Case Report: Kampo Medicine for Non-tuberculous Mycobacterium Pulmonary Disease.

Background: While the number of pulmonary tuberculosis cases has decreased, increase in non-tuberculous mycobacterium pulmonary disease (NTM-PD) is a global problem. Guideline-based therapy for NTM-PD sometimes causes complications that prevent treatment completion, and there are many cases of relapse even if the treatment can be completed. In addition to antibacterial treatment, care of host risk factors, such as aging, lean physique and immunosuppressive state, is also very important for the management of NTM-PD. In Japan, Kampo medicine, a traditional Japanese herbal formulation, used alone or in combination with standard multidrug therapy for NTM-PD, has been found to be effective for such cases. Case Presentation: A 77-year-old lean woman had been diagnosed with Mycobacterium intracellulare pulmonary infection 6 years earlier, and had received the standard multidrug treatment 5 years later at a former hospital due to worsening of her symptoms of cough, breathlessness and hemoptysis. However, the treatment was discontinued within a year due to the development of adverse events. She refused the guideline-based antibacterial treatment, and asked for Kampo medicine instead. Bukuryoshigyakuto was subsequently prescribed, which led to cough and sputum, especially hemosputum, being well controlled. With 3 years of Kampo medicine treatment, she gained weight and her hemosputum disappeared. High-resolution computed tomography images showed improvement in her lung condition, and her sputum smear culture was negative for acid-fast bacillus. Conclusion: Various kinds of Kampo medicines have been used empirically for NTM-PD in Japan. A literature review from 1992 to 2020 showed that hozais, in particular, seem to be key drugs for the treatment of host NTM-PD risk factors. Kampo medicines can contribute to comprehensive treatment for NTM-PD management that does not rely solely on antibacterial drugs.

Multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine: A case report.

FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab is the preferred first-line treatment for right-sided metastatic colorectal cancer with RAS mutation. However, severe adverse events are common in Japanese patients. We report the successful management of multiple stage IV colorectal cancers in a patient who received multidisciplinary treatment, including chemotherapy and Japanese Kampo medicine. A 68-year-old man presented with epigastralgia and appetite loss and was diagnosed with multiple stage IV colorectal cancers. Colonoscopy identified type II tumors in the ascending colon, sigmoid colon, and upper rectum. Histopathological examination of a biopsy specimen revealed well- to moderately differentiated tubular adenocarcinoma. Enhanced computed tomography of the thorax and abdomen showed multiple pulmonary nodules and para-aortic lymph node swelling. Laparoscopic loop-ileostomy was performed to avoid bowel obstruction due to severe stenosis of ascending colon cancer. Intraoperative observation revealed two white nodules suggestive of metastasis in the lateral area of the liver. Therefore, we diagnosed multiple stage IV colorectal cancers with multiple metastases (lung, liver, and distant lymph nodes). His postoperative course was uneventful, and chemotherapy was started. Since the cancer cells harbored a RAS mutation, he received FOLFOXIRI plus bevacizumab. Japanese Kampo medicine consisting of Hangeshashinto and Juzen-taiho-to, to prevent diarrhea and fatigue, was administered daily. After 12 courses of chemotherapy, though circumferential stenosis still existed in the ascending colon, the tumors in the sigmoid colon and upper rectum were unclear. Enhanced computed tomography showed shrinkage of the pulmonary nodules and para-aortic lymph node; therefore, laparoscopic-assisted ileocecal resection was performed. The postoperative histopathological examination revealed moderately differentiated adenocarcinoma. The patient recovered uneventfully, and Kampo medicine consisting of Ninjin'yoeito was administered for postoperative weakness. Administration of adjuvant chemotherapy in this patient led to a near complete response that has been maintained without recurrence for 2 years and 8 months without reduced quality of life.

Phytotherapy for Cachexia: Where Do We Stand?

