Malignancies seldom lead to hyperlactatemia or lactic acidosis. The elimination of the primary tumor is anticipated to result in the amelioration of lactate levels in such situations. A patient with obstructing descending colon cancer was subjected to surgical intervention as their serum lactate levels reached 3.6 mmol/L. The tumor was removed, and the ischemic bowel proximal to it was excised as well. The patient demonstrated signs of recuperation; however, their serum lactate levels persisted at levels exceeding 6.5 mmol/L. Consequently, the patient was subjected to further investigation and surgical intervention. A CT scan of the brain and abdomen indicated metastases to the liver and brain, respectively. The presence of metastases in colonic malignancies may impede the normalization of hyperlactatemia even after excising the primary tumor. The interpretation of lactate levels can be challenging and radiological assessments, including abdominal reexploration, may be required to ascertain the diagnosis.

The clinical Warburg effect is a rare occurrence in cancer biology where tumor cells primarily utilize glycolysis for energy production, leading to significant hypoglycemia and lactate formation. This presentation is associated with a poor prognosis for the patient. In this context, we describe the case of a 53-year-old woman with stage IV mantle cell lymphoma who developed the clinical Warburg effect with solely arrhythmia and without neurological symptoms. She received prompt treatment for glucose stabilization and underwent inpatient chemotherapy. This case underscores the importance of early intervention to reduce tumor burden and highlights the effectiveness of hemodialysis in stabilizing metabolic acidosis. Further investigation into this approach is warranted.

BACKGROUND: Type B lactic acidosis and hypoglycemia can occur in various pediatric conditions. In young children with a history of fasting preceding these metabolic derangements, inborn errors of metabolism should be primarily considered. However, the Warburg effect, a rare metabolic complication, can also manifest in children with hematologic malignancies. Only a few reports of this condition in children have been published in the literature.
OBJECTIVE: To identify the clinical course, treatment strategies, and outcomes of childhood hematologic malignancies with type B lactic acidosis.
METHODS: We performed a comprehensive search of the PubMed, Scopus, and Cochrane databases without any time restriction but limited to English language articles. The databases were last accessed on July 1st, 2023.
RESULTS: A total of 20 publications were included in the analysis, all of which were case reports or case series. No higher quality evidence was available. Among children with hematologic malignancies and Warburg effect, there were 14 cases of acute lymphoblastic leukemia and 6 cases of non-Hodgkin\'s lymphoma including our illustrative case. Lactic acidosis occurred in 55% of newly diagnosed cases and 45% of relapsed cases. The mean age was 10.3 ± 4.5 years, and 80% of cases were male. The mean serum lactate was 16.9 ± 12.6 mmol/L, and 43.8% of the cases had concomitant hypoglycemia. Lactic acidosis initially subsided in 80% of patients receiving chemotherapy compared to 60% in the contrast group. The mortality rate of newly diagnosed cases was 45.5%, while the relapsed cases represented a 100% mortality rate. All 8 patients reported before 2001 died from disease-related complications. However, patients described in reports published between 2003 and 2023 had a 54.5% rate of complete remission.
CONCLUSIONS: This complication has historically led to fatal outcome; however, patients who received chemotherapy showed a more favorable response. Therefore, it is crucial to promptly initiate specific treatment in this context.

BACKGROUND: The Warburg effect is a rare condition in tumor biology, illustrated by significant lactate production in the presence of oxygen. The Warburg effect is associated with very poor prognosis in patients with malignancy.
METHODS: We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation. Her lactic acidosis was initially controlled with a bicarbonate infusion, and the patient was started promptly on steroids, followed by chemotherapy, but her clinical course was complicated by tumor lysis syndrome, acute renal failure requiring hemodialysis, and progressive liver failure. She manifested a temporary clinical response to chemotherapy but eventually died of complications.
CONCLUSIONS: This case demonstrates the importance of prompt recognition of the Warburg effect, aggressive supportive measures, and early initiation of chemotherapy. Future studies are needed to characterize the role of hemodialysis in this setting.

We report a patient with prostate cancer found 2 years after percutaneous arterial embolization (PAE) of the prostate with a rapid increase in prostate specific antigen (PSA) 3 months later, even though the initial result was low. He did not consult a urologist during or after PAE until acute urinary retention developed. The clinical stage was cT2cN1M1b with Gleason grade 5 + 5 = 10. An increase in PSA a short interval after PAE may suggest the presence of prostate cancer. We suggest that patients undergoing PAE should consult a urologist, and that PSA levels should be checked every 3 months in the first year after PSA.

Lactate is a byproduct of anaerobic glycolysis, and hyperlactatemia is commonly seen in critically ill patients. We report a case of an elderly male presenting with undifferentiated constitutional symptoms, anemia, thrombocytopenia, severe lactic acidosis, refractory hypoglycemia, and a newly detected abdominal mass. A dedicated workup ruled out infectious etiologies and revealed metastatic non-Hodgkin\'s lymphoma. This study explores etiologies of type B lactic acidosis in oncology patients, with a focus on Warburg\'s effect, and its potential for prognostication.

