Results of the 2018 Japan Society for Blood Purification in Critical Care survey: current status and outcomes.

Background: The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018. Methods: We analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. Results: BPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality. Conclusion: This large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration : UMIN000027678. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00445-0.

The Japanese Society for Apheresis clinical practice guideline for therapeutic apheresis.

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.

Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials: Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

The Elevation in Preoperative Procalcitonin Is Associated with a Poor Prognosis for Patients Undergoing Resection for Colorectal Cancer.

BACKGROUND: Procalcitonin (PCT) is a well-known marker for bacterial infection; however, the clinical significance of PCT in the long-term prognosis after colorectal cancer (CRC) surgery remains unclear. METHODS: This is a retrospective review of 277 patients that underwent CRC surgery to investigate the relationship between preoperative PCT, clinicopathological condition, cancer-specific overall survival (OS), and relapse-free survival (RFS). RESULTS: Median follow-up interval was 5.0 years in all patients. Thirty-six patients developed recurrence, and 46 patients died due to recurrences or metastases of CRC. Preoperative PCT levels were highest in Stage IV patients. The cancer-specific OS in patients with Stage IV/PCT ≤0.05 ng/mL was significantly higher than those with Stage IV/PCT >0.05 ng/mL (3 years survival; 42.3 vs. 14.3%, p = 0.0413). On multivariate analysis, gender, TNM classification, and PCT were identified as significant risk factors for cancer-specific OS in patients with Stage I-III CRC. The cancer-specific OS rate of these patients with PCT ≥0.08 ng/mL, compared with PCT <0.08 ng/mL, was significantly decreased (5 years survival; 59.1 vs. 92.7%, p < 0.0001). TNM classification was finally identified as an independent risk factor for cancer-specific RFS in these patients by multivariate analysis. CONCLUSION: High preoperative PCT values in CRC patients appeared to be associated with poor OS but not RFS following surgical treatments.

Involvement of TRPV1-containing peripheral sensory efferents in hemodynamic responses in a rat hemorrhagic shock model.

BACKGROUND: Mechanisms underlying hemodynamic disturbance in hemorrhagic shock are not completely understood. Transient receptor potential vanilloid 1-expressing afferents are involved in hemorrhagic shock pathology, and transient receptor potential vanilloid 1 antagonist, capsazepine, acts on the central nervous system to improve mortality in a rat hemorrhagic shock model. In contrast, transient receptor potential vanilloid 1-positive efferents promote vasoactive reactions through the release of neuropeptides, including calcitonin gene-related peptides. This study aimed to investigate whether transient receptor potential vanilloid 1-positive peripheral sensory efferents are involved in hemodynamic responses after hemorrhagic shock. METHODS: Male rats underwent hemorrhagic shock (mean arterial pressure 30 mm Hg for 90 min, followed by resuscitation for 30 min) and received capsazepine (5 µM/kg) 30 min after shock induction. A separate cohort of rats subjected to hemorrhagic shock received hCGRP8-37 (300 µg/kg), a calcitonin gene-related peptide receptor antagonist, at 30, 60, or 90 minutes after shock induction. The 24-hour survival rate, mean arterial pressure, heart rate, arterial blood gas, and plasma calcitonin gene-related peptide levels were measured. Tissue blood flow and oxygenation both in the mesentery and skeletal muscle were also assessed. RESULTS: Capsazepine treatment prevented the hemorrhagic shock-induced increase in plasma calcitonin gene-related peptide levels, and hCGRP8-37 treatment improved the 24-h survival rates after hemorrhagic shock at a time-dependent manner. The hCGRP8-37- or capsazepine-treated rats exhibited tissue oxygenation and metabolic conditions comparable to those in control rats at the end of the experiment. CONCLUSION: Transient receptor potential vanilloid 1 plays a crucial role in hemodynamic responses to hemorrhagic shock, partly via calcitonin gene-related peptide release, involved in its peripheral sensory-efferent functions. The hCGRP8-37 appears to improve peripheral circulatory failure, which may be useful as adjunct treatment after hemorrhagic shock.