BACKGROUND: In contrast to Western medicine which currently offers no approved pharmacotherapy options for cachexia, in Japan multi-component extracts of medicinal plants are used with coverage by the national health insurance. This so called "Kampo" medicine is an example of the modern concept of multi-component/multi-target therapy. For the three traditional preparations Hochuekkito (), Juzentaihoto (), and Rikkunshito (), a multitude of clinical research data relating to cachexia has been published. These preparations are also referred to as "Hozai" (). A similar concept is found in Russian herbal medicine, where the term "Adaptogen" was coined for pharmacologically active substances which enhance adaptive stress repose. METHODS: Scientific literature-including original Japanese articles-was reviewed regarding the effects of these herbal preparations on cachexia. Cachexia is a complex set of symptoms including muscle atrophy with loss of weight, fatigue, and weakness. RESULTS: In a 1985 study by Kuroda et al., Hochuekkito showed efficacy in involuntary weight loss and fatigue in 63% of 162 patients with genitourinary cancer. For cancer-related fatigue, a significant improvement was reported within 2 weeks by Jeong et al. in 2010. In patients with chronic fatigue syndrome, Hochuekkito showed an overall improvement with 8-12 weeks of therapy in a 1997 study by Kuratsune et al. In a 2005 randomized placebo-controlled trial by Satoh et al. on 13 geriatric Q1 patients in a 16-week treatment protocol, Hochuekkito showed significant improvement of general health, physical functioning and the Profile of Mood States (POMS). In 71 geriatric COPD patients in a 2009 placebo-controlled randomized study, Tatsumi et al. found a significant body weight increase and a CRP, TNF-α, IL-6 decrease over 6 months of therapy. For Juzentaihoto in 48 hepatocellular carcinoma patients, Tsuchiya et al. 2008 documented a significantly longer recurrence-free survival (49 vs. 24 months) as compared to the control group (p=0.023). For the much simpler Rikkunshito prescription, a 2011 retrospective study by Fujitsuka et al. on 39 Stage III/IV pancreatic cancer patients treated with Gemcitabine (n=33) or Gemcitabine/Rikkunshito (n=6) showed a significantly prolonged median survival with 224 vs. 378.5 days (p < 0.05). In a 2011 open-label clinical study by Utumi et al. on geriatric cachexia in 6 dementia patients, treatment with Rikkunshito for 4 weeks resulted in a significant body weight increase. In all the above studies, the standardized dosage of 3x2.5 g/d extract granules for most Japanese health insurance-covered Kampo extract-preparations was applied. CONCLUSION: As there is currently no accepted pharmacotherapy option for cachexia available in the West, a transfer of these East Asian gold standard prescriptions into the European market would be desirable. We were further able to demonstrate that the mTOR, interleucin, and melatonin pathways are modified by herbal compounds which thus counteract cachexia. More research in this field is urgently needed in order to provide new, effective treatments for cachexia patients.

Investigation of 375 Patients Who Were Admitted to the Emergency Department in the Acute Ward and Were Administered Kampo Medicine to Improve Early Symptoms / 日本東洋医学雑誌

We examined 375 patients who were administered Kampo medicine for emergency hospitalization in the acute period ward for 6 years and to improve early illness and symptoms. There were many significant uses of hozai. Of the top 5 types of Kampo medicine administered, 4 were hochuekkito, ninjinyoeito, rikkunshito, and daikenchuto. In the case of emergency hospital admission, it was considered that there were many uses of hozai for poor oral intake, walking disorder, and low level of consciousness, among others. Next, there were many risuizai uses.

The translational aspect of complementary and alternative medicine for cancer with particular emphasis on Kampo.

Complementary and alternative medicine (CAM) including Japanese Kampo is known to have anticancer potential. An increasing number of cancer survivors are using CAM for disease prevention, immune system enhancement, and symptom control. Although there have been abundant previous clinical reports regarding CAM, scientific investigations aimed at acquiring quantifiable results in clinical trials, as well as basic research regarding CAM, have only recently been undertaken. Recent studies suggest that CAM enhancement of immune function is related to cytokines. This review provides a translational aspect of CAM, particularly Hozai in Kampo from both scientific and clinical points of view for further development of CAM for cancer treatment.

