Marshall S. Baker

Intraductal papillary mucinous neoplasms: Predictors of malignant and invasive pathology

Objective:Determine whether size and other preoperative parameters predict malignant or invasive intraductal papillary mucinous neoplasia (IPMN). Summary Background Data:From 1991 to 2006, 150 patients underwent 156 operations for IPMN. Methods:Prospectively collected, retrospective review of a single academic institutions experience. All preoperative parameters including a detailed radiologic-based classification of IPMN type, location, distribution, size, number, cytology, and mural nodularity were correlated with IPMN pathology. Results:Malignant IPMN was present in 32% of cases, whereas 19% of cases were invasive. IPMN type and main pancreatic duct diameter were significant predictors of malignant IPMN (P < 0.001). Side-branch lesion number was negatively associated with invasive IPMN (P = 0.03). Side-branch size, location, and distribution did not predict IPMN pathology. The presence of mural nodules was associated with malignant and invasive IPMN (P < 0.001; P < 0.02). Atypical cytopathology was significantly associated with malignant and invasive IPMN (P < 0.001; P < 0.001). Multivariate analysis demonstrated mural nodularity and atypical cytopathology were predictive of malignancy and/or invasion in branch-type IPMN. Conclusions:To lower the rate of invasive pathology, surgery should be recommended for fit patients with main-duct IPMN and for branch-duct IPMN with mural nodularity or positive cytology irrespective of location, distribution, or size.

A prospective single institution comparison of peri-operative outcomes for laparoscopic and open distal pancreatectomy

BACKGROUND Laparoscopic distal pancreatectomy (LP) is an emerging modality for managing benign and premalignant neoplasms of the pancreatic body and tail. The efficacy of LP has been examined in single and multi-institutional retrospective reviews but not compared prospectively to open distal pancreatectomy (ODP). METHODS We maintain a prospectively accruing database tracking peri-operative clinical parameters for all patients presenting to our tertiary care facility for treatment of pancreatic disease. We queried this database for patients undergoing LP or ODP between January 2003 and May 2008. Preoperative, operative, and postoperative characteristics were compared using standard statistical methods. RESULTS One-hundred twelve patients underwent distal pancreatectomy. Eighty-five underwent SDP. Twenty-eight LPs were attempted and 27 completed laparoscopically. One LP was converted to an open procedure because of bleeding and was excluded from study. In comparison to ODP, patients undergoing LP had statistically similar pre-operative demographics, disease comorbidities, tumor size, length of operation, rates of postoperative mortality, postoperative morbidity, and pancreatic fistula. Patients undergoing LP were less likely to have ductal adenocarcinoma and had fewer lymph nodes harvested in their resection but had a significantly shorter postoperative length of stay and significantly lower estimated blood loss than those undergoing ODP. CONCLUSION Laparoscopic distal pancreatectomy is a safe, effective modality for managing premalignant neoplasms of the pancreatic body and tail, providing a morbidity rate comparable to that for ODP and substantially shorter length of stay. Laparoscopic distal pancreatectomy fails to provide a lymphadenectomy comparable to ODP. This may limit the applicability of LP to the treatment of pancreatic adenocarcinoma.

Polymer Scaffolds as Synthetic Microenvironments for Extrahepatic Islet Transplantation

Background. Problems associated with the hepatic transplantation of islets may preclude the broad application of islet transplantation. Thus, we sought to develop an approach to the extrahepatic transplantation of islets using a synthetic biodegradable polymer scaffold. Methods. Microporous polymer scaffolds that allow vascular ingrowth and nutrient diffusion from host tissues were fabricated from copolymers of lactide and glycolide. Murine islets were transplanted without or with a scaffold onto intraperitoneal fat of syngeneic diabetic recipients. Bioluminescence imaging using a cooled charge-coupled device camera, immunohistochemistry, and glycemia were used to assess islet engraftment and function posttransplant. Results. By bioluminescence imaging, islets transplanted on a polymer scaffold remain localized to the transplant site and survive for an extended period of time. Islets transplanted on scaffolds retained the architecture of native islets and developed a functional islet vasculature. Transplantation of marginal masses of islets on the polymer scaffold demonstrated improved islet function compared to transplantation without a scaffold as assessed by the effectiveness of diabetes reversal, including mean time required to achieve euglycemia, weight gain, and glucose levels during an intraperitoneal glucose tolerance test. Conclusion. These findings indicate that a synthetic polymer scaffold can serve as a platform for islet transplantation and improves the function of extrahepatically transplanted islets compared to islets transplanted without a scaffold. The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function.

