Pancreaticoduodenectomy for benign and premalignant pancreatic and ampullary disease: is robotic surgery the better approach?

BACKGROUND: The robotic platform is increasingly being utilized in pancreatic surgery, yet its overall merits and putative advantages remain to be adjudicated. We hypothesize that the benefits of minimally invasive pancreatic surgery are maximized in pancreatic benign and premalignant disease, in the setting of friable pancreatic tissue and small pancreatic duct. METHODS: Retrospective analysis of our prospectively maintained pancreatic database of all consecutive patients who underwent pancreaticoduodenectomy (PD) for benign or premalignant conditions between 2010 and 2020. Peri-operative outcomes and long-term complications were compared between robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD). RESULTS: One hundred and eighty eight (n = 188) patients met our inclusion criteria, of which 68 were OPD and 120 RPD. Malignant histologies were excluded. There were only minor differences in baseline characteristics between the two groups. Post-operative merits of the RPD included lower clinically relevant post-operative pancreatic fistula 10 (8.3%) vs 24 (35.3%), p < 0.001, fewer surgical site infections; 9 (7.5%) vs 11 (16.2%), p = 0.024, shorter operative time, greater lymph node yield; 29 (IQR 21, 38) vs 21 (IQR 13, 34), p = 0.001, and lower 90 days mortality; 1 (0.8%) vs 4 (5.9%), p = 0.039. Rates of long-term complications were similar, exception made for a higher occurrence of small bowel obstruction (SBO) 2 (1.7%) vs 4 (5.9%), p = 0.031 and need for surgical intervention for SBO 0 (0.0%) vs 2 (2.9%), p = 0.019 in the OPD group. CONCLUSION: Our study suggests that RPD benefits include lower 90-day mortality, shorter LOS, and lower rates of selected complications compared to open pancreaticoduodenectomy.

Neoadjuvant Chemotherapy for Pancreatic Adenocarcinoma Lessens the Deleterious Effect of Omission of Adjuvant Chemotherapy.

BACKGROUND: Despite controversy regarding the role of neoadjuvant chemotherapy (NAC) in pancreatic adenocarcinoma, nearly half of resected patients do not receive chemotherapy postoperatively. This study aimed to examine whether use of NAC compensates for omission of adjuvant chemotherapy (AC) for resected pancreatic adenocarcinoma. METHODS: Adults with resected stages 1 to 3 pancreatic adenocarcinoma were enrolled from the National Cancer Database NCDB (2006-2016). Overall survival (OS) analyses were used to examine the impact of NAC on those who did not receive AC. RESULTS: The study analyzed a national cohort of 56,286 patients: 30% without chemotherapy, 11% with NAC, 54% with AC, and 5% with NAC plus AC. Use of NAC increased by more than 400% from 2006 to 2016, whereas the rates for omission of chemotherapy remained unchanged. The OS rates were similar between the patients who received NAC and those who received AC (hazard ratio, 0.97; p = 0.21). Among the patients who did not receive AC, NAC was associated with improved OS (26.7 vs. 18.4 months; p < 0.0001). The patients who did not receive AC but underwent NAC had a median OS comparable with the OS of those who received AC alone (26.9 vs. 24.7 months). In the adjusted analysis, the use of NAC for those without AC was significantly associated with improved OS (estimate, - 0.24; p < 0.0001). CONCLUSIONS: Although data are limited regarding the survival benefit derived from neoadjuvant versus adjuvant chemotherapy in pancreatic adenocarcinoma, nearly half of patients do not receive adjuvant chemotherapy. This study demonstrates that the use of NAC lessens the survival disadvantage caused by omission of AC. Despite controversy, NAC may be considered for pancreatic adenocarcinoma patients given the high likelihood that adjuvant chemotherapy will be omitted.

Long-Term Surgical Complications After Pancreatoduodenectomy: Incidence, Outcomes, and Risk Factors.

