Metabolic management of microenvironment acidity in glioblastoma.

Glioblastoma (GBM), similar to most cancers, is dependent on fermentation metabolism for the synthesis of biomass and energy (ATP) regardless of the cellular or genetic heterogeneity seen within the tumor. The transition from respiration to fermentation arises from the documented defects in the number, the structure, and the function of mitochondria and mitochondrial-associated membranes in GBM tissue. Glucose and glutamine are the major fermentable fuels that drive GBM growth. The major waste products of GBM cell fermentation (lactic acid, glutamic acid, and succinic acid) will acidify the microenvironment and are largely responsible for drug resistance, enhanced invasion, immunosuppression, and metastasis. Besides surgical debulking, therapies used for GBM management (radiation, chemotherapy, and steroids) enhance microenvironment acidification and, although often providing a time-limited disease control, will thus favor tumor recurrence and complications. The simultaneous restriction of glucose and glutamine, while elevating non-fermentable, anti-inflammatory ketone bodies, can help restore the pH balance of the microenvironment while, at the same time, providing a non-toxic therapeutic strategy for killing most of the neoplastic cells.

Management of Glioblastoma Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up.

Few advances have been made in overall survival for glioblastoma multiforme (GBM) in more than 40 years. Here, we report the case of a 38-year-old man who presented with chronic headache, nausea, and vomiting accompanied by left partial motor seizures and upper left limb weakness. Enhanced brain magnetic resonance imaging revealed a solid cystic lesion in the right partial space suggesting GBM. Serum testing revealed vitamin D deficiency and elevated levels of insulin and triglycerides. Prior to subtotal tumor resection and standard of care (SOC), the patient conducted a 72-h water-only fast. Following the fast, the patient initiated a vitamin/mineral-supplemented ketogenic diet (KD) for 21 days that delivered 900 kcal/day. In addition to radiotherapy, temozolomide chemotherapy, and the KD (increased to 1,500 kcal/day at day 22), the patient received metformin (1,000 mg/day), methylfolate (1,000 mg/day), chloroquine phosphate (150 mg/day), epigallocatechin gallate (400 mg/day), and hyperbaric oxygen therapy (HBOT) (60 min/session, 5 sessions/week at 2.5 ATA). The patient also received levetiracetam (1,500 mg/day). No steroid medication was given at any time. Post-surgical histology confirmed the diagnosis of GBM. Reduced invasion of tumor cells and thick-walled hyalinized blood vessels were also seen suggesting a therapeutic benefit of pre-surgical metabolic therapy. After 9 months treatment with the modified SOC and complimentary ketogenic metabolic therapy (KMT), the patient's body weight was reduced by about 19%. Seizures and left limb weakness resolved. Biomarkers showed reduced blood glucose and elevated levels of urinary ketones with evidence of reduced metabolic activity (choline/N-acetylaspartate ratio) and normalized levels of insulin, triglycerides, and vitamin D. This is the first report of confirmed GBM treated with a modified SOC together with KMT and HBOT, and other targeted metabolic therapies. As rapid regression of GBM is rare following subtotal resection and SOC alone, it is possible that the response observed in this case resulted in part from the modified SOC and other novel treatments. Additional studies are needed to validate the efficacy of KMT administered with alternative approaches that selectively increase oxidative stress in tumor cells while restricting their access to glucose and glutamine. The patient remains in excellent health (Karnofsky Score, 100%) with continued evidence of significant tumor regression.

A prospective randomised controlled study comparing bipolar plasma vaporisation of the prostate to monopolar transurethral resection of the prostate.

OBJECTIVES: To compare the safety and efficacy of bipolar transurethral plasma vaporisation (B-TUVP) as an alternative to the 'gold standard' monopolar transurethral resection of the prostate (M-TURP) for the treatment of benign prostatic hyperplasia (BPH) in a prospective randomised controlled study. PATIENTS AND METHODS: In all, 82 patients indicated for prostatectomy were assigned to two groups, group I (40 patients) underwent B-TUVP and group II (42 patients) underwent M-TURP. The safety of both techniques was evaluated by reporting perioperative changes in serum Na+, serum K+, haematocrit (packed cell volume), and any perioperative complications. For the efficacy assessment, patients were evaluated subjectively by comparing the improvement in International Prostate Symptom Score and objectively by measuring the maximum urinary flow rate (Qmax) and post-void residual urine volume (PVR) before and after the procedures. RESULTS: In group II, there was a significant perioperative drop in serum Na+ (from 137.5 to 129.4 mmol/L) and haematocrit (from 42.9% to 38.2%) (both P < 0.001). Moreover, one patient in group II had TUR syndrome. The remote postoperative complication rate was (15%) in group I and comprised of stress urinary incontinence (5%), bladder outlet obstruction (5%), and residual adenoma (5%). In group II, the remote postoperative complication rate was (4.8%), as two patients developed urethral stricture. There were statistically significant improvements in micturition variables postoperatively in both arms, but the magnitude of improvement was statistically more significant in group II. CONCLUSION: B-TUPV seems to be safer than M-TURP; however, the lack of a tissue specimen and the relatively high retreatment rate are major disadvantages of the B-TUVP technique. Moreover, M-TURP appears to be more effective than B-TUPV and its safety can be improved by careful case selection and adequate haemostasis.

Beyond prone position in percutaneous nephrolithotomy: a comprehensive review.

CONTEXT: Percutaneous nephrolithotomy (PNL) is traditionally performed with the patient in the prone position. OBJECTIVE: To assess the efficacy and safety of the prone and supine positions, particularly in obese patients and in those with staghorn calculi. EVIDENCE ACQUISITION: A Medline search was conducted for articles published during the last 10 yr related to PNL in the prone and supine positions. EVIDENCE SYNTHESIS: This search revealed 9 published studies for supine and 25 for prone PNL. None of the supine PNL studies reported visceral injuries, while transfusion rates were 0.0-9.4% and stone-free rates were 69.6-95.0%. One study of supine PNL evaluated a significant proportion of obese patients. Prone PNL studies in obese patients report transfusion rates of 3.2-8.8% and stone-free rates of 79.0-89.2%. In the only randomized study, excluding obese patients and staghorn calculi, operative time favors the supine position. A nonrandomized comparative study demonstrated similar complication rates with insignificant improvement in treatment success for supine PNL; however, when comparing series with similar proportions of staghorn calculi cases, there are slightly improved outcomes for prone PNL. Moreover, comparison of weighted means favors prone PNL. CONCLUSIONS: For obese patients and staghorn calculi, prone PNL appears to be associated with decreased operative times with similar bleeding rates and slightly better stone-free rates than supine PNL.