The Efficacy of Kampo Medicine as a Prophylactic Way to Influenza Virus Type A Infection in an Epidemic Season of 2004/05 / 日本東洋医学雑誌

We retrospectively investigated the prevalence of influenza virus type A infection and the efficacy of Kampo medicine as a prophylactic for handicapped residents at our social welfare institution, during the 2004/5 flu season. Upon studying a nationwide surveillance report for said season, we supposed that it had been difficult to prevent mass infection at our welfare institution with the usual preventive methods, because type B had prevailed for most of the season, and because of the differing type A (AH 3) antigenicity which prevailed late-season, for which there were no type A vaccines.43 of 90 (47.8%) residents given flu vaccinations twice, and 25 of 110 (22.7%) of staff members given flu vaccinations once contracted type A influenza between March and May of 2005. Interestingly, residents who had been administered Hozai for either short-term health problems or chronic disease, demonstrated a low influenza prevalence, there being a statistically significant difference (p<0.05) between our “Hozai” and “non-Hozai” groups. Furthermore Juzentaihoto, known to enhance immune function, seemed beneficial because of its low associated morbidity rate, and only 2 of 8 residents administered it contracted flu. No difference was observed, however, between generalized “Kampo treatment” and “non-Kampo treatment” groups.We consider that certain Kampo medicines may be useful for the prevention of influenza infection, in institutionalized handicapped residents with short-term health problems. Immunological enhancements, and the influence of Hozai are discussed here.

Two Cases of Severe Burn with MRSA Infections Successfully Treated with Juzentaihoto / 日本東洋医学雑誌

Systemic infection by MRSA (Methicillin-resistant Staphylococcus aureus) is a risk in immunodeficient patients such as those with severe burn injuries. Hozai, formulations with tonic effects, may enhance the immune system and we treated two severe burn patients with MRSA infections using Juzentaihoto, which is a remedy for kikyo (deficiency of vital energy) and kekkyo (ketsu deficiency). Both patients suffered flame burns [85% body surface area (BSA) and 40% BSA] and inhalation injuries committing self-immolation. They contracted MRSA in due course and antibiotics such as Arbekacin or Teicoplanin did not control MRSA. Therefore, Juzentaihoto was administered through a nasogastric tube and both of them were finally cured without complications. Juzentaihoto may be useful against fatigue, anemia, malaise, ulcer, and purulent wounds due to severe burns.

Antibacterial Effect of the Kampo Herbal Medicine, Hochu-ekki-to on Methicillin-Resistant Staphylococcus aureus Positive Mice / 日本東洋医学雑誌

A decline in the immunopotential of the host plays an essential role in the occurrence of infections with methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) or other multi-drug resistant microorganisms. In the present study, mytomycin C (MMC)-treated mice with or without the infection of MRSA were used to examine the bacteriostatic action as well as the immunopotentiating action of the promising herbal medicine, Hochu-ekki-to (HET). Basic experimental data showed the drug to be effective in the treatment of MRSA infection. Eight to ten week old male C57BL mice were injected with MMC at a dosage of 5mg/kg/day to inhibit the bone marrow, thus creating a mouse model with reduced immunopotential. A powder extract of HET was administered orally at a dosage of 500mg/kg/day for seven consecutive days. For the infection of MRSA 1×10⁹ cell were injected intraperitoneally. Peritoneal macrophages were prepared by the adherence technique. Macrophage migration, phagocytic activity, and the bactericidal activity were examined by the Boyden chamber method, by the phagocytosis for fluorescent-activated latex beads, and by the nitroblue tetra zolium (NBT) reduction test, respectively.<br>After the administration of HET, the number of white blood cells in the MMC-treated mice recovered to 80% of the normal value. In addition, the phagocytic activity of macrophages increased to 50%, although that of the non-treated group was only 20%. The bactericidal activity also recovered to a level close to the normal value. The ratio of neutrophils in the HET administered MMC-treated group increased to 2.2% (normal mice, 2.6%) whereas that of the MMC-treated control group was 0.5%. Concerning the function of the immunological cells, IL-1beta and IFNgamma levels were recovered by treatment with HET, as observed by IL-1beta, IL-2 and IFNgamma monitoring. The bacterial count in the liver of the MRSA challenged mice, with or without HET administration peaked 6 hours after the challenge. The number of the group with HET administration was, however, much greater than that of the group without HET administration. The bacteria count in the blood showed an increase 12 and 24 hours after the challenge. Even 24 hours after the challenge, a significant number of bacterial cells existed in the blood of the group without HET administration, whereas only a small number of cells were detected 6 hours after the challenge. All of the control mice died 8 days after the MRSA challenge, whereas the survival rates were 60% for HET treatment, 40% for the vancomycin treatment, and 80% for the HET plus vancomycin treatment, respectively.<br>As we move towards a society with a high percentage of elderly people, the authors believe Chinese herbal medicine, which activates the immunopotential, will be very helpful in the treatment of opportunistic infections that are common among elderly patients.