Difference in surgical outcomes of rectal cancer by study design: meta-analyses of randomized clinical trials, case-matched studies, and cohort studies.

BACKGROUND: RCTs are considered the standard in surgical research, whereas case-matched studies and propensity score matching studies are conducted as an alternative option. Both study designs have been used to investigate the potential superiority of robotic surgery over laparoscopic surgery for rectal cancer. However, no conclusion has been reached regarding whether there are differences in findings according to study design. This study aimed to examine similarities and differences in findings relating to robotic surgery for rectal cancer by study design. METHODS: A comprehensive literature search was conducted using PubMed, Scopus, and Cochrane CENTRAL to identify RCTs, case-matched studies, and cohort studies that compared robotic versus laparoscopic surgery for rectal cancer. Primary outcomes were incidence of postoperative overall complications, incidence of anastomotic leakage, and postoperative mortality. Meta-analyses were performed for each study design using a random-effects model. RESULTS: Fifty-nine articles were identified and reviewed. No differences were observed in incidence of anastomotic leakage, mortality, rate of positive circumferential resection margins, conversion rate, and duration of operation by study design. With respect to the incidence of postoperative overall complications and duration of hospital stay, the superiority of robotic surgery was most evident in cohort studies (risk ratio (RR) 0.83, 95 per cent c.i. 0.74 to 0.92, P < 0.001; mean difference (MD) -1.11 (95 per cent c.i. -1.86 to -0.36) days, P = 0.004; respectively), and least evident in RCTs (RR 1.12, 0.91 to 1.38, P = 0.27; MD -0.28 (-1.44 to 0.88) days, P = 0.64; respectively). CONCLUSION: Results of case-matched studies were often similar to those of RCTs in terms of outcomes of robotic surgery for rectal cancer. However, case-matched studies occasionally overestimated the effects of interventions compared with RCTs.

Prediction of surgical difficulty in minimally invasive surgery for rectal cancer by use of MRI pelvimetry.

BACKGROUND: Technical difficulties in rectal surgery are often related to dissection in a limited surgical field. This study investigated the clinical value of MRI pelvimetry in the prediction of surgical difficulty associated with minimally invasive rectal surgery. METHODS: Patients with rectal cancer who underwent laparoscopic or robotic total mesorectal excision between 2005 and 2017 were reviewed retrospectively and categorized according to surgical difficulty on the basis of duration of surgery, conversion to an open procedure, use of the transanal approach, postoperative hospital stay, blood loss and postoperative complications. Preoperative clinical and MRI-related parameters were examined to develop a prediction model to estimate the extent of surgical difficulty, and to compare anastomotic leakage rates in the low- and high-grade surgical difficulty groups. Prognosis was investigated by calculating overall and relapse-free survival, and cumulative local and distant recurrence rates. RESULTS: Of 121 patients analysed, 104 (86·0 per cent) were categorized into the low-grade group and 17 (14·0 per cent) into the high-grade group. Multivariable analysis indicated that high-grade surgical difficulty was associated with a BMI above 25 kg/m2 (odds ratio (OR) 4·45, P = 0·033), tumour size 45 mm or more (OR 5·42, P = 0·042), anorectal angle 123° or more (OR 5·98, P = 0·028) and pelvic outlet less than 82·7 mm (OR 6·62, P = 0·048). All of these features were used to devise a four-variable scoring model to predict surgical difficulty. In patients categorized as high grade for surgical difficulty, the anastomotic leakage rate was 53 per cent (9 of 17 patients), compared with 9·6 per cent (10 of 104) in the low-grade group (P < 0·001). The high-grade group had a significantly higher local recurrence rate than the low-grade group (P = 0·002). CONCLUSION: This study highlights the impact of clinical variables and MRI pelvimetry in the prediction of surgical difficulty in minimally invasive rectal surgery.

