Early Tumor Shrinkage and Depth of Response as Predictors of Survival for Advanced Biliary Tract Cancer: An Exploratory Analysis of JCOG1113.

BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.

A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106.

OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.

Is Low Volume Drainage of Ascites Associated With Improved Survival in Digestive System Cancer Patients With Malignant Ascites?-A Retrospective Cohort Study.

Objectives: To determine whether the volume of paracentesis for malignant ascites in acute care hospital wards is associated with survival and symptom relief. Methods: Patients with malignant ascites caused by digestive system cancer who underwent paracentesis between January 2010 and April 2022 were retrospectively analyzed from medical records. Collected data included the drainage volume per paracentesis procedure, survival time from the first paracentesis procedure, symptoms, and adverse events. According to the volume per paracentesis procedure, we divided the patients into the "small-drainage" (≤1500 mL) and "standard-drainage" (>1500 mL) groups. Results: The median age of the 144 patients was 69 years, 33% were female, and 64% had gastrointestinal cancer. The median survival from the first paracentesis procedure was 36 days. Eighty-nine (61.8%) and 55 (38.2%) patients were allocated to the small-drainage and standard-drainage groups, respectively. The median number of paracentesis procedures in the small-drainage and standard-drainage groups was 12 and 7, respectively (P=.001). The median survival in the small-drainage and standard-drainage groups was 50 and 44 days, respectively (P=.76). The multivariate analysis showed that the amount of drainage per session was not significantly associated with survival. Symptoms improved similarly in the 2 groups. No serious adverse events were observed. Conclusions: Paracentesis was demonstrated to be effective and safe, irrespective of the amount of fluid drained, for patients with malignant ascites in an acute care hospital. Thus, a strategy of limiting the amount of drainage is not associated with longer survival.

A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

BACKGROUND: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety. METHODS: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary. RESULTS: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037). CONCLUSIONS: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.

Single-incision laparoscopic enucleation for pancreatic insulinoma with preoperative nasopancreatic stent placement: A case report.

INTRODUCTION AND IMPORTANCE: Most insulinomas are benign and solitary, with a tumor diameter less than 2 cm; therefore, laparoscopic enucleation, which is a minimally invasive procedure that can preserve the pancreatic parenchyma, is considered an optimal procedure. The key to enucleation is to avoid injury to the main pancreatic duct (MPD). Herein, we present a case in which single-incision laparoscopic enucleation (SILE) was performed for insulinomas, with preoperative nasopancreatic stent (NPS) placement. CASE PRESENTATION: A male patient in his fifties underwent SILE for insulinomas. To prevent injury to the MPD, an NPS was preoperatively placed. All surgical procedures were performed through a single mini-laparotomy site in the umbilicus. NPS placement facilitated identification of the MPD under laparoscopic ultrasonography. Enucleation was successfully completed without any injury to the MPD, and the NPS was removed immediately after confirming that there was no injury to the MPD by the NPS via pancreatography. The postoperative course was uneventful. CLINICAL DISCUSSION: This report serves to highlight the maximum safety and minimal invasiveness of SILE with the preoperative NPS placement. Preoperative NPS placement is useful for avoiding injury to the MPD during enucleation and has the merit of helping to recognize whether leakage occurs by intraoperative pancreatography via the NPS. CONCLUSION: Preoperative NPS placement helps to ensure the safe enucleation of pancreatic insulinomas even in single-incision laparoscopic surgery, with minimal invasiveness and better cosmetic outcomes.

JPN clinical practice guidelines 2021 with easy-to-understand explanations for the management of acute pancreatitis.

BACKGROUND: In preparing the Japanese (JPN) guidelines for the management of acute pancreatitis 2021, the committee focused the issues raised by the results of nationwide epidemiological survey in 2016 in Japan. METHOD: In addition to a systematic search using the previous JPN guidelines, papers published from January 2014 to September 2019 were searched for the contents to be covered by the guidelines based on the concept of GRADE system. RESULTS: Thirty-six clinical questions (CQ) were prepared in 15 subject areas. Based on the facts that patients diagnosed with severe disease by both Japanese prognostic factor score and contrast-enhanced computed tomography (CT) grade had a high fatality rate and that little prognosis improvement after 2 weeks of disease onset was not obtained, we emphasized the importance of Pancreatitis Bundles, which were shown to be effective in improving prognosis, and the CQ sections for local pancreatic complications had been expanded to ensure adoption of a step-up approach. Furthermore, on the facts that enteral nutrition for severe acute pancreatitis was not started early within 48 h of admission and that unnecessary prophylactic antibiotics was used in almost all cases, we emphasized early enteral nutrition in small amounts even if gastric feeding is used and no prophylactic antibiotics are administered in mild pancreatitis. CONCLUSION: All the members of the committee have put a lot of effort into preparing the extensively revised guidelines in the hope that more people will have a common understanding and that better medical care will be spread.

