Although few in patient numbers, this data suggests integration of adjuvant RT in resected pancreatic tail adenocarcinoma may improve OS.

Outcomes of adjuvant radiotherapy and lymph node resection in elderly patients with pancreatic cancer treated with surgery and chemotherapy.

BACKGROUND: We sought to determine the effects of post-operative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients ≥70 years with pancreatic cancer treated with surgery and chemotherapy. METHODS: An analysis of patients ≥70 years with surgically resected pancreatic cancer who received chemotherapy from the SEER database between 2004-2008 was performed to determine association of PORT and LNR on survival. RESULTS: We identified 961 patients who met inclusion criteria. There was a trend towards increased survival associated with PORT in all patients (P=0.052) and N1 patients (P=0.060) but no benefit in N0 patients (P=0.161). There was no difference in OS based on number of lymph nodes removed in all (P=0.741), N0 (P=0.588), and N1 (P=0.070) patients. MVA for all patients revealed that higher T stage, N1, and high grade tumors were prognostic for increased mortality, while there was decreased mortality with PORT and mild benefit with increased lymph nodes resected (P=0.084). CONCLUSIONS: PORT demonstrated no benefit in survival of pancreatic cancer patients ≥70 who are resected and treated with adjuvant chemotherapy. Future investigation will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting.

Adjuvant chemotherapy and outcomes in esophageal carcinoma.

BACKGROUND: Standard treatment for locally advanced esophageal cancer is neoadjuvant chemoradiation followed by surgery. The role of postoperative chemotherapy is unclear. We sought to determine the indications, patterns, and outcomes for adjuvant chemotherapy in esophageal carcinoma. METHODS: This single institution retrospective review included patients with esophageal cancer who received neoadjuvant chemoradiation and surgery at Moffitt. We identified patients in this cohort who additionally received adjuvant chemotherapy. Medical records were reviewed for demographic/clinical information. Survival was estimated using the Kaplan-Meier method and compared by log-rank. Case-control analysis was performed using a 2:1 nearest neighbor propensity score matching algorithm, which included 92 without adjuvant chemotherapy and 46 with adjuvant chemotherapy. RESULTS: We identified 382 patients, 46 of whom received adjuvant chemotherapy. Patients who received adjuvant chemotherapy were younger (60.2 vs. 63.8 years; P=0.047), more likely to have adenocarcinoma (91% vs. 85%; P=0.034), had more advanced ypT and ypN classifications (P<0.001), less response to neoadjuvant therapy (P<0.001), and more margin positivity (15% vs. 4%; P=0.007). With propensity score matching analysis, no variables were significantly different between the two matched groups. Median follow-up times for the entire cohort and for case-control analysis were 2.9 and 2.4 years, respectively. There were no significant differences in overall or recurrence-free survival (RFS) between groups in either analysis. CONCLUSIONS: The role of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery in esophageal cancer is unclear. We found no significant difference in survival based on adjuvant chemotherapy. Future prospective studies should further investigate potential survival benefits and morbidity.

Effect of body mass index on operative outcome after robotic-assisted Ivor-Lewis esophagectomy: retrospective analysis of 129 cases at a single high-volume tertiary care center.

The impact of body weight on outcomes after robotic-assisted esophageal surgery for cancer has not been studied. We examined the short-term operative outcomes in patients according to their body mass index following robotic-assisted Ivor-Lewis esophagectomy at a high-volume tertiary-care referral cancer center and evaluated the safety of robotic surgery in patients with an elevated body mass index. A retrospective review of all patients who underwent robotic-assisted Ivor-Lewis esophagectomy between April 2010 and June 2013 for pathologically confirmed distal esophageal cancer was conducted. Patient demographics, clinicopathologic data, and operative outcomes were collected. We stratified body mass index at admission for surgery according to World Health Organization criteria; normal range is defined as a body mass index range of 18.5-24.9 kg/m2. Overweight is defined as a body mass index range of 25.0-29.9 kg/m2 and obesity is defined as a body mass index of 30 kg/m2 and above. Statistics were calculated using Pearson's Chi-square and Pearson's correlation coefficient tests with a P-value of 0.05 or less for significance. One hundred and twenty-nine patients (103 men, 26 women) with median age of 67 (30-84) years were included. The majority of patients, 76% (N = 98) received neoadjuvant therapy. When stratified by body mass index, 28 (22%) were normal weight, 56 (43%) were overweight, and 45 (35%) were obese. All patients had R0 resection. Median operating room time was 407 (239-694) minutes. When stratified by body mass index, medians of operating room time across the normal weight, overweight and obese groups were 387 (254-660) minutes, 395 (310-645) minutes and 445 (239-694), respectively. Median estimated blood loss (EBL) was 150 (25-600) cc. When stratified by body mass index, medians of EBL across the normal weight, overweight and obese groups were 100 (50-500) cc, 150 (25-600) cc and 150 (25-600), respectively. Obesity significantly correlated with longer operating room time (P = 0.05) but without significant increased EBL (P = 0.348). Among the three body mass index groups there was no difference in postoperative complications including thrombotic events (pulmonary embolism and deep venous thrombosis) (P = 0.266), pneumonia (P = 0.189), anastomotic leak (P = 0.090), wound infection (P = 0.390), any cardiac events (P = 0.793) or 30 days mortality (P = 0.414). Our data study demonstrates that patients with esophageal cancer and an elevated body mass index undergoing robotic-assisted Ivor-Lewis esophagectomy have increased operative times but no significantly increased EBL during the procedure. Other potential morbidities did not differ with the robotic approach.