Anti-endotoxin Properties of Polymyxin B-immobilized Fibers.

Polymyxin B is an antibiotic that shows strong bactericidal activity against Gram-negative bacteria, by binding to and inactivating endotoxin. Systemic administration of polymyxin B in humans is restricted because of its nephrotoxicity and neurotoxicity, and this compound was therefore considered a strong candidate ligand for the extracorporeal selective adsorption of circulating endotoxin in the blood. Toraymyxin® is a direct hemoperfusion column that uses polymyxin B attached to an insoluble carrier to bind endotoxin in the blood. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock.In this chapter, we will review the development, clinical use, and efficacy of Toraymyxin, examine the structure of the Toraymyxin column, and comment on the current position of Toraymyxin in the treatment of severe sepsis and septic shock. We will also highlight some potential new applications of Toraymyxin for pulmonary diseases.

Effects of wearing supportive underwear versus pelvic floor muscle training or no treatment in women with symptoms of stress urinary incontinence: an assessor-blinded randomized control trial.

INTRODUCTION AND HYPOTHESIS: In our previous single-arm pilot study, we reported that ready-made supportive underwear (shaper) was effective in elevating the bladder neck and reducing urinary incontinence (UI) symptoms. The aim of this study was to determine the effects of wearing a shaper compared with pelvic floor muscle training (PFMT) at home using a training compact disc with music, or no treatment, in an assessor-blinded randomized control trial, on reducing UI symptoms. METHODS: Participants aged 30-59 years with symptoms of stress urinary incontinence were randomly assigned to three groups: the shaper group, PFMT group, and no treatment group. The UI episodes/week and the Japanese version of the International Consultation on Incontinence Questionnaire Short-Form were compared between the baseline and the 6th or 12th week of the intervention period. RESULTS: Eighty-nine women who completed the 12-week intervention period were analyzed. After the 12-week intervention period, the improvement rate in UI symptoms (ratio of the case number in which the UI episodes/week decreased at least 50% from the baseline) was 73.3% (22/30 women) in the shaper group, 74.2% (23/31 women) in the PFMT group, and 25.0% (7/28 women) in the no treatment group. The improvement rate in UI symptoms in the shaper and PFMT groups was significantly higher than that in the no treatment group (both P < 0.001). CONCLUSIONS: Wearing supportive underwear (shaper) was almost as effective as PFMT at home in reducing UI symptoms.

Endotoxin adsorption: Direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX).

Toraymyxin® is a medical device developed to adsorb circulating endotoxins in the blood using direct hemoperfusion therapy for patients with septic shock. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock. Since then, Toraymyxin has been safely used in more than 100,000 cases in emergency and intensive care units in Japan. Toraymyxin is currently available for use in the clinical setting in 14 countries worldwide. In this study, we reviewed and introduced the development, clinical use, and efficacy of Toraymyxin and commented on its anticoagulant use and cartridge clotting issue in the treatment of severe sepsis and septic shock. We also highlighted potential new applications of Toraymyxin for longer duration therapy and pulmonary diseases.

ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan.

Irinotecan is a key drug for patients with advanced and recurrent colorectal carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as there is no useful marker to predict chemosensitivity to the drug. The aim of the present study was to evaluate whether the expression levels of adenosine triphosphate-binding cassette sub-family G (WHITE) member 2 (Junior blood group) (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using the resected primary tumor specimens of 189 patients with colorectal cancer, the association between the immunohistochemical expression of ABCG2 protein and the results of the collagen gel droplet embedded culture drug sensitivity test, performed to evaluate the chemosensitivity to SN-38 (an active metabolite of irinotecan), was investigated. Among the 189 patients, 17 received irinotecan-based chemotherapy, and their responses and progression-free survival (PFS) were analyzed. The tumors of patients with increased ABCG2 expression accounted for 60% of the tumors examined, and were significantly more resistant to SN-38, compared with patients with low ABCG2 expression (P<0.001). In a multivariate logistic regression analysis, increased expression of ABCG2 protein was an independent and significant predictor of resistance to SN-38, increasing the risk of resistance by 12-fold. Increased expression of ABCG2 and a low sensitivity to SN-38 was significantly associated with resistance to irinotecan-based chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with increased expression of ABCG2 was significantly shorter, compared with patients with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased immunohistochemical expression of ABCG2 in primary tumors may be a useful predictive biomarker of resistance to irinotecan-based chemotherapy for patients with recurrent or metastatic colorectal cancer.

