Axillary Recurrence After a Tumor-Positive Sentinel Lymph Node Biopsy Without Axillary Treatment: A Review of the Literature

Background

Sentinel lymph node biopsy (SLNB) has become standard of care as a staging procedure in patients with invasive breast cancer. A positive SLNB allows completion axillary lymph node dissection (cALND) to be performed. The axillary recurrence rate (ARR) after cALND in patients with positive SLNB is low. Recently, several studies have reported a similar low ARR when cALND is not performed. This review aims to determine the ARR when cALND is omitted in SLNB-positive patients.

Methods

A literature search was performed in the PubMed database with the search terms ??breast cancer,?? ??sentinel lymph node biopsy,?? ??axillary?? and ??recurrence.?? Articles with data regarding follow-up of patients with SLNB-positive breast cancer were identified. To be eligible, patients should not have received cALND and ARR should be reported.

Results

Thirty articles were analyzed. This resulted in 7,151 patients with SLNB-positive breast cancer in whom a cALND was omitted (median follow-up of 45?months, range 1?C142?months). Overall, 41 patients developed an axillary recurrence. 27 studies described 3,468 patients with micrometastases in the SLNB, of whom 10 (0.3?%) developed an axillary recurrence. ARR varied between 0 and 3.7?%. Sixteen studies described 3,268 patients with macrometastases, 24 (0.7?%) axillary recurrences were seen. ARR varied between 0 and 7.1?%. Details regarding type of surgery and adjuvant treatment were lacking in the majority of studies.

Conclusions

ARR appears to be low in SLNB-positive patients even when a cALND is not performed. Withholding cALND may be safe in breast cancer selected patients such as those with isolated tumor cells or micrometastatic disease.     

Renal distribution of collagen type IV α chains in autosomal-dominant Alport syndrome

Background Autosomal-dominant Alport syndrome is a recognized, but relatively uncommon, form of Alport syndrome. Recently, mutations in theCOL4A3 andCOL4A4 genes, which encode collagen type IV α3 and α4 chains, respectively, have been shown to cause the disease. However, the distribution of α(IV) chains has yet to be determined. Methods To clarify the renal distribution of α(IV) chains, immunohistochemistry of α1(IV) to α6(IV) chains was performed, using chain-specific monoclonal antibodies, raised by us, and an antigen retrieval procedure. Paraffin-embedded renal sections, obtained from 8 patients from 3 families with the disease, were examined. Results The distribution of all 6 α(IV) chains was not significantly different between the 8 patients and the controls. Collagen type IV α1 and α2 chains were ubiquitously expressed, while α3 to α6 chains were detected in the basement membranes of the glomerulus and Bowman's capsule, and/or part of the tubular basement membranes. Conclusions Our findings contrast with those of X-linked and autosomal-recessive Alport syndrome. The distribution pattern of α(IV) chains may provide a useful means of distinguishing the different forms of Alport syndrome.     

Liver Recurrence of a Subcutaneous Temporal Hemangiopericytoma: The Index Case

Introduction  Hemangiopericytoma is an uncommon soft tissue vascular neoplasm. Intraperitoneal hemangiopericytomas such as primary or secondary liver location have been exceptionally described. Its natural history is mostly benign, but recurrences may occur and determining if these late-discovered tumors are distant metastases or synchronous slow and silent-growing locations is sometimes challenging. The histopathological diagnosis and definition of hemangiopericytoma is based on its distinction with solitary fibrous tumors. Liver resection to treat liver hemangiopericytoma seems to be supported by various published experiences. Case presentation  We herein report the first case of liver metastases from a subcutaneous temporal hemangiopericytoma. The patient was treated by a liver resection. CD34 Immunostaining was negative, but strong expression of Bcl2 and CD99 was found in the neoplastic cells. After 1 year of follow-up, the patient is alive without recurrence. Conclusion  To date, published data, including the case herein reported, support the need for a prolonged follow-up and the role of liver resection to treat liver metastases of hemangiopericytomas. Complete resection of all gross disease appears to be the most significant prognostic factor.     