AKT expression is associated with degree of pathologic response in adenocarcinoma of the esophagus treated with neoadjuvant therapy.

BACKGROUND: Neoadjuvant chemoradiation (NCRT) has become standard in the treatment of locally advanced esophageal adenocarcinoma (EAC) with survival correlated to degree of pathologic response. The phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays an important role in tumorgenesis and resistance. We sought to elucidate the role of this pathway in patients with EAC who received NCRT. METHODS: After IRB approval, a prospective trial was initiated in which patients with EAC underwent endoscopic biopsies of normal and tumor tissue prior to instituting NCRT. Patients then proceeded to esophagectomy. The pre-treatment tissues underwent gene expression profiling. SAM method was used to analyze expression of AKT within normal and tumor tissue. Expression was then correlated to degree of pathologic response. RESULTS: One-hundred patients were consented for the study, of which 67 met final eligibility. Nineteen patient's tumors ultimately underwent gene expression profiling via microarray. The differential expression of all AKT isoforms in tumor tissue was markedly overexpressed compared to normal tissue (P=6×10(-5)). There were 3 patients designated as pNR, 6 as pPR, and 10 as pCR. Partial and non-responders had higher expressions of AKT compared to pCR with the non-responders consistently illustrated the highest expression of AKT (P=0.02). There was a significant correlation between individual isoforms of AKT-1, AKT-2, and AKT-3 and degree of pathologic response (P=0.002, 0.04, and 0.04 respectively). CONCLUSIONS: AKT is overexpressed in patients with AC of the esophagus. Moreover, pathologic response to NCRT may be correlated with degree of AKT expression. Additional data is needed to clarify this relationship to potentially add targeted therapies to the neoadjuvant regimen.

Perioperative outcomes associated with robotic Ivor Lewis esophagectomy in patient's undergoing neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCR) for the treatment of esophageal cancer has been associated with increased perioperative morbidity and mortality. Minimally invasive procedures utilizing robotic techniques have been shown to reduce perioperative complications and length of hospitalization (LOH). The purpose of this study is to compare perioperative outcomes between patients undergoing NCR and robotic-assisted Ivor Lewis esophagectomy (RAIL) versus upfront RAIL. METHODS: A database of esophagectomy patients was queried to identify RAIL patients. Differences in perioperative outcomes were analyzed between NCR and non NCR patients. RESULTS: Eighty-nine patients were identified who underwent RAIL Seventy-seven patients (87%) had NCR and 22 patients did not (13%). The median age was 66 (range, 44-83). The median age of the patients treated with NCR was younger {69 [44-83] vs. 64 [46-81] years respectively, P=0.05}. The patients who underwent NCR had a higher BMI then those who went straight to esophagectomy (31 vs. 27; P=0.001). There were no conversions to open laparotomy or thoracotomy in either group. There were no statistically significant differences in the mean operative times and estimated blood loss (EBL) between both groups. Complications occurred in 17 (19.1%) patients. There were no statistically significant differences in the rates of any complications between patients receiving NCR and those that did not receive NCR (P=0.11). There were no deaths in either group. The total number of days in hospital and total number of intensive care unit (ICU) days were also similar in both groups (P=0.25). There was no statistically significant difference in the mean number of lymph nodes harvested in the patients treated with NCR compared with those treated without NCR. CONCLUSIONS: We have demonstrated that RAIL is a safe and feasible option for patients with esophageal cancer. The administration of NCR to RAIL did not result in an increase in perioperative morbidity and mortality. The number of lymph nodes harvested and the completeness of resection was also similar between patients who received NCR and those who did not. Longer follow-up is required in order to determine long term oncologic outcome.

