Four Cases of Acute Kidney Injury Requiring Dialysis in Ultramarathoners.

Transient acute kidney injury (AKI) following ultraendurance footraces is a common biochemical diagnosis. However, severe AKI requiring renal replacement therapy is uncommon in ultramarathoners. We report 4 runners (3 men; mean age, 44 ± 3 y) who required prolonged (10-42 d) dialysis following the Western States 100 Mile Endurance Run over a 3-y span (0.38% of starters). The maximum ambient temperatures on the race day ranged from 36.6° to 38.3°C. The runners presented to local hospitals 17 to 32 h after running, with laboratories confirming rhabdomyolysis, hyponatremia (mean serum sodium concentration, 127±2 mmol⋅L-1), and AKI (mean serum creatinine concentration, 8.5±2 mg⋅dL-1). The case-cluster report highlights the potential synergistic effects of high ambient temperatures, muscle damage, and electrolyte imbalance on protracted renal dysfunction in ultramarathoners competing in a warming world.

Adjuvant Radiation Does Not Affect Locoregional Control Following Resection of Melanoma Satellitosis or In-Transit Disease.

BACKGROUND: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). MATERIALS AND METHODS: Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. RESULTS: 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group (P = 0.805). Median LR-DFS was 5.8 years in the RT group and 9.5 years in the non-RT group (P = 0.604). On multivariable analysis, having a close or positive margin was the only independent predictor of LR-DFS (HR 3.8 95% CI 1.7-8.7). In-transit disease was associated with improved overall survival when compared to satellitosis (HR 0.260, 95% CI 0.08-0.82). DISCUSSION: The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.

A closer look at the natural history and recurrence patterns of high-grade truncal/extremity leiomyosarcomas: A multi-institutional analysis from the US Sarcoma Collaborative.

BACKGROUND/OBJECTIVE: Natural history and outcomes for truncal/extremity (TE) soft tissue sarcoma (STS) is derived primarily from studies investigating all histiotypes as one homogenous cohort. We aimed to define the recurrence rate (RR), recurrence patterns, and response to radiation of TE leiomyosarcomas (LMS). METHODS: Patients from the US Sarcoma Collaborative database with primary, high-grade TE STS were identified. Patients were grouped into LMS or other histology (non-LMS). Primary endpoints were locoregional recurrence-free survival (LR-RFS), distant-RFS (D-RFS), and disease specific survival (DSS). RESULTS: Of 1215 patients, 93 had LMS and 1122 non-LMS. In LMS patients, median age was 63 and median tumor size was 6 cm. In non-LMS patients, median age was 58 and median tumor size was 8 cm. In LMS patients, overall RR was 42% with 15% LR-RR and 29% D-RR. The 3yr LR-RFS, D-RFS, and DSS were 84%, 65%, and 76%, respectively. When considering high-risk (>5 cm and high-grade, n = 49) LMS patients, the overall RR was 45% with 12% LR-RR and 35% D-RR. 61% received radiation. The 3yr LR-RFS (78vs93%, p = 0.39), D-RFS (53vs63%, p = 0.27), and DSS (67vs91%, p = 0.17) were similar in those who did and did not receive radiation. High-risk, non-LMS patients had a similar overall RR of 42% with 15% LR-RR and 30% D-RR. 60% of non-LMS patients received radiation. There was an improved 3yr LR-RFS (82vs75%, p = 0.030) and DSS (77vs65%,p = 0.007) in non-LMS patients who received radiation. CONCLUSIONS: In our cohort, patients with LMS have a low local recurrence rate (12-15%) and modest distant recurrence rate (29-35%). However, LMS patients had no improvement in local control or long-term outcomes with radiation. The value of radiation in these patients merits further investigation.

Retroperitoneal sarcoma perioperative risk stratification: A United States Sarcoma Collaborative evaluation of the ACS-NSQIP risk calculator.