Assessment of the potential risk of infection associated with Clostridium difficile from porcine xenografts

Bakri MM, Sutherland AD, Brown DJ, Vesely P, Crossan C, Scobie L. Assessment of the potential risk of infection associated with Clostridium difficile from porcine xenografts.
Xenotransplantation 2009; 16: 472–476. © 2009 John Wiley & Sons A/S. Abstract: There are numerous concerns over the potential for transfer of pathogens between species during clinical xenotransplantation, and although current clinical application is limited, porcine xenografts have been previously used to treat patients with severe burns. Donor animals providing the xenografts are sourced from a healthy commercial herd, however, as pigs are a known source of zoonotic agents, a number of diseases are required to be excluded from pigs used for xenotransplantation purposes. Many studies have indicated the relevance of viral zoonoses, however, little has been done with regard to the potential for transfer of pathogens related to health care associated infections. Clostridium difficile is a major cause of neonatal enteritis in pigs and an important feature of this organism is that pigs can be asymptomatic carriers. This study has examined the incidence of C. difficile PCR ribotypes present in healthy donor pigs to determine if pig faeces, and in particular, contamination of skin with faecal matter, is a potential route for the transfer of C. difficile. Animals were found to have human ribotype 017 present in the faecal matter, however, no C. difficile was isolated from skin samples taken from the same animals. In addition, due to the risk factors associated with C. difficile infection, the antimicrobial susceptibility of the C. difficile isolates has been determined.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

The effects of cryopreservation on human hepatocytes obtained from different sources of liver tissue

Successful cryopreservation of human hepatocytes is important to establish hepatocyte banks for clinical use or in vitro research. The availability of donor tissue from unused liver segments/lobes and non-heart-beating donors (NHBD) has provided newer sources of hepatocytes. The quality of hepatocytes at the time of cryopreservation is important as cells isolated from liver tissue of borderline quality may not withstand the stresses associated with cryopreservation and subsequent thawing. Human hepatocytes were cryopreserved after isolation from mainly donor tissues (n = 40). In vitro assessment of the viability and function of the fresh and thawed cryopreserved hepatocytes was performed. Viability, attachment efficiency, enzyme activity, and albumin production of hepatocytes were all significantly decreased, and LDH leakage significantly increased, on thawing after cryopreservation. The viability of cryopreserved hepatocytes isolated from tissue rejected for orthotopic liver transplantation (36 +/- 15%) was significantly lower than those isolated from tissue where part was used for liver transplantation (47 +/- 14%, p = 0.002), but there were no significant differences in functional parameters. The viability of cryopreserved hepatocytes isolated from NHBD tissue (29 +/- 9%, p = 0.001) and from steatotic donor tissue (35 +/- 11%, p = 0.019) was significantly lower than those isolated from normal donor tissue (49 +/- 14%). There was no difference in functional parameters, except for albumin production of hepatocytes from NHBD tissue (2.9 +/- 1.0 microg/h/mg protein) being significantly lower than those from normal donor tissue (4.8 +/- 2.8 microg/h/mg protein, p = 0.03). The viability and attachment efficiency of cryopreserved hepatocytes isolated from liver tissue from resections for tumors was significantly higher, and the LDH leakage significantly lower, than those isolated from all donor tissue. Hepatocytes isolated from NHBD and steatotic tissue were more vulnerable to the effects of cryopreservation. Further research is required to improve hepatocyte isolation and cryopreservation protocols for different types of liver tissue.     

Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients

Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1^u to RT1^a). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-γ-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1^u determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.     

