Clinical and pathologic features influencing survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the clinicopathological features that influence survival in patients with resected pancreatic ductal adenocarcinoma (PDA). METHODS: The study used a single institution retrospective review of patients undergoing pancreaticoduodenectomy (PD) for PDA from 1993 to 2010. RESULTS: Two hundred forty-six consecutive cases of resected PDA were identified: 128 males (52 %), median age 68 years. Median hospital length of stay was 8 days and 30-day mortality rate was 2.4 %. There were 101 (41.1 %) postoperative complications, 77 % of which were Dindo-Clavien Grade 3 or less. Overall survival was 85, 63, 25, and 15 % at 6 months, 1 year, 3 years, and 5 years, respectively, with a median survival of 17 months. Multivariate Cox proportional hazard modeling demonstrated lymph node ratio was negatively correlated with survival at all time points. Preoperative hypertension was a poor prognostic factor at 6 months, 3 years, and 5 years. The absence of postoperative complications was protective at 6 months whereas pancreatic leaks were associated with worse survival at 6 months. Abdominal pain on presentation, operative time, and estimated blood loss were also associated with decreased survival at various time points. CONCLUSION: The strongest prognostic variable for short- and long-term survival after PD for PDA is lymph node ratio. Short-term survival is influenced by the postoperative course.

Late complications after pancreaticoduodenectomy with pancreaticogastrostomy.

INTRODUCTION: We investigated complications after pancreaticoduodenectomy (PD) with pancreaticogastrostomy (PG) reconstruction more than 12 months postoperatively. METHODS: Through chart review and outpatient follow-up, we assessed the incidence of new-onset diabetes mellitus (DM) and steatorrhea after PD. RESULTS: Ninety patients underwent PD with PG with a median follow-up of 4.7 years (range 0.4-15.8 years). Of the 77 patients without DM preoperatively, 18 (23.4%) developed DM postoperatively. Those who developed DM were younger at time of surgery than those who did not (60.5 versus 65.8 years; p = 0.021), but postoperative survival did not differ between these groups. The incidence of DM was comparable to the incidence of DM in the general population. Out of 89 patients, 47 (52.8%) now require pancreatic enzyme therapy. The group that developed steatorrhea underwent PD at a younger age (61.4 versus 67.0 years; p = 0.029). CONCLUSIONS: Patients that undergo PD at a younger age are more likely to develop DM and steatorrhea than their older counterparts; patients are as likely as the general population, however, to develop DM after PD with PG.

Support for a postresection prognostic score for pancreatic endocrine tumors.

BACKGROUND: Prognostic scores predicting long-term survival of patients with pancreatic neuroendocrine tumors (PNETs) have been created. The purpose of this study was to validate a prognostic scoring scheme at a single institution. METHODS: We reviewed all resections for PNETs from 1996 to 2004. Prognostic scores based on patient age, tumor grade, and distant metastasis were calculated. Survival was compared with an established postresection prognostic score for PNETs. RESULTS: A total of 34 PNETs were identified. Predicted 5-year survival for prognostic scores of 1, 2, and 3 were 76.7%, 50.9%, and 35.7%, respectively. Final prognostic scores of 1, 2, and 3 were observed in 13 (38%), 18 (53%), and 3 (9%) patients, with observed actual 5-year survivals of 92.3%, 72.2%, and 66.7%, respectively. CONCLUSIONS: PNET prognostic scores were found to be inversely related to survival. PNET postresection prognostic score categories may be useful tools in predicting long-term survival.

The novel antibacterial drug XF-70 is a potent inhibitor of Staphylococcus aureus infection of the burn wound.

The authors report the findings of in vivo studies of XF-70 (a novel, dicationic porphyrin) against Staphylococcus aureus in a murine model of a burn wound infection. Mice received a 15% total body scald burn wound, which were inoculated with S. aureus (1.8 x 10 CFU). After 24 hours, escharectomies were performed and groups (n = 8) received single or two doses (6 hours apart) of XF-70* (100 microg/wound) or silver sulfadiazine, Acticoat, or saline applied topically. Viable bacteria were quantified from homogenized burn tissue biopsies and the spleen by plating dilutions onto agar plates and CFU determination. A single dose of XF-70 reduced bacterial burden by 98.77% (untreated: 2.78 +/- 2.96 x 10 CFU/g vs XF-70 treated: 3.4 +/- 0.19 x 10 CFU/g, P < .01). Two XF-70 doses reduced the growth of S. aureus by 99.96% (1.2 +/- 0.6 x 10 CFU/g, P < .01). These results were similar to the results obtained from commonly used topical antibacterials silver sulfadiazine and Acticoat. The spleens of mice treated with saline had a robust growth of S. aureus (7.0 +/- 1.97 x 10 CFU/g) whereas those treated with one or two XF-70 doses grew only 3.5 +/- 0.002 x 10 CFU/g and 5.7 +/- 0.002 x 10 CFU/g, respectively, a significant (P < .001) reduction in S. aureus dissemination. Single and multiple doses of XF-70 were effective in controlling S. aureus growth in burn wounds and inhibited systemic dissemination of S. aureus. Early treatment of burn wounds with XF-70 may be effective in slowing bacterial dissemination to other tissues.

Pancreaticoduodenectomies in patients without periampullary neoplasms: lesions that masquerade as cancer.

