Recurrence After Transanal Excision of T1 Rectal Cancer: Should We Be Concerned?

PURPOSE Transanal excision is an appealing treatment for low rectal cancers because of its low morbidity, mortality, and better functional results than transabdominal procedures. However, controversy exists about whether it compromises the potential for cure. Several, recent reports of high recurrence rates after local excision prompted us to review our results of transanal excision alone in patients with T1 rectal cancers.METHODS All patients with T1 low rectal cancer undergoing local excision alone between 1980 through 1998 were reviewed for local recurrence, distant metastasis, disease-free interval, results of salvage surgery, and overall and disease-free survival. Demographics, tumor size, distance from anal verge, and preoperative endoluminal ultrasound results also were recorded. Patients with poorly differentiated tumors, perineural or lymphovascular invasion, or with mucinous component were excluded.RESULTS Fifty-two patients underwent transanal excision during the study period. Five-year recurrence was estimated to be 29.38 percent (95 percent confidence interval, 15.39–43.48). For 52 patients, five-year, cancer-specific and overall survival rates were 89 and 75 percent respectively. Fourteen of 15 patients with recurrence underwent salvage treatment with 56.2 percent (95 percent confidence interval, 35.2–90) five-year survival rate. Gender, preoperative staging by endorectal ultrasound, distance from the anal verge, tumor size, location, and T1 status discovered after transanal excision of a villous adenoma did not influence local recurrence or tumor-specific survival.CONCLUSIONS Transanal excision for T1 rectal tumors with low-grade malignancy has a high rate of recurrence. Although overall cancer survival rates might be regarded as satisfactory, this high recurrence and low salvage rate raises the issue about the role of transanal excision alone for early rectal cancer and the possible need for adjuvant therapy or increased role of resective surgery.Presented at the meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, June 3 to 7, 2002.     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Negative Pressure Wound Therapy With Low Pressure and Gauze Dressings to Treat Diabetic Foot Wounds

This study was a prospective cohort study to evaluate negative pressure wound therapy (NPWT) with low pressure and a gauze dressing to treat diabetic foot wounds. Thirty patients with diabetic foot wounds were consented to a prospective study to evaluate wound closure and complications to evaluate NPWT with low pressure (80 mmHg) and a gauze dressing interface (EZCare, Smith and Nephew) for up to 5 weeks. NPWT was changed 3 times a week. Study subjects were evaluated once a week for adverse events and wound measurements. Of study subjects, 43% attained at least a 50% wound area reduction after 4 weeks of therapy. Our results suggest that a high rate of wound closure could be expected with low pressure and a gauze interface.     

TLIF术式在布氏杆菌性脊柱炎病人中的临床疗效及安全性分析

目的 对比分析单纯后路内固定+一期经腰椎间孔病椎间病灶清除(TLIF)与经典的前后联合手术在布氏杆菌性脊柱炎患者中的临床疗效及安全性。 方法 对我院2015年1月至2017年12月收治的93例布病性脊柱炎患者的临床资料进行分析。按手术方式分为观察组(45例)和对照组(48例)。对两组患者的基础数据、临床指标、术前术后各项指标水平以及术后并发症、植骨治愈情况。 结果 观察组与对照组基础数据比较,差异无统计学意义(P>0.05)。观察组患者的手术时间、住院天数、术中出血量及术后下床时间均明显低于对照组(P<0.01)。两组患者术后3个月的ODI、VAS、CRP、ESR及Cobb角均明显低于术前(P<0.05);术后3个月,观察组患者的ODI、VAS、CRP、ESR及Cobb角均明显低于对照组(P<0.05)。观察组术后并发症发生率(4.4%)明显低于对照组(25.0%)(Χ²=7.674,P<0.01)。 结论 TLIF治疗布氏杆菌性脊柱炎患者的临床疗效突出,安全性较好,更有利于患者术后身体的恢复。     

