Influence of pulsatile perfusion preservation on outcomes in kidney transplantation from expanded criteria donors

BACKGROUND: Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function. STUDY DESIGN: Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach. RESULTS: Over a 5-year period, we performed 141 donations-after-brain-death ECD kidney transplantations into adult recipients. A total of 114 kidneys (81%) were managed with combined cold-storage and pulsatile perfusion preservation (PPP), and the remaining 27 (19%) were preserved with cold storage (CS). The PPP group had a higher proportion of kidneys preserved for longer than 30 hours (28% versus 0, p < 0.001) and a longer mean cold ischemia time (24.5 hours PPP versus 19 hours CS, p < 0.01). Other donor and recipient characteristics were similar between groups. Incidence of delayed graft function was 11% in PPP-stored kidneys versus 37% in CS kidneys (p = 0.002). With a mean followup of 27 months, patient (91% PPP versus 96% CS) and kidney graft survival (81% PPP versus 81.5% CS) rates were comparable. Mean 12-month serum creatinine (1.9 mg/dL) and calculated Modification of Diet in Renal Disease glomerular filtration rate (41 mL/min) values were similar between groups. CONCLUSIONS: Despite longer cold ischemia times, recipients of ECD kidneys managed with PPP had similar survival and functional outcomes, but experienced a marked reduction in the rate of delayed graft function.     

Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits

Background

Sunitinib (Sutent) is a Food and Drug Administration–approved receptor tyrosine kinase inhibitor found to reduce postoperative adhesion formation in animal models. The objective of the present study was to evaluate anastomotic healing and potential drug-related toxicities after short-term sunitinib administration in New Zealand White rabbits.

Materials and methods

Under an approved study protocol, 40 rabbits underwent a laparotomy followed by colonic transection and anastomosis. Animals were randomly assigned to treatment with oral sunitinib (10 mg/kg/d) or placebo, received one preoperative dose followed by 10 postoperative doses, and were divided into two groups following the procedure: group I animals were euthanized on completion of drug treatment and group II animals were euthanized 30 d after completion of treatment. Prior to study completion, animals underwent an echocardiogram and laboratory test results were obtained. At necropsy, intestinal bursting strength (in mmHg) was evaluated.

Results

All animals survived until designated euthanasia. There was no evidence of intra-abdominal sepsis or intestinal obstruction. Sunitinib-treated animals were found to have lower intestinal anastomotic strength compared with placebo-treated animals, as measured by bursting pressure at euthanasia, and a greater percentage of bursting at the anastomosis. On echocardiography, all ejection and shortening fractions were within established normal reference values. There were no significant differences in liver enzymes between animals. There were no wound infections, dehiscence, or delayed wound healing in any animal.

Conclusions

These results caution against the administration of sunitinib in cases involving intestinal anastomoses because of the elevated risk of anastomotic leak. No evidence of cardiotoxicity, hepatotoxicity, or detrimental effect on wound healing was found in any animal.     

Contemporary management of breast cancer during pregnancy and subsequent lactation in a multicenter cohort of young women with breast cancer

The incidence of breast cancer diagnosed during pregnancy is increasing. We sought to characterize patient, treatment, pregnancy and lactation factors among young women with newly diagnosed breast cancer during pregnancy in a prospective cohort study. We identified all women who were pregnant when diagnosed with invasive breast cancer among those enrolled in the Young Women's Breast Cancer Study (NCT01468246), and collected details on pregnancy, birth and lactation from surveys, and treatment information medical record review. Of 1302 enrolled participants, 976 women with invasive breast cancer completed full baseline surveys, among whom 39 (4.0%) patients reported being pregnant at diagnosis. Median age at diagnosis was 34 years (range: 25‐40), with stage distribution: I, 28%; II, 44%; III, 23%; and IV, 5%. 74% of patients (29/39) had grade 3 tumors, 59% (23/39) ER‐positive, and 31% (12/39) HER2‐positive disease. 23 (59%) had surgery during pregnancy, 4 (17%) during the first trimester. Among the women who had surgery during pregnancy, 61% (14/23) underwent lumpectomy, 35% (8/23) unilateral, and 4% (1/23) bilateral mastectomy. All patients who had chemotherapy (51%, 20/39) received it in second and third trimesters, and had ACx4. There were 31 live births, 2 spontaneous, and 5 therapeutic abortions. Among live births, 16 (41%) were before 37 weeks of gestation. Three women reported breastfeeding. Within 6 months after delivery, comprehensive staging in 13 patients showed upstaging in four patients. In a contemporary cohort of young women with breast cancer, pregnancy at diagnosis is relatively uncommon. Treatment during pregnancy can generally be consistent with standard surgical and chemotherapy approaches, with attention to timing of therapies. Longer‐term outcomes including effects of some timing issues including delayed use of anti‐HER2 therapy on patient outcomes warrant further research.     

