Incidental radiologic findings in breast cancer patients who undergo staging prior to neo-adjuvant chemotherapy

NCCN guidelines discourage the use of staging imaging for newly diagnosed patients with early breast cancer (BC). When performed, incidental radiologic findings of uncertain significance are often encountered. The purpose of this study was to compare incidental findings seen on staging imaging with distant recurrence in patients undergoing neo-adjuvant chemotherapy (NAC). 396 patients with BC who had NAC from 2008 to 2016 were identified from a prospectively maintained data base. Staging imaging was reviewed. Of 396 patients with BC treated with NAC, patients with a positive PET/CT for metastatic disease (n = 36, 9.1%), those that did not undergo staging imaging (n = 49, 12.4%), or those that did not have a reported incidental finding (n = 49, 12.4%) were excluded from analysis. Of the 262 patients who met criteria, mean age was 50 years (range: 26–88). 201 (76.7%) patients had stage I-II cancer, and 61 (23.3%) patients had stage III cancer. Overall, 146 (55.7%) patients had an incidental finding on imaging. 90 (34.4%) patients had one finding, 42 (16.0%) patients had two, and 14 (5.3%) patients had three or more findings. The majority of incidental findings were seen in the ovary/uterus (29.7%), followed by lung (18.4%), liver (10.3%), and bone (9.0%). 5 (3.4%) patients had additional imaging performed. At mean follow-up of 3.7 years (range: 0.7–10.8), 43 (15.6%) patients had a distant recurrence. Of these patients, only 5 (1.9%) patients had distant metastasis in the same organ that was initially thought to be an incidental finding. Our results suggest that breast cancer patients with incidental findings on preoperative staging imaging are unlikely to be indicative of sites for future metastasis.     

CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein reduces ischemia-reperfusion injury after rat intestinal transplantation

BACKGROUND: Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS: An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken. RESULTS: Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION: The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.     

The benefits and limitations of sentinel lymph node biopsy

Opinion statement The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Staging is based on tumor size and on the presence of lymph node metastases. The number of lymph nodes, although prognostic, no longer impacts treatment options. Sentinel lymph node (SLN) mapping and dissection is a more sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer, providing prognostic information, with less surgical morbidity than with axillary lymph node dissection (ALND). When analyzed by an experienced pathologist with serial sectioning and immunohistochemical evaluation, SLN is the most accurate detection tool used in staging of breast cancer. In many centers that use these staging principles, ALND is no longer performed for histologically negative axillary SLNs. In addition, this technique may also be therapeutic because in most patients, the SLN is the only positive axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who have a high risk of invasive carcinoma, such as those with large tumors, a mass, or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the cases. Women with locally advanced breast cancer may derive great benefit from a minimally invasive approach to the axilla because the extent of nodal involvement is unlikely to change further treatment. For clinically palpable nodes, ALND should be performed for therapeutic and local control. The use of sentinel node mapping in pregnancy is controversial. Vital blue dye is contraindicated in pregnant patients, although some have used radioactive colloid alone to map this subgroup of patients.     

Predictors of survival after In vivo split liver transplantation: analysis of 110 consecutive patients

OBJECTIVE: To determine the factors that influence patient survival after in vivo split liver transplantation (SLT). SUMMARY BACKGROUND DATA: Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. METHODS: During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. RESULTS: Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. CONCLUSIONS: Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.     

Maintenance of Certification and Continuing Medical Education: Are They Still Required?

Annals of Surgical Oncology -     

Pretransplant model to predict posttransplant survival in liver transplant patients