11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess

The adverse metabolic effects of prescribed and endogenous glucocorticoid (GC) excess, Cushing syndrome, create a significant health burden. We found that tissue regeneration of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), rather than circulating delivery, is critical to developing the phenotype of GC excess; 11β-HSD1 KO mice with circulating GC excess are protected from the glucose intolerance, hyperinsulinemia, hepatic steatosis, adiposity, hypertension, myopathy, and dermal atrophy of Cushing syndrome. Whereas liver-specific 11β-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11β-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. These data challenge our current view of GC action, demonstrating 11β-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11β-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome.Estimates suggest that 1–2% of the population of the United States and United Kingdom take prescribed glucocorticoids (GCs) for the treatment of a broad spectrum of inflammatory and autoimmune diseases (1, 2). Despite the efficacy of GCs, 70% of patients experience an adverse systemic side-effect profile. The resultant Cushingoid features include central obesity, proximal myoatrophy, hypertension, skin thinning, osteoporosis, hepatic steatosis, insulin resistance, and type 2 diabetes (3, 4). Collectively, this contributes to increased risk of cardiovascular morbidity and mortality (5, 6). These features are replicated in patients with much rarer endogenous GC excess (Cushing syndrome), as first described by Harvey Cushing in 1932 (7). Current medical therapeutic options that reverse the tissue-specific consequences of hypercortisolism are limited.GC availability and action depend not only upon circulating levels but also on tissue-specific intracellular metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). Key metabolic tissues including liver, adipose tissue, and skeletal muscle express 11β-HSD type 1 (11β-HSD1), which coverts inactive cortisone to active cortisol [11-dehydrocorticosterone (11DHC) and corticosterone (CORT) in rodents, respectively] (8). In the setting of GC excess, the relative contribution to the metabolic effects induced by GCs of simple delivery of active GCs (cortisol or CORT) to a target tissue, compared with the regeneration of active GCs by 11β-HSD1 within the tissue, has not been determined.Type 2 11β-HSD (11β-HSD2) is predominately expressed in the kidney, colon, and salivary gland and catalyzes the inactivation of cortisol to cortisone (CORT to 11DHC in rodents). This not only protects the mineralocorticoid receptor from occupancy by cortisol but also crucially provides substrate for 11β-HSD1 in peripheral tissues.Transgenic animal models have highlighted the critical role of 11β-HSD1 in the regulation of metabolic phenotype in individual tissues. Mice overexpressing 11β-HSD1, specifically in adipose tissue, develop visceral obesity, insulin resistance, dyslipidemia, and hypertension (9, 10). Similarly, liver-specific 11β-HSD1 overexpression results in insulin resistance and hypertension, but not obesity (11). Importantly, circulating CORT levels were not elevated in either model, suggesting increased intracellular GC availability underpins the observed phenotypes. Indeed, this was confirmed in the adipose-specific 11β-HSD1–overexpressing mice, where twofold higher intraadipose CORT levels were recorded in comparison with WT controls (9). Ultimately, this has led to the development of selective 11β-HSD1 inhibitors as a potential treatment for patients with diabetes, obesity, and hypertension (12, 13).Although it is clear that 11β-HSD1 has a critical role to play in governing GC availability, its potential dynamic role in the setting of GC excess has not been fully explored (14–16). We have previously reported a patient with Cushing disease who was protected from the classic Cushing phenotype, owing to a functional defect in 11β-HSD1 activity, as evidenced by serum and urinary biomarkers (17). Based on this observation, we have hypothesized that tissue intrinsic 11β-HSD1 activity is the major determinant of the manifestations of GC excess and that 11β-HSD1 deletion will ameliorate the associated metabolic abnormalities. To determine the relative tissue-specific contribution to this effect, we have generated tissue-specific 11β-HSD1 deletions in liver and adipose tissue.     

Interventions in the management of infection in the foot in diabetes: a systematic review

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high‐quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections as of June 2018. This systematic review is an update of previous reviews, the first of which was undertaken in 2010 and the most recent in 2014, by the infection committee of the International Working Group of the Diabetic Foot. We defined the context of literature by formulating clinical questions of interest, then developing structured clinical questions (PICOs) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and the methodological quality. Our literature search identified a total of 15 327 articles, of which we selected 48 for full‐text review; we added five more studies discovered by means other than the systematic literature search. Among these selected articles were 11 high‐quality studies published in the last 4 years and two Cochrane systematic reviews. Overall, the outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetic foot were broadly equivalent across studies, except that treatment with tigecycline was inferior to ertapenem (±vancomycin). Similar outcomes were also reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high‐quality evidence to assess the effect of various adjunctive therapies, such as negative pressure wound therapy, topical ointments or hyperbaric oxygen, on infection related outcomes of the diabetic foot. In general, the quality of more recent trial designs are better in past years, but there is still a great need for further well‐designed trials to produce higher quality evidence to underpin our recommendations.     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.