BACKGROUND: Long-term complications following pancreatoduodenectomy (PD) can significantly impact quality of life and healthcare utilization. Most reports focus on short-term (within 90 days) PD outcomes; however, the incidence and risk factors for long-term complications (> 90 days) remain to be evaluated. We sought to identify the incidence, outcomes, and risk factors for long-term complications post-PD. METHODS: All PD survivors between 2010 and 2017 were identified from a single-institutional database. Long-term complications (> 90 days post-PD and not resulting from cancer recurrence), including biliary stricture, cholangitis, pancreatitis, peptic ulcer, small bowel obstruction, and incisional hernia, were identified. Logistic regression was used to identify perioperative predictors of long-term complications. RESULTS: Of 906 PDs, 628 long-term survivors met criteria for analysis (mean age of 65.3 years, 47% female). Median follow-up and overall survival were 51.1 months (95% CI 47.6, 55.7) and 68.5 months (95% CI 57.9, 81.4), respectively. A total of 198 (31.5%) experienced at least one long-term complication. Complications included incisional hernia (17.7%), biliary stricture or cholangitis (8.0%), pancreatitis (5.7%), small bowel obstruction (4.3%), and peptic ulcer (3.2%). In total, 108 (17.2%) of the complications required an intervention, nearly half of which were surgical. On multivariable analysis, several predictors of long-term complications were identified: obesity (BMI ≥ 30 kg/m2), postoperative wound infection, prolonged index length of stay, readmission (< 90 days), operative approach (open vs. robotic), and pylorus-preservation. CONCLUSION: Long-term complications occur in nearly a third of PDs and nearly one-fifth of all PDs require re-intervention. Several modifiable predictors of long-term complications were identified.

Predictors of Disease Progression or Performance Status Decline in Patients Undergoing Neoadjuvant Therapy for Localized Pancreatic Head Adenocarcinoma.

INTRODUCTION: Neoadjuvant therapy (NT) is a growing strategy in localized head pancreatic adenocarcinoma (PDC). However, a significant portion of NT patients do not reach resection due to disease progression or performance status decline. We sought to identify predictors of disease progression or performance status decline during NT. METHODS: Retrospective cohort analysis of consecutive patients with localized head-PDC who received NT at a tertiary referral center between 2005 and 2017. Univariate and multivariate (MVA) analysis were performed to identify factors associated with disease progression or performance status decline during NT preventing surgical resection. RESULTS: A total of 479 patients with PDC underwent NT; 71.2% proceeded to surgery, 20.5% had disease progression, and 8.3% experienced performance status decline. Median OS was 28 [95% confidence interval (CI) 23.8-32.3], 12.8 (CI 11.2-14.3), and 6.9 (CI 5.2-9.4) months, respectively (p < 0.05). MVA predictors of disease progression were larger clinical CT tumor size [odds ratio (OR) 1.03, CI 1.0-1.1], unplanned change in NT regimen (OR 2.6, CI 1.0-6.9), hospital admission during NT (OR 2.2, CI 1.2-3.9), and lack of CA19-9 response (OR 4.4, CI 4.0-8.4). MVA predictors of performance status decline were increasing age (OR 1.1, CI 1.0-1.2), presence of pre-NT diabetes (OR 3.8, CI 1.3-11.3), hospital admission during NT (OR 14.0, CI 3.9-49.8), and lack of CA19-9 response (OR 4.7, CI 1.4-15.5). CONCLUSIONS: This analysis identifies several predictors of disease progression and performance status decline during NT for PDC. Knowledge of these factors informs the physician on the risks and limitations of NT and provides insight to guide patient selection and counseling.

Metastatic extrapleural malignant solitary fibrous tumor presenting with hypoglycemia (Doege-Potter syndrome).

We report a rare case of metastatic malignant solitary fibrous tumor (SFT) that presented with hypoglycemia because of insulin growth factor-2 production. Initial workup included computed tomography imaging that revealed a large, partially necrotic liver mass, a hypervascular pancreatic head lesion, and 2 renal lesions. Following hepatic resection, pancreatic head resection and nephrectomy, all these lesions demonstrated pathological findings that were consistent with SFT. The patient also had a history of an intracranial mass that had been previously resected and treated with gamma knife therapy at an outside institution, which was found to also be SFT. Six months after initial pancreatic head resection, the patient developed a new lesion involving the pancreatic tail that was found to represent recurrent metastatic SFT. This case emphasizes the highly aggressive nature of extrapleural SFT, while rare, and the role of imaging in follow-up for disease recurrence.

