Survival Outcomes for Metaplastic Breast Cancer Differ by Histologic Subtype

Background

Metaplastic breast carcinoma (MBC) is a rare, aggressive subtype of breast cancer associated with poorer overall survival than other triple-negative breast cancers. This study sought to compare survival outcomes among histologic subtypes of MBC with those of non-metaplastic triple-negative breast cancer.

Methods

Clinicopathologic and treatment data for all patients with non-metastatic, pure MBC undergoing surgery from 1995 to 2017 and for a large cohort of patients with other types of triple-negative breast cancer during that period were collected from an institutional database. The MBC tumors were classified as having squamous, spindle, heterologous mesenchymal, or mixed histology. Survival outcomes were compared using the Kaplan-Meier method.

Results

Of 132 MBC patients, those with heterologous mesenchymal MBC (n?=?45) had the best 5-year overall and breast cancer-specific survival (BCSS, 88%; 95% confidence interval [CI], 0.78–0.99), whereas those with squamous MBC had the worst survival (BCSS, 56%; 95% CI, 0.32–0.79). Overall survival, BCSS, and recurrence-free survival were worse for the patients with MBC than for the patients who had non-MBC triple-negative breast cancer, with a clinicopathologically adjusted recurrence hazard ratio of 2.4 (95% CI, 1.6–3.3; p?<?0.001). Of the 10 MBC patients who received neoadjuvant chemotherapy, 4 progressed while receiving treatment, and 3 had no response.

Conclusions

Metaplastic breast carcinoma is associated with worse survival than other triple-negative breast cancers. The heterologous mesenchymal subtype is associated with the best survival, whereas the squamous subtype is associated with the worst survival. These data call for research to identify therapies tailored to MBC’s unique biology.

     

Outcome of renal transplants from pediatric donors <5 yr of age

AIM: Outcomes of single renal transplants from donors <5 yr old have traditionally been inferior to those from older donors. We retrospectively studied our experience with patients who received renal transplants, either individually or en bloc, from young donors (<5 yr of age) to determine the utility of these organs. We also compared the outcomes of these transplant patients maintained on either cyclosporine- (CyA) or tacrolimus-based (TRL) immunosuppression regimens. PATIENTS: Ninety-eight patients received transplants at our center from donors <5 yr of age between August 1993 and August 2003. They were followed-up from 12 months to 11 yr. Patients were divided into four groups based on whether they received single or en bloc transplants, and whether CyA or TRL was the base immunosuppressive agent. Patients in group I (n = 13) received single pediatric kidneys and were treated with CyA regimens; group II patients (n = 26) also received single pediatric kidneys, but were treated with TRL regimens; group III patients (n = 31) were transplanted en bloc and were treated with CyA; and group IV patients (n = 28) received en bloc transplants and were treated with TRL. RESULTS: One-year patient and death-censored graft survival was not significantly different between recipients of en bloc vs. single grafts (i.e. 88 and 85% vs. 90 and 87%, respectively), or between the four treatment groups (group I: 85 and 85%, group II: 92 and 88%, group III: 87 and 84%, and group IV: 89 and 86%, respectively). The overall 1-yr rejection rate was 30% (29 of 98), which was significantly higher in the CyA-treated patients 19 of 44; i.e. 43%, than in TRL-treated patients 10 of 54, i.e. 19%, p = 0.03). In the en bloc recipients, seven grafts (12%) were lost as a result of vascular thrombosis. Notably, none of the single kidneys were lost because of vascular thrombosis. At the end of follow-up the creatinine levels of both groups were comparable. CONCLUSIONS: Pediatric donor kidneys transplanted individually provide for equal patient and graft survival when compared with en bloc transplants. TRL can be used reduce the detrimental effect of acute rejection on graft growth and function when compared with CyA. Single use of such kidneys can safely and efficaciously be transplanted into adult recipients, greatly expanding the donor pool.     

Ureterosigmoidostomy: Is it a Viable Procedure in the Age of Continent Urinary Diversion and Bladder Substitution?

Between January 1977 and June 1985, 63 patients requiring supravesical diversion underwent ureterosigmoidostomy with an antireflux technique. Of the patients 49 had bladder cancer and 14 had other conditions. Two patients died in the postoperative period. Postoperatively, all patients were instructed to empty the rectum frequently, and received bicarbonate and potassium supplementation.Median followup was 41 months (range 3 to 70). Renal function remained stable in 92 percent of the patients. Radiographic deterioration occurred in 23 percent of the renal units, which was severe in 7 percent. These results indicate that the short and intermediate followup results with ureterosigmoidostomy are comparable to those of an ileal conduit. The method has the added advantage of being a form of continent diversion. We believe that ureterosigmoidostomy remains a viable and convenient alternative in select patients with bladder cancer who are not suitable for other forms of continent diversion or bladder substitution.     