ANTECEDENTES: Las dificultades técnicas en la cirugía del recto a menudo están relacionadas con la disección en un campo quirúrgico limitado. Este estudio se propuso investigar la utilidad clínica de la pelvimetría con MRI para predecir la dificultad quirúrgica asociada con la cirugía mínimamente invasiva del recto. MÉTODOS: Pacientes con cáncer de recto sometidos a resección total del mesorrecto laparoscópica o robótica entre 2005 y 2017 fueron revisados retrospectivamente y categorizados de acuerdo con la dificultad técnica en base al tiempo operatorio, conversión, uso de abordaje transanal, estancia hospitalaria postoperatoria, pérdida sanguínea y complicaciones postoperatorias. Se examinaron parámetros clínicos preoperatorios y relacionados con la MRI para desarrollar un modelo de predicción que estimara el grado de dificultad técnica y pudiera comparar la tasa de dehiscencias anastomóticas en los grupos de bajo y alto riesgo. También se evaluó el pronóstico con el cálculo de la supervivencia global, supervivencia libre de recidiva y tasas acumuladas de recidiva local y a distancia. RESULTADOS: De un total de 121 pacientes analizados, 104 pacientes (85,9%) fueron categorizados en el grupo con bajo grado de dificultad técnica, mientras que 17 pacientes (14,1%) lo fueron en el grupo de alto grado. En el análisis multivariable, un alto grado de dificultad técnica se asociaba con un índice de masa corporal (body mass index, BMI) > 25 kg/m2 (razón de oportunidades, odds ratio (OR), 4,5; P = 0,033), tamaño tumoral ≥ 45 mm (OR, 5,4; P = 0,042), ángulo anorrectal ≥ 123 grados (OR, 6,0; P = 0,028), estrecho pélvico < 82,7 mm (OR, 6,6; P = 0,048); en consecuencia, todas estas características fueron utilizadas para establecer un modelo de puntuación con 4 variables que pudiera predecir la dificultad técnica. En los pacientes categorizados como de alto grado de dificultad técnica, la tasa de dehiscencia anastomótica fue del 52,9%, mientras que en el grupo de bajo grado fue del 9,6% (P < 0,001). Finalmente, el grupo con alto grado mostró una tasa significativamente más elevada de recidiva local en comparación con el grupo de bajo grado (P = 0,002). CONCLUSIÓN: Este estudio pone de relieve el impacto de variables clínicas y de la pelvimetría con MRI para predecir la dificultad técnica en la cirugía mínimamente invasiva del recto.

Non-invasive three-dimensional bone-vessel image fusion using black bone MRI based on FIESTA-C.

AIM: To evaluate the image quality of bone-vessel fused volume-rendering (VR) images reconstructed by three-dimensional "black bone" magnetic resonance imaging (MRI) based on the fast imaging employing steady-state acquisition cycled phases (FIESTA-C) sequence and time-of-flight magnetic resonance angiography (TOF-MRA). MATERIALS AND METHODS: Seventeen patients were analysed in this retrospective study. All patients underwent both MRI techniques including FIESTA-C and TOF-MRA and computed tomography angiography (CTA). MRI- and CT-based bone-vessel VR images were reconstructed. Visual depictions of frontal and parietal branches from the superficial temporal artery (STA) were independently scored by three experienced radiological technologists using a four-grade system. RESULTS: In the visual evaluation, the scores of the both right and left frontal branches in MRI-based VR image were significantly larger those at CT (p<0.01, respectively). The scores of both the right and left parietal branches tended to be larger in MRI-based than that in CT-based VR imaging, but were not significantly so (p=0.06, 0.13 respectively). In the interobserver agreement analysis, κ values were all good (range: 0.6-0.76) for STA branch evaluation in MRI-based VR images. CONCLUSION: MRI bone-vessel fused VR imaging can non-invasively depict STA frontal branches with better visibility compared to the CT-based VR imaging. This technique may be useful for the preoperative evaluation of donor branches for STA-middle cerebral artery bypass surgery.

