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Dominic E Sanford,
Brian A Belt,
Roheena Z Panni,
Allese B Mayer,
Anjali D Deshpande,
Danielle Carpenter,
Jonathan B Mitchem,
Stacey Plambeck-Suess,
Lori A Worley,
Brian D Goetz,
Andrea Wang-Gillam,
Timothy J Eberlein,
David G Denardo,
Peter Goedegebuure, David C Linehan
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ABSTRACT: PURPOSE: To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (IM; CCR2+/CD14+) as immunotherapeutic targets in the treatment of pancreatic cancer (PC). EXPERIMENTAL DESIGN: Survival analysis was performed to determine if the prevalence of pre-operative blood monocytes correlates with survival in PC patients following tumor resection. IM prevalence in the blood and bone marrow of PC patients and controls was compared. CCL2 expression by human PC tumors was compared to normal pancreas. The immunosuppressive properties of IM and macrophages in the blood and tumors, respectively, of PC patients were assessed. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine PC. RESULTS: Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in PC patients with resected tumors. IM are increased in the blood and decreased in the bone marrow of PC patients compared to controls. An increased ratio of IM in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human PC produces CCL2, and immunosuppressive CCR2+ macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes IM and macrophages from the primary tumor and premetastatic liver resulting in enhanced anti-tumor immunity, decreased tumor growth, and reduced metastasis. CONCLUSIONS: IM recruitment is critical to PC progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease.
Clinical Cancer Research 05/2013; · 7.74 Impact Factor
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ABSTRACT: OBJECTIVES: Jaundice impairs cellular immunity, an important defence against the dissemination of cancer. Jaundice is a common mode of presentation in pancreatic head adenocarcinoma. The purpose of this study was to determine whether there is an association between preoperative jaundice and survival in patients who have undergone resection of such tumours. METHODS: Thirty possible survival risk factors were evaluated in a database of over 400 resected patients. Univariate analysis was used to determine odds ratio for death. All factors for which a P-value of <0.30 was obtained were entered into a multivariate analysis using the Cox model with backward selection. RESULTS: Preoperative jaundice, age, positive node status, poor differentiation and lymphatic invasion were significant indicators of poor outcome in multivariate analysis. Absence of jaundice was a highly favourable prognostic factor. Interaction emerged between jaundice and nodal status. The benefit conferred by the absence of jaundice was restricted to patients in whom negative node status was present. Five-year overall survival in this group was 66%. Jaundiced patients who underwent preoperative stenting had a survival advantage. CONCLUSIONS: Preoperative jaundice is a negative risk factor in adenocarcinoma of the pancreas. Additional studies are required to determine the exact mechanism for this effect.
HPB 04/2013; · 1.60 Impact Factor
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ABSTRACT: OBJECTIVES: Pancreatic leak is a morbid complication following left pancreatectomy, which results in prolonged hospitalization, additional diagnostic testing and invasive procedures. The present authors have previously demonstrated that mesh reinforcement of stapled left pancreatectomy results in fewer pancreatic leaks. This study was conducted to investigate whether mesh reinforcement also results in cost benefits for the health care system. METHODS: A cost benefit model was developed to estimate net cost savings from the payer's perspective. The model is based on the results of a randomized, single-blinded trial of mesh versus no mesh reinforcement of the pancreatic remnant after left pancreatectomy. A two-way sensitivity analysis was conducted to determine the model's sensitivity to fluctuations in the cost of mesh and the effectiveness of the mesh in reducing clinically significant leaks. RESULTS: Average total costs for an episode of care were US$13 337 and US$15 505 for patients who did and did not receive mesh, respectively, which indicates savings of US$2168. Two-way sensitivity analysis showed that, given a probability of 1.9% for developing a clinically significant leak in patients in whom mesh reinforcement was used, the strategy would continue to save costs if mesh were priced at ≤US$1804. CONCLUSIONS: Mesh reinforcement decreases clinically significant pancreatic leaks. Despite the additional cost of mesh reinforcement, the use of mesh reinforcement results in overall cost savings for the health care system because of the resultant decrease in the occurrence of clinically significant leaks.