Permanent acceptance of both cardiac and skin allografts using a mild conditioning regimen for the induction of stable mixed chimerism in mice

Patients who are receiving an organ transplant nowadays are sentenced to the life-long administration of immunosuppressive drugs, which have serious side effects. The reliable induction of donor-specific tolerance therefore remains a major goal in organ transplantation. Previously, we have developed a sublethal, non-myeloablative murine model in which permanent mixed, multilineage chimerism and donor-specific tolerance are established. Our model involves engraftment of fully allogeneic T cell depleted donor bone marrow cells in low dose irradiated and anti-CD3 treated major histocompatibility complex (MHC)-disparate recipient mice. To investigate whether vascularized organ grafts are accepted in our model, we performed heterotopic heart transplantations in our mixed chimeric mice. Chimeric mice permanently accepted hearts from the bone marrow donor (>130 days) and rapidly rejected third party-type allografts (median survival time 9 days). Untreated control recipient mice rejected both donor- and third party-type allografts. In addition, mice that accepted their cardiac grafts, donor-specific acceptance of skin grafts was observed. In conclusion, the establishment of stable mixed chimerism with this low-toxicity regimen resulted in permanent donor-specific acceptance of vascularized organ as well as skin grafts across a full MHC barrier.     

The role of ultrasound and magnetic resonance in local drug delivery

Local drug delivery has recently attracted much attention since it represents a strategy to increase the drug concentration at the target location and decrease systemic toxicity effects. Ultrasound can be used in different ways to trigger regional drug delivery. It can cause the local drug release from a carrier vehicle and the local increase of cell membrane permeability either by a mechanical action or by a temperature increase. Ultrasound contrast agents may enhance these effects by means of cavitation. Ultrasound can be focused deep inside the body into a small region with dimensions on the order of 1 mm. Several types of drug microcarriers have been proposed, from nano- to micrometer sized particles. The objective of real-time imaging of local drug delivery is to assure that the delivery takes place in the target region, that the drug concentration and the resulting physiological reaction are sufficient, and to intervene if necessary. Ultrasound and nuclear imaging techniques play an important role. MRI is rather insensitive but allows precise targeting of (focused) ultrasound, can provide real-time temperature maps, and gives access to a variety of imaging biomarkers that may be used to assess drug action. Examples from recent articles illustrate the potential of the principles of ultrasound-triggered local drug delivery.     

Cardiovascular risk,obesity, and myocardial blood flow in postmenopausal women

Background. This study was designed to determine whether overweight or obese status is independently associated with myocardial flow reserve (MFR), an established predictor of cardiovascular mortality, in a group of postmenopausal women with no previous cardiovascular disease. Postmenopausal women are the largest group of overweight and physically inactive individuals in the United States. Increased body mass index (BMI) is consistently associated with increased cardiovascular mortality in this population. Whether this is because of obesity itself or the accompanying increase in cardiovascular risk factors (CRFs) remains controversial. Methods. We examined the relationship of myocardial blood flow (MBF), coronary vascular resistance, and MFR to BMI in 60 postmenopausal women with no coronary heart disease. Subjects underwent dynamic N-13 ammonia positron emission tomography for the measurement of MBF and MFR. Baseline demographics, CRF, and hemodynamic parameters were recorded for each subject. Datasets were divided into 3 groups according to BMI: normal (18 to 24), overweight (25 to 29), and obese (≥30). Results. The overweight and obese groups showed significantly higher resting MBF and lower MFR than the normal-weight group (both P<.001), even after adjusting for CRF. A further analysis of subjects without any CRF (n=35) showed that the MFR remained significantly lower in the obese compared with normal-weight subjects (P=.05). Levels of known markers of vascular inflammation (high-sensitivity C-reactive protein and homocysteine) and high-density lipoprotein cholesterol levels correlated with declining MFR. Conclusions. These findings provide a mechanistic link between obesity and coronary heart disease in this population. This study was funded by a Veterans Health Administration MERIT Review Award. C.S.D. is on the Speaker’s Bureau at Pfizer, Inc., and has received grant support from Pfizer, Inc., Eli Lilly & Co., and the Veterans Health Administration.