Refractory Lactic Acidosis and Hypoglycemia in a Patient With Metastatic Esophageal Cancer Due to the Warburg Effect.

The Warburg effect describes a phenomenon in which tumor cells switch their metabolic machinery towards a glycolytic state even in the presence of normal oxygen concentration, resulting in excess lactate production. Lactic acidosis due to the Warburg effect in malignancy is a rare but potentially life-threatening emergency mainly described in hematological malignancies but can occur in non-hematological solid malignancies. To our knowledge, we present the first reported case of lactic acidosis due to the Warburg effect in metastatic esophageal cancer. A 44-year-old male was found to have an esophageal mass and likely hepatic metastases during his hospitalization for altered mental status due to severe hypercalcemia. He was re-admitted two days after discharge for persistent vomiting and an inability to tolerate an oral diet. The lab revealed elevated lactate levels (5.2 mmol/L), metabolic acidosis (pH 7.23), and hypoglycemia (48 mg/dL), all of which were persistent throughout hospitalization despite treatment with intravenous (IV) infusions of dextrose in sodium bicarbonate, IV boluses of dextrose, and IV thiamine. An esophagogastroduodenoscopy with a biopsy of the esophageal mass revealed squamous cell carcinoma of the esophagus. Given the presence of stage IV disease and poor functional status, the patient opted for in-patient hospice, where he passed away. Since prompt diagnosis and initiation of chemotherapy, if possible, are the only effective interventions for this potentially fatal complication, it is important to increase awareness of this underrecognized metabolic and oncologic emergency among physicians.

Impact of P16 Positivity on Clinical Outcomes in Nasopharyngeal Carcinoma: A Single Institution Study.

Introduction Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique geographical distribution. It is prevalent in East and Southeast Asia and rare in non-endemic countries like the USA. P16 is a tumor suppressor gene and there are limited studies with inconsistent results describing the association of its positivity in immunohistochemistry and clinical outcomes. In this retrospective study, we compared progression-free survival (PFS) and overall survival (OS) based on p16 positivity in 60 patients with NPC. Materials and methods Patients aged above 18 years and followed between July 2015 and December 2020 were included in the study. P16 positivity was based on the immunohistochemistry of the biopsy sample. We compared PFS and OS among all p16-positive and negative patients, and then among patients with advanced disease (stage III or IV), and between p16-positive, negative, and unknown status patients. Results There were 15 p16-positive, and 28 p16-negative, with a median age of 54.3 years and 55.7 years respectively. Most patients in both groups were male, Caucasian, and had advanced disease (stage III or stage IV). Both median PFS (p=0.838) and OS (p=0.776) were 84 months in the p16-negative group but were not reached during the study period in the p16-positive group. Among advanced-stage patients, the PFS (p=0.873), and OS (p=0.773) of both groups were not statistically significant. P16 status was unknown for 17 patients, and PFS (p=0.785) and OS (p=0.901), when compared among patients with p16-positive, negative, and unknown status, were also statistically non-significant. Discussion and conclusion Our analysis suggests that p16 status does not predict clinical outcomes in NPC patients. Our sample size was limited but is larger than most studies describing this association. With different studies in the literature reporting disparate findings, we recommend larger prospective studies to better illustrate the impact of p16 positivity on clinical outcomes in NPC.

Development of Merkel Cell Carcinoma in a Patient Receiving Rituximab.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and aggressive dermatological neoplasm. It is commonly reported in Caucasian ethnicities, and almost 50% of the patients have a concomitant malignancy and are on immunosuppressive chemotherapy. Here, we present a 79-year-old woman with a history of relapsed Stage II, grade III follicular lymphoma, receiving maintenance rituximab infusions. She presented with a raised erythematous papule on her left cheek. An excisional biopsy of the lesion confirmed a diagnosis of Merkel cell carcinoma. After which, she underwent a wider excision with 1-2 cm margins. PET scan did not reveal any FDG-avid uptake lesions that would be concerning for metastatic disease. However, she underwent a sentinel lymph node biopsy which was also negative. Thus, the diagnosis was finalized as Stage I (T1 N0 M0) MCC. There are only two reported cases in literature about the significant progression of Merkel cell carcinoma in patients who coincidentally were receiving rituximab as a part of treatment for another disease. This raises questions for future investigation and research on whether there is a direct association between rituximab use specifically and the rapid growth of MCC.

Use of circulating tumour DNA in nasopharyngeal carcinoma to detect minimal residual disease.

Circulating tumour DNA (ctDNA) is defined as short DNA sequences shed by tumour cells into the systemic circulation. A promising use of ctDNA includes the detection of minimal residual disease (MRD) and is currently being studied in multiple types of solid tumours. Literature for the use of individualised ctDNA in nasopharyngeal carcinoma (NPC) is not available, although circulating Epstein-Barr virus DNA level is validated as a prognostic factor. We present a man in his 40s diagnosed with stage IV NPC who was started on chemotherapy with cis-platinum and gemcitabine. Serial monitoring of ctDNA completed to aid in detecting MRD after treatment demonstrated initial up-trending values correlating with subsequent imaging findings showing progression. Reinitiation of a different chemotherapy regimen significantly improved the ctDNA level, with corresponding imaging exhibiting a similar response. This case provides insight into the potential use of ctDNA in NPC and the benefit of serial ctDNA monitoring during treatment.