Claudio A. Redaelli

Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma

Mortality rates associated with pancreatic resection for cancer have steadily decreased with time, but improvements in long‐term survival are less clear. This prospective study evaluated risk factors for survival after resection for pancreatic adenocarcinoma.

Randomized clinical trial of pylorus-preserving duodenopancreatectomy versus classical Whipple resection - : long term results

It is not known whether pylorus‐preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures.

Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury.

Proinflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. The role of interleukin (IL)-18, a new member of the IL-1 family, in brain trauma has not been reported to date. The authors investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in CSF of CHI patients. In the mouse model, intracerebral IL-18 was induced within 24 hours by ether anesthesia and sham operation. Significantly elevated levels of IL-18 were detected at 7 days after CHI and in human CSF up to 10 days after trauma. Published data imply that IL-18 may play a pathophysiological role in inflammatory CNS diseases; therefore its inhibition may ameliorate outcome after CHI. To evaluate the functional aspects of IL-18 in the injured brain, mice were injected systemically with IL-18–binding protein (IL-18BP), a specific inhibitor of IL-18, 1 hour after trauma. IL-18BP—treated mice showed a significantly improved neurological recovery by 7 days, accompanied by attenuated intracerebral IL-18 levels. This demonstrates that inhibition of IL-18 is associated with improved recovery. However, brain edema at 24 hours was not influenced by IL-18BP, suggesting that inflammatory mediators other than IL-18 induce the early detrimental effects of intracerebral inflammation.

Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy.

BACKGROUND The role of preoperative biliary drainage in patients with biliary obstruction undergoing pancreatoduodenectomy remains controversial. Several authors failed to show any effect of preoperative biliary drainage, whereas others even reported an increased morbidity following pancreatoduodenectomy. METHODS Retrospective analysis was performed in a consecutive series of 257 patients undergoing pancreatoduodenectomy between November 1993 and November 1999. RESULTS Ninety-nine patients (38%) underwent preoperative biliary drainage for a median time period of 10 days (range 1 to 41) prior to resection. Cumulative postoperative morbidity was 47% (120 patients), the reoperation rate was 4.3% (11 patients), and mortality was 2.3% (6 patients). There was no difference in total morbidity, infectious complications, reoperation rate, mortality, or long-term survival between patients with or without preoperative biliary drainage. CONCLUSIONS Preoperative biliary instrumentation and biliary drainage do not affect early or late outcome in patients undergoing pancreatoduodenectomy.

Intrathecal Levels of Complement-Derived Soluble Membrane Attack Complex (sC5b-9) Correlate with Blood–Brain Barrier Dysfunction in Patients with Traumatic Brain Injury

It has become evident in recent years that intracranial inflammation after traumatic brain injury (TBI) is, at least in part, mediated by activation of the complement system. However, most conclusions have been drawn from experimental studies, and the intrathecal activation of the complement cascade after TBI has not yet been demonstrated in humans. In the present study, we analyzed the levels of the soluble terminal complement complex sC5b-9 by ELISA in ventricular cerebrospinal fluid (CSF) of patients with severe TBI (n = 11) for up to 10 days after trauma. The mean sC5b-9 levels in CSF were significantly elevated in 10 of 11 TBI patients compared to control CSF from subjects without trauma or inflammatory neurological disease (n = 12; p < 0.001). In some patients, the maximal sC5b-9 concentrations were up to 1,800-fold higher than in control CSF. The analysis of the extent of posttraumatic blood-brain barrier (BBB) dysfunction, as determined by CSF/serum albumin quotient (Q(A)), revealed that patients with a moderate to severe BBB impairment (mean Q(A) > 0.01) had significantly higher intrathecal sC5b-9 levels as compared to patients with normal BBB function (mean Q(A) < 0.007; p < 0.0001). In addition, a significant correlation between the individual daily Q(A) values and the corresponding sC5b-9 CSF levels was detected in 8 of 11 patients (r = 0.72-0.998; p < 0.05). These data demonstrate for the first time that terminal pathway complement activation occurs after head injury and suggest a possible pathophysiological role of complement with regard to posttraumatic BBB dysfunction.

High coincidence of Mirizzi syndrome and gallbladder carcinoma

BACKGROUND Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied. METHODS Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study. RESULTS Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation. CONCLUSIONS There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.

Preoperative Galactose Elimination Capacity Predicts Complications and Survival After Hepatic Resection

