Outcomes of robot-assisted versus conventional laparoscopic low anterior resection in patients with rectal cancer: propensity-matched analysis of the National Clinical Database in Japan.

BACKGROUND: Robot-assisted laparoscopic surgery has several advantages over conventional laparoscopy. However, population-based comparative studies for low anterior resection are limited. This article aimed to compare peri-operative results of robot-assisted low anterior resection (RALAR) and laparoscopy. METHODS: This retrospective cohort study used data from patients treated with RALAR or conventional laparoscopic low anterior resection (CLLAR) between October 2018 and December 2019, as recorded in the Japanese National Clinical Database, a data set registering clinical information, perioperative outcomes, and mortality. Of note, the registry does not include information on the tumour location (centimetres from the anal verge) and diverting stoma creation. Perioperative outcomes, including rate of conversion to open surgery, were compared between RALAR and CLLAR groups. Confounding factors were adjusted for using propensity score matching. RESULTS: Of 21 415 patients treated during the study interval, 20 220 were reviewed. Two homogeneous groups of 2843 patients were created by propensity score matching. The conversion rate to open surgery was significantly lower in the RALAR group than in the CLLAR group (0.7 versus 2.0 per cent; P < 0.001). The RALAR group had a longer operating time (median: 352 versus 283 min; P < 0.001), less intraoperative blood loss (15 versus 20 ml; P < 0.001), a lower in-hospital mortality rate (0.1 versus 0.5 per cent; P = 0.007), and a shorter postoperative hospital stay (median: 13 versus 14 days; P < 0.001) compared with the CLLAR group. The CLLAR group had a lower rate of readmission within 30 days (2.4 versus 3.3 per cent; P = 0.045). CONCLUSION: These data highlight the reduced conversion rate, in-hospital mortality rate, intraoperative blood loss, and length of postoperative hospital stay for rectal cancer surgery in patients treated using robot-assisted laparoscopic surgery compared with laparoscopic low anterior resection.

Rectal cancer lateral lymph nodes: multicentre study of the impact of obturator and internal iliac nodes on oncological outcomes.

BACKGROUND: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. METHODS: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. RESULTS: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease. CONCLUSION: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. METHODS: From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. RESULTS: The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). WHAT IS NEW AND CONCLUSION: Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care.

Early results of multicenter phase II trial of perioperative oxaliplatin and capecitabine without radiotherapy for high-risk rectal cancer: CORONA I study.

BACKGROUNDS: Perioperative introduction of developed chemotherapy into the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. However, the most prevalent treatment for high-risk LARC remains preoperative chemoradiotherapy (CRT) in Western countries. PATIENTS AND METHODS: A phase II trial was undertaken to evaluate safety and efficacy of perioperative XELOX without radiotherapy (RT) for patients with high-risk LARC. Patients received 4 cycles of XELOX before and after surgery, respectively. Primary endpoint was disease-free survival. RESULTS: We enrolled 41 patients between June 2012 and April 2014. The completion rate of the preoperative XELOX was 90.3%. Twenty-nine patients (70.7%) could start postoperative XELOX, 15 of these patients (51.7%) completed 4 cycles. Allergic reaction to oxaliplatin was experienced by 5 patients (17.2%) during postoperative XELOX. One patient received additional RT after preoperative XELOX. Consequently, the remaining 40 patients underwent primary resection. Major complications occurred in 6 of 40 patients (15.0%). Pathological complete response (pCR) rate was 12.2%, and good tumor regression was exhibited in 31.7%. N down-staging (cN+ to ypN0) and T down-staging were detected in 56.7% and 52.5%, respectively. Clinical T4 tumor was a predictor of poor pathological response (p < 0.001). CONCLUSIONS: We could show the favorable pCR rate after preoperative XELOX alone. However, the T and N down-staging rate was likely to be insufficient. When tumor regression is essential for curative resection, the use of preoperative CRT is likely to be recommended. For patients with massive LN metastasis, the additional Bev to NAC might be a promising option.