Spontaneous hypoglycemia in nondiabetic patients poses a diagnostic challenge. Hypoglycemia in malignancy has several etiologies; an extremely rare mechanism is the Warburg effect causing excess lactate production and avid glucose consumption. We describe the clinical course of a 52-year-old man admitted for chest wall mass and severe but asymptomatic hypoglycemia. Laboratory workup was obtained for insulin vs noninsulin-mediated hypoglycemia, and biopsy of the chest wall mass and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) scan were performed. D10 infusion and intravenous/oral steroids started for severe hypoglycemia. Chemotherapy was initiated after biopsy, and blood glucose (BG) and lactate levels followed with clinical response in tumor size and changes in PET/CT. Investigations were significant for venous BG in the 40s (Ademolus Classification of Hypoglycemia grade 2 hypoglycemia), plasma insulin of less than 2 µU/mL (2-20 µU/mL), C-peptide of 0.2 ng/mL (0.8-6.0 ng/mL), insulin-like growth factor 2 (IGF-2) of 113 ng/mL (333-967 ng/mL), serum lactate of 16 mmol/L (0.5-2 mmol/L), and albumin of 2.3 g/dL (3.4-5.4 g/dL). Biopsy showed diffuse large B-cell lymphoma, and PET revealed highly FDG-avid disease in the chest, abdomen, and pelvis, but no FDG uptake was seen in the brain. Hypoglycemia and lactic acidosis improved remarkably after chemotherapy. PET/CT at 4 weeks showed complete metabolic response with reappearance of physiological FDG uptake in the brain. Noninsulin-mediated hypoglycemia was likely due to the combination of profound malnutrition and rapid glucose use by cancer cells. The patient presented with exaggerated Warburg effect (hyper-Warburgism), evident by extreme glucose consumption, severe lactic acidosis, and large tumor burden on PET/CT. Absence of cognitive symptoms was probably due to use of lactate by the brain. Chemotherapy corrected these abnormalities rapidly, and must be instituted in a timely manner.

[This corrects the article DOI: 10.3389/fnins.2020.00390.].

Background: Recently, the ketogenic diet has been proposed as an adjunct treatment for a range of medical conditions including weight loss, diabetes, cancer, and neurodegenerative diseases. Because malignant CNS tumors are highly dependent on glucose, the use of a ketogenic diet as an adjunct therapy is currently being explored. This case series summarizes our experience implementing a ketogenic diet for patients with CNS malignancies. Methods: Patients diagnosed with CNS malignancies following a ketogenic diet were identified between 2015 and 2017. Malignancies included confirmed diagnoses of glioblastoma (GBM), astrocytoma, or oligodendroglioma. With guidance from a registered dietitian, ketone levels, glucose levels, and weight were regularly collected for several patients along with patient-reported symptoms and adverse effects. Interested patients were asked to follow a 3:1 ketogenic diet for 120 days. The ketogenic diet is a high-fat, moderate protein, and very low carbohydrate diet, where patients limited carbohydrate intake to ≤20 g per day. Brain imaging was reviewed. A series of descriptive analyses were conducted. Results: The ketogenic diet was initiated in 12 patients of which 8 patients contributed data on their blood glucose and ketone levels. The majority of patients were male (n = 10) with a median age of 45 (range 32-62). Diagnoses included GBM (n = 6), grade 2/3 astrocytomas (n = 5) and one patient with a grade 2 spinal cord astrocytoma. Ten of the 12 patients were receiving concurrent treatment; two received supportive care only. The majority of patients with evaluable data (n = 8) maintained ketone levels above 0.5 mM for the duration of 120-day period. Ketone levels generally increased from baseline while glucose levels and BMI decreased. Overall, patients reported improved symptoms over the course of the diet. Imaging also suggested improved disease control and reduction in vasogenic edema. Conclusion: Taking advantage of a tumor\'s metabolic inflexibility can have a positive impact on patients, particularly those with CNS malignancies. More structured and statistically planned clinical trials are needed to determine the margin of impact of a ketogenic diet.

Alzheimer\'s Disease (AD) is a neurodegenerative progressive disorder for which there is currently no cure. Recent research demonstrates a robust correlation between type-2 diabetes mellitus (T2DM) and the development of MCI and AD, now referred to as type-3 diabetes. Both AD and T2DM, as metabolic pathologies, can be traced to the level of mitochondrial function. The metabolic hypothesis suggests that the cause of AD might be rooted in mitochondrial dysfunction accompanied by fuel shortage in the brain. Although glucose is known to be the deferred source of fuel for cells, ketone bodies have been observed to provide metabolically compromised brain cells with an alternative fuel source, bypassing deficiencies in GLUT transport due to increased insulin resistance. By keeping glucose and insulin levels low to allow for the production of ketones, there is evidence that mitochondrial function will be restored and cognition/memory improved. Further, visible red or near-infrared (NIR) light has been shown to heal and stimulate damaged tissue by interacting with the mitochondria to restore function. This case study evaluates the effects of a 10-week clinically prescribed ketogenic nutrition protocol combined with transcranial photobiomodulation (PBM) with a 59-year-old male, heterozygous ApoE4 carrier, with a dual diagnosis of mild AD and an 11 year history of insulin dependent type 2 diabetes (T2DM). Statistically significant results reflect an 83% reduction in HOMA-IR; 64% decrease in the triglyceride/HDL ratio; HgA1c reduction from 9.44% to 6.4%; 57% decrease in VLDL and triglycerides; and normalized cognition as measured via the MoCA (Montreal Cognitive Assessment), 26/30 post intervention.