Safety of advanced laparoscopic hepatectomy for elderly patients: a Japanese nationwide analysis.

BACKGROUND: Although basic laparoscopic hepatectomy (LH) has become the standard procedure for hepatectomy, the safety of advanced LH remains to be clarified, especially in elderly patients. We investigated the safety of advanced LH in elderly Japanese patients. METHODS: Elderly patients (≥ 65 years) who underwent advanced LH between 2016 and 2021 were analyzed using a nationwide claims database in Japan. The perioperative outcomes of patients who underwent open hepatectomy (OH group) or LH (LH group) were compared using propensity score matching (PSM). The primary outcome was in-hospital mortality. The E-value method was performed to assess the strength of the outcome point estimates against possible unmeasured confounding factors. RESULTS: Among 5,021 patients, eligible patients were classified into the OH (n = 4,152) and LH (n = 527) groups. The median patient age was 74 years in both groups. Hepatocellular carcinoma and metastatic liver tumors were the major indications for hepatectomy (OH: 52.5% versus 30.6%; LH: 60.7% versus 26.4%). After PSM, in-hospital mortality rates for OH and LH were 1.7 and 0.76%, respectively. The risk ratio was 0.45 (95% confidence interval, 0.16-1.25; E-value = 3.87). Compared with OH, LH was associated with a longer anesthesia time (411 versus 432 min), lower rate of blood product use (red blood concentrate: 33.5% versus 20.3%; fresh frozen plasma: 29.2% versus 17.1%), and shorter hospital stay (13 versus 12 days). CONCLUSIONS: In elderly patients, the safety of advanced LH was similar to that of advanced OH, or might be better in Japan under the current policy of hospital accreditation.

Appropriate dose of regorafenib based on body weight of colorectal cancer patients: a retrospective cohort study.

PURPOSE: Previous randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight. METHODS: We used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups. RESULTS: We identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 - 1.39, Table 3) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 - 1.37). CONCLUSION: The findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.

Efficacy of Daikenchuto in the prevention of bowel obstruction in patients with colorectal cancer undergoing laparoscopic surgery: An observational study using a Japanese administrative claims database.

PURPOSE: Daikenchuto is an herbal medicine widely used in Japan without clear evidence to prevent bowel obstruction after abdominal surgery. We evaluated the efficacy of Daikenchuto in laparoscopic surgery for colorectal cancer (CRC). METHODS: We included patients from the medical claims databases diagnosed with CRC between January 2012 and December 2019 and treated with laparoscopic surgery. We compared the Daikenchuto and control groups to evaluate early bowel obstruction (EBO) events for 1 year. The Daikenchuto group included patients prescribed Daikenchuto on postoperative day (POD) 0 or 1. An EBO event was defined as the use of a nasogastric tube, transnasal ileus tube, endoscopic balloon dilatation, or the requirement of reoperation for bowel obstruction from PODs 1 to 364. RESULTS: In total, 46,458 patients met the eligibility criteria; 2407 and 44,051 patients were included in the Daikenchuto and control groups, respectively. Some of the patient's characteristics were significantly different between the groups. The frequencies of EBO events in the Daikenchuto and control groups were 5.7% (95% confidence interval: 4.8-6.7) and 4.6% (4.4-4.8), respectively. The most frequent events were nasogastric tube (3.1%, 2.9%) and transnasal ileus tube insertions (1.4%, 0.8%) in the Daikenchuto and control groups, respectively. The hospital stay was significantly shorter in the Daikenchuto group than in the control; this trend was confirmed in the sensitivity analysis. CONCLUSIONS: Daikenchuto did not demonstrate efficacy for EBO. It might be adequate for shortening patient's hospital stay. Further studies are warranted.

Recent Trend of Using Computed Tomography to Diagnose Pediatric Appendicitis at the First Hospital Visit: A Descriptive Study Using a Medical Claims Database.