OBJECTIVE: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables. SUMMARY BACKGROUND DATA: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes. Such goals can be realized only through the development of prognostic models that predict survival following OLT. METHODS: Variables that may affect patient survival following OLT were analyzed in hepatitis C (HCV) recipients at the authors' center, since HCV is the most common indication for OLT. The resulting patient survival model was examined and refined in HCV and non-HCV patients in the United Network for Organ Sharing (UNOS) database. Kaplan-Meier methods, univariate comparisons, and multivariate Cox proportional hazard regression were employed for analyses. RESULTS: Variables identified by multivariate analysis as independent predictors for patient survival following primary transplantation of adult HCV recipients in the last 10 years at the authors' center were entered into a prognostic survival model to predict patient survival. Accordingly, mortality was predicted by 0.0293 (recipient age) + 1.085 (log10 recipient creatinine) + 0.289 (donor female gender) + 0.675 urgent UNOS - 1.612 (log10 recipient creatinine times urgent UNOS). The above variables, in addition to donor age, total bilirubin, prothrombin time (PT), retransplantation, and warm and cold ischemia times, were applied to the UNOS database. Of the 46,942 patients transplanted over the last 10 years, 25,772 patients had complete data sets. An eight-factor model that accurately predicted survival was derived. Accordingly, the mortality index posttransplantation = 0.0084 donor age + 0.019 recipient age + 0.816 log creatinine + 0.0044 warm ischemia (in minutes) + 0.659 (if second transplant) + 0.10 log bilirubin + 0.0087 PT + 0.01 cold ischemia (in hours). Thus, this model is applicable to first or second liver transplants. Patient survival rates based on model-predicted risk scores for death and observed posttransplant survival rates were similar. Additionally, the model accurately predicted survival outcomes for HCV and non-HCV patients. CONCLUSIONS: Posttransplant patient survival can be accurately predicted based on eight straightforward factors. The balanced application of a model for liver transplant survival estimate, in addition to disease severity, as estimated by the model for end-stage liver disease, would markedly improve survival outcomes and maximize patients' benefits following OLT.     

Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival

The purpose of this study was to determine the prevalence and risk factors of metastases in hepatocellular carcinoma (HCC) patients and analyze the effects of different locations of metastases on survival. Retrospective analysis was performed on 347 HCC patients who received a metastatic workup including bone scan and computed tomography scans of chest, abdomen, and pelvis. Clinical and tumor characteristics were evaluated as risk factors for metastasis by univariate and multivariate methods. Survival was analyzed by Kaplan-Meier and Cox regression methods. One hundred forty-five patients had metastases: 72 had thoracic, 57 had abdominal, and 34 had bone metastases. Significant differences were noted with weight loss, hepatitis C, tumor grade, tumor multifocality, size, and alkaline phosphatase levels between the metastases group and the nonmetastases group by univariate analysis. Poor differentiation, multilobar spread, and size (> or = 5 cm) were strongest predictors of metastatic disease by logistic regression. Patients with thoracic metastases had significantly poorer survival. HCC metastasis is prevalent on initial presentation. Evaluation for liver transplantation or curative resection requires a full metastatic workup. Poor differentiation, larger tumors, and those with multilobar spread have increased risk for metastasis. Patients with thoracic spread have poor prognosis as compared to other locations of metastasis.     

Recombinant P selectin glycoprotein ligand ameliorates chronic ischemia and reperfusion injury after rat intestinal transplantation

Previous studies have demonstrated that the blockade of P selectin through the administration of recombinant P Selectin Glycoprotein Ligand (rPSGL-1Ig) in a model of rat intestinal ischemia and reperfusion injury (IRI) afforded short-term improvement in outcome. The aim of this study was to investigate the long-term consequences of such therapy. IRI was induced in a model of isogeneic intestinal transplantation (ITx) using Lewis rats wherein intestines were procured, cold preserved in lactated Ringer solution for 6 h, and transplanted orthotopically. rPSGL-1Ig (0.4 mg/kg/dose) or saline was administered intravascularly into the intestine prior to storage and into the recipient prior to reperfusion. Separate survival and analysis groups were undertaken. For analysis, animals were sacrificed at day 3, 7, 30, and 100 after ITx. Transplanted ileal tissue was procured and stored for analysis that included histopathology, quantitative cytokine rtPCR, and hemoxygenase-1 (HO-1) and anti-apoptotic (Bcl-2, Bcl-xl) protein expression. Statistical comparison was performed using a Student’s t test. Survival at 100 days was markedly (P < 0.05) improved in the rPSGL-1Ig treated group (90%) versus saline-treated control group (40%). Histopathology was markedly improved at 100 days. At all time points, rtPCR demonstrated significantly (P < 0.05) lower mRNA production in treated animals of the cytokines: TNF-α, IL-6, TGF-β, and β-FGF. Western blot analysis demonstrated increased production of the protective proteins HO-1, Bcl-2, and Bcl-xl with rPSGL-1Ig treatment. Early blockade of P selectin at the time of ITx-associated IRI using rPSGL-1Ig led to significant improvement in survival, reductions in tissue injury on histopathology, reduction in mRNA production for chronic inflammatory cytokines, and increased protection of cellular protective proteins. This data indicate that the control of the early events associated with IRI leads to improvement in long-term isograft inflammatory parameters in a model of rat ITx.