Maurice Willis

Cancer cachexia and anabolic interventions: a case report

BackgroundStandard-of-care (SOC) cancer treatments are primarily aimed at reducing size and progression of a tumor. There is a need for successful supplemental anabolic therapies to combat cancer cachexia in addition to these SOC treatment modalities. Anabolic interventions, including testosterone and amino acid supplements, may be beneficial in reducing and/or reversing muscle wasting in these patient populations.MethodsA 48-year-old Caucasian female with recurrent cervical cancer was scheduled to receive three 21-day cycles of cisplatin and topetecan chemotherapy. She qualified, consented, and enrolled into a blinded interventional pilot study where she received daily whey protein (10xa0g, three times per day with meals) and a weekly injection of testosterone enanthate (100xa0mg intramuscular) before and during the SOC chemotherapy treatment period. Body composition, serum inflammatory markers, mixed muscle protein synthesis and breakdown rates, physical function, fatigue, and quality of life were assessed before and after the intervention period.ResultsBody composition, as assessed by an increase in body weight and lean body mass and reduction in fat mass; physical function; fatigue; and quality of life each improved across the entire intervention period despite general increases in inflammatory markers and no improvements in muscle protein turnover towards the end of the intervention.ConclusionsConcomitant treatment of oral amino acids and testosterone may be a viable therapeutic option for fighting cachexia and improving body composition and quality of life during chemotherapeutic treatment of recurrent cervical cancer. These positive outcomes may be attainable over time despite overall poor inflammatory status.

Isotopic decay of urinary or plasma 3-methylhistidine as a potential biomarker of pathologic skeletal muscle loss

BackgroundSkeletal muscle loss accompanying aging or cancer is associated with reduced physical function and predicts morbidity and mortality. 3-Methylhistidine (3MH) has been proposed as a biomarker of myofibrillar proteolysis, which may contribute to skeletal muscle loss.MethodsWe hypothesized that the terminal portion of the isotope decay curve following an oral dose of isotopically labeled 3MH can be measured non-invasively from timed spot urine samples. We investigated the feasibility of this approach by determining isotope enrichment in spot urine samples and corresponding plasma samples and whether meat intake up to the time of dosing influences the isotope decay.ResultsIsotope decay constants (k) were similar in plasma and urine, regardless of diet. Post hoc comparison of hourly sampling over 10xa0h with three samples distributed over 10 or fewer hours suggests that three distributed samples over 5–6xa0h of plasma or urine sampling yield decay constants similar to those obtained over 10xa0h of hourly sampling.ConclusionThe findings from this study suggest that an index of 3MH production can be obtained from an easily administered test involving oral administration of a stable isotope tracer of 3MH followed by three plasma or urine samples collected over 5–6xa0h the next day.

Microarray, gene sequencing, and reverse transcriptase-polymerase chain reaction analyses of a cryptic PML-RARA translocation

Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid leukemia (AML) specifically characterized by the t(15;17)(q22;q12) translocation. The t(15;17) results in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) genes. Rare cryptic fusions often associated with small genomic insertions can best be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) although conventional chromosomal studies or even fluorescence in situ hybridization (FISH) analyses appear normal. We report here an APL clone with a cryptic PML-RARA fusion that returned negative results by both karyotyping and fluorescence in situ hybridization (FISH), but returned positive results by RT-PCR analysis. A single nucleotide polymorphism (SNP) microarray analysis was used in this case to help resolve the discordance, revealing a 49-kilobase intragenic PML gene duplication. A dual color dual fusion PML-RARA FISH probe set identified a small, extra PML signal in a chromosome other than 15 or 17. Although coinsertion of a RARA sequence could be detected by neither FISH nor array, the RT-PCR positivity is consistent with this fusion ectopic to the natural gene loci. The findings highlight the clinical utility of microarray in cases of cryptic PML-RARA fusion.

Hyalinizing clear cell carcinoma of the tonsil and its treatment

Hyalinizing clear cell carcinoma (HCCC) is a rare neoplasm affecting mainly the minor salivary glands of the oral cavity. We describe an unusual case of HCCC involving the tonsil and its successful management. A 67-year-old Hispanic woman was discovered to have an asymptomatic right tonsillar mass on routine clinic visit that revealed HCCC on biopsy. A right radical tonsillectomy was performed and pathology confirmed HCCC with positive deep surgical margins. She declined the recommended adjuvant radiation therapy. A follow-up CT of the neck with contrast done a year later revealed a suspicious area of enhancement around the prior resection margin with regional cervical lymphadenopathy. Further workup, including biopsy, confirmed local recurrence. She was treated with definitive cisplatin-based chemoradiotherapy, achieving complete response. She remains without recurrence with more than 24 months of follow-up.

Impending Carotid Blowout Syndrome

Introduction Neglected head and neck squamous cell carcinoma is unusual in clinical practice. In this late stage of the disease, vascular complications are often treated emergently. One of the most feared complications is carotid blowout syndrome (CBS), which is defined as rupture of the carotid artery or branches caused by the tumor mass compromising the vascular axis or as a result of chemoradiation therapy. The level of severity is further subdivided into three clinical syndromes: threatened blowout, which refers to a clinically exposed vessel or radiologic evidence of tumor invasion to the vascular structure; impending blowout, when a herald bleed has settled spontaneously; and acute carotid blowout syndrome, with profuse, uncontrollable bleeding. There are no objective reports of optimal management of these lesions and only a few case descriptions with single-modality intervention. We present a case of advanced giant-size head and neck squamous cell carcinoma that was successfully treated with induction docetaxel, fluorouracil, and cisplatin, followed by embolization and concurrent cetuximab with radiation therapy.

A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women: Testosterone therapy ameliorates cancer-related muscle loss

Cancer cachexia negatively impacts cancer‐related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.

Sarcomatoid carcinoma of the oral cavity during pregnancy

Abstract Head and neck cancer in pregnancy is a rare disease and difficult to manage. Few case reports exist in the medical literature. We present the case of a pregnant woman with squamous cell carcinoma of the oral cavity. While initial management in the general population may consist of surgery and, if not possible, concomitant chemotherapy and radiation, these modalities were not an option for this patient given her pregnant state. As an alternative, she was treated through gestation with neoadjuvant chemotherapy. She experienced significant reduction in tumor size and associated symptoms, and fetal growth remained normal and there were no fetal myelosuppresive effects noted at birth. Risks of chemotherapy and radiation in pregnancy are reviewed.