OBJECTIVE: We recognize that computed tomography (CT) should not be used to diagnosis pediatric appendicitis due to radiation exposure. However, few studies have recently shown a trend in its use. This study aimed to investigate the annual use of CT for the diagnosis of pediatric appendicitis at the first hospital visit. METHODS: This was a descriptive study using nationwide claims data. We extracted the data of children younger than 15 years who underwent imaging tests to diagnose acute and suspected appendicitis at the first visit between January 2008 and September 2018. We summarized the patient characteristics and the percentage of CT, ultrasonography (US), or CT/US utilization by year, age, and department. RESULTS: We identified 6658 children who underwent CT (2349 [35.8%]), US (53,57 [54.5%]), and CT/US (634 [9.7%]). The annual CT use dropped from 43.1% in 2012 to 29.4% in 2018. According to age group, the highest percentage of CT use in 2018 was 84.6% in preschool children, followed by adolescents (40.3%), upper-grade (26.0%), and lower-grade (15.0%) children. Data of annual CT use by department revealed that CT usage was much higher in internal and emergency medicine than in pediatrics. Furthermore, adolescents accounted for approximately 50% of CT use in internal medicine. CONCLUSIONS: The percentage of CT use for pediatric appendicitis at the first visit declined annually. However, CT use still tended to be higher in preschool- and adolescent-aged children, or in departments other than pediatrics. Further studies are required to clarify the clinical benefits of CT use to diagnose pediatric appendicitis.

Clinical epidemiology and pharmacoepidemiology studies with real-world databases.

Hospital-based registry data, including patients' information collected by academic societies or government based research groups, were previously used for clinical research in Japan. Now, real-world data routinely obtained in healthcare settings are being used in clinical epidemiology and pharmacoepidemiology. Real-world data include a database of claims originating from health insurance associations for reimbursement of medical fees, diagnosis procedure combinations databases for acute inpatient care in hospitals, a drug prescription database, and electronic medical records, including patients' medical information obtained by doctors, derived from electronic records of hospitals. In the past ten years, much evidence of clinical epidemiology and pharmacoepidemiology studies using real-world data has been accumulated. The purpose of this review was to introduce clinical epidemiology and pharmacoepidemiology approaches and studies using real-world data in Japan.

Intergenerational comparison of 5-HT3RA in the prevention of chemotherapy-induced nausea and vomiting in gastric cancer patients receiving cisplatin-based chemotherapy: an observational study using a Japanese administrative claims database.

PURPOSE: In chemotherapy-induced nausea and vomiting (CINV), the superiority of the second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) over the first-generation 5-HT3RA is shown in the delayed emesis in cycle 1. We evaluate the antiemetic efficacy in real-world clinical practice that has not been sufficiently investigated in clinical trials. METHODS: We included patients who were diagnosed with gastric cancer between April 2012 and June 2017 from the medical claims databases and were treated with cisplatin (≥ 50 mg/m2) and standard antiemetic therapy (5-HT3RA + neurokinin-1 receptor antagonist [NK1RA] + dexamethasone). We compared the second-generation 5-HT3RA (2nd group) and the first-generation 5-HT3RA (1st group) groups to evaluate the additional antiemetic drug as the CINV event. RESULTS: In total, 3798 patients were extracted; 1440 and 2358 patients were included in the 1st and 2nd groups, respectively. The clinical and demographic characteristics did not differ between the groups. In the overall (days 1-6) in cycle 1, 51.7% and 44.3% of patients in the 1st and 2nd groups, respectively, had a CINV event. In the acute phase (days 1-2), 38.7% and 30.2% and in the delayed phase (days 3-6), 35.8% and 32.1% of patients in the 1st and 2nd groups, respectively, had a CINV event. Furthermore, the CINV event trend was the same as in cycles 1 to 5. CONCLUSION: The proportion of CINV events in the 2nd group was smaller than that in the 1st group at any cycle. These findings may suggest consistent antiemetic efficacy of second-generation 5-HT3RA throughout the cycle.