The indolent nature of pulmonary metastases from ductal adenocarcinoma of the pancreas.

BACKGROUND AND OBJECTIVES: The natural history of pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) is not well studied. Limited evidence suggests patients with isolated pulmonary metastases from PDAC follow a more benign clinical course than those with other sites of metastases. METHODS: We performed a retrospective review of all patients with pulmonary metastases from PDAC from 2000 to 2010 and analyzed survival utilizing the Kaplan-Meier method based upon location of first metastasis (lung first, intra-abdominal first, or synchronous intra-abdominal and lung metastases). RESULTS: Median survival among subjects with lung as the only site of metastases was significantly longer than those with other metastatic patterns. In subjects that had undergone resection of their PDAC, survival in those with lung as a first site of recurrence remained significantly longer than those with abdominal first or synchronous intra-abdominal and lung recurrence. Among resected patients that developed lung only recurrence, survival was significantly prolonged (67.5 months) in those who underwent surgical resection/stereotactic radiosurgery compared to chemotherapy (33.8 months) or observation (29.9 months) for treatment of lung recurrence. CONCLUSION: Patients with isolated pulmonary recurrence from PDAC may realize a survival benefit from surgical intervention or stereotactic radiosurgery compared to chemotherapy or observation for treatment of lung recurrence.

Abdominal compartment syndrome is an early, lethal complication of acute pancreatitis.

Data defining the optimal management of abdominal compartment syndrome resulting from acute pancreatitis are lacking. We investigated the outcomes of patients with acute pancreatitis who underwent surgery for treatment of abdominal compartment syndrome at a tertiary referral center. An electronic database was searched to identify patients with acute pancreatitis who underwent laparotomy between January 1, 2000, and December 31, 2009, for treatment of abdominal compartment syndrome. Twelve patients underwent decompressive laparotomy for abdominal compartment syndrome. The median interval between onset of pancreatitis and laparotomy was 4.5 days. Nine patients underwent a laparotomy within seven days of onset of pancreatitis. As a result of cardiopulmonary instability, four decompressive laparotomies were performed in the intensive care unit. In 11 patients, cardiopulmonary improvement was observed. Statistically significant improvements were seen across multiple physiologic parameters. Despite this initial improvement, six patients (50%) died from multisystem organ failure. Two patients survived without need for pancreatic débridement. Abdominal compartment syndrome is an uncommon but likely underrecognized and highly lethal complication of acute pancreatitis that should be considered in patients who become critically ill early in the course of their pancreatitis. Prompt recognition and decompressive laparotomy may rescue some of these patients and does not mandate future débridement.

Validity and interrater reliability of a regional mock oral board examination.

BACKGROUND: There have been decreasing pass rates recently on the American Board of Surgery Certifying Examination (ABSCE). General surgery residents from the University of Pittsburgh Medical Center, the West Penn Allegheny Health System, the Conemaugh Health System, and Mercy Hospital participate in a mock oral board examination, which is similar to the ABSCE. The aims of the study are to compare examinee performance on the mock oral boards with the ABSCE and to evaluate the interrater reliability of examiner pairs. METHODS: In this retrospective study from 2003 to 2010, outcomes on the mock oral boards and the first attempt of the ABSCE for chief residents were compared for the 4 regional residency programs. Interrater reliability for examiner pairs was evaluated with agreement and kappa statistics. Nonparametric statistics were performed, with α = 0.05. RESULTS: A total of 32 of 38 (84.2%) chief residents passed the mock oral boards. The median score for each of the 3 rooms was 6 (clear pass). A total of 37 of 38 (97.4%) residents passed the ABSCE. The sensitivity of the mock oral boards was 83.8%, with a positive predictive value of 96.9%, and an accuracy of 81.6%. A total of 25 of 47 (53.2%) examiner pairs were from the same residency institution, whereas 22 of 47 (46.8%) were from different institutions. The median agreement was 100% (interquartile range (IQR) [100% - 100%]). The median kappa statistic was 1.00 (IQR [0.38-1.00]). The Mann-Whitney U tests showed no difference in agreement or kappa for examiner pairs from the same or from different institutions (p> 0.05). CONCLUSIONS: The mock oral boards have substantial sensitivity and positive predictive value in relation to the ABSCE. There are also very high levels of interrater agreement and interrater reliability. This regional mock oral board examination is valuable for ABSCE preparation.