Clinical significance of dual-energy CT-derived iodine quantification in the diagnosis of metastatic LN in colorectal cancer.

BACKGROUND: The purpose of this study was to evaluate the diagnostic value of dual-energy computed tomography (DECT) in detecting lymph node (LN) metastasis in patients with colorectal cancer. METHODS: Data from 81 LNs from 28 patients with colorectal adenocarcinoma were retrospectively analyzed. All patients received DECT before surgery without any neoadjuvant therapy. The diagnostic value was assessed using the iodine concentration (IC). RESULTS: In the pathological findings, 35 (43.2%) LNs from 13 patients were metastatic and 46 (56.8%) LNs from 17 patients were non-metastatic. The mean IC of metastatic LNs in the portal venous phase (PP) was 1.60 mg/ml, which was significantly lower compared with non-metastatic LNs (3.25 mg/ml, p < 0.001). Receiver operating characteristic (ROC) analysis revealed that the IC in PP had the highest ability to discriminate LN metastasis (area under the ROC curve [AUC] 0.932). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IC in PP (cutoff 2.1 mg/ml) were 87.0%, 88.6%, 85.3%, 90.0%, and 87.9%, respectively. When clinically obvious metastatic LNs in conventional CT findings were excluded, 50 LNs remained (5 metastatic and 45 non-metastatic LNs). In this subgroup analysis, the IC in PP remained the most powerful predictor of metastatic LNs (cutoff: 2.1 mg/ml, AUC 0.933). CONCLUSIONS: The evaluation of IC in DECT may improve the diagnostic capabilities of discriminating metastatic LNs. This method may be particularly useful when conventional CT findings lead to equivocal results.

An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients.

BACKGROUND: In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle. METHODS: Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350). RESULTS: The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70). CONCLUSIONS: Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan.

Aggressive surgical treatment with bony pelvic resection for locally recurrent rectal cancer.

BACKGROUND: In the current era of total mesorectal excision, local relapse remains a main cause of recurrence. Although standard treatment for locally recurrent rectal cancer (LRRC) has not been established, R0 resection represents the only potentially curative treatment. However, extended surgery accompanying bony pelvic resection is technically demanding and is still challenging. METHODS: Studied were 35 patients with LRRC who underwent combined resection of bony pelvis between August 2006 and October 2013. Safety and prognostic factors for survival were analyzed. Median follow-up was 33 months. RESULTS: Sacrectomy was performed in 32 patients and 3 patients underwent combined resection of the pubis and ischium. The dominant operative procedure was total pelvic exenteration in 30 (86%) patients. R0 resection was achieved in 27 (77%) patients. No patients died. Pelvic sepsis was the most frequent complication (40%). Recurrence developed in 20 (57%), with the lung the most frequent site (10 patients). Three-year local relapse-free survival (LRFS) and disease-free survival (DFS) were 72.1% and 32.7%, respectively. On multivariate analysis, R1 resection was the only independent risk factor for local recurrence (p = 0.010), and concomitant liver metastasis and initial non sphincter-preserving surgery were independent predictors of worse DFS (p = 0.008 and p = 0.042, respectively). CONCLUSIONS: Aggressive surgical treatment combined with bony resection for carefully selected patients with LRRC was safe with a high rate of R0 resection and favorable LRFS. However, DFS was not satisfactory even after R0 resection and the main cause was lung metastasis. Preventing distant recurrence might be a key to improve survival.

Necrotising soft-tissue infections of the upper limb: risk factors for amputation and death.

