Various interactions between biological, psychological, and social factors should be considered for the prevention of cancer. Endometrial cancer, which is a common gynecological cancer worldwide, ranks 6th among all cancers in women when the incidence has been ageadjusted [1]. The rate of incidence of endometrial cancer was 6.5 (per 100,000 women) in 2015, which is a four- to five-fold increase over the past 3 decades [2]. A large variation among the incidence rates internationally has been reported and the incidence rate in Japan is lower than that in Western countries; however, the incidence of endometrial cancer has increased 1.5-fold among the Japanese migrants in the United States and three- to four-fold among the Japanese Americans born in the United States when compared that of Japanese women living in Japan [3]. These findings suggest that a health-related lifestyle is related to the risk of endometrial cancer and epidemiological studies have investigated the dietary effects on endometrial cancer [4]. Thus, we have investigated the food intake frequency for the patients and healthy volunteers by using a frequency questionnaire. Results of a case-control study showed that the consumption of green tea and coffee were negatively associated with the risk of endometrial endometrioid adenocarcinoma (EEA) [5]. Furthermore, our study suggested that a higher intake of vegetables, peanuts, fish, and boiled eggs was associated with a reduced risk of EEA. A higher intake of instant noodles, instant food items, and deep-fried foods was associated with an increased risk of EAA when compared that of Japanese women who have a lower intake [6]. These findings suggest that foods containing polyphenols with antioxidant properties, omega-3 fatty acids [7], and vitamin D [8] could play a role in prevention, while instant foods that are high in rich fatty acids could increase the risk of EEA. Also, it is reported that Japanese foods are rich in these nutrients [9,10]. Thus, the intake of traditional Japanese foods, which is characterized by the relatively high amounts of fish and vegetables when compared to that of the Western diet, might be appropriate for the prevention of EEA in Japanese women.
The other characteristics of Japanese medicine in gynecological cancers are supportive cancer treatments and care. Surgery, radiotherapy, and chemotherapy along with anticancer drugs are the standard treatments for cancer. In addition, physicians can use Western-style medicine and traditional Japanese herbal (Kampo) medicine to manage patients in Japan. One hundred-forty-eight Kampo medicines were permitted into the health insurance system in Japan. Kampo medicine includes multi crude drugs; therefore each Kampo medication has effects on more than one system including the central nervous system, autonomic nervous system, immune system, absorption-metabolism, inflammation, circulation, as well as harmonization of the whole body. Multidisciplinary treatment can achieve the effects of holistic medicine through the integration of Western medicine and Kampo. The investigation showed that one-fourth of Japanese gynecological cancer patients take Kampo medicine [11]. A national survey showed that over 90% of physicians in the cancer treatment hospitals have prescribed Kampo medicine; over 70% of those physicians use Kampo medicine for patients with cancer [12].
There were some reports in which Kampo medicine was used to control cancer-related symptoms. Daikenchuto (see STORK [13,14]) can improve abdominal pain and ileus that occurs after abdominal surgery. It supports movement and microcirculation of the bowel by promoting the secretion of motilin [15-19], substance P [18-21], calcitonin gene-related peptide [19-21], and adrenomedullin [22-25], as well as by activating the transient receptor potential vanilloid [26,27]. Rikkunshito (see STORK [13,14]) can reduce nausea and vomiting and alleviate the loss of appetite during chemotherapy by antagonizing the 5-HT3, 5-HT2B, and 5-HT2C receptors, resulting in the prevention of the cisplatin-induced decrease in ghrelin levels and the restoration of food intake [28,29]. Taxanes and platinum analogs are used for chemotherapy in gynecological cancer treatment and these agents can cause chemotherapy-induced peripheral neuropathy. Goshajinkigan (see STORK [13,14]) reduces the symptoms of chemotherapy-induced peripheral neuropathy and improves the quality of life during the treatment of cancer. Several mechanisms have been suggested by which goshajinkigan may alleviate peripheral neuropathy; it improves numbness/pallesthesia via the opioid system with the release of dynorphin and it improves the circulation and the blood supply to the nerves by promoting the production of nitric oxide [30,31]. Another report shows that goshajinkigan reduced the transmitter proteins and sensory receptors associated with C-fiber activation [32]; this effect may be a mechanism for the prevention of oxaliplatin-induced neuropathy. The oral administration or topical application of hangeshashinto (see STORK [13,14]) can improve stomatitis, a complication of chemotherapy, by directly inhibiting PGE2 production [33]. Several reports suggest that some ingredients of hangeshashinto inhibit PGE2 production and/or COX-2 expression [34,35]. Fatigue and malaise frequently occurs during palliative care stage. Hochuekkito (see STORK [13,14]), juzentaihoto (see STORK [13,14]), and ninjin’yoeito (see STORK [13,14]) supports vitality and harmony between the body and mind. Kampo medicine was used for the treatment of cancer-related numbness, constipation, anorexia, muscle cramps, and fatigue [36].
The knowledge of integrative medicine with Western and traditional medicines have been applied for the treatment and prevention of gynecological cancer in Japan. Further cohort or controlled studies will promote its use for disease control and support of the patient’s quality of life.
Competing Interests
Shin Takayama, Takehiro Numata, Minoru Ohsawa, and Tadashi Ishii, belong the Department of Kampo and Integrative medicine, Tohoku University School of Medicine. The department received a grant from Tsumura, a Japanese manufacturer of Kampo medicine; however, the grant was used as per Tohoku University rules. This potential conflict of interests was addressed by the Tohoku University Benefit Reciprocity Committee and was managed appropriately.