BACKGROUND: Most pancreaticoduodenectomies (PDs) are performed to treat periampullary malignancies (PMs). Final pathologic analysis on these specimens does not always contain PMs. Our aim was to classify diseases that preoperatively mimic PMs. METHODS: A prospective database of PDs performed at a single institution was reviewed. Clinicopathologic data on patients without PM on pathologic review with preoperative suspicion of PM were studied. RESULTS: Of the 461 PDs performed at our institution, 45 (10%) had no PM; of these cases, 35 (78%) were performed for a clinical suspicion of malignancy. The final pathologic review showed chronic pancreatitis (CP) in 23 (66%) patients, biliary tract disease in 10 (28%) patients, duodenal ulcer in 1 (3%) patient, and distal common bile duct stricture with localized pancreatic fibrosis in 1 (3%) patient. CONCLUSION: Most patients undergoing PD have evidence of a PM. A subset of patients may have lesions that mimic a PM. In these patients, when PM cannot be ruled out, if possible, they should be offered PD.

Does lymph node ratio impact survival in resected periampullary malignancies?

BACKGROUND: Lymph node ratio (LNR) has been associated with long-term survival in patients with pancreatic adenocarcinoma; however, this has not been demonstrated in other periampullary malignancies. The purpose of this study was to determine if LNR is associated with survival in other periampullary malignancies. METHODS: A retrospective review of a prospective database of 522 pancreaticoduodenectomies (PDs) performed between 1988 and 2007 was undertaken. Clinicopathologic data were collected, and LNR was calculated. Patients with positive lymph node (LN) status were placed into the following groups: (1) LNR = 0; (2) LNR < or =0.2; (3) LNR < or =0.4; and (4) LNR >0.4. RESULTS: Of the 364 malignancies identified, there were 219 (60%) pancreatic adenocarcinomas, 36 (10%) duodenal adenocarcinomas, 75 (21%) ampullary adenocarcinomas, and 35 (10%) cholangiocarcinomas. Positive LN status affected patient survival in all malignancies studied. Increasing LNR is associated with decreased survival in PA (P = .03) and AA (P = .04). CONCLUSIONS: Positive LN status in all patients with periampullary malignancies is associated with worse survival rates than in those with no evidence of disease. LNR is inversely associated with survival rates in pancreatic and ampullary adenocarcinoma patients.

Preoperative liver function tests and hemoglobin will predict complications following pancreaticoduodenectomy.

INTRODUCTION: Previous studies identified an association between dilated pancreatic and biliary ducts and lower rates of pancreatic leak after pancreaticoduodenectomy, but it remains unclear whether elevated liver function tests are also associated with lower rates of complications. The purpose of this study was to determine if preoperative liver function tests are associated with postoperative complications. MATERIALS AND METHODS: We identified 452 patients who received a pancreaticoduodenectomy from 1990-2007. Clinicopathological data was collected for each patient, and regression analyses were performed to identify predictors of postoperative complications. RESULTS: Of the patients studied, 289 (64%) experienced no postoperative complications. In univariate analysis, patients with a low or normal preoperative aspartate aminotransferase (p = 0.03) or alkaline phosphatase (p = 0.03), had higher rates of complications. Multivariate analysis confirmed an elevated alkaline phosphatase was associated with a lower incidence of complications (OR = 0.56, p = 0.02), while preoperative anemia was found to be a predictor of complications following pancreaticoduodenectomy (OR = 2.01, p = 0.02). CONCLUSION: Anemic patients and those with normal liver function tests were more likely to experience complications after pancreaticoduodenectomy. This may represent extent of disease and tumors not causing biliary or pancreatic dilatation, respectively. Precautions, such as intraoperative ductal stents, should be considered when operating on this group of patients to minimize complications.

A cytokeratin- and calretinin-negative staining sarcomatoid malignant mesothelioma.

Malignant Mesothelioma, or mesothelioma, is a mesothelial-based malignancy that may occur in the pleura, pericardium and peritoneum. Mesothelioma is a very aggressive cancer with limited treatment, and a median survival of about 1 year. At times, the diagnosis of mesothelioma may be problematic. The final diagnosis of mesothelioma relies on histology and often is dependent upon immunohistochemistry. It is generally assumed that mesotheliomas must stain positive for cytokeratin and calretinin and negative staining for these markers would rule out the diagnosis. We encountered a patient with a pleural-based, cytokeratin- and calretinin-negative sarcomatoid malignancy. These negative stainings would rule out the diagnosis of mesothelioma but, after careful consideration of the patient's clinical records, and additional histological and immunohistochemical studies, we conclude that this patient suffered from mesothelioma of the sarcomatoid type.

Important region in the beta-spectrin C-terminus for spectrin tetramer formation.

Many hereditary hemolytic anemias are due to spectrin mutations at the C-terminal region of beta-spectrin (the betaC region) that destabilize spectrin tetramer formation. However, little is known about the betaC region of spectrin. We have prepared four recombinant beta-peptides of different lengths from human erythrocyte spectrin, all starting at position 1898 of the C-terminal region, but terminating at position 2070, 2071, 2072 or 2073. Native polyacrylamide gel electrophoresis showed that the two peptides terminating at positions 2070 and 2071 did not associate with an N-terminal region alpha-peptide (Spalpha1-156) in the micromolar range. However, the peptides that terminated at positions 2072 and 2073 associated with the alpha-peptide. Circular dichroism results showed that the unassociated helices in both alpha- and beta-peptides became associated, presumably to form a helical bundle, for those beta-peptides that formed an alphabeta complex, but not for those beta-peptides that did not form an alphabeta complex. In addition, upon association, an increase in the alpha-helical content was observed. These results showed that the beta-peptides ending prior to residue 2072 (Thr) would not associate with alpha-peptide, and that no helical bundling of the partial domains was observed. Thus, we suggest that the C-terminal segment of beta-spectrin, starting from residue 2073 (Thr), is not critical to spectrin tetramer formation. However, the C-terminal region ending with residue 2072 is important for its association with alpha-spectrin in forming tetramers.