Comparative effectiveness of minimally invasive and open distal pancreatectomy for ductal adenocarcinoma.

IMPORTANCE: Multicenter studies indicate that outcomes of open (ODP) and minimally invasive distal pancreatectomy (MIDP) are equivalent for benign lesions. However, data for pancreatic carcinoma are limited. OBJECTIVE: To compare outcomes of ODP and MIDP for early-stage pancreatic ductal carcinoma to determine relative safety and oncologic efficacy. DESIGN: Retrospective analysis of 62 consecutive patients undergoing ODP or MIDP for pancreatic ductal carcinoma by intention to treat with propensity scoring to correct for selection bias. SETTING: A high-volume university center for pancreatic surgery. PARTICIPANTS: Sixty-two patients at a single institution. INTERVENTIONS: Patients underwent ODP or MIDP. MAIN OUTCOME MEASURES: Perioperative mortality, morbidity, readmission, postoperative complications, disease progression, and overall survival. RESULTS: Thirty-four patients underwent ODP, and 28 underwent MIDP with 5 conversions to ODP. No significant differences in age, body mass index, performance status, tumor size, or radiographic stage were identified. High rates of margin-negative resection (ODP, 88%; MIDP, 86%) and median lymph node clearance (ODP, 12; MIDP, 11) were achieved in both groups with equal rates and severity of postoperative complications (ODP, 50%; MIDP, 39%) and pancreatic fistula (ODP, 29%; MIDP, 21%). Despite conversions, intended MIDP was associated with reduced blood loss (P = .006) and length of stay (P = .04). Conversion was associated with a poor histologic grade and positive nodes. Median overall survival for the entire cohort was 19 (95% CI, 14-47) months. Minimally invasive distal pancreatectomy was performed increasingly in later study years and for patients with a higher Charlson-Age Comorbidity Index. Overall survival after ODP or intended MIDP was equivalent after adjusting for comorbidity and year of surgery (relative hazard, 1.11 [95% CI, 0.47-2.62]). CONCLUSIONS AND RELEVANCE: We detected no evidence that MIDP was inferior to ODP based on postoperative outcomes or overall survival. This conclusion was verified by propensity score analysis with adjustment for factors affecting selection of operative technique.

Practice-based learning and improvement: a two-year experience with the reporting of morbidity and mortality cases by general surgery residents.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) core competency of practice-based learning and improvement can be assessed with surgical Morbidity and Mortality Conference (MMC). We aim to describe the MMC reporting patterns of general surgery residents, describe the adverse event rate for patients and compare that with existing published rates, and describe the nature of our institutional adverse events. We hypothesize that reporting patterns and incidence rates will remain constant over time. METHODS: In this retrospective cohort study, archived MMC case lists were evaluated from January 1, 2009 to December 31, 2010. The reporting patterns of the residents, the adverse event ratios, and the specific categories of adverse events were described over the academic years. χ(2) and Fisher's exact tests were used to compare across academic years, using an α = 0.05. RESULTS: There were 85 surgical MMC case lists evaluated. Services achieved a reporting rate above 80% (p < 0.001). The most consistent reporting was done by postgraduate year (PGY) 5 level chief residents for all services (p > 0.05). Out of 11,368 patients evaluated from complete MMC submissions, 289 patients had an adverse event reported (2.5%). This was lower than published reporting rates for patient adverse event rates (p < 0.001). Adverse event rates were consistent for residents at the postgraduate year 2, 4, and 5 levels for all services (p > 0.05). Over 2 years, 522 adverse events were reported for 461 patients. A majority of adverse events were from death (24.1%), hematologic and/or vascular events (16.7%), and gastrointestinal system events (16.1%). CONCLUSIONS: Surgery resident MMC reporting patterns and adverse event rates are generally stable over time. This study shows which adverse event cases are important for chief residents to report.