HPB 02/2013; · 1.60 Impact Factor
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ABSTRACT: To correlate microscopic margin status with survival and local control in a large cohort of patients from a high-volume pancreatic cancer center.
Retrospective database review. A uniform procedure for margin analysis was used with 4-color inking (neck, portal vein groove, uncinate, and posterior pancreatic margin) by the surgeon in the operating room.
A tertiary care hospital.
We reviewed patients who underwent pancreaticoduodenectomy between September 1, 1997, and December 31, 2008, from a prospective, institutional database.
Using Cox regression models, we identified pathologic characteristics associated with local recurrence (LR) after controlling for potential confounding variables. Overall and LR-free survival curves were generated by the Kaplan-Meier method.
Of 285 patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma, 97 (34.0%) had 1 or more positive microscopic margins (uncinate, 16.5%; portal vein groove, 8.8%; neck, 7.7%; and posterior, 10.5%). A total of 198 patients (69.5%) recurred, with the first site of failure being LR only in 47 (23.7%), local plus distant recurrence in 42 (21.2%), and distant recurrence only in 109 (55.1%). Patients with LR only were significantly more likely to have lymph node involvement (adjusted hazard ratio, 2.66; 95% CI, 1.25-5.63) or a positive posterior margin (adjusted hazard ratio, 4.27; 95% CI, 2.07-8.81). Patients with a positive posterior margin had significantly poorer LR-free survival with (P < .001) or without (P = .01) lymph node involvement.
When systematically assessed, the incidence of positive microscopic margins is high. Positive posterior margins and lymph node involvement were each independently and significantly associated with LR.
Archives of surgery (Chicago, Ill.: 1960) 08/2012; 147(8):753-60. · 4.32 Impact Factor
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ABSTRACT: IntroductionThe risks of developing sinistral portal hypertension as a result of occlusion of the splenic vein close to its termination
during a Whipple procedure are unclear. Our purpose was to compare the pattern of venous collateral development after splenic
vein ligation in an extended Whipple procedure with the pattern of collateral development in cases of sinistral portal hypertension.
MethodsFive patients underwent an extended Whipple procedure in which the splenic vein was divided and not reconstructed. Six to
eight months later detailed mapping of venous return from the spleen was determined by contrast-enhanced multidetector computed
tomography or in one case by 3D contrast-enhanced MRI. Spleen size and length of residual patent splenic vein were also measured.
The literature on sinistral portal hypertension was evaluated to ascertain whether the venous collateral pattern in cases
of left-sided portal hypertension was similar to the pattern that developed when the splenic vein was ligated at its termination
in the Whipple procedure.
ResultsA length of splenic vein remained patent in all five patients, measuring 4.5 to 11.5cm from the spleen. Splenomegaly did
not develop. Blood returned from the spleen by multiple collaterals including collaterals in the omentum and mesocolon. These
types of collaterals do not develop in sinistral portal hypertension, nor is residual patent splenic vein seen.
ConclusionsLigation of the splenic vein close to its termination in five patients resulted in a pattern of venous return different from
patients that have developed left-sided portal hypertension.
KeywordsWhipple procedure–Mesenteric vein resection–Superior mesenteric vein–Portal vein–Splenic vein–Sinestral portal hypertension–Left sided portal hypertension
Journal of Gastrointestinal Surgery 04/2012; 15(11):2070-2079. · 2.83 Impact Factor
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ABSTRACT: Pancreatic leak or fistula is the most frequent complication after left pancreatectomy. We performed a single-blinded, parallel-group, randomized controlled trial comparing stapled left pancreatectomy with stapled left pancreatectomy using mesh reinforcement of the staple line with either Seamguard or Peristrips Dry.
All patients undergoing left pancreatectomy at a large tertiary hospital were eligible for participation. Patients were randomized to either mesh reinforcement or no-mesh reinforcement intraoperatively after being determined a candidate for resection. Patients were blinded to the result of their randomization for 6 weeks. Primary outcome measure was clinically significant leak as defined by the ISGPF (International Study Group on Pancreatic Fistula) pancreatic leak grading system.