Clinical Outcomes of Acute Appendicitis During Pregnancy: Conservative Management and Appendectomy.

PURPOSE: We have described the epidemiology, diagnostic modality, treatment patterns, and outcomes of acute appendicitis during pregnancy. METHODS: Using a nationwide claim-based database in Japan, we analyzed the data of pregnant patients who were diagnosed with appendicitis between January 2005 and May 2019. Patient characteristics, imaging studies, length of hospital stay, proportion of fetal losses, complications, and type of antibiotics were examined. RESULTS: The study included 169 patients, of whom 113 patients (67%) underwent conservative management, and appendectomies were performed on 56 patients (open 25% and laparoscopic 8%). The proportion of ultrasonography, computed tomography, and magnetic resonance imaging were 97%, 17%, and 5% (for conservative management); 88%, 39%, and 13% (for appendectomy); 86%, 38%, and 21% (for open appendectomy); and 93%, 43%, and 14% (for laparoscopic appendectomy), respectively. The proportion of complicated appendicitis was 6% in conservative management and 41% in appendectomy (40% in open appendectomy and 43% in laparoscopic appendectomy), respectively. The incidence of fetal loss was 4% in conservative management, 5% in appendectomy (2% in open appendectomy, and 14% in laparoscopic appendectomy). However, there was only one fetal loss (in laparoscopic appendectomy) in the same case of hospitalization. There were no maternal deaths or serious complications after any treatment. CONCLUSION: All treatments showed acceptable outcomes in appendicitis during pregnancy. Conservative management is considered an acceptable option, especially in uncomplicated cases of appendicitis in pregnant women.

Effectiveness of barrier agents for preventing postoperative bowel obstruction after laparoscopic surgery: a retrospective cohort study.

PURPOSE: The effectiveness of using anti-adhesion agents in laparoscopic surgery is controversial. We compared the outcomes of patients exposed to anti-adhesion agents (barrier group) with those of patients not exposed (no barrier group) in laparoscopic surgery. METHODS: Using a nationwide claim-based database in Japan, we analyzed data from patients who underwent laparoscopic surgery between 2005 and 2019 and compared the patient characteristics and the proportion of those with bowel obstruction between the barrier and no barrier groups. We also performed several sensitivity and subgroup analyses. RESULTS: Of the 57,499 patients who met the inclusion criteria, 14,360 and 43,139 were assigned to the barrier and no barrier groups, respectively. The proportion of patients with a bowel obstruction in the two groups did not differ among all patients hospitalized for obstruction (1.1 vs. 1.1%, p = 0.63) and those requiring surgery (0.2 vs. 0.2%, p = 0.39). In the sensitivity analysis with propensity score matching, the incidences of bowel obstruction between the barrier and non-barrier groups were equivocal (1.3 vs. 1.6%), but statistically marginal (chi-square test, p = 0.035; log-rank test, p = 0.09). CONCLUSION: The use of barrier agents for adhesive prevention did not show clear effectiveness for the prevention of bowel obstruction after laparoscopic surgery for unselected cases. Further studies focusing on more specific procedures are needed.

Laparoscopic versus open repair for inguinal hernia in children: a retrospective cohort study.

PURPOSE: We compared the outcomes of laparoscopic surgery (LS) with those of open surgery (OS) for unilateral and bilateral pediatric inguinal hernia. METHODS: Using a nationwide claim-based database in Japan, we analyzed data from children younger than 15 years old, who underwent inguinal hernia repair between January 2005 and December 2017. Patient characteristics, incidence of reoperation, postoperative complications, length of hospital stay, and duration of anesthesia were compared between LS and OS for unilateral and bilateral hernia. RESULTS: Among 5554 patients, 2057 underwent LS (unilateral 1095, bilateral 962) and 3497 underwent OS (unilateral 3177, bilateral 320). The incidence of recurrence was not significantly different between OS and LS (unilateral: OS 0.2% vs. LS 0.3%, p = 0.44, bilateral: OS 0.6% vs. LS 0.6%, p = 1.00). The incidence of metachronous hernias was significantly higher in the OS group than in the LS group (4.8% vs. 1.0%, p < 0.001). The surgical site infection rate was significantly lower after OS than after LS for unilateral surgeries (0.9% vs. 2.2%, p = 0.002). There was no difference between OS and LS in the length of hospital stay. CONCLUSION: Both OS and LS had a low incidence of recurrence in children; however, the incidence of metachronous hernias was lower for LS, which may influence operative technique decisions.