C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management.

BACKGROUND: The American Joint Committee on Cancer (AJCC) has proposed the inclusion of pretreatment serum carcinoembryonic antigen (CEA) level (C-stage) into the conventional TNM staging system of colon cancer. We assessed the prognosis of various stages of colon cancer after such an inclusion. METHODS: Data for all patients (N = 17 910) diagnosed with colonic adenocarcinoma (AJCC stages I, IIA, IIB, IIC, IIIA, IIIB, IIIC, and IV, based on TNM staging system) between January 1, 2004, and December 31, 2004, with a median follow-up of 27 months (range 0-35 months), were collected from the Surveillance, Epidemiology, and End Results database. C-stage (C0-stage = normal CEA level; C1-stage = elevated CEA level) was assigned to all patients with available CEA information (n = 9083). Multivariable analyses using Cox proportional hazards models were used to identify independent factors associated with prognosis. Prognosis of overall stages (AJCC stages I-IV and C0 or C1) was analyzed using Kaplan-Meier survival curves. All statistical tests were two-sided. RESULTS: C1-stage was independently associated with a 60% increased risk of overall mortality (hazard ratio of death = 1.60, 95% confidence interval = 1.46 to 1.76, P < .001). Overall survival was decreased in patients with C1-stage cancer compared with C0-stage cancer of the respective overall stages (P < .05). Similarly, decreased overall survival was noted in patients with stage I C1 cancer compared with stage IIA C0 or stage IIIA C0 cancer (P < .001), in patients with stage IIA C1 cancer compared with stage IIIA C0 (P < .001), and in patients with stage IIB C1 or stage IIC C1 cancer compared with stage IIIB C0 cancer (P < .001). CONCLUSIONS: C-stage was an independent prognostic factor for colon cancer. The results support routine preoperative CEA testing and C-staging upon diagnosis of colon cancer and the inclusion of C-stage in the conventional TNM staging of colon cancer.

Meckel's diverticulum--a high-risk region for malignancy in the ileum. Insights from a population-based epidemiological study and implications in surgical management.

BACKGROUND: Surgical management of incidental Meckel's diverticulum(MD) is a highly debated controversial issue that has never been discussed from the oncological standpoint. OBJECTIVE: To describe the epidemiology and risk of Meckel's diverticulum cancer (MDC) and compare it with other ileal malignancies. METHODS: Data were obtained from 163 cases of MDC and 6214 cases of non-Meckelian ileal cancer, between 1973 and 2006, from the Surveillance, Epidemiology, and End Results database. RESULTS: Mean annual incidence was 1.44 (± 1.12) per 10 million population,with a 5-fold increase in the last few decades. Incidence increases with age,with a mean age at diagnosis of 60.6 (±15.1) years. Adjusted risk of cancer in the MD was at least 70 times higher than any other ileal site. Disease was localized in 67% at presentation and malignant carcinoids constituted the major histologic type (77%). One-third of patients have had lifetime occurrence of other malignancies and in 13% of these patients, MDC was the first malignancy. Median tumor size was 7 mm. Median overall survival was 173 months (95% confidence interval [CI], 124-221 months), with 1- and 5-year relative survival rates of 85.8% (95% CI, 76.9%-91.4%) and 75.8% (95%CI, 64.9%-83.8%), respectively. Cox proportional hazards model revealed that age, histologic type, and metastatic disease were independent factors affecting survival. CONCLUSIONS: MD is a "hot-spot" or high-risk area for cancer in the ileum.With risk that increases with age and high possibility of curative resection with negligible operative mortality, incidental MD is best treated with resection.

Medullary carcinoma of the large intestine: a population based analysis.

Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.

Short- and long-term costs of laparoscopic colectomy are significantly less than open colectomy.