Impact of Drain Insertion After Perforated Peptic Ulcer Repair in a Japanese Nationwide Database Analysis.

BACKGROUND: Many perforated peptic ulcers (PPUs) require surgical repair due to diffuse peritonitis. However, few studies have examined the clinical effects of postoperative drainage after PPU repair. This study aimed to investigate the drain insertion rates in patients who underwent PPU repair in Japan, and to clarify the impact of drain insertion on the postoperative clinical course. METHODS: A retrospective nationwide cohort study was performed using administrative claims data of patients who had undergone PPU repair between 2010 and 2016. These patients were divided into two groups based on whether or not they had received a postoperative abdominal drain. Using propensity score matching, we compared the incidences of postoperative interventions for abdominal complications between both groups. RESULTS: A total of 4869 patients from 324 hospitals were analyzed. At the hospital level, drains were placed in all PPU repair patients in 229 (70.7%) hospitals. At the patient level, 4401 patients (90.4%) had drains inserted. The drain group was associated with a higher emergency admission rate, poorer preoperative shock status, longer anesthetic time, and a higher amount of intra-abdominal irrigation. In the propensity score-matched patients, the drain group had a significantly lower incidence of postoperative interventions than the no-drain group (1.9 vs. 5.6%; risk ratio = 0.35; 95% confidence interval 0.16-0.73; P = 0.003). CONCLUSION: Postoperative drainage was performed in the majority of patients who underwent PPU repair in Japan. Drainage following PPU repair may facilitate patient recovery by reducing the need for postoperative interventions.

Revisiting the treatment strategy for rectal cancer through the pattern of local recurrence.

BACKGROUND: Local recurrence after rectal cancer surgery is categorized as lymphatic spread (pelvic sidewall node (PSN)) and other types. This study aimed to investigate the risk factors associated with different patterns of local recurrence and to optimize the treatment strategy after rectal cancer surgery. METHODS: Patients with cStage I-III rectal cancer who underwent surgery at our institute were included in this study. Local recurrence was categorized as follows: (1) PSN recurrence and (2) "other" types of local recurrence. The risk factors associated with each type of recurrence (metastasis) were investigated. RESULTS: A total of 212 patients with mid/low rectal cancer were included in this study (cStage I: 66; cStage II/III: 146). Additional treatment was employed in selected patients with high-risk features (n = 45; pelvic sidewall dissection: 18; preoperative chemo (radio)therapy: 37). Potential lateral node metastasis was significantly associated with PSN enlargement on imaging findings (no/yes, odds ratio (OR): 9.1; p = 0.007). The "other" local recurrence type was significantly associated with 3 different factors as follows: clinical circumferential resection margin (no/yes; OR: 18.0; p = 0.001), tumor histology (well and moderately/poorly differentiated, OR: 17.3; p = 0.008), and tumor diameter (p = 0.018). Among 146 cStage II/III patients, 66 (45.2%) who did not have any of the abovementioned 4 risk factors experienced no local recurrence even when no additional treatment was employed. CONCLUSIONS: Risk factors may differ for different types of postoperative local recurrence patterns in rectal cancer. Recognizing these risk factors based on pretreatment findings can allow the optimization of treatment strategies for rectal cancer.

Lysyl oxidase secreted by tumour endothelial cells promotes angiogenesis and metastasis.

BACKGROUND: Molecules that are highly expressed in tumour endothelial cells (TECs) may be candidates for specifically targeting TECs. Using DNA microarray analysis, we found that the lysyl oxidase (LOX) gene was upregulated in TECs compared with its expression in normal endothelial cells (NECs). LOX is an enzyme that enhances invasion and metastasis of tumour cells. However, there are no reports on the function of LOX in isolated TECs. METHODS: TECs and NECs were isolated to investigate LOX function in TECs. LOX inhibition of in vivo tumour growth was also assessed using ß-aminopropionitrile (BAPN). RESULTS: LOX expression was higher in TECs than in NECs. LOX knockdown inhibited cell migration and tube formation by TECs, which was associated with decreased phosphorylation of focal adhesion kinase (Tyr 397). Immunostaining showed high LOX expression in human tumour vessels in vivo. Tumour angiogenesis and micrometastasis were inhibited by BAPN in an in vivo tumour model. CONCLUSION: LOX may be a TEC marker and a possible therapeutic target for novel antiangiogenic therapy.