[Seven Cases of Metastatic Colorectal Cancer Treated with Dose-Reduced and Duration-Reduced Regorafenib Treatment].

Regorafenib is widely used for patients with metastatic colorectal cancer, following disease progression with standard therapies.However, regorafenib has severe toxicities; therefore, careful monitoring and treatment are necessary.Several studies have investigated the efficacy of initial dose reductions.We started regorafenib doses from 80 mg, with a duration of 1 week on and 1 week off, after which we gradually increased the dosage and duration.From September 2015 to March 2017, we treated 7 consecutive patients who received regorafenib following standard chemotherapy for metastatic colorectal cancer.The average age was 73 years and average BMI was 23.3.The average total dose was 15,960(2,240-28,000)mg, and the average treatment duration was 243(50-379)days.The mean survival from the start of regorafenib was 399(median 407, 262-622)days.Adverse events of Grade 3 or higher were observed in 1 patient(14%).

[Two Cases of HER2-Positive Gastric Cancer with Multiple Liver Metastases Leading to Conversion Therapy with Chemotherapy].

Case 1: A 69-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab to treat advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T3N2M1[P0, CYX, H1]). After 12 courses, liver metastases were absent on computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. It has been 22 months since the patient had gastrectomy without recurrence of the cancer. Case 2: A 70-year-old man underwent chemotherapy with capecitabine plus cisplatin plus trastuzumab for treatment of advanced gastric cancer that was diagnosed as cStage IV adenocarcinoma(T4aN1M1[P0, CY0, H1]). After 12 courses, regrowth of multiple liver metastases led to a treatment with weekly paclitaxel plus trastuzumab as a second-line chemotherapy. After 9 courses of second-line chemotherapy, multiple liver metastases were absent in computed tomography images. The patient underwent total gastrectomy with D2 lymphadenectomy. A small white nodule on the surface of S2 and S3 of the liver led to the patient receiving a partial liver resection. The pathological finding of the resected liver specimen was a metastasis of an adenocarcinoma. During continuous chemotherapy with weekly paclitaxel plus trastuzumab after gastrectomy, multiple liver metastases were revealed. The patient died 19 months after gastrectomy.

Effect of prior depression diagnosis on bipolar disorder outcomes: A retrospective cohort study using a medical claims database.

BACKGROUND: Bipolar disorder often emerges from depressive episodes and is initially diagnosed as depression. This study aimed to explore the effects of a prior depression diagnosis on outcomes in patients diagnosed with bipolar disorder. METHODS: This cohort study analyzed data of patients aged 18-64 years who received a new bipolar disorder diagnosis in Japan, using medical claims data from January 2005 to October 2020 provided by JMDC, Inc. The index month was defined as the time of the bipolar diagnosis. The study assessed the incidence of psychiatric hospitalization, all-cause hospitalization, and mortality, stratified by the presence of a preceding depression diagnosis and its duration (≥1 or <1 year). Hazard ratios (HRs) and p-values were estimated using Cox proportional hazards models, adjusted for potential confounders, and supported by log-rank tests. RESULTS: Of the 5595 patients analyzed, 2460 had a history of depression, with 1049 experiencing it for over a year and 1411 for less than a year. HRs for psychiatric hospitalization, all hospitalizations, and death in patients with a history of depression versus those without were 0.92 (95% CI = 0.78-1.08, p = 0.30), 0.87 (95% CI = 0.78-0.98, p = 0.017), and 0.61 (95% CI = 0.33-1.12, p = 0.11), respectively. In patients with preceding depression ≥1 year versus <1 year, HRs were 0.89 (95% CI = 0.67-1.19, p = 0.43) for psychiatric hospitalization, 0.85 (95% CI = 0.71-1.00, p = 0.052) for all hospitalizations, and 0.25 (95% CI = 0.07-0.89, p = 0.03) for death. CONCLUSION: A prior history and duration of depression may not elevate psychiatric hospitalization risk after bipolar disorder diagnosis and might even correlate with reduced hospitalization and mortality rates.