BACKGROUND: The financial impact of laparoscopic colectomy remains poorly defined. We report the short-term costs of laparoscopic colectomy (LC) as compared with open colectomy (OC) in a high-volume tertiary care hospital, and are the first to incorporate the costs of late, colectomy-related complications in an analysis of long-term costs. METHODS: A retrospective analysis of patients undergoing elective laparoscopic (n = 76) or open (n = 162) colon resection between January 2004 and December 2006 was performed. Primary endpoints were total hospital cost of the index admission and total hospital cost for any subsequent admission for treatment of a colectomy-related complication. RESULTS: Two-hundred thirty-eight patients met inclusion criteria. Mean total hospital cost was significantly greater for patients undergoing OC (US $17,686 per patient versus US $14,518, P = 0.0003). Mean total operative costs were equivalent (US $7,451 OC versus US $7,794 LC, P = 0.274). Average length of stay was shorter for LC (5.2 versus 6.9 days, P < 0.0001). Late complication rates were 5.6% (OC) and 2.6% (LC). Integrating the cost of late complications further increased the disparity between the total cost of OC (US $18,296 per patient, 3.4% increase) as compared with LC (US $14,789, 1.9% increase). CONCLUSION: We demonstrate both short- and long-term financial benefits of LC in a high-volume tertiary care hospital.

Insulin therapy and glycemic control in hospitalized patients with diabetes during enteral nutrition therapy: a randomized controlled clinical trial.

OBJECTIVE: To compare two subcutaneous insulin strategies for glycemic management of hyperglycemia in non-critically ill hospitalized patients with diabetes during enteral nutrition therapy (ENT). RESEARCH DESIGN AND METHODS: Fifty inpatients were prospectively randomized to receive sliding-scale regular insulin (SSRI) alone (n = 25) or in combination with insulin glargine (n = 25). NPH insulin was added for persistent hyperglycemia in the SSRI group (glucose >10 mmol/l). RESULTS: Glycemic control was similar in the SSRI and glargine groups (mean +/- SD study glucose 8.9 +/- 1.6 vs. 9.2 +/- 1.6 mmol/l, respectively; P = 0.71). NPH insulin was added in 48% of the SSRI group subjects. There were no group differences in frequency of hypoglycemia (1.3 +/- 4.1 vs. 1.1 +/- 1.8%; P = 0.35), total adverse events, or length of stay. CONCLUSIONS: Both insulin strategies (SSRI with the addition of NPH for persistent hyperglycemia and glargine) demonstrated similar efficacy and safety in non-critically ill hospitalized patients with type 2 diabetes during ENT.

Loss of heterozygosity predicts poor survival after resection of pancreatic adenocarcinoma.

BACKGROUND: American Joint Committee on Cancer (AJCC) staging for pancreatic adenocarcinoma is a validated predictor of prognosis but insufficiently discriminates postresection survival. We hypothesized that genetic analysis of resected cancers would correlate with tumor biology and postoperative survival. METHODS: Resected pancreatic ductal and ampullary adenocarcinomas (n = 50) were analyzed for loss of heterozygosity (LOH) at 15 markers including 5q(APC), 6q(TBSP2), 9p(p16), 10q(PTEN), 12q(MDM2), 17p(TP53), and 18q(DCC/SMAD4). KRAS exon 1 mutations were detected by sequencing. The primary endpoint of this interim data analysis was survival at 18 month median follow-up. RESULTS: Negative margins were achieved in 43 (86%) cases. AJCC stage was: Ia/b (3), IIa (16), IIb (31). KRAS mutations were detected in 31 cases (62%) and LOH in 26 (52%) with mean fractional allelic loss score 23 +/- 16%. Median survival was significantly shorter with LOH (15.2 months versus not reached; p = 0.021) and KRAS mutations (19.6 months versus not reached; p = 0.038). Combining KRAS mutation with LOH was a powerful negative predictor in Cox regression (HR = 10.6, p = 0.006). Stage, nodal and margin status were not predictive of survival. CONCLUSION: LOH and KRAS mutations indicate aggressive tumor biology and correlate strongly with survival in resected pancreatic ductal and ampullary carcinomas. Genetic analysis may improve risk stratification in future clinical trials.

