Feasibility of transanal minimally invasive surgery for total pelvic exenteration for advanced primary and recurrent pelvic malignancies.

BACKGROUND: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2-45 months). RESULTS: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36-74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561-1082), and the median intraoperative blood loss was 195 ml (30-1520). The Clavien-Dindo classifications of the postoperative complications were as follows: grade 0-2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). CONCLUSIONS: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate.

The advanced lung cancer inflammation index predicts outcomes in patients with Crohn's disease after surgical resection.

AIM: Precise biomarkers for predicting prognosis could help to identify high-risk Crohn's disease (CD) patients to facilitate better follow-up during the postoperative course. In this study, the primary aim is the identification of the most reliable nutrition marker that predicts surgical relapse in CD patients. METHOD: We first evaluated the predictive value of various nutrition markers for postoperative surgical relapse in CD patients and identified the advanced lung cancer inflammation index (ALI) as a promising biomarker. Then, we assessed the clinical significance of preoperative ALI in CD patients using two cohorts. RESULTS: Preoperative ALI showed the highest correlation with reoperation rate compared with other nutritional parameters in CD patients receiving surgical resection (sensitivity 53%, specificity 86%, area under the curve 0.71). Lower levels of preoperative ALI were significantly correlated with the presence of perianal disease. A lower level of preoperative ALI was an independent prognostic factor for reoperation rate after an intestinal resection (hazard ratio 3.37, 95% CI 1.38-10.12, P = 0.006), and the prognostic impact of preoperative ALI was successfully validated in an independent cohort using the same cut-off value. CONCLUSION: Preoperative ALI might be useful for postoperative management of CD patients.

Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis: a case series of 15 patients.

OBJECTIVE: We aimed to describe the clinical characteristics and treatment course of hypertrophic pachymeningitis (HPM) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We retrospectively analysed 15 patients (11 men and four women). HPM was diagnosed based on thickening and enhancing of the brain and/or spinal dura mater on gadolinium-enhanced magnetic resonance imaging (MRI) T1 sequence. RESULTS: The median age at HPM onset was 60 years. Headache and cranial nerve impairment were observed in 14 and 10 patients, respectively. Otitis media and/or mastoiditis were found as complications of AAV in 11 patients. Fourteen patients were classified as having granulomatosis with polyangiitis (GPA). Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, and double-positive ANCA were identified in seven patients, five patients, and one patient, respectively. With MRI, thickening of the dura mater in the cranial fossa and tentorium cerebelli was found in 10 and eight patients, respectively. For remission induction, all patients were treated with corticosteroids, and immunosuppressants were added in 10 patients. Dura mater thickening partially improved in all patients, and cranial neuropathy completely remitted in eight patients. In a median follow-up of 43 months, four patients had HPM relapse and underwent reinduction therapy. All six patients treated with cyclophosphamide at initial therapy did not relapse. CONCLUSIONS: HPM was mostly associated with patients with GPA with otitis media and/or mastoiditis having either type of ANCA serology. Treatment with corticosteroids with or without immunosuppressants was effective. However, HPM relapse occasionally occurred, especially when cyclophosphamide was not used in initial treatment.

The correlation of urinary podocytes and podocalyxin with histological features of lupus nephritis.

Objectives The objective of this study was to test the correlation of urinary podocyte number (U-Pod) and urinary podocalyxin levels (U-PCX) with histology of lupus nephritis. Methods This was an observational, cross-sectional study. Sixty-four patients were enrolled: 40 with lupus nephritis and 24 without lupus nephritis (12 lupus nephritis patients in complete remission and 12 systemic lupus erythematosus patients without lupus nephritis). Urine samples were collected before initiating treatment. U-Pod was determined by counting podocalyxin-positive cells, and U-PCX was measured by sandwich ELISA, normalized to urinary creatinine levels (U-Pod/Cr, U-PCX/Cr). Results Lupus nephritis patients showed significantly higher U-Pod/Cr and U-PCX/Cr compared with patients without lupus nephritis. U-Pod/Cr was high in proliferative lupus nephritis (class III±V/IV±V), especially in pure class IV (4.57 (2.02-16.75)), but low in pure class V (0.30 (0.00-0.71)). U-Pod/Cr showed a positive correlation with activity index ( r=0.50, P=0.0012) and was independently associated with cellular crescent formation. In contrast, U-PCX/Cr was high in both proliferative and membranous lupus nephritis. Receiver operating characteristic analysis revealed significant correlation of U-Pod/Cr with pure class IV, class IV±V and cellular crescent formation, and the combined values of U-Pod/Cr and U-PCX/Cr were shown to be associated with pure class V. Conclusions U-Pod/Cr and U-PCX/Cr correlate with histological features of lupus nephritis.

Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in inflammatory bowel disease: a pilot study.

Introduction Fistula formation around the ostomy site is a stoma-related complication often requiring surgical intervention. This complication may be caused by sutures or may develop as a complication of inflammatory bowel disease. Before conducting a clinical trial, we set out to investigate the safety of ostomy creation with fewer sutures using tissue adhesives in this pilot study. Methods Patients with inflammatory bowel disease who required surgery with ostomy creation at the Hyogo College of Medicine between January 2014 and December 2015 were enrolled. Safety was assessed by evaluating the incidence of stoma-related complications. Ostomy was restricted to loop ileostomy and was created with two sutures and tissue adhesives. Results A total of 14 patients were enrolled. Mean body mass index was 18.9 ± 2.0 kg/m2. There were no cases of ostomy retraction and no severe adverse events were observed. Conclusions This pilot study demonstrates that ostomy creation using tissue adhesives is safe. Although retraction and adverse events were not observed, even in patients with inflammatory bowel disease who generally exhibit delayed wound healing, the body mass index was extremely low in this series. This study does not strongly recommend ostomy creation with tissue adhesives; further studies are needed to clarify the efficacy and safety of the procedure.

Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction.

We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was ≥15-30 µg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin ≥15 µg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 µg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 µg/ml. In conclusion, achievement of Cmin of 15-30 µg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients.

Value of pre- and postoperative meticillin-resistant Staphylococcus aureus screening in patients undergoing gastroenterological surgery.

BACKGROUND: Data supporting active surveillance of meticillin-resistant Staphylococcus aureus (MRSA) for the prevention of postoperative infection remain controversial. AIM: To investigate the efficacy of MRSA screening in patients undergoing gastroenterological surgery. METHOD: Nasal carriage of MRSA was screened using a polymerase chain reaction (PCR) assay on two gastroenterological surgery wards (A and B). Occurrence of postoperative MRSA infection was analysed according to nasal MRSA carriage status (pre-operative carriage and postoperative acquisition). FINDINGS: The incidence of pre-operative MRSA carriage was 9.7% on Ward A and 4.3% on Ward B (P = 0.009). Postoperative nasal MRSA acquisition was confirmed in 16.2% and 6.0% of patients, respectively (P < 0.001). There was no significant difference in the incidence of MRSA surgical site infections (SSIs) between patients with and without pre-operative nasal colonization on either ward. On Ward A, where MRSA nasal acquisition was more common, the MRSA infection rate in patients with postoperative nasal acquisition was 26.8%, which was significantly higher than the rates in patients with pre-operative MRSA colonization and patients without colonization during hospitalization. Postoperative nasal MRSA acquisition was an independent factor associated with MRSA infection on both wards [Ward A: odds ratio (OR) 7.192, 95% confidence interval (CI) 2.981-17.352; Ward B: OR 5.761, 95% CI 1.429-23.220]. CONCLUSION: MRSA SSIs were prevented by a screening-based strategy in pre-operative MRSA carriers. Postoperative nasal acquisition was a significant factor affecting MRSA infection, and the effect of screening varied according to the incidence of postoperative MRSA acquisition on the ward.