Necrotising soft-tissue infections (NSTIs) of the upper limb are uncommon, but potentially life-threatening. We used a national database to investigate the risk factors for amputation of the limb and death. We extracted data from the Japanese Diagnosis Procedure Combination database on 116 patients (79 men and 37 women) who had a NSTI of the upper extremity between 2007 and 2010. The overall in-hospital mortality was 15.5%. Univariate analysis of in-hospital mortality showed that the significant variables were age (p = 0.015), liver dysfunction (p = 0.005), renal dysfunction (P < 0.001), altered consciousness (p = 0.049), and sepsis (p = 0.021). Logistic regression analysis showed that the factors associated with death in hospital were age over 70 years (Odds Ratio (OR) 6.6; 95% confidence interval (CI) 1.5 to 28.2; p = 0.011) and renal dysfunction (OR 15.4; 95% CI 3.8 to 62.8; p < 0.001). Univariate analysis of limb amputation showed that the significant variables were diabetes (p = 0.017) mellitus and sepsis (p = 0.001). Multivariable logistic regression analysis showed that the factors related to limb amputation were sepsis (OR 1.8; 95% CI 1.5 to 24.0; p = 0.013) and diabetes mellitus (OR 1.6; 95% CI 1.1 to 21.1; p = 0.038). For NSTIs of the upper extremity, advanced age and renal dysfunction are both associated with a higher rate of in-hospital mortality. Sepsis and diabetes mellitus are both associated with a higher rate of amputation.

Effectiveness of brief suicide management training programme for medical residents in Japan: a cluster randomized controlled trial.

Aims. To evaluate the effectiveness of a brief suicide management training programme for Japanese medical residents compared with the usual lecture on suicidality. Methods. In this multi-center, clustered randomized controlled trial, the intervention group attended a structured suicide management programme and the control group, the usual lecture on depression and suicidality. The primary outcome was the difference in residents' cumulative competency score to manage suicidal persons from baseline (T0) to 1 month after the intervention (T2), determined using the Suicide Intervention Response Inventory (SIRI-1) score, at individual level. Results. Analysis of 114 residents (intervention group n = 65, control group n = 49) assigned to two clusters in each group revealed no change in SIRI-1 score from T0 to T2 or immediately after the intervention (T1) between the two groups. As a secondary analysis, discrepancy in judgement between the participants and Japanese suicidologists was examined immediately after the intervention in the adjusted model, with a mean difference in score of 9.98 (95% confidence interval: 4.39-15.56; p = 0.001). Conclusions. The structured programme was not proven to improve competency in suicide management when measured by the SIRI-1 score. Further elaboration of the programme and valid measurement of its outcome would be needed to show the program's effectiveness.

Soft-plastic brace for lower limb fractures in patients with spinal cord injury.

STUDY DESIGN: Retrospective study at a rehabilitation center. OBJECTIVES: Patients with spinal cord injury, even if they are wheelchair users, sometimes suffer from fractures of the lower limb bones. As their bones are too weak to have surgery, and because a precise reduction is not required for restoration, such patients are often indicated for conservative treatment. This case series study investigated the use of a hinged, soft-plastic brace as a conservative approach to treating fractures of the lower extremities of patients with spinal cord injury. SETTING: National Rehabilitation Center, Japan. METHODS: Fifteen patients (male, n=10; female, n=5; average age, 52.7 years) with 19 fractures of the femur or the tibia who were treated with a newly-developed hinged, soft-plastic brace were studied. All of them used wheelchairs. We analyzed the time taken for fracture union and for wearing orthotics, degree of malalignment, femorotibial angle and side effects. RESULTS: The fractures in this series were caused by relatively low-energy impact. The average time taken for fracture union was 80.1 (37-189) days, and the average amount of time spent wearing orthotics was 77.9 (42-197) days. On final X-ray imaging, the average femorotibial angle was 176.9° (s.d. ±8.90), and 15° of misalignment in the sagittal plane occurred in one patient. CONCLUSION: A hinged, soft-plastic brace is a useful option as a conservative approach for treating fractures of the lower extremities in patients with spinal cord injury.

Rectal duplication cyst successfully treated by laparoscopic total mesorectal excision using the prolapsing technique.