Selective estrogen receptor modulators and deep venous thrombosis after an emergent operation in senior women.

BACKGROUND: Selective estrogen receptor modulators (SERMs), clinically applied to osteoporosis, may have potential risk of deep venous thrombosis (DVT) and discontinuation of SERMs may be required before surgery. However, we cannot discontinue SERMs for a certain duration, when patients undergo an emergent operation. CASE PRESENTATION: We reported two aged patients undergoing an emergent orthopedic surgery for lower extremities while taking SERMs for osteoporosis before the operation. DVT was newly developed in one patient and worsened in the other patient after the operation. We found eight aged patients underwent the same operation while taking SERMs for recent 3 years, including the two cases and DVT did not occur in the other six patients. Thus, the incidence of DVT in our patient population was 25%. CONCLUSION: We showed that DVT developed or worsened after operation in two patients taking SERMs before operation. Ultrasound examination after operation may be recommended in these population. (149 words).

Comparative effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with venous thromboembolism: A cohort study.

BACKGROUND: Although several studies have compared the effectiveness and safety of rivaroxaban and apixaban in patients with venous thromboembolism (VTE), direct comparison of these drugs with edoxaban is lacking. OBJECTIVE: We compared the effectiveness and safety of edoxaban, rivaroxaban, and apixaban in patients with VTE. PATIENTS/METHODS: In this retrospective cohort study using a Japanese hospital administrative database, we identified three mutually exclusive groups of patients with VTE beginning treatment with edoxaban, rivaroxaban, or apixaban. Primary effectiveness outcome was recurrent VTE, and principal safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding. Subjects were followed for up to 180 days. Baseline characteristics among groups were balanced using propensity score matching weights. RESULTS: Three thousand three hundred sixty-nine edoxaban, 1592 rivaroxaban, and 1998 apixaban initiators were identified. There were no significant differences among the three drugs in the prevention of recurrent VTE (adjusted incidence rate ratio [aIRR], 0.77; 95% confidence interval [CI], 0.45-1.30 for edoxaban vs. rivaroxaban; aIRR, 0.92; 95% CI, 0.54-1.56 for edoxaban vs. apixaban; and aIRR, 1.20; 95% CI, 0.69-2.10 for rivaroxaban vs. apixaban), or in the risk of intracranial hemorrhage or gastrointestinal bleeding (aIRR, 1.57, 95% CI, 0.85-2.90 for edoxaban vs. rivaroxaban; aIRR, 1.30, 95% CI, 0.76-2.23 for edoxaban vs. apixaban; and aIRR, 0.83, 95% CI, 0.42-1.64 for rivaroxaban vs. apixaban). CONCLUSIONS: In routine care, edoxaban, rivaroxaban, and apixaban appear to have similar effectiveness and safety in the treatment of VTE.

Comparison of laparoscopic and open inguinal hernia repair in adults: A retrospective cohort study using a medical claims database.

