Trends in patterns of treatment and survival of colorectal cancer patients using cancer registry data in Japan: 1995-2015.

Recent advances in treating colorectal cancer (CRC) have increased the importance of multidisciplinary treatment. This study aimed to clarify trends in the treatment and survival of CRC using population-based cancer registry data in Japan. We analyzed the survival of CRC cases diagnosed from 1995 through 2015 from a population-based cancer registry of six prefectures. The year of diagnosis was classified into five periods, and the trends in the detailed categorization of treatments and survival were identified. We calculated net survival and excess hazard of death from cancer using data on 256,590 CRC patients. The use of laparoscopic surgery has been increasing since 2005 and accounts for the largest proportion of treatment types in the most recent period. Net survival of CRC patients diagnosed after 2005 remained high for laparoscopic surgery and endoscopic surgery (endoscopic mucosal resection or endoscopic submucosal dissection). There was an upward trend in treatment with chemotherapy in addition to open and laparoscopic surgery. Using the excess hazard ratio at the regional stage since 2005, there has been a significant improvement in survival in the younger age group and the rectum cancer group. By type of treatment, there was a tendency toward significant improvement in the open surgery + chemotherapy group. We clarified the trends in treating CRC and the associated trends in survival. Continuous survey based on population-based data helps monitor the impact of developments in treatment.

Fibroblast growth factor signalling regulates the development of tooth root.

Fibroblast growth factor (FGF) signalling plays a crucial role in the morphogenesis of multiple tissues including teeth. While the role of the signal has been studied in tooth crown development, little is known about root development. Of several FGF ligands involved in hard tissue formation, we suggest that FGF18 regulates the development of murine tooth roots. We implanted FGF18-soaked heparin beads into the lower first molar tooth buds at postnatal day 6 (P6), followed by transplantation under the kidney capsule. After 3 weeks, FGF18 significantly facilitated root elongation and periodontal tissue formation compared to the control. In situ hybridisation showed that Fgf18 transcripts were initially localised in the dental pulp along Hertwig's epithelial root sheath at P6 and P10 and subsequently in the dental follicle cells at P14. Fgf receptors were expressed in various dental tissues during these stages. In vitro analysis using the dental pulp stem cells revealed that FGF18 inhibited cell proliferation and decreased expression levels of osteogenic markers, Runx2, Alpl and Sp7. Consistently, after 1 week of kidney capsule transplantation, FGF18 application did not induce the expression of Sp7 and Bsp, but upregulated Periostin in the apical region of dental mesenchyme in the grafted molar. These findings suggest that FGF18 facilitates molar root development by regulating the calcification of periodontal tissues.

IRIS U kit usefulness in transanal total mesorectal excision for lower rectal cancer to avoid urethral injury.

Transanal total mesorectal excision (taTME) has improved the laparoscopic dissection for rectal cancer in the narrow pelvis. Although taTME has more clinical benefits than laparoscopic surgery, such as a better view of the distal rectum and direct determination of distal resection margin, an intraoperative urethral injury could occur in excision ta-TME. This study aimed to determine the feasibility and efficacy of the ta-TME with IRIS U kit surgery. This retrospective study enrolled 10 rectal cancer patients who underwent a taTME with an IRIS U kit. The study endpoints were the safety of access (intra- or postoperative morbidity). The detectability of the IRIS U kit catheter was investigated by using a laparoscope-ICG fluorescence camera system. Their mean age was 71.4±6.4 (58-78) years; 80 were men, and 2 were women. The mean operative time was 534.6 ± 94.5 min. The coloanal anastomosis was performed in 80%, and 20% underwent abdominal peritoneal resection. Two patients encountered postoperative complications graded as Clavien-Dindo grade 2. The transanal approach with IRIS U kit assistance is feasible, safe for patients with lower rectal cancer, and may prevent intraoperative urethral injury.

Short-term Outcomes of Laparoscopic and Open Distal Pancreatectomy Using Propensity Score Analysis: A Real-world Retrospective Cohort Study.