Congenital alimentary tract duplication is a rare disease. It most frequently occurs in the ileum, with the rectum being the rarest site. Herein, we report a 38-year-old woman who was referred to our hospital because of severe anal pain. On digital examination, a smooth, round, rubbery mass was palpable; it was located 5 cm from the anal verge in the posterior rectal wall. A CT scan demonstrated a 5-cm cystic lesion located anterior to the sacrum that was displacing the rectum anteriorly. Spontaneous remission of the tumor was evident; however, after 5 months of follow-up, the patient experienced the same severe anal pain. MRI demonstrated a recurrent cystic lesion. To prevent further complications and to confirm or deny malignancy, laparoscopic total mesorectal excision using the prolapsing technique was performed. Pathologically, the cystic lesion was diagnosed as a rectal duplication cyst. This is the first report of a rectal duplication cyst successfully treated by laparoscopic total mesorectal excision.

MEFV mutation analysis of familial Mediterranean fever in Japan.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever with serosal inflammation. FMF gene (MEFV) mutations have been identified primarily in patients from Mediterranean populations. Although several clinical cases have been reported in Japan, there have been few reports to date on mutation analysis. We studied FMF patients and their relatives to examine the clinical and genetic features of this disease in the Japanese population. METHODS: Twelve Japanese FMF patients who met the Tel Hashomer criteria and a total of 17 relatives from 5 of 10 families underwent molecular genetic studies to detect MEFV mutations. The characteristics of these Japanese FMF patients and geno-phenotypical correlations were examined. RESULTS: Almost all of our patients had been suffering for a long time from fever of unknown origin and one patient also had systemic amyloidosis. In our 12 FMF patients, we detected the substitutions E84K, L110P, E148Q, R761H and M694I. We also newly diagnosed 2 relatives as having FMF based on clinical symptoms and the existence of FMF mutations. One patient was homozygous for E148Q, the patient with systemic amyloidosis was a homozygote for M694I and 4 patients from 3 families were compound heterozygotes for E148Q and M694I. Three patients in one family were compound heterozygotes for E148Q, L110P and M694I. There were 3 patients who were heterozygous for E84K, L110P-E148Q or M694I and had no other nucleotide changes in the exons of MEFV. On the other hand, 2 relatives who had never experienced symptoms of FMF were homozygous for L110P-E148Q as well as compound heterozygous for E148Q/E148Q-R761H. E148Q and M694I were the most frequently detected substitutions in our study. CONCLUSIONS: MEFV mutations occur in Japanese FMF patients though FMF is rare in Japan. The identification of MEFV mutations could be a reliable diagnostic test for FMF. The results of genetic analyses on 14 Japanese FMF patients in this study revealed that E148Q and M694I are frequent alleles.

[An infant case of a rupture of chordae tendineae; report of a case].

We report a case of 5-month-old boy with severe mitral regurgitation due to a rupture of chordae tendinae. Cardiac echography showed a prolapse of the anterior cusp of the mitral valve. He was progressively deteriorated despite maximal medical treatment, and a surgical intervention was performed 15 hours after the onset. The operative finding was a rupture of chordae tendinae attached to the anterior cusp of the mitral valve. The infant underwent mitral valve plasty using artificial chordae together with partial annulo-plasty. A rupture of chordae tendineae is extremely rare in infants, and its cause is yet unknown. Chordal reconstruction is feasible even at this early stage of life, although the long-term follow-up is mandatory.

Clinicopathological significance of fibrous tissue around fixed recurrent rectal cancer in the pelvis.