Tumor-to-tumor metastasis: an extremely rare combination with renal cell carcinoma as the donor and a pancreatic neuroendocrine tumor as the recipient.

BACKGROUND: Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another tumor. Herein, we report an extremely rare case of a renal cell carcinoma metastasis into a pancreatic neuroendocrine tumor exhibiting a tumor-to-tumor metastasis. Ours is the third reported case worldwide. CASE PRESENTATION: The patient, a 72-year-old male, was referred to our hospital for further examination and treatment due to high levels of prostate-specific antigen. A left renal tumor and pancreatic head tumor were revealed incidentally on screening computed tomography. There were suspected to be a renal cell carcinoma and primary pancreatic neuroendocrine tumor or pancreatic metastasis from the renal cell carcinoma according to preoperative examination. The left nephrectomy and subtotal stomach-preserving pancreaticoduodenectomy were performed because of the pancreatic tumor indicated for operation in either case of diagnosis. Postoperative pathological examination showed a diagnosis of clear cell renal cell carcinoma for the left renal tumor. The pancreatic tumor was diagnosed with clear cell renal cell carcinoma metastasis into the pancreatic neuroendocrine tumor, that is to say tumor-to-tumor metastasis. CONCLUSION: In some cases, conservative approach is selected for pancreatic neuroendocrine tumor patients who meet some requirements. However, if such patients exhibit tumor-to-tumor metastasis which combines with renal cell carcinoma and pancreatic neuroendocrine tumor as this case, conservative approach leads to progression of renal cell carcinoma. Therefore, conceiving the possibility of tumor-to-tumor metastasis, it is necessary to carefully choose a treatment plan for pancreatic neuroendocrine tumor patients associated with renal cell carcinoma, not easily choosing conservative approach.

National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan.

BACKGROUND: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Modified Socratic Method (planned and executed by Takada) for medical education: Grade II Acute Cholecystitis of Tokyo Guidelines 2018 as an example case.

BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.

IL-17A-Mediated Immune-Inflammatory Periarticular Mass and Osteolysis From Impingement in Ceramic-On-Ceramic Total Hip Arthroplasty.

We present a rare case of symptomatic adverse local tissue reaction in a 54-year-old female patient who had undergone total hip arthroplasty with ceramic-on-ceramic bearing. Inflammatory periarticular mass and osteolysis developed in the absence of cobalt chrome alloy interfaces and a modular neck component. On the pathologic images, there was no clear evidence of gross metal staining of tissues, metal corrosion, and ceramic or metal wear particles. However, there were impingement scars on the titanium alloy femoral neck and acetabular cup associated with a high combined anteversion angle of 75° (stem: 40° and cup: 35°), suggesting titanium debris release in vivo. Immunohistochemical staining proved a predominant infiltration of CD4+ T cells and the corresponding IL-17A response to metal. We conclude that neck-rim impingement may lead to the development of adverse local tissue reaction (periarticular mass and osteolysis) due to a metal hypersensitivity with the production of proinflammatory cytokines (IL-17A) by CD4+ T cells even in ceramic-on-ceramic total hip arthroplasty.

A case with massive hemobilia long-term after internal drainage surgery for congenital biliary dilation.