OBJECTIVE: This study aimed to compare the short-term outcomes between laparoscopic and open distal pancreatectomy for lesions of the distal pancreas from a real-world database. BACKGROUND: Reports on the benefits of laparoscopic distal pancreatectomy include 2 randomized controlled trials; however, large-scale, real-world data are scarce. METHODS: We analyzed the data of patients undergoing laparoscopic or open distal pancreatectomy for benign or malignant pancreatic tumors from April 2008 to May 2020 from a Japanese nationwide inpatient database. We performed propensity score analyses to compare the inhospital mortality, morbidity, readmission rate, reoperation rate, length of postoperative stay, and medical cost between the 2 groups. RESULTS: From 5502 eligible patients, we created a pseudopopulation of patients undergoing laparoscopic and open distal pancreatectomy using inverse probability of treatment weighting. Laparoscopic distal pancreatectomy was associated with lower inhospital mortality during the period of admission (0.0% vs 0.7%, P <0.001) and within 30 days (0.0% vs 0.2%, P =0.001), incidence of reoperation during the period of admission (0.7% vs 1.7%, P =0.018), postpancreatectomy hemorrhage (0.4% vs 2.0%, P <0.001), ileus (1.1% vs 2.8%, P =0.007), and shorter postoperative length of stay (17 vs 20 d, P <0.001). CONCLUSIONS: The propensity score analysis revealed that laparoscopic distal pancreatectomy was associated with better outcomes than open surgery in terms of inhospital mortality, reoperation rate, postoperative length of stay, and incidence of postoperative complications such as postpancreatectomy hemorrhage and ileus.

The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma.

BACKGROUND: Complex hepatocellular carcinoma (HCC) prognostic biomarkers have been reported in various studies. We aimed to establish biomarkers that could predict prognosis, and formulate a simple classification using non-invasive preoperative blood test data. METHODS: We retrospectively identified 305 patients for a discovery cohort who had undergone HCC-related hepatectomy at four Japanese university hospitals between January 1, 2011 and December 31, 2013. Preoperative blood test parameter optimal cut-off values were determined using receiver operating characteristic curve analysis. Cox uni- and multivariate analyses were used to determine independent prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. Validation was performed with 267 patients from three other hospitals. RESULTS: In multivariate analysis, α-fetoprotein (AFP, p < 0.001), protein induced by vitamin K absence or antagonist-II (PIVKA-II, p = 0.006), and C-reactive protein (CRP, p < 0.001) were independent prognostic factors for overall survival (OS). AFP (p = 0.007), total bilirubin (p = 0.001), and CRP (p = 0.003) were independent recurrent risk factors for recurrence-free survival (RFS). CART analysis results formed OS (CRP, AFP, and albumin) and RFS (PIVKA-II, CRP, and total bilirubin) decision trees, based on machine learning using preoperative serum markers, with three risk classifications. Five-year OS (low risk, 80.0%; moderate risk, 56.3%; high risk, 25.2%; p < 0.001) and RFS (low risk, 43.4%; moderate risk, 30.8%; high risk, 16.6%; p < 0.001) risks differed significantly. These classifications also stratified OS and RFS risk in the validation cohort. CONCLUSION: Three simple risk classifications using preoperative non-invasive prognostic factors could predict prognosis.

Trends in the stage distribution of colorectal cancer during the COVID-19 pandemic in Japan: a nationwide hospital-claims data analysis.

BACKGROUND: The COVID-19 pandemic has affected cancer care. The aim of this study was to clarify the trend of colorectal cancer (CRC) stage distribution in Japan during the COVID-19 pandemic. METHODS: In this retrospective study, we used an inpatient medical claims database established at approximately 400 acute care hospitals. From the database, we searched patients who were identified as having the main disease (using ICD-10codes [C18.0-C20]) between January 2018 and December 2020. A multivariate logistic regression analysis was used to determine the impact of the pandemic on CRC stage distribution each month, and the odds ratio (OR) for late-stage cancer was calculated. RESULTS: We analyzed 99,992 CRC patients. Logistic regression analysis, including the interaction term between increased late-stage CRC effect during the pandemic period and by each individual month, showed that the OR for late-stage CRC was highest in July during the pandemic, at 1.31 (95%CI: 1.13- 1.52) and also significantly higher in September at 1.16 (95%CI: 1.00- 1.35). CONCLUSION: We investigated the trend of CRC stage distribution during the COVID-19 pandemic using a nationwide hospital-claims database in Japan, and found that the proportion of early-stage cancers tended to decrease temporarily after the state of emergency declaration due to the COVID-19 pandemic, but the effect was only temporary.

Time to Treatment Initiation for Six Cancer Types: An Analysis of Data from a Nationwide Registry in Japan.