Pyomyositis at the surgical site in a patient with chronic myeloid leukemia: a case report and literature review.

BACKGROUND: Pyomyositis is a rare, subacute, deep pyogenic infection of the muscle tissue. This disease has been previously described in patients that were immunocompromised due to a hematological malignancy. CASE PRESENTATION: A 68-year-old man with a history of chronic myeloid leukemia was treated with imatinib. He was diagnosed with ascending colon cancer and underwent curative surgery. His postoperative course was uneventful, and he was healthy at 6 months after surgery, allowing for reinitiation of imatinib therapy. After the reinitiation of therapy, a computed tomography (CT) scan revealed a mass shadow in the right iliopsoas muscle. This lesion was clinically diagnosed as recurrent colon cancer with an abscess, which was resected surgically. A pathological examination uncovered both edema and inflammation. Two months after the second surgery, imatinib therapy was reinitiated; however, he again developed painful swelling and erythema in his right thigh. A CT scan revealed a similar shadow as described previously. He was then diagnosed with pyomyositis; he underwent incisional drainage and was administered linezolid. Following the treatment for pyomyositis, there was no cancer recurrence or evidence of any recurrent pyomyositis. CONCLUSIONS: Findings from this case suggest that both undergoing surgery and receiving imatinib therapy may modulate an individual's immune response, whereby the surgical site becomes more prone to infection and may predispose an individual to pyomyositis. The case report is followed by a discussion of the literature regarding this disease, including potential risk factors and the underlying pathogenesis.

[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].

PURPOSE: We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS: We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS: We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).

Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). CASE PRESENTATION: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. CONCLUSION: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

A complete response to mFOLFOX6 and panitumumab chemotherapy in advanced stage rectal adenocarcinoma: a case report.

BACKGROUND: Pathological complete remission of advanced stage rectal adenocarcinoma by chemotherapy alone is rare. A case of advanced stage, low-lying rectal adenocarcinoma in which a complete response to treatment was obtained with mFOLFOX6 and panitumumab (Pmab) is reported. CASE PRESENTATION: A 53-year-old man was referred to Shiga University of Medical Science hospital Shiga, Japan, complaining of bloody stool. Gastrointestinal endoscopy was performed, and advanced stage rectal adenocarcinoma was diagnosed. Computed tomography (CT) revealed regional lymph node metastases in the mesorectum. Neoadjuvant chemotherapy (NAC) with mFOLFOX6 and Pmab was planned.Endoscopy following four courses of chemotherapy revealed that the rectal cancer had been markedly reduced, and the results of biopsies of the rectal tumor were negative for cancer. On CT, the mesorectal lymph node metastases had disappeared. Total intersphincteric resection (ISR) with a handsewn coloanal anastomosis was performed. Histological examination showed a complete response to mFOLFOX6 and Pmab in advanced stage rectal cancer. CONCLUSION: The result seen in this case suggests that short-term NAC with mFOLFOX6 and Pmab was effective for low-lying rectal adenocarcinoma.

Single-Arm Pilot Study to Determine the Effectiveness of the Support Power of Underwear in Elevating the Bladder Neck and Reducing Symptoms of Stress Urinary Incontinence in Women.