BACKGROUND: Currently, there is an unwavering consensus that the standard surgery for congenital biliary dilation (CBD) is extrahepatic bile duct resection and choledochojejunostomy. However, decades prior, choledochocyst-gastrointestinal anastomosis without extrahepatic bile duct resection (internal drainage surgery, IDS) was preferred for CBD because of its simplicity. Currently, there is almost no chance of a surgeon encountering a patient who has undergone old-fashioned IDS, which has been completely obsolete due to the risk of carcinogenesis from the remaining bile duct. Moreover, the pathological condition long after IDS is unclear. Herein, we report a case of life-threatening bile duct bleeding as well as carcinoma of the bile duct 62 years after IDS in a patient with CBD. CASE PRESENTATION: An 82-year-old Japanese woman with hemorrhagic shock due to gastrointestinal bleeding was transferred to our hospital. She had a medical history of unspecified surgery for CBD at the age of 20. Based on imaging findings and an understanding of the historical transition of the surgical procedure for CBD, the cause of gastrointestinal bleeding was determined to be rupture of the pseudoaneurysm of the dilated bile duct that remained after IDS. Hemostasis was successfully performed by transcatheter arterial embolization (TAE) in an emergency setting. Then, elective surgery for extrahepatic bile duct resection and choledochojejunostomy was performed to prevent rebleeding. Pathological examination revealed severely and chronically inflamed mucosa of the bile duct. Additionally, cholangiocarcinoma (Tis, N0, M0, pStage 0) was incidentally revealed. CONCLUSION: It has been indicated that not only carcinogenesis, but also a risk of life-threatening bleeding exists due to long-lasting chronic inflammation to the remnant bile duct after IDS for CBD. Additionally, both knowledge of which CBD operation was performed, and an accurate clinical history are important for the diagnosis of hemobilia.

Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113.

JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504-0.937) in the low CCr group. Although the total number of incidences of all Grade 3-4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. METHODS: In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. CONCLUSIONS: This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Large Diaphragm Defect Reconstruction Using Reverse Latissimus Dorsi Muscle Flap.

Surgical treatment of bronchobiliary fistula (BBF) is difficult. A 47-year-old woman presented with a cough with yellow yielding sputum due to BBF. The patient had the adhesion of the liver, diaphragm, and lung. We performed liver, diaphragm, and lung resections. Patient had a large defect of diaphragm. Diaphragm reconstruction was performed using a pedicled reverse latissimus dorsi muscle flap. No flap necrosis was observed. Seven months after surgery, the patient did not present yellow yielding sputum and the BBF was not observed in the computed tomography. This surgical procedure was useful for treating the diaphragm defect both safely and easily. We believe that the reverse pedicled latissimus dorsi muscle flap is a reliable alternative for large diaphragm reconstruction after severe BBF.

Do Polyethylene Supra-Macroparticles Lead to Pseudotumor Formation in Metal-on-Polyethylene Total Hip Arthroplasty?

We describe 2 cases of pseudotumors induced by an unusual size of polyethylene wear particle after metal-on-polyethylene total hip arthroplasty (MoP THA). The supra-macroparticles of size >100 µm originated from a polyethylene liner with relatively small cup anteversion, potentially leading to excessive loading and increased wear of the anterior edge of the polyethylene liner. Histopathology showed a foreign-body reaction to the polyethylene particles without an adverse reaction to metal debris and with no severe signs of corrosion at the head-neck junction, which have been noted in past reports of pseudotumors in MoP THA. It has been suggested that the large polyethylene wear particles might be the cause of pseudotumor formation in MoP THA.

Does artificial aging correctly predict the long-term in-vivo degradation behavior in zirconia hip prostheses?

BACKGROUND: Accelerated hydrothermal aging has long been one of the most widely accepted quality control tests for simulating low-temperature degradation (LTD) in zirconia-containing implants used in total hip arthroplasty (THA). However, it is still unclear how much consistency there is between the experimental prediction from the internationally-standardized tests and the actual measurements from surgically-removed implants after a long period of implantation. This question is fundamentally related to a lack of understanding of mechanical/tribological contribution to the in-vivo LTD kinetics. OBJECTIVE: The main purpose of this study is to validate the clinical relevance of standardized accelerated aging by comparing artificially-aged and in-vivo used prostheses, and to clarify the long-term effects of in-vivo mechanics/tribology on the LTD progression upon service in the body environment. METHODS: Surface magnitudes of phase transformation and residual stress in zirconia femoral head retrievals (13.1-18.4 yrs) were evaluated by using confocal Raman microspectroscopy. RESULTS: The long-term aging behavior in unworn head surface was in agreement with the experimental prediction estimated as 1 h aging at 134 °C = 4 years in-vivo. However, the current aging protocols based on ASTM and ISO criteria were not accurately predictive for the worn surfaces, and the tribologically-induced phase transformation and tensile stress were up to 6.5-times and 3.3-times higher than the environmentally-induced ones. CONCLUSION: Our study suggests that wear/scratching, frictional heating, tribochemical reactions, and metal transfer may become far more intense triggers to phase transformation than the mere exposure to body fluid.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer.

The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.