Exploring the Potential Use of Natural Products Together with Alkalization in Cancer Therapy.

Cancer treatment is a significant focus in medicine, owing to the increasing global incidence of cancers. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with supplementation with natural products may confer benefits to cancer patients, by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Corrigendum: Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study.

[This corrects the article DOI: 10.3389/fonc.2023.1179049.].

Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study.

Background: In hepatocellular carcinoma (HCC) patients, is difficult to prevent recurrence even when remission is achieved. In addition, even with the advent of drugs that are effective for the treatment of HCC, a satisfactory extension of patient survival has not been achieved. To overcome this situation, we hypothesized that the combination of alkalization therapy with standard treatments will improve the prognosis of HCC. We here report the clinical results of HCC patients treated with alkalization therapy at our clinic. Patients and methods: Patients with HCC treated at Karasuma Wada Clinic (in Kyoto, Japan), from January 1, 2013, to December 31, 2020 were analyzed. Overall survival (OS) from both the time of diagnosis and the start of alkalization therapy for each patient was compared. The mean urine pH was also calculated as a surrogate marker of tumor microenvironment pH, and OS from the start of alkalization therapy was compared between patients with a mean urine pH of ≥ 7.0 and those with a mean urine pH of < 7.0. Results: Twenty-three men and six women were included in the analysis, with a mean age at diagnosis of 64.1 years (range: 37-87 years). Seven of the 29 patients had extrahepatic metastases. Patients were divided into two groups according to their mean urine pH after the initiation of alkalization therapy: 12 of the 29 patients had a mean urine pH of ≥ 7.0, and 17 had a mean urine pH of < 7.0. The median OS from diagnosis was 95.6 months (95% confidence interval [CI] = 24.7-not reached), and from the start of alkalization therapy was 42.3 months (95% CI = 8.93-not reached). The median OS from the start of alkalization therapy in patients with a urine pH of ≥ 7.0 was not reached (n = 12, 95% CI = 3.0-not reached), which was significantly longer than that in patients with a pH of < 7.0 (15.4 months, n = 17, 95% CI = 5.8-not reached, p < 0.05). Conclusions: The addition of alkalization therapy to standard therapies may be associated with more favorable outcomes in HCC patients with increased urine pH after alkalization therapy.

Potential of Alkalization Therapy for the Management of Metastatic Pancreatic Cancer: A Retrospective Study.

Current treatments for patients with pancreatic cancer offer limited benefits. In this study, we applied alkalization therapy, which was efficacious for other solid tumors at our clinic, to stage 4 pancreatic cancer patients, and investigated its effect on disease prognosis. Patients with metastatic pancreatic cancer who were treated at Karasuma Wada Clinic in Kyoto, Japan, between January 2011 and April 2022, were included in the study. All patients received alkalization therapy (a combination of an alkaline diet, bicarbonate, and citric acid administration), alongside standard chemotherapy. Urine samples were collected to assess urine pH as a marker of whole-body alkalization. In the 98 patients analyzed, the median overall survival (OS) from the time of diagnosis was 13.2 months. Patients with a mean urine pH of 7.5 or greater had a median OS of 29.9 months, compared with 15.2 months for those with a mean urine pH of 6.5 to 7.5, and 8.0 months for those with a mean urine pH of less than 6.5, which suggests a trend of a longer OS in patients with a higher urine pH (p = 0.0639). Alkalization therapy may offer a viable approach to extending the survival of stage 4 pancreatic cancer patients, who typically have an unfavorable prognosis.

Clinical review of alkalization therapy in cancer treatment.

One of the most unique characteristics of cancer metabolism is activated aerobic glycolysis, which is called the "Warburg effect", and is a hallmark of cancer. An acidic tumor microenvironment (TME) resulting from activated anaerobic glycolysis is associated with cancer progression, multi-drug resistance, and immune escape. Several in vitro and in vivo studies reported that neutralization of the acidic TME by alkalizing agents, such as bicarbonate, resulted in the suppression of cancer progression and a potential benefit for anti-cancer drug responses. In clinical settings, alkalizing effects were achieved not only by alkalizing agents, but also by a following a particular diet. An epidemiological study demonstrated that more fruits and vegetables and less meat and dairy products are associated with an increase in urine pH, which may reflect the alkalizing effect on the body. However, it remains unclear whether alkaline dietary intervention improves the effects of cancer treatment. Moreover, there are few clinical reports to date regarding cancer treatments being performed on patients together with alkalization therapy. In this review, we investigated whether alkalization therapy, which includes an alkaline diet and/or alkalizing agents, improves cancer treatment.

Electromagnetic navigation bronchoscopy versus virtual bronchoscopy navigation for improving the diagnosis of peripheral lung lesions: analysis of the predictors of successful diagnosis.

PURPOSE: To investigate if electromagnetic navigation bronchoscopy (ENB) improves the diagnostic yield for peripheral lung lesions from that achieved by virtual bronchoscopy navigation (VBN). METHODS: This retrospective study compared the results of 100 ENB-transbronchial lung biopsies (TBLBs) with those of 50 VBN-TBLBs at a single institution. RESULTS: ENB improved the diagnostic yield significantly compared with VBN (64.0% for 19.4 ± 9.0 mm tumors vs. 46.0% for 27.6 ± 8.9 mm tumors; p < 0.0001). Irrespective of the bronchus sign, ENB was more favorable than VBN, with 81.0% (47/58) achieved by ENB vs. 60.0% (21/35) achieved by VBN in the presence of the positive bronchus sign (p = 0.0283), and 40.5% (17/42) achieved by ENB vs. 13.3% (2/15) achieved by VBN in the absence of the bronchus sign (p = 0.0431). Univariate analysis identified tumor size (p = 0.0048), amount of intravenous sedation (p = 0.0182), registration time (p = 0.0111), minimum distance to target (p = 0.0244), and the bronchus sign (p < 0.0001) as factors that affected the yield significantly for ENB. Multivariate analysis identified the bronchus sign (odds ratio 6.74; 95% CI 1.84-24.7) and the registration time (OR 1.01; 95% CI 1.00-1.02) as significant factors. CONCLUSIONS: Despite the bronchus sign being a significant factor, ENB improved the diagnostic yield of smaller lesions significantly, compared with VBN, regardless of the bronchus sign.

