Methods: A retrospective multicenter study was conducted. The study participants included 345 patients who underwent surgery for spinal metastases from 2010 to 2020 at nine referral spine centers in Japan. Data for each patient were extracted from medical records. To identify the factors predicting survival prognosis after surgery, univariate analyses were performed using a Cox proportional hazards model. Results: The mean age was 65.9 years. Common primary tumors were lung (n=72), prostate (n=61), and breast (n=39), and 67.8% (n=234) presented with osteolytic lesions. The epidural spinal cord compression scale score 2 or 3 was recognized in 79.0% (n=271). Frankel grade A paralysis accounted for 1.4% (n=5), and 73.3% (n=253) were categorized as intermediate or high risk according to the new Katagiri score. The overall survival rates were -71.0% at 6 months, 57.4% at 12, and 43.3% at 24. In the univariate analysis, Frankel grade A (hazard ratio [HR], 3.59; 95% confidence interval [CI], 1.23–10.50; p<0.05), intermediate risk (HR, 3.34; 95% CI, 2.10–5.32; p<0.01), and high risk (HR, 7.77; 95% CI, 4.72–12.8; p<0.01) in the new Katagiri score were significantly associated with poor survival. On the contrary, postoperative chemotherapy (HR, 0.23; 95% CI, 0.15–0.36; p<0.01), radiation therapy (HR, 0.43; 95% CI, 0.26–0.70; p<0.01), and both adjuvant therapy (HR, 0.21; 95% CI, 0.14–0.32; p<0.01) were suggested to improve survival. Conclusions Surgical indications for patients with Frankel grade A or intermediate or high risk in the new Katagiri score should be carefully considered because of poor survival. Chemotherapy or radiation therapy should be considered after surgery for better survival.

Methods: We investigated patients who underwent surgical intervention for LL-OVC (L3, L4, and/or L5) with symptomatic foraminal and/or central stenosis from eight spine centers. Only patients with a minimum follow-up duration of 1 year were included. We developed new criteria to grade vertebral collapse severity (grade 1, 0%–25%; grade 2, 25%–50%; grade 3, 50%–75%; and grade 4, 75%–100%). The clinical features and outcomes were compared based on the collapse grade and surgical procedures performed (i.e., decompression alone, posterior lateral fusion [PLF], lateral interbody fusion [LIF], posterior/transforaminal interbody fusion [PLIF/TLIF], or vertebral column resection [VCR]). Results: In this study, 59 patients (average age, 77.4 years) were included. The average follow-up period was 24.6 months. The clinical outcome score (Japanese Orthopaedic Association score) was more favorable in the LIF and PLIF/TLIF groups than in the decompression alone, PLF, and VCR groups. The use of VCR was associated with a high rate of revision surgery (57.1%). No significant difference in clinical outcomes was observed between the collapse grades; however, grade 4 collapse was associated with a high rate of revision surgery (40.0%). Conclusions When treating LL-OVC, appropriate instrumented reconstruction with rigid intervertebral stability is necessary. According to our newly developed criteria, LIF may be a surgical option for any collapse grade. The use of VCR for grade 4 collapse is associated with a high rate of revision.

　　Epidermal growth factor receptor (EGFR) gene mutation examination is now performed in most medical institutions in order to select the molecular targeted medicine for lung cancer. It became clear that the positive rate of the biopsy material was lower than that of the surgical sample in this hospital. The cause was attributed to false negatives due to low tumor cell content in biopsy specimens. We investigated the presence of the mutation using surgical samples and preoperative biopsy specimens from the same patients in 13 cases. Furthermore, we investigated the tumor cell content of the biopsy specimens by cell counting. Results showed that 3 of 6 biopsy specimens that were associated with positive surgical samples were judged to be negative. The tumor cell content was less than 5% in all negative cases. Regarding EGFR gene mutation examination, we should carefully determine tumor cell content when using biopsy specimens.

MHLW released a guideline for Risk Management Plan (RMP) in April 2012, in order to manage the risk of pharmaceutical products from the development stage towards post marketing period. The guideline suggests to determine Safety Specification and to develop Pharmacovigilance Plan (PVP) and Risk Minimization Plan aligned to the ICH E2E guideline. However, in some of the RMPs, which had been published online (as of August 2014), conventional (Special) Drug Use Results Surveys are planned as a “universal” PVP regardless of the impact, severity and characteristics of the risks. Our JPMA taskforce (Data Science Expert Committee) summarized report and published in August 2014. In this report, we explained how to evaluate safety events based on evidence level for safety specification and how to develop PVP. Also, we would like to propose KAIZEN activities for RMP improvement as follows:
1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully.
2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development.
3. Safety profiles should be discussed thoroughly on DSUR development among stakeholders in order to clarify safety specification at NDA. Research questions for each different risk and missing information should be established according to PECO, which will flow into appropriate PVP planning.
4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s).
We expect all stakeholders, including clinical development specialists in industry, regulatory authorities, and academia, to have better understating of RMP principle and to manage and implement it more appropriately in a scientific manner.