Gene expression signature and response to the use of leucovorin, fluorouracil and oxaliplatin in colorectal cancer patients

PURPOSE: FOLFOX (a combination of leucovorin, fluorouracil and oxaliplatin) has achieved substantial success in the treatment of colorectal cancer (CRC) patients. However, about half of all patients show resistance to this regimen and some develop adverse symptoms such as neurotoxicity. In order to select patients who would benefit most from this therapy, we aimed to build a predictor for the response to FOLFOX using microarray gene expression profiles of primary CRC samples. PATIENTS AND METHODS: Forty patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received modified FOLFOX6. Responders and nonresponders were determined according to the best observed response at the end of the first-line treatment. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. We identified discriminating genes whose expression differed significantly between responders and nonresponders and then carried out supervised class prediction using the k-nearest-neighbour method. RESULTS: We identified 27 probes that were differentially expressed between responders and nonresponders at significant levels. Based on the expression of these genes, we constructed a FOLFOX response predictor with an overall accuracy of 92.5%. The sensitivity, specificity, positive and negative predictive values were 78.6%, 100%, 100% and 89.7%, respectively. CONCLUSION: The present model suggests the possibility of selecting patients who would benefit from FOLFOX therapy both in the metastatic and the adjuvant setting. To our knowledge, this is the first study to establish a prediction model for the response to FOLFOX chemotherapy based on gene expression by microarray analysis (AU)

Implementation of a hospital-wide project for appropriate antimicrobial prophylaxis.

The aim of this study was to confirm the effect of implementing a hospital-wide project for appropriate use of antimicrobial prophylaxis (AMP) to reduce the rate of antibiotic-resistant organisms. Fifteen different manuals for each surgical department have been simultaneously implemented since February 2007. Compliance rate was compared between pre- and postintervention periods (3 months for each period). As an effect of this intervention, we analyzed changes in the rates of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus among organisms isolated postoperatively. The number of operations was 1,627 in both periods. Among patients whose surgeries were longer than 3 h in duration, 75% received an additional intraoperative antimicrobial dose in the postintervention period and 23% in the preintervention period (P < 0.001). Although most patients received postoperative AMP with an interval of q12 h in the preintervention period, 63% of the patients received AMP with an interval of q8 h in the postintervention period. The duration of AMP use was reduced from 2.4 ± 1.9 to 1.6 ± 1.5 days (P < 0.001). Forty-seven percent of patients discontinued AMP within 24 h and 81% within 48 h. Isolation rates of P. aeruginosa among all gram-negative organisms significantly decreased from 13% (68/538 patients) to 7.3% (37/509 patients) (P = 0.004). Execution of a hospital-wide project to promote the appropriate use of AMP, including shortening the duration of AMP use, was useful to decrease the rate of P. aeruginosa isolated postoperatively.

Impact of a hospital-wide programme of heterogeneous antibiotic use on the development of antibiotic-resistant Gram-negative bacteria.

Although antibiotic heterogeneity has been proposed as a strategy to limit the emergence of antibiotic resistance, few clinical studies have been conducted to validate the concept. This paper evaluates a hospital-wide strategy of heterogeneous antibiotic use intended to reduce infections caused by resistant Gram-negative rods (GNR). A strategy termed 'periodic antimicrobial monitoring and supervision' (PAMS) was implemented between September 2006 and February 2008. The 18 month intervention period was compared with the preceding 18 months (12 months pre-establishment and 6 months preparation). During PAMS, recommended, restricted and off-supervised classes of antibiotics active against more resistant GNR were changed every 3 months according to the antimicrobial usage density and rates of resistance to those antibiotics in Pseudomonas aeruginosa during the preceding term. Usage of five categories of antibiotics was supervised by four full-time staff. Antibiotic heterogeneity was estimated using the Peterson index (AHI). AHI estimates were 0.66 and 0.74 during the observation period but rose after the introduction of PAMS (period 1: 0.84; period 2: 0.94; period 3: 0.88). The incidence of patients from whom resistant GNR were isolated decreased significantly (P<0.001), whereas isolation of multidrug-resistant (MDR) GNR decreased from 1.7% to 0.5% (P<0.001). There was no significant difference in the incidence of extended spectrum beta-lactamase-producing organisms. Rates of imipenem resistance among Pseudomonas aeruginosa improved during PAMS2. PAMS facilitated hospital-wide heterogeneous antibiotic usage which was associated with reduced rates of resistant GNR.

Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions.

OBJECTIVES: To determine if the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification of lupus nephritis (LN) is helpful in predicting renal outcome. METHODS: A total of 92 patients with LN who underwent renal biopsy in our hospital were re-classified according to the ISN/RPS 2003 criteria. RESULTS: The mean patient age was 36.8 yrs and the median observation period was 65 months. The relative frequency for each class was as follows: Class I (minimal mesangial LN) 0%, Class II (mesangial proliferative LN) 13%, Class III (focal LN) 17%, Class IV (diffuse LN) 60% and Class V (membranous LN) 10%. Within Class IV, diffuse segmental (Class IV-S) was 25% and diffuse global (Class IV-G) 75%. During the observation period, renal function was more likely to deteriorate in Class IV-G cases than in Class IV-S cases. Importantly, when Class IV-G was subdivided into cases involving active lesion alone [IV-G (A)] or chronic lesion [IV-G (A/C)], the majority of cases in IV-G (A) was nephrotic, but responded well to therapy. In contrast, renal function declined only in IV-G (A/C) cases. Patients with Class IV-G (A/C) had persistent proteinuria in spite of intensified therapies. Moreover, the higher proportion of chronic lesions was related with the deterioration of renal function. CONCLUSIONS: This study showed that in Class IV-G cases, renal outcome differed in the presence of chronicity. Chronicity could be a critical factor in predicting outcome. Thus, the revised classification of LN is clinically valuable in identifying different renal outcomes among patients with diffuse LN.

Expression of IL-19 and its receptors in RA: potential role for synovial hyperplasia formation.

OBJECTIVE: IL-19 is a novel cytokine of the IL-10 family. In this study, we sought to examine whether IL-19 plays a role in the pathogenesis of RA. METHODS: Expression of IL-19, IL-20 receptor 1 (IL-20R1) and IL-20R2 was examined by RT-PCR and immunohistochemical analysis in rheumatoid synovium. The effects of IL-19 on synovial cells established from rheumatoid synovium (RASCs), with regard to IL-6 production and signal transducers and activators of transcription3 (STAT3) activation, were examined by ELISA and western blot analysis, respectively. The effect of IL-19 on RASC apoptosis was examined by Hoechst staining, flow cytometry analysis of annexin V binding and caspase-3 activity. RESULTS: IL-19, IL-20R1 and IL-20R2 mRNA were detected by RT-PCR in synovial tissues from RA patients. Immunohistochemical analysis showed IL-19 was predominantly expressed in the hyperplastic lining layers of RA synovial tissues. The majority of IL-19-positive cells were vimentin-positive and CD68-positive synovial cells, serving as markers of fibroblasts and macrophages, respectively. IL-20R1 and IL-20R2 (IL-20Rs) were expressed in both the lining and sublining layers of RA synovium. In RASC, IL-19 was induced by lipopolysaccharide stimulation and constitutive expression of IL-20Rs was observed, suggesting IL-19 has an autocrine action. In terms of this function, IL-19 induced STAT3 activation and increased IL-6 production by RASC above the medium control. Moreover, IL-19 significantly reduced RASC apoptosis induced by serum starvation. CONCLUSIONS: These data suggest that IL-19, produced by synovial cells, promotes joint inflammation in RA by inducing IL-6 production and decreasing synovial cell apoptosis.

Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population.

BACKGROUND: Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-gamma and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis. METHODS: Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at -607C/A and -137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls. RESULTS: In UC, the -137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The -137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (-607A, -137C), which had a lower promoter activity and IFN-gamma mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences. CONCLUSIONS: IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC.

Pressure-temperature-induced denaturation of yeast phosphoglycerate kinase, a double-domain protein.