BACKGROUND: The ACS-NSQIP risk calculator predicts perioperative risk. This study tested the calculator's ability to predict risk for outcomes following retroperitoneal sarcoma (RPS) resection. METHODS: The United States Sarcoma Collaborative database was queried for adults who underwent RPS resection. Estimated risk for outcomes was calculated twice in the risk calculator, once using sarcoma-specific CPT codes and once using codes indicative of most comorbid organ resection (eg nephrectomy). ROC curves were generated, with area under the curve (AUC) and Brier scores reported to assess discrimination and calibration. An AUC < 0.6 was considered ineffective discrimination. A negative ▲ Brier indicated improved performance relative to baseline outcome rates. RESULTS: In total, 482 patients were identified with a 42.3% 90-day complication rate. Discrimination was poor for all outcomes except "all complications" and "renal failure." Baseline outcome rates were better predictors than calculator estimates except for "discharge to nursing or rehab facility" and "renal failure." Replacing sarcoma-specific CPT codes with resection-specific codes did not improve performance. CONCLUSION: The ACS-NSQIP risk calculator poorly predicted outcomes following RPS resection. Changing sarcoma-specific CPT to resection-specific codes did not improve performance. Comorbidities in the calculator may not effectively capture perioperative risk. Future work should evaluate a sarcoma-specific calculator.

Tonsillar Kaposi sarcoma in a renal transplant patient.

Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus-8 (HHV-8) infection. KS is most often seen in individuals with acquired immunodeficiency syndrome but can occur in patients who are on immunosuppressive therapy. While the skin and oral mucosa are the typical sites for KS, lesions of the tonsil are quite rare with only a few reported cases. Here, we present a case of tonsillar KS occurring in a renal transplant patient. He presented with dysphagia, odynophagia, and weight loss. Oral examination revealed tonsillar hypertrophy with purple discoloration. Imaging revealed diffuse enlargement of Waldeyer's ring with enlarged right cervical lymph nodes, worrisome for post-transplant lymphoproliferative disorder. Microscopic examination of the tonsillectomy specimen showed a vascular proliferation positive for HHV-8, consistent with KS. The patient was subsequently treated with immunosuppression reduction and the addition of sirolimus, which resulted in complete resolution of oropharyngeal and cervical lesions.

PLR and NLR Are Poor Predictors of Survival Outcomes in Sarcomas: A New Perspective From the USSC.

BACKGROUND: Elevations in inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), are reportedly associated with decreased overall survival (OS) or recurrence-free survival (RFS) in patients with numerous cancers. A large multicenter sarcoma data set was used to determine if elevated NLR or PLR was associated with worse survival and can guide treatment selection. MATERIALS AND METHODS: A total of 409 patients with a primary retroperitoneal sarcoma (n = 268) or truncal (n = 141) sarcoma from 2000 to 2015 were analyzed using the US Sarcoma Collaboration database. Binary NLR and PLR values were developed using receiver operating characteristic curves. Kaplan-Meier model and Cox proportional hazards model identified predictors of decreased OS and RFS. Point biserial analyses were used to correlate binary and continuous data. RESULTS: Neither elevated NLR nor PLR was predictive of decreased OS or RFS. These findings persisted despite exclusion of comorbid inflammatory conditions. Further, NLR and PLR were not correlated with tumor grade. In multivariate models, decreased RFS was associated with tumor factors (e.g., positive margins, tumor grade, tumor size, necrosis, positive nodes); decreased OS was associated with histologic subtype, male gender, and nodal involvement. CONCLUSIONS: Although several small studies have suggested that elevated NLR and PLR are associated with decreased survival in patients with abdominal or truncal sarcoma, this large multicenter study demonstrates no association with decreased OS, decreased RFS, or tumor grade. Rather, survival outcomes are best predicted using previously established tumoral factors.

A novel, simplified, externally validated staging system for truncal/extremity soft tissue sarcomas: An analysis of the US Sarcoma Collaborative database.

BACKGROUND: The 8th edition AJCC staging system for truncal/extremity soft tissue sarcoma (STS) offers significant changes from the 7th. However the complexity of both limits their clinical utility. METHODS: Patients with truncal/extremity STS undergoing resection from 2000 to 2016 at seven institutions of the US Sarcoma Collaborative were analyzed. The proposed staging system was externally validated using the National Cancer Database (NCDB). RESULTS: Of 1318 patients, mean age was 59 years, and 54% were male. Median tumor size was 9 cm; 72% were high grade. Applying 8th edition staging, there was no differentiation between stages IA/IB ( P = 0.92), and clinically similar outcomes between stages II/IIIA. Receiver operating characteristic (ROC) analysis identified 7.5 cm as the ideal tumor size discriminating 5-year OS for high-grade tumors. Therefore, a simplified staging system defining all low-grade tumors as stage I, high-grade < 7.5 cm as stage II, high-grade > 7.5 cm as stage III, and metastatic disease as stage IV improved stratification (all P < 0.05). The C-statistic was noninferior to the 8th edition. External validation in the NCDB confirmed optimal stratification (all P < 0.01). CONCLUSIONS: Our proposed staging system maintains prognostic significance between stages within a simplified system. For high-grade tumors, a cutoff of 7.5 cm, instead of 5 cm, maintains discrimination for survival and could be a more clinically applicable cutoff for future clinical trials.