Outcomes of resected pancreatic cancer in patients age ≥70.

OBJECTIVE: To determine outcomes of patients ≥70 years with resected pancreatic cancer. METHODS: A study was conducted to identify pancreatic cancer patients ≥70 years who underwent surgery for pancreatic carcinoma from 2000 to 2012. Patients were excluded if they had neoadjuvant therapy. The primary endpoint was overall survival (OS). RESULTS: We identified 112 patients with a median follow-up of surviving patients of 36 months. The median patient age was 77 years. The median and 5 year OS was 20.5 months and 19%, respectively. Univariate analysis (UVA) showed a significant correlation for increased mortality with N1 (P=0.03) as well as post-op CA19-9 >90 (P<0.001), with a trend towards decreased mortality with adjuvant chemoradiation (P=0.08). Multivariate analysis (MVA) showed a statistically significant increased mortality associated with N1 (P=0.008), post-op CA19-9 >90 (P=0.002), while adjuvant chemoradiation (P=0.04) was associated with decreased mortality. CONCLUSIONS: These data show that in patients ≥70, nodal status, post-op CA19-9, and adjuvant chemoradiation, were associated with OS. The data suggests that outcomes of patients ≥70 years who undergo upfront surgical resection are not inferior to younger patients.

Body Mass Index and Perioperative Complications After Esophagectomy for Cancer.

BACKGROUND: Given the increasing rate of obesity, the effects of excessive body weight on surgical outcomes constitute a relevant quality of care concern. Our aim was to determine the relationship between preoperative body mass index (BMI) on perioperative complications after esophagectomy for cancer. METHODS: From our comprehensive esophageal cancer database consisting of 510 patients, we identified 166 obese (BMI ≥30), 176 overweight (BMI 25-29), and 148 normal-weight (BMI 20-24) patients. Malnourished patients (BMI of <20) were excluded. Incidence of preoperative risk factors and perioperative complications in each group were analyzed. RESULTS: The patient group consists of 420 men and 70 women with a mean age at time of surgery were 64 years (range 28-86 years). The categories of patients (obese, overweight, and normal-weight) were similar in terms of demographics and comorbidities, with the exception of a younger age (62.5 years vs 66.2 years vs 65.3 years, P = 0.002), and a higher incidence of diabetes (23.5% vs 11.4% vs 10.1%, P = 0.001) and hiatal hernia (28.3% vs 14.8% vs 20.3%, P = 0.01) for obese patients. More patients with BMI >24 were found with adenocarcinoma, compared with the normal-weight group (90.8% vs 90.9% vs 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6% vs 54.5% vs 66.2%, P = 0.004). The type of surgery performed, overall blood loss, extent of lymphadenectomy, rate of resections with negative margins, and postoperative complications were not influenced by BMI on univariate and multivariate analysis. CONCLUSIONS: In our experience, BMI did not affect number of harvested lymph-nodes, rates of negative margins, and morbidity and mortality after esophagectomy for cancer. In our experience, esophagectomy could be performed safely and efficiently in mildly obese patients.

Robotic Whipple Procedure for Pancreatic Cancer: The Moffitt Cancer Center Pathway.

BACKGROUND: Resection of malignancies in the head and uncinate process of the pancreas (Whipple procedure) using a robotic approach is emerging as a surgical option. Although several case series of the robotic Whipple procedure have been reported, detailed descriptions of operative techniques and a clear pathway for adopting this technology are lacking. METHODS: We present a focused review of the procedure as it applies to pancreatic cancer and describe our clinical pathway for the robotic Whipple procedure used in pancreatic cancer and review the outcomes of our early experience. A systematic review of the literature is provided, focusing on the indications, variations in surgical techniques, complications, and oncological results of the robotic Whipple procedure. RESULTS: A clinical pathway has been defined for preoperative training of surgeons, the requirements for hospital privileges, patient selection, and surgical techniques for the robotic Whipple procedure. The robotic technique for managing malignant lesions of the pancreas head is safe when following well-established guidelines for adopting the technology. Preliminary data demonstrate that perioperative convalescence may exceed end points when compared with the open technique. CONCLUSIONS: The robotic Whipple procedure is a minimally invasive approach for select patients as part of multidisciplinary management of periampullary lesions in tertiary centers where clinicians have developed robotic surgical programs. Prospective trials are needed to define the short- and long-term benefits of the robotic Whipple procedure.