One hundred patients were randomized to either mesh (54) or no-mesh (46) reinforcement of their pancreatic transection. There was 1 death in each group. ISGPF grade B and C leaks were seen in 1.9% (1/53) of patients undergoing resection with mesh reinforcement and 20% (11/45) of patients without mesh reinforcement (P = .0007).
Mesh reinforcement of pancreatic transection line significantly reduces the incidence of significant pancreatic fistula in patients undergoing left pancreatectomy.
Clinicaltrials.gov: NCT01359410.
Annals of surgery 04/2012; 255(6):1037-42. · 7.90 Impact Factor
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ABSTRACT: Pancreatic neuroendocrine neoplasms are rare malignancies for which the ideal staging method remains controversial. Ki-67 is a cell proliferation marker that has been shown to have some utility in predicting prognosis in neuroendocrine neoplasms. We sought to test the predictive ability of Ki-67 staining for disease recurrence and overall survival (OS) in pancreatic neuroendocrine neoplasms.
The medical records of patients who underwent pancreatic resection for pancreatic neuroendocrine neoplasms at a tertiary referral hospital from 1994 to 2009 were reviewed. The pathologic specimens of all were stained for Ki-67 and recorded as percentage of cells staining positive per high-powered field. The 10-year disease-free and OSs were analyzed.
We identified 140 patients. Gender and age were not associated with increased risk of disease recurrence. Patients with tumors >4 cm or with Ki-67 staining >9% were more likely to have disease recurrence (P = .0454 and .047) and have decreased OS (P < .0001 and .0007).
Increasing tumor size and increasing Ki-67 staining both correlate with increased risk of disease recurrence and decreased OS. Designing a staging system that incorporates both of these clinical variables will enable better identification of patients at risk for recurrent pancreatic neuroendocrine neoplasms.
Surgery 04/2012; 152(1):107-13. · 3.10 Impact Factor
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ABSTRACT: Tumors of the neck of the pancreas may involve the superior mesenteric and portal veins as well as the termination of the splenic vein. This presents a difficult problem since the pancreas cannot be transected through the neck as is standard in a Whipple procedure. Here, we present our method of resecting such tumors, which we term "Whipple at the Splenic Artery (WATSA)".
The superior mesenteric and portal veins are isolated below and above the pancreas, respectively. The pancreas and splenic vein are divided just to the right of the point that the splenic artery contacts the superior border of the pancreas. This plane of transection is approximately 2 cm to the left of the pancreatic neck and away from the tumor. The superior mesenteric artery is cleared from the left side of the patient. With the specimen remaining attached only by the superior mesenteric and portal veins, these structures are clamped and divided. Reconstruction is performed with or without a superficial femoral vein graft. The splenic vein is not reconstructed.
Ten cases have been performed to date without mortality. We have previously shown that the pattern of venous collateral development following occlusion of the termination of the splenic vein in the manner described is not similar to that of cases of sinistral (left sided) portal hypertension.
Whipple at the splenic artery (WATSA) is a safe method for resection of tumors of the neck of the pancreas with vein involvement. It should be performed in high-volume pancreatic surgery centers.
Journal of Gastrointestinal Surgery 03/2012; 16(5):1048-54. · 2.83 Impact Factor
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ABSTRACT: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immunosuppressive cells that are upregulated in cancer. Little is known about the prevalence and importance of MDSC in pancreas adenocarcinoma (PA).
Peripheral blood, bone marrow, and tumor samples were collected from pancreatic cancer patients, analyzed for MDSC (CD15(+)CD11b(+)) by flow cytometry and compared to cancer-free controls. The suppressive capacity of MDSC (CD11b(+)Gr-1(+)) and the effectiveness of MDSC depletion were assessed in C57BL/6 mice inoculated with Pan02, a murine PA, and treated with placebo or zoledronic acid, a potent aminobisphosphonate previously shown to target MDSC. The tumor microenvironment was analyzed for MDSC (Gr1(+)CD11b(+)), effector T cells, and tumor cytokine levels.