Does the number of sentinel lymph nodes removed affect the false negative rate for head and neck melanoma?

BACKGROUND AND OBJECTIVES: Head and neck (HN) cutaneous melanoma is associated with worse disease-free survival compared to non-HN cutaneous melanoma, possibly due to inadequate staging. We aim to determine if a higher yield of sentinel lymph nodes (SLNs) affected rates of sentinel lymph node biopsy (SLNB) positivity. METHODS: Two Cancer Registries were used to identify patients who underwent SLNB for HN melanoma. A false negative (FN) was defined by nodal recurrence after negative SLNB. RESULTS: Out of 333 patients who underwent SLNB, 20% (n = 69) had a positive SLN with a FN rate of 6.3%. Those with three or more SLNs had a higher rate of SLN positivity (23.8% [17.5-29.9% CI] vs 16.4% [10.7-23.6% CI]), a lower FN rate (16.7% [10.2-21.2% CI] vs 35.3% [27.1-42.9% CI]), and higher sensitivity (83.3% [82.59-84.09% CI] vs 65.7% [64.87-66.53% CI]) compared to those with one or two SLNs. Of patients in Group 1 (one or two SLNs) with a positive SLN who underwent completion lymph node dissection (20/23), 47% (33-61% CI) had one or more positive non-sentinel nodes compared to 29% (16-51%) of patients in Group 2 (three or more SLNs) (42/46). CONCLUSION: In HN melanoma cases in which multiple nodes are identified, removal of all SLNs will more adequately stage patients.

Over-expression of the cucumber expansin gene (Cs-EXPA1) in transgenic maize seed for cellulose deconstruction.

Plant cell wall degradation into fermentable sugars by cellulases is one of the greatest barriers to biofuel production. Expansin protein loosens the plant cell wall by opening up the complex of cellulose microfibrils and polysaccharide matrix components thereby increasing its accessibility to cellulases. We over-expressed cucumber expansin in maize kernels to produce enough protein to assess its potential to serve as an industrial enzyme for applications particularly in biomass conversion. We used the globulin-1 embryo-preferred promoter to express the cucumber expansin gene in maize seed. Expansin protein was targeted to one of three sub-cellular locations: the cell wall, the vacuole, or the endoplasmic reticulum (ER). To assess the level of expansin accumulation in seeds of transgenic kernels, a high throughput expansin assay was developed. The highest expressing plants were chosen and enriched crude expansin extract from those plants was tested for synergistic effects with cellulase on several lignocellulosic substrates. Activity of recombinant cucumber expansin from transgenic kernels was confirmed on these pretreated substrates. The best transgenic lines (ER-targeted) can now be used for breeding to increase expansin expression for use in the biomass conversion industry. Results of these experiments show the success of expansin over-expression and accumulation in transgenic maize seed without negative impact on growth and development and confirm its synergistic effect with cellulase on deconstruction of complex cell wall substrates.

Current management and treatment strategies for breast cancer.

PURPOSE OF REVIEW: Breast cancer is the most common malignancy in women in the United States and the second most common cause of cancer death in women. This review will focus on the current and clinically relevant recommendations for breast cancer diagnosis, staging, and treatment. RECENT FINDINGS: Screening for breast cancer is based on patient history, exam, mammography, and ultrasound. In select patient populations, MRI adds additional detection benefit. Once pathology is found, nipple-sparing mastectomy is felt to be an oncologically well tolerated procedure for both ductal carcinoma in situ and invasive tumors in properly selected patients. Prophylactic mastectomy rates are increasing despite no clear survival benefit. Sentinel lymph node biopsy continues to be the staging procedure of choice, but data are available that completion axillary dissection for a positive sentinel node may not affect outcomes. SUMMARY: Strategies for caring for breast cancer patients continue to evolve. Multiple variables including genetic predisposition, disease burden, tumor markers, receptor status, and patient preference are integral to the decision making for each individual patient.