INTRODUCTION: This study aimed to investigate and compare the surgical complications following laparoscopic inguinal hernia repair (LIHR) with those following open inguinal hernia repair (OIHR). METHODS: This was a retrospective cohort study based on nationwide claims data. We extracted the data of patients aged ≥20 years who underwent inguinal hernia repair (IHR) between 2009 and 2020. The primary outcome was postoperative complications of IHR, and the secondary outcomes were recurrence of hernia and length of hospital stay. Patient characteristics were adjusted with propensity score (PS) matching, the annual proportions of LIHR versus OIHR were summarized, and the surgical outcomes of each IHR were analyzed. RESULTS: Of the 15 728 eligible patients, 6512 underwent LIHR. The proportion of LIHR increased from 14.7% to 52.8% annually during the study period. From the analysis of 6060 pairs created by PS matching, the risk of surgical site infection (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.56-0.86; P = .0007), and acute postoperative pain (OR 0.69; 95% CI 0.60-0.79; P < .0001), and chronic postoperative pain (OR 0.83; 95% CI 0.70-0.98; P = .0291) were significantly lower with LIHR than with OIHR. The recurrent rate was not significantly different between the LIHR and OIHR groups (OR, 0.68; 95% CI 0.45-1.01; P = .0558). Furthermore, no significant difference was found in the length of hospital stay between the LIHR and OIHR groups (2.91 ± 1.94 days vs 2.97 ± 2.61 days, difference ± SE: 0.06 ± 0.04, P = .1307). CONCLUSION: LIHR might be superior to OIHR in terms of fewer surgical complications and might be preferred over OIHR in the future.

Salvage Therapy After Regorafenib or Trifluridine/Tipiracil Treatment of Metastatic Colorectal Cancer: A Conditional Landmark Analysis.

BACKGROUND/AIM: This study aimed to describe the chemotherapy effects after trifluridine/tipiracil (TFTD) and/or regorafenib treatment in colorectal cancer (CRC) patients. PATIENTS AND METHODS: Patients receiving regorafenib or TFTD for metastatic CRC during 2013-2018 were selected and divided into two groups: one with additional chemotherapy after regorafenib or TFTD (CTX group) and one without additional chemotherapy (Non-CTX group). Patients were followed up from a landmark point (90 days from the last day of administration of regorafenib or TFTD). We compared overall survival (OS) between the groups. RESULTS: The median OS was 7.7 months in the CTX group and 4.1 months in the non-CTX groups. Several sensitivity analyses did not negate the survival advantage detected in the CTX group. CONCLUSION: The chemotherapy after regorafenib or TFTD was associated with prolonged OS in advanced CRC patients. Further study is required to determine appropriate treatment choice.

Effectiveness and Safety of Regorafenib vs. Trifluridine/Tipiracil in Unresectable Colorectal Cancer: A Retrospective Cohort Study.

INTRODUCTION: Compared with the best supportive care, a survival benefit of using regorafenib and trifluridine/tipiracil (TFTD) in patients with colorectal cancer has been shown in previous randomized controlled trials (RCTs). However, there is no RCT or large-scale observational study directly comparing regorafenib and TFTD. PATIENTS AND METHODS: We used a nationwide claims database in Japan and compared the effectiveness of regorafenib and TFTD for metastatic colorectal cancer during 2013 to 2018. The patients were divided into 4 groups (regorafenib monotherapy, regorafenib/TFTD: regorafenib followed by TFTD, TFTD monotherapy, and TFTD/regorafenib: TFTD followed by regorafenib). Overall survival (OS) and adverse events were compared between the groups. In a subgroup analysis, we also compared treatment effectiveness between the group in which regorafenib was administered first and the group in which TFTD was administered first. RESULTS: We identified 7279 patients (regorafenib: 1501, regorafenib/TFTD: 973, TFTD: 3777, and TFTD/regorafenib: 1028). The corresponding median OS was 6.4, 16.4, 10.2, and 16.9 months, respectively. A log-rank test showed significant intergroup differences (P < .001). In the subgroup analysis, the group in which TFTD was administered first showed significantly longer OS. The incidences of most adverse events were the lowest in the TFTD group. The TFTD group showed longer OS than the regorafenib group, and sequential drug use resulted in the most prolonged OS. CONCLUSION: Our findings indicate that it might be better to prescribe TFTD first. Furthermore, owing to the longer OS than monotherapy, sequential administration of regorafenib and TFTD ought to be considered.