Patients with PA demonstrated increased frequency of MDSC in the bone marrow and peripheral circulation which correlated with disease stage. Normal pancreas tissue showed no MDSC infiltrate, while human tumors avidly recruited MDSC. Murine tumors similarly recruited MDSC that suppressed CD8(+) T cells in vitro and accelerated tumor growth in vivo. Treatment with zoledronic acid impaired intratumoral MDSC accumulation resulting in delayed tumor growth rate, prolonged median survival, and increased recruitment of T cells to the tumor. This was associated with a more robust type 1 response with increased levels of IFN-γ and decreased levels of IL-10.
MDSC are important mediators of tumor-induced immunosuppression in pancreatic cancer. Inhibiting MDSC accumulation with zoledronic acid improves the host anti-tumor response in animal studies suggesting that efforts to block MDSC may represent a novel treatment strategy for pancreatic cancer.
Cancer Immunology and Immunotherapy 01/2012; 61(9):1373-85. · 3.70 Impact Factor
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ABSTRACT: The radical antegrade modular pancreatosplenectomy (RAMPS) procedure is a modification of standard distal pancreatosplenectomy. It was designed to provide the operative approach developed for cancers of the head of the pancreas to cancers of the body and tail of the pancreas, particularly with respect to the extent of node dissection and emphasis on obtaining microscopically negative tangential margins. The purpose of this report is to provide long-term survival results.
Forty-seven patients had RAMPS between 1999 and 2008. The decision to perform anterior vs posterior RAMPS was based on the position of the tumor as assessed by preoperative computed tomograms. Patients were entered in a prospective database and followed at intervals.
Thirty-two patients had anterior RAMPS and 15 had posterior RAMPS. Twenty-four patients had resection of 33 organs in addition to the left adrenal gland in the posterior RAMPS. Specimens were inked in the operating room. Mean tumor size was 4.4 cm. Negative tangential margins were obtained in 89% of specimens. Overall, the R0 rate was 81%. Mean lymph node count was 18. There were no 30-day or in-hospital mortalities. Mean and median follow-up times of living patients were 44.4 and 26.4 months. Median survival was 26 months and 5-year overall actuarial survival was 35.5%. The actual survival of 23 patients whose surgery was performed more than 5 years before the time of analysis was 30.4%.
RAMPS is associated with high negative tangential margin rates and very satisfactory survival rates for this aggressive tumor.
Journal of the American College of Surgeons 01/2012; 214(1):46-52. · 4.55 Impact Factor
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[show abstract]
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ABSTRACT: The risks of developing sinistral portal hypertension as a result of occlusion of the splenic vein close to its termination during a Whipple procedure are unclear. Our purpose was to compare the pattern of venous collateral development after splenic vein ligation in an extended Whipple procedure with the pattern of collateral development in cases of sinistral portal hypertension.
Five patients underwent an extended Whipple procedure in which the splenic vein was divided and not reconstructed. Six to eight months later detailed mapping of venous return from the spleen was determined by contrast-enhanced multidetector computed tomography or in one case by 3D contrast-enhanced MRI. Spleen size and length of residual patent splenic vein were also measured. The literature on sinistral portal hypertension was evaluated to ascertain whether the venous collateral pattern in cases of left-sided portal hypertension was similar to the pattern that developed when the splenic vein was ligated at its termination in the Whipple procedure.
A length of splenic vein remained patent in all five patients, measuring 4.5 to 11.5 cm from the spleen. Splenomegaly did not develop. Blood returned from the spleen by multiple collaterals including collaterals in the omentum and mesocolon. These types of collaterals do not develop in sinistral portal hypertension, nor is residual patent splenic vein seen.
Ligation of the splenic vein close to its termination in five patients resulted in a pattern of venous return different from patients that have developed left-sided portal hypertension.
Journal of Gastrointestinal Surgery 09/2011; 15(11):2070-9. · 2.83 Impact Factor
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ABSTRACT: The need for mesenteric venous resection (MVR) is determined by a combination of preoperative radiologic and intraoperative surgical assessments. A single-centre review was performed to determine how efficient these processes are in evaluating the need for MVR.
A retrospective study was performed of 343 patients who received resection for adenocarcinoma of the head of the pancreas, 100 of whom underwent MVR. Three radiologic signs (abutment, fat plane obliteration, focal narrowing) were evaluated for their ability to predict the need for MVR. Pathologic assessment was performed to determine if MVR had been necessary to achieve negative-margin (R0) resection. Microscopic tumour in the vein wall, or within 1 mm of the vein wall, was considered to indicate that MVR had been necessary to achieve an R0 resection.