Survival after resection for lung cancer is the outcome that matters

BACKGROUND: Lung cancer is the leading cause of cancer mortality in the United States. Stage-specific survival is well documented in national data sets; however, there remains limited recording of longitudinal survival in individual centers. METHODS: The VistA Surgery Package was employed to list operations performed by the thoracic surgery service at one Veterans Administration (VA) Medical Center. RESULTS: During a period of 107 months, 416 thoracic operations were performed, 211 of them for lung cancer. Stage distribution was 66% stage I, 18% stage II, 12% stage III, and 4% stage IV. During follow-up, 102 patients died, 57 of them from disease-specific causes. Median survival was 39 months for stage I. Disease-specific median survival was 83 months for stage I, and 5-year survival was 52% (72% for stage IA and 32% for stage IB). CONCLUSIONS: Pulmonary resection offers high disease-free survival for early-stage lung cancer. Decentralized hospital computer programming (DHCP) allows individual oncology programs to reliably measure survival. Use of this important outcome measure in quality improvement programs facilitates realistic counseling of patients and meaningful assessments of practice effectiveness.     

Results of routine shunting and patch closure during carotid endarterectomy

BackgroundThe role of shunting and patching during carotid endarterectomy remains controversial.MethodsThis is a retrospective case series evaluating consecutive patients undergoing carotid endarterectomy with routine shunting and patching. The primary endpoints were perioperative stroke, arterial injury, and lesion recurrence by duplex.ResultsOf the 220 operations performed, 43% were for symptomatic disease. Successful shunt placement occurred in 98%, with no shunt-related injuries. There was 1 minor perioperative stroke and no major strokes. At a mean follow-up of 24 months (median = 12 months), there was 1 restenosis potentially related to shunt placement. The incidence of asymptomatic >50% stenosis in the patched segment was 8%.ConclusionsA combined policy of routine shunting and patching simplifies intraoperative decision making with results that rival or exceed those of trials in which their use was not standardized. Shunts need not be avoided because of concern of arterial injury.     

Serum xylosyltransferase 1 level increases during early posttraumatic osteoarthritis in mice with high bone forming potential

Increased proteoglycan (PG) synthesis is essential for the stimulation of cartilage repair processes that take place during the reversible phase of osteoarthritis (OA). In articular cartilage, xylosyltransferase 1 (Xylt1) is the key enzyme that initiates glycosaminoglycan (GAG) chain synthesis by transferring the first sugar residue to the PG core protein. Biological activity of PGs is closely linked to GAG biosynthesis since their polyanionic nature directly contributes to the proper hydration and elastic properties of the cartilage tissue present at the articular interface. The aim of this study was to investigate whether variations in the level of Xylt1 present in serum can be used to predict OA disease progression. The influence of bone forming activity on the systemic release of this enzyme was addressed by experimentally-inducing OA in mice of two different genetic backgrounds that were previously characterized for their distinct bone metabolism: C57BL/6J (B6, high bone remodelers) or C3H/HeJ (C3H, high bone formers). Serum was collected after medial meniscectomy or sham surgeries in young adult mice of these two strains over a period of 3.5months at which point knee histopathology was assessed. A significant increase in serum Xylt1 levels observed shortly after meniscectomy positively correlated with severe cartilage damage evaluated by histological assessment at later time points in mice of the C3H background. In contrast, no temporal regulation of Xylt1 level was found between meniscectomies and control surgeries in B6 mice, which developed OA at a slower rate. Additionally, longitudinal evaluation of the serum levels of other markers of cartilage/bone metabolism (C1,2C, osteocalcin) did not reveal any association with late knee damages. Our results strongly support the idea that serum Xylt1 has a clinical value for monitoring risk of OA progression in young adults with high bone forming potential. Ultimately, the understanding of posttraumatic mechanisms regulating PG synthesis and their modification by GAG will be essential so that interventions that stimulate cartilage regrowth can be undertaken prior to irreversible destruction of the joint tissue. This article is part of a Special Issue entitled "Osteoarthritis".     