Male sexual function after laparoscopic total mesorectal excision.

AIM: The aim of this prospective study was to clarify the frequency of male sexual dysfunction after laparoscopic total mesorectal excision (LTME) and to examine the relationship between pelvic autonomic nerve (PAN) preservation status and functional outcomes. METHOD: Candidates for LTME were included in this study. PAN preservation status after LTME was examined in detail by video review. Patients completed a functional questionnaire (the International Index of Erectile Function) before and 3, 6 and 12 months after the operation. RESULTS: Twenty-six patients who underwent LTME were assessable. Detailed video reviews identified inadvertent PAN damage during surgery. PAN injury was observed in 11 cases (41%), including eight cases (32%) of inadvertent PAN damage (incomplete preservation group). There was a trend toward increasing inadvertent PAN injury rate in patients with high body mass index and large tumours. The results from all patients who underwent LTME showed no deterioration in total International Index of Erectile Function or its domain scores 12 months after surgery. In the incomplete preservation group, these scores temporarily decreased (3 and 6 months after surgery), but such deterioration was not observed in the complete preservation group. Most of the 12 patients with potentially active erectile function before the operation recovered this function, and only one patient (7%) with PAN injury was still judged as inactive 12 months after surgery. CONCLUSION: The proportion of patients with sexual dysfunction after LTME is low. With the enhanced visibility of the laparoscope, inadvertent PAN injury was detected in a significant number of cases and associated with transient deterioration of sexual function.

Biglycan is a specific marker and an autocrine angiogenic factor of tumour endothelial cells.

BACKGROUND: We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs. METHODS: The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients. RESULTS: Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. CONCLUSION: These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium.

BACKGROUND: Tumour stromal cells differ from its normal counterpart. We have shown that tumour endothelial cells (TECs) isolated from tumour tissues are also abnormal. Furthermore, we found that mRNAs of vascular endothelial growth factor-A (VEGF-A) and cyclooxygenase-2 (COX-2) were upregulated in TECs. Vascular endothelial growth factor-A and COX-2 are angiogenic factors and their mRNAs contain an AU-rich element (ARE). AU-rich element-containing mRNAs are reportedly stabilised by Hu antigen R (HuR), which is exported to the cytoplasm. METHODS: Normal endothelial cell (NEC) and two types of TECs were isolated. We evaluated the correlation of HuR and accumulation of VEGF-A and COX-2 mRNAs in TECs and effects of HuR on biological phenotypes of TECs. RESULTS: The HuR protein was accumulated in the cytoplasm of TECs, but not in NECs. Vascular endothelial growth factor-A and COX-2 mRNA levels decreased due to HuR knockdown and it was shown that these ARE-mRNA were bound to HuR in TECs. Furthermore, HuR knockdown inhibited cell survival, random motility, tube formation, and Akt phosphorylation in TECs. CONCLUSION: Hu antigen R is associated with the upregulation of VEGF-A and COX-2 mRNA in TECs, and has an important role in keeping an angiogenic switch on, through activating angiogenic phenotype in tumour endothelium.

Three-year cardiovascular events and disease progress in patients with peripheral arterial disease: results from the Japan Medication Therapy for Peripheral Arterial Disease (J-METHOD).