Radiologic evaluation (showing any of the three signs) had sensitivity of only 60%. Overall, 40% of the patients who required MVR showed none of the signs. Specificity was 77%. A total of 80% of patients who underwent MVR had either microscopic invasion or abutment. R0 resection at the vein margin was achieved in 98% of patients in both the MVR and non-MVR groups.
Preoperative radiologic evaluation is not highly reliable in predicting the need for MVR. Therefore, surgical teams performing resections of cancers of the head of the pancreas must be skilled in MVR as the need for this procedure may arise unexpectedly. Surgical assessment of the need for MVR has an accuracy of about 80% and is nearly 100% accurate in determining when MVR is not required.
HPB 09/2011; 13(9):633-42. · 1.60 Impact Factor
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Amy C Fox,
Elise R Breed,
Zhe Liang,
Andrew T Clark,
Brendan R Zee-Cheng,
Katherine C Chang,
Jessica A Dominguez,
Enjae Jung,
W Michael Dunne,
Eileen M Burd,
Alton B Farris, David C Linehan,
Craig M Coopersmith
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ABSTRACT: Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.
The Journal of Immunology 08/2011; 187(4):1950-6. · 5.79 Impact Factor
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John R Hornick,
Fabian M Johnston,
Peter O Simon,
Morgan Younkin,
Michael Chamberlin,
Jonathan B Mitchem,
Riad R Azar, David C Linehan,
Steven M Strasberg,
Steven A Edmundowicz,
William G Hawkins
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ABSTRACT: Although benign ampullary tumors are removed endoscopically, due to their potential to progress to malignant disease, the favored treatment for adenocarcinoma is pancreaticoduodenectomy. We reviewed our institution's experience in order to identify which patients were at highest risk of disease progression following surgical resection, as well as evaluate whether localized T1 tumors are best treated by pancreaticoduodenectomy.
We retrospectively reviewed 157 patients who presented with an ampullary mass, from 2001 to 2010, and identified 51 with benign adenoma and 106 with adenocarcinoma.
Patients with malignant tumors most often presented with larger tumors and jaundice, which alone was predictive of survival (OR = 67). Forty-five percent of patients with pathologically confirmed T1 tumors had positive lymph nodes and median survival was modest at 60 months. Lymph node involvement was predictive of recurrence and decreased survival.
Patients with malignant tumors often present with jaundice and larger tumors. These findings should warrant suspicion for cancer and expedited preoperative workup. Based on our finding that nearly half the patients with T1 tumors had positive lymph nodes, we recommend pancreaticoduodenectomy for any patient with biopsy proven adenocarcinoma who is a suitable candidate for surgery.
Surgery 08/2011; 150(2):169-76. · 3.10 Impact Factor
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Archives of surgery (Chicago, Ill.: 1960) 05/2011; 146(5):604-5. · 4.32 Impact Factor
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ABSTRACT: Delayed gastric emptying (DGE) through a gastroenterostomy is a clinical problem that affects many patients who have a standard Whipple procedure. A new method, which is associated with a low rate of DGE, is described.