Successful Resection of Rapidly Growing Cavitary Infarction After Pulmonary Emboli.

Pulmonary cavitation rarely occurs after pulmonary infarction. Compared with bland infarction, infectious cavitary infarction has a higher mortality rate and requires an aggressive surgical approach to improve the outcome. We herein report a cavitary infarction with Pseudomonas infection that rapidly and destructively grew after the development of bilateral pulmonary emboli despite administration of anticoagulation therapy with antibiotics. The pulmonary infarction was successfully resected by right upper lobectomy.

Refractory pneumothorax and hemothorax associated with metastatic scalp angiosarcoma.

BACKGROUND: Pulmonary metastasis of scalp angiosarcoma (SA) is a rare, but life-threatening disease, challenging to diagnose and manage. We report two cases of pneumothorax and hemothorax with pathologically proven metastasis of SA in the parietal pleura, which was not predictable from images and difficult to manage. PATIENT A: A 73-year-old man with SA underwent chemoradiotherapy and surgical resection for primary skin lesion, was sent to our department to treat right empyema, which was developed during chest tube drainage for pneumothorax. Computed tomography (CT) showed multiple bullous lesions. We performed repetitive video-assisted thoracoscopic surgery (VATS) for the debridement and hemostasis; however, hemothorax was uncontrollable. The repeated cytology of pleural effusion showed no malignancy. We eventually performed fenestration and metastatic SA was pathologically diagnosed by the biopsy of parietal pleura. The patient developed respiratory failure and uncontrolled anemia, which were fatal. PATIENT B: A 71-year-old man with SA previously treated with chemoradiotherapy was referred to our department for left pneumothorax. CT showed multiple bullous lesions at apex without any changes at parietal pleura. VATS was performed and the apex bullous lesion with air leakage was resected. The parietal pleura showed several dark-red spots and the biopsy was undertaken. The pathological diagnosis was a metastasis of SA along with visceral pleura and parietal pleura. The patient then developed right pneumothorax and left hemopneumothorax. Bilateral pleurodesis was ineffective and the patient died due to deteriorating general condition. CONCLUSIONS: In patients with a history of SA who develop pneumothorax and hemothorax, metastatic SA to visceral and parietal pleura should be always considered. Surgical biopsy, not cytology, is needed for pathological diagnosis. Lesions in the parietal pleura prior to hemothorax were thoracoscopically observed in one case. Surgeons must recognize that conventional surgical intervention or pleurodesis will have unsatisfactory results.

Paratracheal Middle Mediastinal Thymic Carcinomas.

We describe case studies of two patients who underwent resection of paratracheal middle mediastinal thymic carcinomas. In both patients, complete resection of these masses via right thoracotomy was performed using three-dimensional computed tomography. Final pathologic diagnoses were thymic squamous cell carcinoma and thymic atypical carcinoid tumor. Challenges and debates in preoperative, intraoperative, and postoperative management are discussed in this article.

Manifestation of congenital pulmonary airway malformation in a 26-year-old adult, requiring surgery.

This is a case of type 1 congenital pulmonary airway malformation in the left lower lobe of a 26-year-old male. At the age of 1 year, he developed a pulmonary cystic lesion, which was considered to be bronchopulmonary sequestration. He grew up healthy and showed no impairment during exercise; however, giant bullous lesion development along with compressed left upper lobe and mediastinum was recently noted; consequently, the patient was referred to our hospital for further examination. We diagnosed congenital pulmonary airway malformation and performed left lower lobectomy. Postoperative course was uneventful, but a restrictive change on pulmonary function test did not improve. This unusual course of congenital pulmonary airway malformation with bullous changes suggests the importance of early-stage resection.

High kurtosis of intracranial electroencephalogram as a marker of ictogenicity in pediatric epilepsy surgery.

OBJECTIVE: We determined whether kurtosis analysis of intracranial electroencephalogram (EEG) can estimate the localization of the epileptogenic zone. METHODS: We analyzed 29 pediatric epilepsy patients who underwent intracranial EEG before focal resective surgery. We localized the brain regions with high kurtosis, the seizure onset zone (SOZ) and the regions with high-rate, high-amplitude and long-duration interictal paroxysms ≥20 Hz. We tested correlations between the surgical resection of those regions and post-surgical seizure outcome, and correlations between kurtosis and the rate/amplitude/duration of interictal paroxysms. RESULTS: The resection of the regions with high kurtosis correlated with 1-year post-surgical seizure outcome (p=0.028) but not with 2-year outcome. Kurtosis showed more significant correlation with 1-year seizure outcome than the SOZ and the rate/amplitude/duration of interictal paroxysms. Kurtosis showed positive, independent correlations with the amplitude and duration of interictal paroxysms (p<0.0001) but not with the rate (p=0.4). CONCLUSIONS: The regions with high kurtosis provide more reliable information to predict seizure outcome than the SOZ and the regions with high-rate/amplitude and long-duration interictal paroxysms. Kurtosis reflects combined effects of the amplitude and duration of the interictal paroxysms. SIGNIFICANCE: High kurtosis suggests the regions with acquired ictogenicity within the irritative zone.