Outcomes of Therasphere Radioembolization for Colorectal Metastases.

INTRODUCTION: The liver is the most common site for colorectal cancer (CRC) metastases. Radioembolization with yttrium-90 (Y90) represents an alternative approach in the management of unresectable hepatic colorectal metastases. The objective of this study was to evaluate outcomes after treatment with Y90. MATERIALS AND METHODS: A retrospective review of patients undergoing Y90 glass microsphere treatment for metastatic CRC from 2009 to 2013 was conducted. Multivariable analysis (MVA) of factors related to overall survival (OS) was performed using the Cox proportional hazard and OS estimates were calculated using the Kaplan-Meier method. RESULTS: We identified 68 patients. Median and 2-year OS were 11.6 months and 34%. For patients with ≤ 25% hepatic burden of disease (HBD) and 1 chemotherapy regimen, 2-year OS was 63%. Median and 2-year OS for patients with ≤ 25% versus > 25% HBD were 19.6 months and 42% versus 3.4 months and 0% (P < .0001). Univariate analysis revealed that higher HBD, ≥ 3 lines of chemotherapy received, and higher carcinoembryonic antigen (CEA) were found to be significant predictors of worse OS. MVA revealed age, > 25% HBD, ≥ 3 lines of chemotherapy, and higher CEA were independently prognostic for increased mortality, and resected status of the primary tumor was associated with decreased mortality. The presence of extrahepatic metastases was not prognostic. Toxicities were mild and only 5 patients experienced Grade 3/4 biochemical toxicity. CONCLUSION: Yttrium-90 was associated with acceptable OS with minimal morbidity in this series. Minimal exposure to chemotherapy and low HBD were found to be associated with better OS, however, even patients with chemotherapy-refractory disease received a benefit from treatment.

Comparative long-term outcomes of upfront resected pancreatic cancer after preoperative biliary drainage.

BACKGROUND: We evaluated whether preoperative biliary drainage was predictive of recurrence and survival among patients with resectable pancreatic cancer. METHODS: Patients with pancreatic cancer who were treated with upfront surgery between 2000 and 2012 were identified and stratified by preoperative percutaneous transhepatic cholangiogram-guided drainage (PTBD), placement of endoscopic stents (ERCP), or no biliary drainage (NBD). The primary endpoint was overall survival. RESULTS: We identified 193 patients with resectable pancreatic head cancer (33 PTBD; 96 ERCP; and 64 NBD). Key differences between the three groups were more patients who underwent >1 preoperative biliary procedures (p = 0.004) in the PTBD cohort. PTBD patients had a significant increase in hepatic recurrence rate compared with patients who did not undergo PTBD (44.8 vs. 23.3 %, p = 0.02). PTBD patients also had worse overall survival. Median and 5-year survival for PTBD, ERCP, and NBD patients were 17.5 months and 3 %, 22.4 months and 24 %, and 28.9 months and 32 %, respectively (p = 0.002). MVA revealed that percutaneous drainage was an independent predictor of worse overall survival [HR 1.76, 95 % CI (1.05-2.99), p = 0.03]. CONCLUSIONS: Patients with resectable pancreatic cancer who receive PTBD have more advanced disease, higher hepatic recurrence, and worse survival.

Adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy.