BACKGROUND: Fibrous tissue around a locally recurrent rectal tumour is an interesting histological feature, but its clinicopathological significance has not been investigated. METHODS: This retrospective study examined clinicopathological findings in 48 patients who underwent curative total pelvic exenteration with distal sacrectomy (TPES) between 1992 and 2004. Data were analysed with respect to fibrosis around the recurrent tumour, categorized into one of three groups: no fibrosis (f0), partial fibrosis (f1) or circumferential fibrosis (f2). RESULTS: Ten, 17 and 21 patients had f0, f1 and f2 fibrosis respectively, with 5-year survival of none, four and eight patients respectively. The overall survival of patients with circumferential fibrosis was significantly better than that in patients with no fibrosis (P = 0.003). Univariable analysis showed that a high level of sacrectomy (P = 0.036), absence of lymphatic invasion (P = 0.031) and circumferential fibrosis (P = 0.039) were significantly associated with better overall survival. In multivariable analysis, circumferential fibrosis (P = 0.031) and low serum carcinoembryonic antigen levels (P = 0.044) were independent factors for a favourable outcome. CONCLUSION: The outcome of patients with locally recurrent rectal cancer after curative TPES appears to be better when circumferential fibrosis is present around the tumour.

Clinicopathological significance of microscopic abscess formation at the invasive margin of advanced low rectal cancer.

BACKGROUND: The aim of this study was to evaluate the clinicopathological significance of microscopic abscess formation (MAF) at the invasive front of advanced low rectal cancer. METHODS: The clinicopathological features of 226 consecutive patients with low rectal cancer, who underwent curative resection between May 1997 and December 2002, were analysed. RESULTS: Fifty-seven (25.2 per cent) of the 226 tumours had MAF and 169 (74.8 per cent) did not. Patients with tumours showing MAF were more likely to have extended surgery than those without MAF: 47 versus 31.4 per cent respectively underwent non-sphincter-preserving surgery (P=0.029) and 82 versus 60.9 per cent underwent lateral lymph node dissection (P=0.003). The incidence of lymph node metastases was lower in patients with MAF (30 versus 53.3 per cent; P=0.002). Univariable analysis of disease-free survival revealed that depth of invasion (P<0.001), lymph node status (P<0.001), histological type (P=0.035), lymphatic invasion (P<0.001), venous invasion (P<0.001), perineural invasion (P<0.001), focal dedifferentiation (P<0.001) and MAF (P<0.001) were significant prognostic factors. Multivariable analysis showed that lymph node status (P<0.001), perineural invasion (P=0.002), venous invasion (P=0.033) and MAF (P=0.012) remained independent prognostic factors. CONCLUSION: MAF may reflect indolent tumour behaviour and a more favourable outcome in patients with advanced low rectal cancer.

Reduction of prolonged postoperative hospital stay after laparoscopic surgery for colorectal carcinoma.

BACKGROUND: In evaluating the quality of laparoscopic surgery (LS) for colorectal carcinoma, many previous reports have used median or range values to assess the length of postoperative hospital stay and to show the complication and conversion rates separately. However, with this method, it is impossible to assess the proportion of patients who required prolonged postoperative hospital stay because of perioperative morbidities. This study investigated the proportion of patients who benefited from LS as minimally invasive surgery by assessing the percentage of patients who required prolonged postoperative hospital stay because of major perioperative morbidities. METHODS: A review of 202 patients who underwent LS for colorectal carcinoma at the authors' hospital between January 2002 and December 2004 was performed. Short-term outcomes were compared among the patients who underwent LS in 2002, 2003, and 2004. RESULTS: No significant differences were observed in baseline characteristics among the groups, and all the procedures in this study were completed laparoscopically. There were no significant differences in the operative times and intraoperative blood losses among the groups. Most of the patients resumed liquid intake on postoperative day 1 and solid food on day 3. However, there was a significant difference in the rate of postoperative prolonged hospital stays by year of surgery. In 2004, 97.3% of the patients (72/74) undergoing LS could be discharged to home within 8 days postoperatively. Major complications occurred at a low rate of 1.4% (1/74) in 2004. Regarding the reasons for prolonged postoperative hospital stay, inappropriate judgment of the physician in charge, based primarily on requests from patients without medical necessity, disappeared in 2004. CONCLUSIONS: When LS is performed properly by specialists who have accumulated sufficient experience in both LS and conventional open surgery for colorectal carcinoma, up to 97% of patients undergoing LS can benefit from minimally invasive surgery.