BACKGROUND: Delay in the time to treatment initiation (TTI) may adversely affect the survival of patients, but its current status in Japan is unknown. This study aims to describe the TTI for six cancer types: lung, breast, colorectal, stomach, head and neck (H&N), and cervical. Data for this study were derived from a nationwide registry in Japan. METHODS: This observational study employed the national database of hospital-based cancer registries (HBCRs) and health services utilization data. Using HBCR data, we identified all patients with cancer who started their cancer therapy at the same hospitals between January 1 and December 31, 2017. We calculated the TTI for each cancer type and treatment option, stratifying the results by age group and geographical region. RESULTS: The overall median TTI was 33 days, with shorter TTIs for colorectal and H&N cancers and chemotherapy. The TTI was the shortest for younger patients and the longest for the elderly, especially for lung cancer. When categorized by eight Japanese geographical regions, Tohoku and Kanto had the longest TTI. The result remained the same even after adjusting cancer type, treatment, age, and stage information. CONCLUSION: For colorectal and H&N cancers, in which a longer TTI is associated with a poorer prognosis, TTI was found to be particularly shorter. Although we could not discuss our results in light of the patient survival in this study, future research should explore the best balance between thorough evaluation before treatment and necessary time for that.

Association of two-staged surgery with systemic perioperative complications in lateral lumbar interbody fusion for adult spinal deformity: a propensity score-weighted study.

PURPOSE: Adult spinal deformity (ASD) surgery carries a higher risk of perioperative systemic complications. However, evidence for the effect of planned two-staged surgery on the incidence of perioperative systemic complications is scarce. Here, we evaluated the effect of two-staged surgery on perioperative complications following ASD surgery using lateral lumbar interbody fusion (LLIF). METHODS: The study was conducted under a retrospective multi-center cohort design. Data on 293 consecutive ASD patients (107 in the two-staged group and 186 in the one-day group) receiving corrective surgery using LLIF between 2012 and 2021 were collected. Clinical outcomes included occurrence of perioperative systemic complications, reoperation, and intraoperative complications, operation time, intraoperative blood loss, transfusion, and length of hospital stay. The analysis was conducted using propensity score (PS)-stabilized inverse probability treatment weighting to adjust for confounding factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a PS-weighted cohort. RESULTS: In this cohort, 19 (18.4%) patients in the two-staged group and 43 (23.1%) patients in the one-day group experienced any systemic perioperative complication within 30 days following ASD surgery. In the PS-weighted cohort, compared with the patients undergoing one-day surgery, no association with the risk of systemic perioperative complications was seen in patients undergoing two-staged surgery (PS-weighted OR 0.78, 95% CI 0.37-1.63; p = 0.51). CONCLUSION: Our study suggested that two-staged surgery was not associated with risk for perioperative systemic complications following ASD surgery using LLIF.

[A Systematic Review of Clinical and Epidemiological Studies Using Record Linkage Data between Hospital Based Cancer Registries and Biospecimen Data].

INTRODUCTION: Recently, registry-based cancer research linking biobanks with clinical information has become practical. In fact, hospital-based cancer registries(HBCR)are considered appropriate for basic medical information provision to link with biospecimen data since they can capture accurate information about cancer incidence and prognosis. The aim of this systematic review was to examine HBCR and biospecimen data uses in clinical and epidemiological studies. METHODS: We searched PubMed and Google Scholar for articles regarding HBCR and biospecimen data uses published before November 2019. Selected articles were summarized by study design into HBCR usage, biospecimen data usage, exposure, outcome, informed consent, and participant numbers. RESULT: Of the 2,767 identified articles, 148 studies were included in this review. In cohort studies, most HBCR usage was noted for patient selection, and most biospecimen data usage was factors affecting prognosis. Meanwhile, in case-control studies, most HBCR usage was noted for cancer incidence identification, and most biospecimen data usage was factors affecting cancer incidence. CONCLUSION: HBCR and biospecimen data usage in clinical and epidemiological studies were found to be different based on study design. Linkage of HBCR and biospecimen data will enable researchers to conduct clinical and epidemiological studies that correspond to varying research question types.

Combined in silico analysis identified a putative tooth root formation-related gene, Chd3, which regulates DNA synthesis in HERS01a cells.

There exists a close connection between changes occurring in the teeth and those occurring in the jaw during the evolutionary process. In mammals, the roots of teeth are supported, along with periodontal ligaments and alveolar bones by a unique structure termed the gomphosis. In the present study, we performed combined in silico analysis using the information obtained from various DNA microarrays and identified 19 putative tooth root formation-related genes. Furthermore, quantitative PCR was performed on the candidate genes, Chd3 was confirmed as having sufficient expression levels in the early stage of tooth root formation and increased gene expression toward the middle stage. A high degree of Chd3 gene expression was observed in secretory ameloblasts and Hertwig's epithelial root sheath (HERS), but low expression was observed in developing odontoblasts and stellate reticulum. The CHD3 foci were observed in the nucleus of the HERS01a cells. In addition, knockdown experiments using SiChd3 suggested the involvement of Chd3 in the suppression of DNA synthesis. These results suggested that Chd3 plays a role in DNA synthesis in HERS cells for promoting tooth root development.