Norovirus infection is a common cause of epidemic winter vomiting and diarrhea. The symptoms that present, such as vomiting, diarrhea, fever and abdominal pain, normally disappear within 1 to 3 days, although some fatal cases are reported in the elderly.During the two months from December 1, 2005 to January 31, 2006, we prescribed ogonto to twenty patients who presented with vomiting or diarrhea in a nursing home, and examined prescription times and illness durations, other drugs used, and whether there were any transfusion or complications.The number of ogonto doses given was from 1 to 12. Fifteen cases (75%) were dosed 3 times or less, and four cases were only dosed once. In terms of illness duration: eleven cases were cured in less than 24 hours; six cases were cured from 24 hours to less than 48 hours; two cases were cured from 48 hours to less than 72 hours; and one case was cured from 72 hours to less than 96 hours. Overall, seventeen cases (85%) were cured in less than 48 hours.Regarding the other treatment and complications: domperidone was used in four cases; and a transfusion was given in six cases. Aspiration pneumonia occurred in one case, but no patient required hospital treatment. Norovirus infection is usually treated only with symptomatic therapy, so we think Kampo therapy should be available because when started at an early stage, it can prevent this disease from becoming severe.

We reported two cases successfully treated with sano-to (Senkin-Ho). Case 1 was a 63-year old female, who visited our department in December 2004 complaining of polyarthralgia, a burning sensation in the hands and feet, irritability and chilliness. We prescribed sano-to (Senkin-Ho). The visual analogue scale (VAS) decreased from 100 mm on the first visit to 23 mm 10 months later in October 2005. Case 2 was a 62-year old female, who came to our department complaining of whole body pain in August 2004. Various Kampo medicines were tried but proved ineffective, and in June 2005 she was hospitalized. At that time, in addition to whole body pain, she complained of a burning sensation in her feet, psychological anxiety, and chillness. We prescribed sano-to (Senkin-Ho). After 2 months, her VAS decreased from 80 mm to 20 mm. We consider that sano-to (Senkin-Ho) should be prescribed more actively when patients suffer from painful diseases accompanied with subjective symptoms such as a burning sensation in the hands and feet, psychological symptoms, and chilliness.
Feet, unit of measurement ; Burning sensation ; Chills ; Cases ; symptoms <1>

We present a case of megacolon successfully treated with Kampo medicine. A 65-year-old male diagnosed with megacolon in 1999, came to our department in July 2003 complaining of severe abdominal distention. We successively used different Kampo formulae, in accordance with the diagnostic standard known as “SHO” which were: Daikenchu-to, Koboku-sanmotsu-to, Chukenchu-to, and Koboku-sanmotsu-to again. Daikenchu-to was only partly effective. Koboku-sanmotsu-to made the abdominal distention worse, forcing a change of drug. Chukenchu-to relieved the symptoms for some time, but the patient had to be hospitalized because of pseudoaldosteronism caused by the drug. Koboku-sanmotsu-to, however, worked smoothly on the second occasion and the symptoms disappeared. The efficacy of Koboku-sanmotsu-to was completely different on the two occasions it was used. This suggests that the pathological conditions were in a state of change, and these changes were identical to changes of SHO. This case reinforces the importance of detecting changes of the SHO accurately.

We report three cases of pneumonia successfully treated with Kampo therapy. Case 1 was a 69-year-old female who was hospitalized with a fever and cough. Administration of Keishinieppiitto led to an improvement in her cough and a rapid reduction of fever, and we continued her treatment using Kampo medicine only. By the 7th day of admission, the infiltration shadow had disappeared, and on the 11th day, laboratory data on WBC and CRP had decreased to a normal range. Case 2 was a 66-year-old female who was hospitalized with cough, sputum and fever. She received modern western medical treatment, including antibiotics for one month, but her symptoms showed little improvement. After we administered Saiko-keishi-kankyo-to-go-Hange-koboku-to, her symptoms gradually improved. By the 15 th day of admission, her CRP levels had decreased to 0.7mg/dL, and the infiltrative shadow had disappeared. Case 3 was a 78-year-old male who was hospitalized with cough, sputum, anorexia and general malaise. A multiple nodular lesion in the lung was also detected by chest CT. Consequent diagnostic examinations were conducted, while providing him with Saikokeishito. Although the final diagnosis was pneumonia, of unknown etiology, his fever decreased and on further examination his laboratory data had improved. If a Kampo formula is selected in accordance with the diagnosis of Kampo medicine, we consider that pneumonia can be treated with Kampo medicine without the use of antibiotics.

Ogikeishigomotsuto is a Kampo formula used for numbness or body pains. We experienced 29 cases in which attending physicians believed the drug would be effective. In 18 cases the drug was effective and in 11 cases it was not. We analyzed the difference in subjective symptoms between the responder group and the non-responder group. We concluded that some symptoms could be indicators for choosing the formula. Hypersensitivity to cold and heaviness of the whole body has previously been reported in many articles. In our cases, we observed a high incidence and specificity of the symptoms reported above, as well as arthralgia, dry skin and irritability in the responder group compared to the non-responder group. We believe these newly detected subjective symptoms can also be indicators for choosing Ogikeishigomotsuto.