BACKGROUND: The objective of this study was to determine the effects of postoperative radiation therapy (PORT) and lymph node dissection (LND) on survival in patients with pancreatic cancer. METHODS: The 2004 to 2008 Surveillance, Epidemiology, and End Results (SEER) database was analyzed to identify patients with pancreatic cancer who underwent surgery and received chemotherapy and to evaluate the correlation between overall survival (OS), PORT, and LND. RESULTS: In total, 2966 patients were identified who underwent pancreatic resection (1842 PORT, 1124 no PORT). Median survival, 1-year OS, and 3-year OS were 21 months, 77%, and 28%, respectively, with PORT versus 20 months, 70%, and 25%, respectively, without PORT (P = .02). Subset analysis revealed that the benefit of PORT was limited to lymph node-positive (N1) patients. Median survival, 1-year OS, and 3-year OS for patients with N1 disease were 19 months, 73%, and 25%, respectively, for those who received PORT versus 18 months, 67%, and 20%, respectively, for those who did not receive PORT (P < .01). An increasing lymph node count was associated with increased survival on multivariate analysis in all patients and in patients with N1 disease (both P < .001). Significant cutoff points for OS based on LND in patients with N1 disease were identified for those who had ≥8, ≥10, ≥12, ≥15, and ≥20 lymph nodes resected. Multivariate analysis for OS revealed that increasing age, T3 and T4 tumors, N1 stage, and moderately and poorly differentiated grade were prognostic for increased mortality, while female gender, PORT, and LND were prognostic for decreased mortality. In patients with N1 disease, other than patient age, all of these factors remained significant. In patients with N0 disease, only T1 and T2 tumor classification and having a tumor that was less than high grade were associated with survival benefit. CONCLUSIONS: This SEER analysis demonstrated an associated survival benefit of PORT and LND in patients with N1, surgically resected pancreatic cancer who received chemotherapy.

Effect of body mass index in patients undergoing resection for gastric cancer: a single center US experience.

INTRODUCTION: With rising obesity in the USA, the impact of body mass index (BMI) on survival in gastric cancer remains unclear. METHODS: An institutional database of patients undergoing surgical evaluation for gastric cancer was reviewed. Patients were stratified by the following BMI: <18.5, 18.5-25, 25.1-30, and >30. Clinicopathologic factors and overall survival (OS) were analyzed. RESULTS: From 1997 to 2012, 222 patients underwent exploration for gastric adenocarcinoma. 186 (84%) had BMI recorded: nine (5%) <18.5, 72 (39%) 18.5-25, 62 (33%) 25.1-30, and 43 (23%) >30. One hundred thirty-five (73%) ultimately underwent resection. Although American Society of Anesthesiology score and blood loss were not associated with increasing BMI, operative time was longer, p = 0.02. Proximal location, perineural invasion, lymphovascular invasion, positive surgical margins, and positive lymph nodes (LN+) were all associated with worse OS but not with increased BMI. Although increased BMI was associated with a lower lymph node count, p = 0.004, the number of LN + and final pathologic stage were not associated with BMI. Additionally, use of neoadjuvant or adjuvant chemotherapy was not associated with BMI. Median OS was 22 months. Median OS was improved with increased BMI: 21 months for <18.5, 13 months 18.5-25, 28 months 25-30, and 34 months >30, p = 0.02. Disease-free survival (DFS) was similar: 2 months for <18.5, 7 months 18.5-25, 15 months 25.1-30, and 15 months >30, p = 0.02. CONCLUSION: Although BMI may impact the technical difficulty of resection for gastric cancer, increasing BMI is not associated with more advanced disease. In this experience, increased BMI does not adversely impact OS or DFS.

Prognostic impact of lymph node retrieval and ratio in gastric cancer: a U.S. single center experience.

INTRODUCTION: Increased lymph node (LN) retrieval for gastric cancer has been associated with improved overall survival (OS). This study examines the impact of number of examined LN (eLN) and lymph node ratio. METHODS: Patients referred for surgical care of gastric cancer were stratified by number of eLN, positive LNs (LN+), and lymph node ratio (LN+/eLN). Clinicopathologic factors were compared; OS and disease-free survival (DFS) were the primary endpoints. RESULTS: From 1997 to 2012, 222 patients, median age 67 (range, 17-92) years, were analyzed. Of 220 (99 %) explored, 164 (74 %) underwent resection. Median OS was 22 (range, 0.3-140) months. Perineural and lymphovascular invasion and poor differentiation adversely affected OS, p < 0.05. A median 14 eLN (range, 0-45), with median 1 LN+ (range, 0-31), was observed. There were no OS or DFS differences when comparing the eLN groups. Both OS and DFS were impacted by LN+. Lymph node ratio demonstrated worse median OS with increasing ratio: 49 months (0) to 37 months (0.01-0.2), 27 months (0.21-0.5), and 12 months (>0.5), p < 0.0001. DFS was similar: 35 months (0), decreasing to 22 months (0.01-0.2), 13 months (0.21-0.5), and 7 months (>0.5), p < 0.0001. CONCLUSION: Number of eLN did not impact survival, while LN+ adversely affected survival. Lymph node ratio may predict prognosis better than number of eLN or LN+ in gastric cancer.