High-Resolution Electrochemical Mapping of the Hydrogen Evolution Reaction on Transition-Metal Dichalcogenide Nanosheets.

High-resolution scanning electrochemical cell microscopy (SECCM) is used to image and quantitatively analyze the hydrogen evolution reaction (HER) catalytically active sites of 1H-MoS2 nanosheets, MoS2 , and WS2 heteronanosheets. Using a 20 nm radius nanopipette and hopping mode scanning, the resolution of SECCM was beyond the optical microscopy limit and visualized a small triangular MoS2 nanosheet with a side length of ca. 130 nm. The electrochemical cell provides local cyclic voltammograms with a nanoscale spatial resolution for visualizing HER active sites as electrochemical images. The HER activity difference of edge, terrace, and heterojunction of MoS2 and WS2 were revealed. The SECCM imaging directly visualized the relationship of HER activity and number of MoS2 nanosheet layers and unveiled the heterogeneous aging state of MoS2 nanosheets. SECCM can be used for improving local HER activities by producing sulfur vacancies using electrochemical reaction at the selected region.

Postnatal development of bitter taste avoidance behavior in mice is associated with ACTIN-dependent localization of bitter taste receptors to the microvilli of taste cells.

Bitter taste avoidance behavior (BAB) plays a fundamental role in the avoidance of toxic substances with a bitter taste. However, the molecular basis underlying the development of BAB is unknown. To study critical developmental events by which taste buds turn into functional organs with BAB, we investigated the early phase development of BAB in postnatal mice in response to bitter-tasting compounds, such as quinine and thiamine. Postnatal mice started to exhibit BAB for thiamine and quinine at postnatal day 5 (PD5) and PD7, respectively. Histological analyses of taste buds revealed the formation of microvilli in the taste pores starting at PD5 and the localization of type 2 taste receptor 119 (TAS2R119) at the microvilli at PD6. Treatment of the tongue epithelium with cytochalasin D (CytD), which disturbs ACTIN polymerization in the microvilli, resulted in the loss of TAS2R119 localization at the microvilli and the loss of BAB for quinine and thiamine. The release of ATP from the circumvallate papillae tissue due to taste stimuli was also declined following CytD treatment. These results suggest that the localization of TAS2R119 at the microvilli of taste pores is critical for the initiation of BAB.

Amelogenin X impacts age-dependent increase of frequency and number in labial incisor grooves in C57BL/6.

Labial grooves in maxillary incisors have been reported in several wild-type rodent species. Previous studies have reported age-dependent labial grooves occur in moderate prevalence in C57BL/6 mice; however, very little is known about the occurrence of such grooves. In the present study, we observed age-dependent groove formation in C57BL/6 mice up to 26 months after birth and found that not only the frequency of the appearance of incisor grooves but also the number of grooves increased in an age-dependent manner. We examined the molecular mechanisms of age-dependent groove formation by performing DNA microarray analysis of the incisors of 12-month-old (12M) and 24-month-old (24M) mice. Amelx, encoding the major enamel matrix protein AMELOGENIN, was identified as a 12M-specific gene. Comparing with wild-type mice, the maxillary incisors of Amelx-/- mutants indicated the increase of the frequency and number of labial grooves. These findings suggested that the Amelx gene impacts the age-dependent appearance of the labial incisor groove in C57BL/6 mice.

Harmine promotes molar root development via SMAD1/5/8 phosphorylation.

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo. Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs.

Comparison of Regeneration of Remnant Liver After Hemihepatectomy with or Without the Middle Hepatic Vein.

BACKGROUND: There is no consensus about remnant liver regeneration associated with middle hepatic vein (MHV) resecting. METHODS: Seventy-five patients who underwent hemihepatectomy were retrospectively analysed with respect to remnant liver regeneration. The liver remnant volume (LRV) and each sectional volume were postoperatively measured with multidetector computed tomography at day 7 and months 1, 2, 5, and 12 after the operation. RESULTS: In right hemihepatectomy cases, the regeneration rate of LRV in the MHV preservation group was significantly higher than that of the MHV resection group at months 5 and 12. In particular, the regeneration rate of remnant segment IV peaked at day 7 and was shrunk after 1 month, and was significant higher in the MHV preservation group. In left hemihepatectomy cases, the regeneration rate of LRV at month 12 was significantly higher in the MHV preservation group. The regeneration rate of the remnant anterior section peaked at 1 month and was shrunk. CONCLUSION: In this study, the MHV should be preserved or reconstructed whenever possible during hepatic hemihepatectomy. Hepatic regeneration in the MHV perfusion region becomes poor within 7 days to 1 month after surgery (UMIN000023714).