OBJECTIVES: To verify the effectiveness of support power of underwear (the shaper) to elevate bladder neck and to reduce symptoms of stress urinary incontinence (SUI). METHODS: This was a single-arm pilot study conducted in Japan by using the shaper (SLIM-up-Pants with Style Science, Wacoal Corporation, Kyoto, Japan). The bladder neck position in a sitting posture was recorded using an open-configuration magnetic resonance system and then compared between parous women with SUI, without and with the shaper. Women wore the shaper during the daytime for 12 weeks, followed by one week during which they did not wear the shaper. The symptoms of urinary incontinence (UI) were assessed based on the 1-h pad test, the Japanese version of the International Consultation Incontinence Questionnaire-Short Form, and the incontinence diary. RESULTS: Forty-five Japanese women with SUI, aged between 27 and 65 years, were included. When the shaper was worn, the bladder neck was found to be significantly elevated by 11.5 mm (median; P < 0.05/6 = 0.008). After 12 weeks, all symptoms of UI decreased significantly (P < 0.05/3 = 0.016), and the bladder neck was further elevated by 4.7 mm (median; P < 0.001) even when not wearing the shaper. In addition, after one week of not wearing the shaper, the bladder neck position remained elevated and symptoms of UI did not recur immediately. CONCLUSION: The shaper was considered to be effective in elevating the bladder neck and reducing symptoms of UI.

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report.

In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was approved in Japan for clinical use against chemotherapy-refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC cases were administered immunohistochemistry with cetuximab as salvage monotherapy. The safety, side-effects and clinical efficacy of the treatment, including response rate, time to treatment failure, progression-free and overall survival, K-ras mutation status and impact on outcome, were investigated. The patient tumor growth control rate (TCR) was 38%, the mean time to progression (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2-12.4] and the mean overall survival (OS) was 49.4 weeks (95% CI, 30.1-68.8). The most common adverse reactions reported were skin reactions, including acne (67%), hand-foot syndrome (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the present single-center study demonstrated that cetuximab monotherapy is beneficial for the treatment of chemotherapy-refractory patients with mCRC and that it has an acceptable level of safety and manageable side-effects.

Differences in chemosensitivity between primary and metastatic tumors in colorectal cancer.

PURPOSE: We retrospectively evaluated the in vitro chemosensitivity of primary site and metastatic site tumors in colorectal cancer. METHODS: Various resected tumor samples (33 from lymph nodes, 42 from liver, six from lung, and 68 primary tumors) were assessed via a collagen gel droplet-embedded culture drug sensitivity test to determine chemosensitivity to a single agent or a combination of agents. RESULTS: Sensitivity to combination chemotherapy was significantly higher than that of monotherapy in the primary site group, lymph node group, and liver group. There was significant difference between chemosensitivity of primary site and that of liver metastasis in each agent (5-FU, p<0.001; SN38, p = 0.045; 5-FU/SN38, p<0.001; OHP, p = 0.037; 5-FU/OHP, p = 0.045). CONCLUSIONS: Tumors showed greater in vitro chemosensitivity to combination therapy when compared with monotherapy. Further, tumors that had metastasized to the liver were more resistant to chemotherapy when compared with matched primary tumors.

Clinical potential of the anticancer drug sensitivity test for patients with synchronous stage IV colorectal cancer.

PURPOSE: We retrospectively evaluated the clinical efficacy and feasibility of a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to guide therapy for patients with stage IV colorectal cancer (CRC). METHODS: We investigated 38 patients with stage IV CRC. All patients were younger than 85 years and had untreated evaluable metastatic lesions. The primary tumors were surgically resected, and the tissue samples were investigated by CD-DST. Patients treated with in vitro sensitive drugs were defined as Group A (n = 14), while those treated with in vitro non-sensitive drugs were defined as Group B (n = 24). We evaluated response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: RR was 85.71 % in Group A and 41.67 % in Group B (p = 0.0079). The median PFS was 696.5 days in Group A and 297.5 days in Group B (p = 0.0326). The median OS was 1,023.4 days in Group A and 518.5 days in Group B (p = 0.0061). CONCLUSIONS: The CD-DST can define chemoresistant and chemosensitive tumors. The use of CD-DST might be one of the tools to supplement informed consent prior to initiation of therapy.