ObjectiveTo analyze a single center’s 6-year experience with 258 consecutive patients undergoing major hepatic resection for primary or secondary malignancy of the liver, and to examine the predictive value of preoperative liver function assessment. Summary Background DataDespite the substantial improvements in diagnostic and surgical techniques that have made liver surgery a safer procedure, careful patient selection remains mandatory to achieve good results in patients with hepatic tumors. MethodsIn this prospective study, 258 patients undergoing hepatic resection were enrolled: 111 for metastases, 78 for hepatocellular carcinoma (HCC), 21 for cholangiocellular carcinoma, and 48 for other primary hepatic tumors. One hundred fifty-eight patients underwent segment-oriented liver resection, including hemihepatectomies, and 100 had subsegmental resections. Thirty-two clinical and biochemical parameters were analyzed, including liver function assessment by the galactose elimination capacity (GEC) test, a measure of hepatic functional reserve, to predict postoperative (60-day) rates of death and complications and long-term survival. All variables were determined within 5 days before surgery. Data were subjected to univariate and multivariate analysis for two patient subgroups (HCC and non-HCC). The cutoffs for GEC in both groups were predefined. Long-term survival (>60 days) was subjected to Kaplan-Meier analysis and the Cox proportional hazard model. ResultsIn the entire group of 258 patients, a GEC less than 6 mg/min/kg was the only preoperative biochemical parameter that predicted postoperative complications and death by univariate and stepwise regression analysis. A GEC of more than 6 mg/min/kg was also significantly associated with longer survival. This predictive value could also be shown in the subgroup of 180 patients with tumors other than HCC. In the subgroup of 78 patients with HCC, a GEC less than 4 mg/min/kg predicted postoperative complications and death by univariate and stepwise regression analysis. Further, a GEC of more than 4 mg/min/kg was also associated with longer survival. ConclusionsThis prospective study establishes the preoperative determination of the hepatic reserve by GEC as a strong independent and valuable predictor for short- and long-term outcome in patients with primary and secondary hepatic tumors undergoing resection.

Liver surgery in the era of tissue-preserving resections: early and late outcome in patients with primary and secondary hepatic tumors.

AbstractDuring recent decades, the understanding of the segmental-oriented liver anatomy has enabled development of resection of isolated liver segments or sectors as dictated by the localization and extent of the mass lesion. These newer surgical procedures provide the advantage of maximal preservation of functional parenchyma, therefore minimizing the occurrence of postoperative liver failure and, at the same time, expanding the indications for surgery. We analyzed the results after classical hemihepatectomies and segment-based resections in a consecutive, nonselected patient group. During the 7-year period between November 1993 and November 2000, 270 patients with primary or secondary liver tumors were treated in our hospital; 167 of these patients underwent curative resections and their relevant data were entered into a statistical database. There were 77 classical hemihepatectomies and 90 tissue-preserving resections. Total mortality and morbidity for the series was 3.6% and 29.9%, respectively. Morbidity but not mortality was significantly lower after tissue-preserving resections than after classical hemihepatectomy. Median follow-up was 36 months. Survival was comparable for the two different surgical approaches for patients with secondary liver malignancies. In contrast, patients with hepatocellular carcinomas lived significantly longer after tissue-preserving resections. Tissue-preserving liver resection is a safe technique allowing maximal preservation of functional parenchyma without compromising radicality. Therefore, tissue-preserving resection is especially useful for patients with hepatocellular carcinomas and cirrhosis.

Circulatory and Anatomic Differences among Experimental Gastric Tubes as Esophageal Replacement

Abstract. In this experimental study we measured microcirculatory and anatomic differences among a newly developed technique of gastroplasty—fundus rotation gastroplasty (FRG)—and conventional (CG) and reversed (RG) gastric tubes as substitutes for the thoracic and cervical esophagus. After transhiatal esophageal resection, 36 large white pigs were randomly assigned to have an FRG, CG, or RG. Tube length, gastric volume, and compliance as well as blood flow in the tube and the remaining gastric reservoir (by laser Doppler flowmetry) were measured. The FRG tubes were 35.9 ± 3.1 cm long, RG 38.7 ± 3.3 cm, and CG 27.3 ± 2.1 cm (p< 0.05). Gastric compliance was 20.8 ml in the FRG and 3.2 ml and 2.9 ml in the CG and RG, respectively (p < 0.001). Blood flow was significantly higher in FRG tubes than in RG tubes or CG tubes, resulting in a lower anastomotic failure rate (2/12 FRG, 6/12 CG, 7/12 RG). Hence a rotation flap of the gastric fundus (FRG) yields a long, well perfused tube by maintaining the blood supply of the gastric lesser curvature. FRG appears to be a good alternative to CG or RG as a substitute for the thoracic and cervical esophagus.

Hyperthermia Preconditioning Induces Renal Heat Shock Protein Expression, Improves Cold Ischemia Tolerance, Kidney Graft Function and Survival in Rats

Background: Evidence indicates that hyperthermia preconditioning (HP) can be protective in kidney transplantation, possibly through increased heat shock protein (HSP) expression. A detailed study about individual HSPs and functional preservation is lacking, however. Therefore, we studied the effects of HP on kidney graft survival, function and HSP expression. Methods: Male Lewis rats were or were not subjected to whole-body hyperthermia 24 h prior to kidney procurement. Kidneys were stored in UW solution at 4°C for 32, 40 or 45 h. Recipient kidneys were both removed and single isografts transplanted orthotopically. Results: HP strongly induced HSP72 and HSP32 expression. Following 32-hour cold ischemia, most animals survived even without prior HP. However, HP strongly reduced functional impairment induced by cold ischemia. Following 40-hour cold ischemia, kidneys from donors without HP did not recover function and all animals died within 3 days. In contrast, HP-exposed kidneys tolerated 40-hour storage significantly better, with 44% of rats surviving until sacrifice on day 7. In these animals, renal function was still better compared to animals with 32-hour-stored kidneys without HP. Histological alterations were also diminished following HP. Conclusion: Our data show that HP induces renal HSP72 and, for the first time, HSP32. HP increases survival following transplantation and acts by improving several parameters of kidney function including proteinuria, volume output and creatinine clearance.