Risk factors for implant removal after spinal surgical site infection.

PURPOSE: Few studies have investigated the risk factors for implant removal after treatment for spinal surgical site infection (SSI). Therefore, there is no firmly established consensus for the management of implants. We aimed to investigate the incidence and risk factors for implant removal after SSI managed with instrumentation, and to examine potential strategies for avoiding implant removal. METHODS: Following a survey of seven spine centers, we retrospectively reviewed the records of 55 patients who developed SSI and were treated with reoperation, out of 3967 patients who had spinal instrumentation between 2003 and 2012. We examined implant survival rate and applied logistic regression analysis to assess the potential risk factors for implant removal. RESULTS: The overall rate of implant retention was 60% (33/55). A higher implant retention rate was observed for posterior cervical surgery than for posterior-thoracic/lumbar surgery (100 vs. 49%, P < 0.001). On univariate analysis, significant risk factors for implant removal included greater blood loss, delay of reoperation, and delay of intervention with effective antibiotics. Multivariate analysis revealed that a delay in administering effective antibiotics was an independent and significant risk factor for implant removal in posterior-thoracic/lumbar surgery (odds ratio 1.17; 95% confidence interval 1.02-1.35, P = 0.028). CONCLUSIONS: Patients with SSI who underwent posterior cervical surgery are likely to retain the implants. Immediate administration of effective antibiotics improves implant survival in SSI treatment. Our findings can be applied to identify SSI patients at higher risk for implant removal.

Analysis of detailed clinical characteristics of spinal subdural hematoma following lumbar decompression surgery.

BACKGROUND: Only a few reports have described symptomatic patients with postoperative spinal subdural hematoma (SSH) for which further surgery may have been required. No report has focused on the detailed clinical characteristics of postoperative SSH, including asymptomatic cases, in a case series. The reasons for this may be that SSH is an implicitly recognized rare entity, and there is no established consensus regarding the significance of performing postoperative magnetic resonance imaging (MRI) for all cases and the time at which to perform it. In this case-controlled retrospective analysis, we attempted to identify a detailed clinical presentation of SSH after open lumbar decompression surgery using MRI taken uniformly at 14 days before hospital discharge. METHODS: We retrospectively studied 196 patients who underwent routine MRI following open lumbar spinous process-splitting decompression surgery between 2012 and 2016. We assessed the frequency, clinical presentation, and radiological findings of SSH that developed postoperatively. Furthermore, we used a multivariate analysis to identify factors that were postulated to increase the risk of SSH postoperatively. RESULTS: None of the patients developed serious neurologic deficits, such as paresis or bladder and bowel dysfunction that required emergency evacuation. However, our results showed that postoperative SSHs, including asymptomatic SSHs, developed considerably frequently (43/182 patients, 23.6%). Furthermore, of the 43 patients with SSH, three presented with new postoperative neurologic findings that were strongly suspected to be associated with SSH. Multivariate analysis identified that preoperative hypertension (adjusted odds ratio [aOR]: 2.501, P = 0.018), anticoagulant therapy (aOR: 2.716, P = 0.021), and multilevel procedures (aOR: 2.327, P = 0.034) were significant risk factors of postoperative SSH. CONCLUSIONS: Spine surgeons should be aware that postoperative SSH is not rare and is a potential cause of recurrent pain or neurologic deterioration perioperatively.

[A case of adult gastric volvulus treated using upper gastrointestinal series].

Here, we report a case of adult gastric volvulus that was treated using an upper gastrointestinal series and provide a review of relevant reports. A 55-year-old woman presented with upper abdominal pain. Abdominal computed tomography revealed mesenteroaxial gastric volvulus. We performed an upper gastrointestinal series after the placement of a nasogastric tube. We successfully performed detorsion by repositioning. There was no recurrence of gastric volvulus after the detorsion. However, considering the risk of recurrence, we also performed laparoscopic gastropexy. The postoperative course was uneventful, and she was discharged from the hospital on postoperative day 3. No recurrence of symptoms has been observed to date.