AIM: To investigate the current status of peripheral arterial disease (PAD) drug treatment in Japan, and the effects of drug treatment, risk factors, and complications on disease progress and onset of cardiovascular events in PAD patients. METHODS: In this prospective observational cohort study, 557 PAD patients were followed up for 3 years, and the current status of PAD treatment, risk factors, and cardiovascular events were monitored. RESULTS: Three drugs, i.e., beraprost sodium, cilostazol, and aspirin, were most frequently used. The patients who had undergone vascular reconstruction of the lower limbs before enrollment showed significant improvement in ABI. Among the patients who had not undergone vascular reconstruction before enrollment, there was a significant improvement in ABI after treatment with beraprost. During the observation period, cardiovascular deaths occurred in 35 patients (6.3%), heart diseases in 63 (11.3%), brain diseases in 39 (7.0%), and events in the lower limbs in 94 (16.9%). The factors affecting the increase of the cardiovascular events were explored by multivariate analysis (Cox regression analysis). As a result, age (75 years or older), ischemic heart disease and increase in severity on the Fontaine classification were identified as significant factors for cardiovascular deaths, whereas kidney disorders and increase in severity on the Fontaine classification were identified for heart diseases, the number of oral drugs for treating PAD was identified for brain diseases, and age (younger than 75 years), dialysis, ABI (less than 0.7) and aspirin were identified for the events in the lower limbs. CONCLUSION: As a result of the three-year follow-up on the Japanese PAD cohort, the current status of PAD treatment, risk factors, and cardiovascular events could be identified.

Comparison of insulin detemir and insulin glargine on glycemic variability in patients with type 1 and type 2 diabetes.

AIMS: To compare the glycemic variability of insulin detemir and insulin glargine in type 1 and type 2 diabetic patients. METHODS: 15 type 1 and 14 type 2 diabetic patients receiving intensive insulin therapy with insulin glargine were enrolled. Before and after switching insulin glargine to insulin detemir, we assessed fasting glucose variability using the standard deviation (SD) and the coefficient of variance (CV) of self-monitored fasting blood sugar (FBS) levels. RESULTS: The SD and CV values were significantly decreased in type 1 diabetes after switching the therapy, though there was no significant difference in type 2 diabetes. The frequency of hypoglycemia was decreased in type 1 diabetes and there was no change in type 2 diabetes. The changes of the CV value also showed significant positive correlation with fasting serum CPR levels in all patients and total insulin dose in type 1 diabetes. The changes of frequency of hypoglycemia showed significant positive correlation with total and basal insulin dose adjusted for body weight in type 1 diabetes. CONCLUSION: The present study demonstrated lower within-subject variability of insulin detemir compared to insulin glargine, suggesting that the basal insulin replacement with insulin detemir may provide a useful therapeutic strategy for uncontrolled type 1 diabetes with high glucose variability.

Malpositioned spinal instrument as a possible cause of superficial siderosis.

STUDY DESIGN: Case report. OBJECTIVE: To report a patient with superficial siderosis as a complication after posterior fixation surgery for odontoid fracture. SETTING: Department of Neurosurgery, Hokkaido University, Japan. METHODS: A 36-year-old man had undergone C1-C2 posterior fixation using lamina hooks for an odontoid fracture in 1997. In 2003, he presented with hearing loss and ataxia; and in 2006, a diagnosis of superficial siderosis was made and spinal instrument malpositioning was detected. RESULTS: The malpositioned instrument, suspected as the cause of superficial siderosis, was removed. CONCLUSIONS: Superficial siderosis of the central nervous system is rare; it results in progressive hearing loss, cerebellar ataxia and pyramidal sign. Chronic hemorrhage in the subarachnoid space precipitates hemosiderin around the cerebellum and brainstem resulting in neurological symptoms. Recurrent hemorrhage and cervical root pathology, for example, root avulsion, are factors; the symptoms worsen gradually and result in hemostasis. Superficial siderosis because of complications from spinal instrumentation surgery is extremely rare. If the instrument is malpositioned in the subarachnoid space, we suggest its removal.