Cholestatic jaundice and bone lesions in an elderly woman.

BACKGROUND: A 74-year-old Caucasian female presented with jaundice, clay-colored stools, diarrhea, and fatigue of 3 months' duration, accompanied by a weight loss of 6.8 kg. Physical examination demonstrated mild hepatomegaly. Initial blood work revealed abnormal liver biochemistries with a cholestatic pattern. An abdominal CT scan showed intrahepatic bile-duct dilatation without masses but with multiple lytic and blastic bone lesions. A sacral bone biopsy established the diagnosis. INVESTIGATIONS: Endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, CT scan, bone biopsy and liver biopsy. DIAGNOSIS: Systemic mastocytosis affecting the biliary system resulting in a primary-sclerosing-cholangitis-like picture combined with diffuse blastic and lytic bone lesions. MANAGEMENT: Biliary stenting, histamine 1- and 2-receptor blockers, and chemotherapy (cladribine).

A New Microarray, Enriched in Pancreas and Pancreatic Cancer cDNAs to Identify Genes Relevant to Pancreatic Cancer.

BACKGROUND: Identification and characterization of genes that are relevant to pancreatic cancer remains a priority for developing detection and diagnostic tests and identifying targets for treatment. MATERIALS AND METHODS: In order to discover relevant genes, we developed a microarray composed of 5763 pancreas and pancreatic cancer cDNA clones, representing genes of known and unknown function. The Pittsburgh Pancreas Enriched ARray (PittPEAR) was used to compare the gene expression differences between pancreatic cancer and normal pancreas. RESULTS: Two hundred and sixty-four genes were identified: 85 were overexpressed and 176 were underexpressed in cancer compared to normal tissue. Two of the top five genes included the cell cycle division 37 (CDC37) and period Drosophila homolog protein 1 (PER1), which play critical roles in cell division and transcriptional regulation, respectively. Underexpression of many genes probably reflected the loss of acinar and islet cells from the tumors. The biological functions of overexpressed genes include immune response genes, cytoskeletal and genes related to the extracellular matrix, cell invasion, migration, adhesion and motility. Apoptosis and transcription factor genes were also identified. CONCLUSION: We conclude that the PittPEAR microarray provides a useful tool for identifying genes that are relevant to the development and maintenance of pancreatic cancer.

Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy.

OBJECTIVE: To investigate the initiation of a complex inflammatory response within the human intestinal muscularis intraoperatively so as to determine the clinical applicability of the inflammatory hypothesis of postoperative ileus. SUMMARY BACKGROUND DATA: Mild intestinal manipulation in rodents initiates the activation of transcription factors, upregulates proinflammatory cytokines, and increases the release of kinetically active mediators (nitric oxide and prostaglandins), all of which results in the recruitment of leukocytes and a suppression in motility (i.e., postoperative ileus). METHODS: Human small bowel specimens were harvested during abdominal procedures at various times after laparotomy. Histochemical and immunohistochemical techniques were applied to intestinal muscularis whole-mounts. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed for interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Signal transducers and activators of transcription (STAT) protein phosphorylation was determined by electromobility shift assay. Organ bath experiments were performed on jejunal circular smooth muscle strips. GW274150C and DFU were used in vitro as iNOS and COX-2 inhibitors. RESULTS: Normal human muscularis externa contained numerous macrophages that expressed increased lymphocyte function associated antigen-1 (LFA-1) immunoreactivity as a function of intraoperative time. RT-PCR demonstrated a time-dependent induction of IL-6, IL-1beta, TNF-alpha, iNOS, and COX-2 mRNAs within muscularis extracts after incision. Mediators were localized to macrophages with STAT protein activation in protein extracts demonstrating local IL-6 functional activity. DFU alone or in combination with GW274150C increased circular muscle contractility. Specimens harvested after reoperation developed leukocytic infiltrates and displayed diminished in vitro muscle contractility. CONCLUSIONS: These human data demonstrate that surgical trauma is followed by resident muscularis macrophage activation and the upregulation, release, and functional activity of proinflammatory cytokines and kinetically active mediators.