Pressure-induced denaturation of yeast phosphoglycerate kinase was studied at various temperatures, as a model double-domain protein, using intrinsic fluorescence, 4th derivative absorbance, CD, and DSC. A thermodynamic transition intermediate was observed in the pressure-denaturation, as was reported for the cold denaturation. From the different response of Trp and Tyr residues, as monitored by fluorescence and 4th derivative absorbance changes, the C-terminal domain carrying all the Trp residues seemed to exert structural changes at relatively lower pressure. A further structural change involving both domains was observed at higher pressures. The two-step changes occurred almost simultaneously during heat denaturation.

Extremely high levels of C-reactive protein in patients with acute lupus serositis.

Abstract We present the cases of two patients (19- and 40-year-old women) with systemic lupus erythematosus (SLE) who showed marked elevation of C-reactive protein (CRP). In both patients, pleural and/or peritoneal effusions were caused by lupus serositis. Methylprednisolone pulse therapy was effective in improving the serositis and normalizing CRP. Although it is generally considered that the CRP response is relatively weak in lupus patients, these cases suggest that a strong CRP response can occur in a subset of SLE.

Long-term results of stapled and hand-sewn anastomoses in patients with Crohn's disease.

AIM: This study aimed at determining the reoperation rates of patients with anastomoses for Crohn's disease. The outcome of patients undergoing stapled anastomoses was compared with that of patients having hand-sewn anastomoses. METHODS: Sixty-three patients undergoing intestinal resection for Crohn's disease at our institution from 1987 to 1996 were studied in a prospective, randomized trial. The group undergoing stapling comprised 30 patients and 37 anastomoses. The group with a hand-sewn anastomosis comprised 33 patients and 45 anastomoses. The median follow-up period was 87 (range 36-140) months. RESULTS: There were no significant differences in operative indications or patients' age and sex between the groups. There was a significant difference in cumulative recurrences between the groups (Cox-Mantel test: p = 0.022). CONCLUSION: A stapled anastomosis after resection for Crohn's disease may delay reoperation in patients with symptomatic recurrence.

[PL granule-induced pneumonia requiring mechanical ventilation].

PL granule is one of the most common forms of composite medicine for colds in Japan, including acetaminophen. We report a case of PL granule-induced pneumonia that required mechanical ventilation. A 72-year old man who had been prescribed amiodarone for more than one year before for arrhythmogenic right ventricular dystrophy, repeatedly took PL granules at one-week intervals because of sneezing and fever. He then underwent acute respiratory failure. He needed mechanical ventilation for severe hypoxemia, but recovered with glucocorticoid pulse therapy. Because the blastoid transformation test using his peripheral blood lymphocytes was positive on stimulation with PL granules, but negative on amiodarone stimulation, he was diagnosed as having drug (PL granule)-induced pneumonia. Only one case of PL granule-induced pneumonia and seven of acetaminophen-induced pneumonia have been reported. None of these patients needed mechanical ventilation. PL granule-induced pneumonia should be treated cautiously because of possible acute exacerbation.

Half-life of blood carboxyhemoglobin after short-term and long-term exposure to carbon monoxide.

BACKGROUND: In models of smoke inhalation injury and carbon monoxide poisoning blood carboxy-hemoglobin (COHb) levels decrease faster than predicted by the generally recognized half-life of COHb. We studied the effects of duration of exposure to carbon monoxide (CO) on the subsequent CO elimination. METHODS: Each of four sheep were insufflated with CO gas mixtures either for a few minutes (short-term exposure) or for several hours (long-term exposure), then ventilated with air for 3 hours. Serial COHb concentrations were analyzed by using a two-compartment, single central outlet mathematical model. RESULTS: Short-term exposures exhibited biphasic decreases of COHb concentration compatible with a two-compartment model; an initial rapid decrease (half-life 5.7 +/- 1.4 minutes) was followed by a slower phase (103 +/- 20.5 minutes). Long-term exposures exhibited almost monophasic decreases, which were nevertheless compatible with the model (half-life, 21.5 +/- 2.1 and 118 +/- 11.2 minutes). CONCLUSION: This study demonstrated different patterns of CO elimination curve, which suggests distribution of CO to two compartments having different rates of equilibration.