Gonadotropin-releasing hormone agonist inhibits physiologic ovarian follicular loss in rats

To study the effect of long-term use of GnRH agonists on the number and size distribution of ovarian follicles, two experiments were performed on adult female rats. Treatment was continued for 52 days in Experiment 1 and for 229 days in Experiment 2. Every sixteenth section from one ovary of each rat was examined using a light microscope attached to a BioQuant image analysis computer system. In Experiment 3, control and previously treated rats were mated with known male breeders and the number and normalcy of the offspring evaluated. The results indicate that in rats treated with GnRH agonist: 1) the total number of follicles, the number and percentage of follicles less than 35 microns in diameter were significantly higher than in the control group: 2) the number and percentage of follicles greater than 50 microns in diameter were significantly lower than control: and 3) the number of rats that got pregnant and the litter size were not significantly different from control. We conclude that GnRH agonists inhibit the physiologic process of follicle recruitment and loss and that fertility is preserved after long-treatment administration of GnRH agonists.     

Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.

OBJECTIVE: This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.     

Toxoplasma encephalitis in a HIV patient: unusual involvement of the corpus callosum

In patients with acquired immuno-deficiency syndrome, the differential diagnosis between primary brain lymphoma and toxoplasma encephalitis is not radiologically always straightforward, especially in the presence of a solitary cerebral lesion. In this context, involvement of the corpus callosum is almost exclusively associated with primary brain lymphoma. We describe here an HIV-infected patient who presented with a single and large cerebral lesion affecting the corpus callosum, suggestive of primary brain lymphoma on MRI-scan but who nonetheless responded clinically and radiologically to an anti-toxoplasma drug trial confirming the diagnosis of toxoplasma encephalitis.     

Orthogonal extraction/chromatography and UPLC, two powerful new techniques for bioanalytical quantitation of desloratadine and 3-hydroxydesloratadine at 25 pg/mL

Validation of the bioanalytical method for determination of desloratadine and 3-hydroxydesloratadine was conducted using ultra high pressure liquid chromatography (UPLC) in conjunction with mix mode solid phase extraction. The dynamic range of the assay was from 0.025 ng/mL to 10 ng/mL using 96-well solid phase extraction. On an UPLC system, the inter-run accuracy was better than 94.7% for desloratadine (n = 18) and 94.0% for 3-hydroxydesloratadine (n = 18). The between-run precision (%CV) ranged from 2.6% to 9.8% for desloratadine (n = 18) and 3.1% to 11.1% for 3-hydroxydesloratadine (n = 18). The limit of quantitation represented 0.478 pg and 0.525 pg of extracted material injected on-column for desloratadine and 3-hydroxydesloratadine, respectively. The total run time was slightly over 2 min per sample. The approach of orthogonal extraction/chromatography and UPLC significantly improves assay performance while also increasing sample throughput for drug development studies.     

Incisional hernia after liver transplantation

BACKGROUND: Incisional hernia is a potential complication of orthotopic liver transplantation (OLT), with various options for repair. STUDY DESIGN: We conducted a retrospective review of a series of adult patients with incisional hernias after OLT to identify risk factors and to compare methods of repair. RESULTS: Incisional hernia repair was performed in 44 of 959 patients (4.6%) who underwent OLT from 1999 to 2005. Mean age at time of OLT was 53 years, and 73% were men. One or more complications of OLT occurred in 33 patients (75%) and included reoperation for bile leak or hemoperitoneum (34%), pulmonary problems (27%), early acute rejection (7%), and severe ascites and retransplantation (5% each). Incisional hernia was diagnosed at 419 days (range 62 to 1,524 days) and repaired at 471 days (range 109 to 1,581 days) after OLT. Presentation included pain or discomfort (78%) and incarceration or strangulation (5%); 17% were asymptomatic. Herniorrhaphy techniques included fascial repair with onlay polypropylene mesh reinforcement (n=25, 57%); fascial repair only (n=15, 34%); or inlay mesh sewn to fascial edges (n=4, 9%). Complications of repair included recurrence in seven patients (16%) and wound infection and seroma in one patient each. Recurrence occurred in five patients with primary repair and two with mesh techniques (33% versus 6%, p=0.04). CONCLUSIONS: Incisional hernia is a late complication of OLT for which male gender and early post-OLT complications are risk factors. Repair is safe when undertaken after acute problems have resolved and is best accomplished using mesh reinforcement of autologous tissue.