In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection

Background. Bioluminescence imaging (BLI) modalities are being developed to monitor islet transplant mass and function in vivo. The aim of this study was to use the BLI system to determine how the change in functional islet mass correlated to metabolic abnormalities during the course of alloimmune rejection in a murine transplant model. Methods. Islets obtained from a transgenic mouse strain (FVB/NJ-luc) that constitutively expressed firefly luciferase were transplanted to various implantation sites of syngeneic wild-type FVB/NJ or allogeneic Balb/C streptozotocin-induced diabetic recipients. In vivo graft luminescent signals were repeatedly measured after transplantation using the BLI system and related to blood glucose levels and graft site histologic findings. Results. The BLI signals were detected in as few as 10 islets implanted in the renal subcapsular space, intrahepatic, intraabdominal, and subcutaneous locations. There was a linear relationship between the number of islets transplanted and luminescence intensity. In isografts, stable luminescence intensity signals occurred within 2 weeks of transplantation and remained consistent on a long-term basis (18 months) after transplantation. In allografts, after normoglycemia was achieved and stable luminescence intensity occurred, graft bioluminescent intensity progressively decreased several days before permanent recurrence of hyperglycemia as a result of histologically proven rejection ensued. Conclusions. Bioluminescence imaging is a sensitive method for tracking the fate of islets after transplantation and is a useful method to detect early loss of functional islet mass caused by host immune responses even before overt metabolic dysfunction is evident. Bioluminescence imaging holds promise for use in designing and testing interventions to prolong islet graft survival.

Early National Experience with Laparoscopic Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Comparison of Laparoscopic Pancreaticoduodenectomy and Open Pancreaticoduodenectomy from the National Cancer Data Base

BACKGROUND There is considerable debate about the safety and clinical equivalence of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for pancreatic ductal adenocarcinoma (PDCA). STUDY DESIGN We queried the National Cancer Data Base to identify patients undergoing LPD and OPD for PDCA between 2010 and 2011. Chi-square and Students t-tests were used to evaluate differences between the 2 approaches. Multivariable logistic regression modeling was performed to identify patient, tumor, or facility factors associated with perioperative mortality. RESULTS Four thousand and thirty-seven (91%) patients underwent OPD. Three hundred and eighty-four (9%) patients underwent LPD. There were no statistical differences between the 2 surgical cohorts with regard to age, race, Charlson score, tumor size, grade, stage, or treatment with neoadjuvant chemoradiotherapy. Laparoscopic pancreaticoduodenectomy demonstrated a shorter length of stay (10 ± 8 days vs 12 ± 9.7 days; p < 0.0001) and lower rates of unplanned readmission (5% vs 9%; p = 0.027) than OPD. In an unadjusted comparison, there was no difference in 30-day mortality between the LPD and OPD cohorts (5.2% vs 3.7%; p = 0.163). Multivariable logistic regression modeling predicting perioperative mortality controlling for age, Charlson score, tumor size, nodal positivity, stage, facility type, and pancreaticoduodenectomy volume identified age (odds ratio [OR] = 1.05; p < 0.0001), positive margins (OR = 1.45; p = 0.030), and LPD (OR = 1.89; p = 0.009) as associated with an increased probability of 30-day mortality; higher hospital volume was associated with a lower risk of 30-day mortality (OR = 0.98; p < 0.0001). In institutions that performed ≥10 LPDs, the 30-day mortality rate of the laparoscopic approach was equal to that for the open approach (0.0% vs 0.7%; p = 1.00). CONCLUSIONS Laparoscopic pancreaticoduodenectomy is equivalent to OPD in length of stay, margin-positive resection, lymph node count, and readmission rate. There is a higher 30-day mortality rate with LPD, but this appears driven by a surmountable learning curve for the procedure.

Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors

PURPOSE The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs. METHODS We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival. RESULTS The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths. CONCLUSION Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size.

Sequential Kidney/Islet Transplantation Using Prednisone-Free Immunosuppression

Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet‐after‐kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8–10 000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet‐after‐kidney transplantation is described using the steroid‐free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265 888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75–80%; c) viability: > 95% (trypan blue exclusion); and d) mean islet potency (static low‐high glucose challenge): 4.16 ± 1.91‐fold increase. Post‐transplant the patients hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post‐transplant as basal and Ensure® (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C‐peptide levels peaked and stabilized. Twenty‐four‐hour continuous glucose monitoring confirmed moment‐to‐moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

The laparoscopic approach to distal pancreatectomy for ductal adenocarcinoma results in shorter lengths of stay without compromising oncologic outcomes

BACKGROUND The oncologic equivalence of laparoscopic distal pancreatectomy (LDP) to open pancreatectomy (ODP) for ductal adenocarcinoma (DAC) is not established. METHODS The National Cancer Data Base was used to compare perioperative outcomes following LDP and ODP for DAC between 2010 and 2011. RESULTS One hundred forty-five patients underwent LDP; 625 underwent ODP. Compared with ODP, patients undergoing LDP were older (68 ± 10.1 vs 66 ± 10.5 years, P = .027), more likely treated in academic centers (70% vs 59%, P = .01), and had shorter hospital stays (6.8 ± 4.6 vs 8.9 ± 7.5 days, P < .001). Demographic data, lymph node count, 30-day unplanned readmission, and 30-day mortality were identical between groups. Multivariable regression identified a lower probability of prolonged length of stay with LDP (odds ratio .51, 95% confidence interval .327 to .785, P = .0023). There was no association between surgical approach and node count, readmission, or mortality. CONCLUSION LDP for DAC provides shorter postoperative lengths of stay and rates of readmission and 30-day mortality similar to OPD without compromising perioperative oncologic outcomes.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. PART I: Diagnosis‐clinical staging and pathology

Biliary tract cancers (gallbladder cancer, intra‐ and extra‐hepatic cholangiocarcinoma, and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases. J. Surg. Oncol. 2012; 106:332–338.

Adding days spent in readmission to the initial postoperative length of stay limits the perceived benefit of laparoscopic distal pancreatectomy when compared with open distal pancreatectomy

BACKGROUND Published comparisons of laparoscopic (laparoscopic distal pancreatectomy [LDP]) to open distal pancreatectomy (ODP) identify improved lengths of stay (LOS) after LDP but do not include data on readmissions. METHODS Demographic, operative, and postoperative outcomes data for patients undergoing LDP or ODP between August 2007 and December 2009 were culled from our prospectively accruing pancreatic database. Electronic medical records were reviewed to determine cause, treatment, and LOS for readmissions. RESULTS Patients undergoing LDP were statistically identical to those undergoing ODP in regard to age, presentation, demographic characteristics, comorbidities, operative times, tumor sizes, morbidity, mortality, and pancreatic fistula rates. The initial LOS was statistically shorter for those undergoing LDP (4.8 ± .1 days vs 8.7 ± .1 days, P < .001). The readmission rate for LDP was statistically higher than for ODP (25% vs 8%, P < .05). Overall LOS for LDP was 7.2 ± .3 days versus 9.3 ± .1 days for ODP (P = .2). CONCLUSIONS Adding readmission LOS to initial LOS eliminates the perceived effect of LDP to accelerate recovery.