Sodium phenylbutyrate improved the clinical state in an adult patient with arginase 1 deficiency.

An adult female patient was diagnosed with arginase 1 deficiency (ARG1-D) at 4 years of age, and had been managed with protein restriction combined with sodium benzoate therapy. Though the treatment was successful in ameliorating hyperammonemia, hyperargininemia persisted. After being under control with a strict restriction of dietary protein, severe fall of serum albumin levels appeared and her condition became strikingly worsened. However, after sodium phenylbutyrate (NaPB) therapy was initiated, the clinical condition and metabolic stability was greatly improved. Current management of ARG1-D is aimed at lowering plasma arginine levels. The nitrogen scavengers, such as NaPB can excrete the waste nitrogen not through the urea cycle but via the alternative pathway. The removal of nitrogen via alternative pathway lowers the flux of arginine in the urea cycle. Thereby, the clinical complications due to insufficient amount of protein intake can be prevented. Thus, NaPB therapy can be expected as a useful therapeutic option, particularly in patients with ARG1-D.

Comparison of Standard Initial Dose and Reduced Initial Dose Regorafenib for Colorectal Cancer Patients: A Retrospective Cohort Study.

BACKGROUND: The benefit of regorafenib for colorectal cancer patients was demonstrated in previous randomized studies. However, these studies showed a high rate of treatment-related adverse events, and adverse events were more common in Japanese patients. Some studies showed fewer adverse events and a longer survival time with a reduced initial dose. However, the benefits of a reduced initial dose of regorafenib have only been evaluated in small samples. OBJECTIVE: Our objective was to analyze the efficacy of initial regorafenib dose reduction compared with a standard dose for colorectal cancer patients. PATIENTS AND METHODS: We used a hospital-based nationwide claims database. Patients who received regorafenib for metastatic colorectal cancer between June 2013 and July 2017 were included in this study. We divided the patients into a standard initial dose group (standard group) and a reduced initial dose group (reduced group). Overall survival (OS) and adverse events were compared between the two groups. We performed propensity score matching for sensitivity analysis. RESULTS: We included 2376 patients (1208 in the standard group and 1168 in the reduced group). The median OS was 12.3 months (95% confidence interval (CI): 11.0-13.3) in the standard group and 12.6 months (95% CI: 11.7-13.6) in the reduced group. A log-rank test showed no significant difference between the two groups (p = 0.41). Most adverse events occurred less frequently in the reduced group. In the sensitivity analysis, there was no significant difference for OS. CONCLUSIONS: No significant difference was observed for OS between the standard group and the reduced group. However, there were fewer adverse events in the reduced group. The optimal initial dose of regorafenib should be identified in further studies.

Laparoscopic incisionless stoma creation for patients with colorectal malignant stricture.

BACKGROUND: Minimally invasive techniques have been applied with increasing frequency to stoma creation. A recent focus in the field of minimally invasive surgery is laparoscopic single-site surgery. The aim of this study was to assess whether this procedure is a feasible option compared with other techniques of stoma creation. MATERIALS AND METHODS: We introduced laparoscopic surgery to fecal diversion in April 2010 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. This technique was performed on 53 patients, including 15 laparoscopic single-site surgeries, from April 2010 to December 2011. RESULTS: Of these 15 cases, 8 ileostomies and 7 colostomies were created. The mean operative time was 65.9 minutes (range, 32 to 93 min). The estimated volume of blood loss was small in all cases. There were no intraoperative complications. All patients started an oral diet on the second postoperative day with the exception of 1 patient who suffered from prolonged paralytic ileus. CONCLUSIONS: A laparoscopic single-site approach to stoma creation may be a feasible option in fecal diversion.