Journal of Gastrointestinal Surgery 02/2011; 15(8):1468-71. · 2.83 Impact Factor
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ABSTRACT: Lymph node status is one of the most important predictors of survival in pancreatic ductal adenocarcinoma. Surgically resected pancreatic adenocarcinoma is often locally invasive and may invade directly into peripancreatic lymph nodes. The significance of direct invasion into lymph nodes in the absence of true lymphatic metastases is unclear. The purpose of this study was to retrospectively compare clinical outcome in patients with pancreatic ductal adenocarcinoma with direct invasion into peripancreatic lymph nodes with patients with node-negative adenocarcinomas and patients with true lymphatic lymph node metastasis. A total of 380 patients with invasive pancreatic ductal adenocarcinoma classified as pT3, were evaluated: ductal adenocarcinoma with true lymphatic metastasis to regional lymph nodes (248 cases), ductal adenocarcinoma without lymph node involvement (97 cases), and ductal adenocarcinoma with regional lymph nodes involved only by direct invasion from the main tumor mass (35 cases). Isolated lymph node involvement by direct invasion occurred in 35 of 380 (9%) patients. Overall survival for patients with direct invasion of lymph nodes (median survival, 21 mo; 5-year overall survival, 36%) was not statistically different from patients with node-negative adenocarcinomas (median survival, 30 mo; 5-year overall survival, 31%) (P=0.609). Patients with node-negative adenocarcinomas had an improved survival compared with patients with lymph node involvement by true lymphatic metastasis (median survival, 15 mo; 5-year overall survival, 8%) (P<0.001) regardless of the number of lymph nodes involved by adenocarcinoma. There was a trend toward decreased overall survival for patients with 1 or 2 lymph nodes involved by true lymphatic metastasis compared with patients with direct invasion of tumor into lymph nodes (P=0.056). However, this did not reach statistical significance. Our results indicate that patients with isolated direct lymph node invasion have a comparable overall survival with patients with node-negative adenocarcinomas as opposed to true lymphatic lymph node metastasis.
The American journal of surgical pathology 02/2011; 35(2):228-34. · 4.06 Impact Factor
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Jennifer L Gnerlich,
Jonathan B Mitchem,
Joshua S Weir,
Narendra V Sankpal,
Hiroyuki Kashiwagi,
Brian A Belt,
Matthew R Porembka,
John M Herndon,
Timothy J Eberlein,
Peter Goedegebuure, David C Linehan
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ABSTRACT: An important mechanism by which pancreatic cancer avoids antitumor immunity is by recruiting regulatory T cells (Tregs) to the tumor microenvironment. Recent studies suggest that suppressor Tregs and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Because IL-6 in the presence of TGF-β has been shown to inhibit Treg development and induce Th17 cells, we hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression. Pan02 murine pancreatic tumor cells that secrete TGF-β were transduced with the gene encoding IL-6. C57BL/6 mice were injected s.c. with wild-type (WT), empty vector (EV), or IL-6-transduced Pan02 cells (IL-6 Pan02) to investigate the impact of IL-6 secretion in the tumor microenvironment. Mice bearing IL-6 Pan02 tumors demonstrated significant delay in tumor growth and better overall median survival compared with mice bearing WT or EV Pan02 tumors. Immunohistochemical analysis demonstrated an increase in Th17 cells (CD4(+)IL-23R(+) cells and CD4(+)IL-17(+) cells) in tumors of the IL-6 Pan02 group compared with WT or EV Pan02 tumors. The upregulation of IL-17-secreting CD4(+) tumor-infiltrating lymphocytes was substantiated at the cellular level by flow cytometry and ELISPOT assay and mRNA level for retinoic acid-related orphan receptor γt and IL-23R by RT-PCR. Thus, the addition of IL-6 to the tumor microenvironment skews the balance toward Th17 cells in a murine model of pancreatic cancer. The delayed tumor growth and improved survival suggests that induction of Th17 in the tumor microenvironment produces an antitumor effect.
The Journal of Immunology 10/2010; 185(7):4063-71. · 5.79 Impact Factor
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ABSTRACT: Bile duct injuries incurred during laparoscopic cholecystectomies remain a major complication in an otherwise safe surgery. These injuries are potentially avoidable with proper techniques and correct interpretation of the anatomy. The scope of the injury can range from a simple cystic duct leak to the injury of the left and right hepatic duct confluence. The key to successful outcomes from these injuries is to know when a referral to a specialized tertiary center is necessary. Evaluation and treatment of bile duct injuries is complex and often requires the expertise of an advanced endoscopist, interventional radiologist, and hepatobiliary surgeons. Before any planned intervention or operative repair, detailed evaluation of the biliary system and its associated vasculature is required. Better outcomes are achieved when patients are referred to centers specialized in biliary injury evaluation, treatment, and performing pretreatment planning early.
Surgical Clinics of North America 08/2010; 90(4):787-802. · 2.14 Impact Factor
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CancerSpectrum Knowledge Environment 12/2009; 102(2):135-7; author reply 137. · 14.07 Impact Factor