Genome-wide scan for prostate cancer susceptibility genes using families from the University of Michigan prostate cancer genetics project finds evidence for linkage on chromosome 17 near BRCA1

BACKGROUND: Previous linkage studies have suggested prostate cancer susceptibility genes located on chromosomes 1, 20, and X. Several putative prostate cancer candidate genes have also been identified including RNASEL, MSR1, and ELAC2. Presently, these linkage regions and candidate genes appear to explain only a small proportion of hereditary prostate cancer cases suggesting the need for additional whole genome analyses. METHODS: A genome-wide mode-of-inheritance-free linkage scan, using 405 genetic markers, was conducted on 175 pedigrees, the majority containing three or more affected individuals diagnosed with prostate cancer. Stratified linkage analyses were performed based on previously established criteria. RESULTS: Results based on the entire set of 175 pedigrees showed strong suggestive evidence for linkage on chromosome 17q (LOD = 2.36), with strongest evidence coming from the subset of pedigrees with four or more affected individuals (LOD = 3.27). Race specific analyses revealed strong suggestive evidence for linkage in our African-American pedigrees on chromosome 22q (LOD = 2.35). CONCLUSIONS: Genome-wide analysis of a large set of prostate cancer families indicates new areas of the genome that may harbor prostate cancer susceptibility genes. Specifically, our linkage results suggest that there is a prostate cancer susceptibility gene on chromosome 17 that is independent of ELAC2. Further research including combined analyses of independent genome-wide scan data may clarify the most important regions for future investigation.     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.     

Liposarcoma of the head and neck: The University of Texas M. D. Anderson Cancer Center experience

Background.

Our aim was to review our experience with liposarcoma of the head and neck region.

Methods.

This is a retrospective case series at a comprehensive cancer center (1945–2005).

Results.

Of 30 patients, 10 (33%) were initially misdiagnosed. Local recurrences were common (overall rate = 53%), and 4 patients (13%) developed distant metastases. Decreased crude disease‐specific survival rates were significantly associated with recurrence (especially distant recurrence [0%]), age less than 38 years (40%), and pleomorphic subtype (45%); however, in Kaplan‐Meier analyses, only larger tumor size, negative margins, round cell subtype, and pleomorphic subtype were associated with significantly decreased disease‐specific survival (log‐rank test p = .048, .041, .021, and .012, respectively).

Conclusions.

Based on this limited experience and existing literature, we continue to recommend surgery with negative margins as the treatment of choice and that adjuvant therapies should be considered in patients with high‐grade histology, large tumors, positive margins, or certain subsites. © 2008 Wiley Periodicals, Inc. Head Neck, 2009     

Single Port Access (SPA) Cholecystectomy: Two Year Follow-up

Introduction:

Laparoscopy is a constantly evolving field of surgery. New technology, applications, and benefits prompt continual improvement. We have developed a Single Port Access (SPA) surgical technique that allows for the entire cholecystectomy to be performed through a single incision within the umbilicus while maintaining safe standard dissection and retraction techniques of currently performed multi-port laparoscopic cholecystectomy.

Methods:

Fifteen consecutive patients underwent SPA cholecystectomy. Indications were cholelithiasis, cholecystitis, CBD stones, and biliary akinesia. The entire procedure was performed through a single umbilical incision measuring <1.8 cm within the umbilicus. Three trocars and a rigid grasper were inserted through separate fascial sites within the same skin incision. The cholecystectomy procedures are then performed in the standard fashion described in multi-port cholecystectomy.

Results:

Fifteen patients successfully underwent Single Port Access cholecystectomy. One patient required a second 5-mm port site secondary to difficulty with retraction of a large liver. Operative times averaged 107 minutes. Blood loss, patient recovery, and outcomes have been comparable to those of standard multi-port procedures. No umbilical hernias have been seen at 2 years of follow-up.

Conclusion:

We present the SPA cholecystectomy as an alternative to multi-port cholecystectomy. In the first 2 years, SPA surgery has evolved into a technique easily taught and performed without the restrictions of new equipment or added cost.