Developing a predictive model for distinguishing invasive nail unit melanoma from nail unit melanoma in situ.

BACKGROUND: Clinical information that distinguishes invasive nail unit melanoma from nail unit melanoma in situ before surgery would aid physicians in the decision-making process and estimating prognosis. However, limited information is available on the detailed demographic and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ for differential diagnosis. OBJECTIVE: This study aimed to investigate the demographic data and dermoscopic features of invasive nail unit melanoma and nail unit melanoma in situ and establish a predictive model for differentiating these two forms of nail unit melanoma. METHODS: A retrospective observational study of ninety-seven patients diagnosed with nail unit melanoma (59 in situ and 38 invasive cases) in four healthcare centres in South Korea (three tertiary referral hospitals and one second referral hospital) from March 2014 to December 2019. RESULTS: A multivariable analysis revealed that ulcer (odds ratio = 21.6, confidence interval = 2.1-219.8, P = 0.009), total melanonychia (odds ratio = 17.6, confidence interval = 3.0-104.0, P = 0.002), nail plate destruction (odds ratio = 10.9, confidence interval = 2.0-59.4, P = 0.006) and polychromia (odds ratio = 5.3, confidence interval = 1.36-20.57, P = 0.016) were distinctive dermoscopic features of invasive nail unit melanoma. A predictive model with scores ranging from 0 to 6 points demonstrated a reliable diagnostic value (C-statistic = 0.902) in differentiating invasive nail unit melanoma from nail unit melanoma in situ. CONCLUSIONS: Invasive nail unit melanoma and nail unit melanoma in situ have different dermoscopic features. A predictive model based on morphologic dermoscopic features could aid in differentiating invasive nail unit melanoma from nail unit melanoma in situ.

Early complications after percutaneous radiofrequency ablation for hepatocellular carcinoma: an analysis of 1,843 ablations in 1,211 patients in a single centre: experience over 10 years.

AIM: To evaluate the incidence of adverse events and associated factors after radiofrequency ablation (RFA) in patients with hepatocellular carcinoma within 30 days. MATERIALS AND METHODS: The early complications that occurred within 30 days after RFA at a single institution from January 2000 to July 2010 were reviewed in order to evaluate the morbidity, mortality, and risk factors associated with the complications. In total, 1,211 patients (845 men, 70.5%) with a mean age of 68 years (range, 27-88 years) underwent 1,843 RFA procedures. RESULTS: The overall incidence rate of complications was 6.8% (125 cases). Major complications (n=36, 2%) included liver abscess (n=15, 0.8%), intraperitoneal bleeding (n=8, 0.4%), liver failure (n=5, 0.3%), variceal bleeding (n=3, 0.2%), haemothorax (n=2, 0.1%), cholecystitis (n=2, 0.1%), and bowel perforation (n=1, 0.1%). Among the minor complications (n=89, 4.8%), the most common was the post RFA syndrome accompanied by pain and fever (n=75, 4.1%). Other minor complications included significant pleural effusion (n=7, 0.4%), skin wound infection (n=4, 0.2%), and thermal injuries to the skin (n=3, 0.2%). Procedural infections significantly increased with tumour size (OR=1.379; 95% confidence interval [CI], 1.191-1.579; p<0.001), and multiple overlapping ablations (OR=1.118; 95% CI, 1.019-1.227, p=0.018). Thrombocytopenia (<50,000/µl), prothrombin time, and serum albumin level were significantly associated with post-RFA bleeding episodes (p=0.041, p=0.021, and p=0.003, respectively). The overall mortality rate was 0.3% (three cases of hepatic failure, two case of sepsis, and one case of renal failure). CONCLUSIONS: RFA is a safe and effective local treatment for hepatocellular carcinoma. Careful selection of patients and appropriate RFA planning could decrease procedural mortality and morbidity.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass.

BACKGROUND/OBJECTIVES: High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. SUBJECTS/METHODS: A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. RESULTS: Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. CONCLUSIONS: High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

Gastric bypass in Type 2 diabetes with BMI < 30: weight and weight loss have a major influence on outcomes.

AIM: To assess factors influencing glycaemic control following gastric bypass surgery in patients with Type 2 diabetes and BMI< 30 kg/m(2) . METHODS: Prospective longitudinal study of 103 patients with inadequate glycaemic control who underwent gastric bypass surgery at Soonchunhyang University, Seoul, Korea (n = 66) and Min-Sheng General Hospital, Taipei, Taiwan (n = 37). Procedures were performed August 2009 to January 2011. Key outcome measures were excellent glycaemic control of Type 2 diabetes defined as HbA1c < 42 mmol/mol (≤6%); inadequate response defined as HbA1c > 53 mmol/mol (> 7%). Analysis was conducted using binary logistic regression, and cut-points obtained from receiver operator characteristics. RESULTS: Excellent glycaemic control was achieved in 31 (30%) at 1 year. Diabetes duration of < 7 years and BMI > 27 kg/m(2) provided independent predictors and useful cut-points. Likelihood of excellent glycaemic control for an individual could be estimated using loge (Odds) = -6.7 + (0.26 × BMI) + (-1.2 × diabetes duration). Baseline BMI of < 27 kg/m(2) and baseline C-peptide of < 2.0ng/ml, best predicted a poor glycaemic response. In those with favourable baseline characteristics percentage weight loss (%WL) had a dominant influence on glycaemic outcomes. Baseline C-peptide (> 2.4 ng/ml) and subsequent percentage weight loss (> 16%) were associated with excellent glycaemic control. Higher BMI was associated with greater percentage weight loss. CONCLUSION: In patients with Type 2 diabetes and BMI < 30 kg/m(2) , glycaemic response to gastric bypass is predicted by higher baseline BMI, shorter disease duration and higher fasting C-peptide. Post-surgery weight loss has a dominant effect. Baseline BMI and weight loss have a major influence on outcomes.

Classification and valuation of postoperative complications in a randomized trial of open versus laparoscopic ventral herniorrhaphy.

PURPOSE: Generic instruments used for the valuation of health states (e.g., EuroQol) often lack sensitivity to notable differences that are relevant to particular diseases or interventions. We developed a valuation methodology specifically for complications following ventral incisional herniorrhaphy (VIH). METHODS: Between 2004 and 2006, 146 patients were prospectively randomized to undergo laparoscopic (n = 73) or open (n = 73) VIH. The primary outcome of the trial was complications at 8 weeks. A three-step methodology was used to assign severity weights to complications. First, each complication was graded using the Clavien classification. Second, five reviewers were asked to independently and directly rate their perception of the severity of each class using a non-categorized visual analog scale. Zero represented an uncomplicated postoperative course, while 100 represented postoperative death. Third, the median, lowest, and highest values assigned to each class of complications were used to derive weighted complication scores for open and laparoscopic VIH. RESULTS: Open VIH had more complications than laparoscopic VIH (47.9 vs. 31.5%, respectively; P = 0.026). However, complications of laparoscopic VIH were more severe than those of open VIH. Non-parametric analysis revealed a statistically higher weighted complication score for open VIH (interquartile range: 0-20 for open vs. 0-10 for laparoscopic; P = 0.049). In the sensitivity analysis, similar results were obtained using the median, highest, and lowest weights. CONCLUSION: We describe a new methodology for the valuation of complications following VIH that allows a direct outcome comparison of procedures with different complication profiles. Further testing of the validity, reliability, and generalizability of this method is warranted.

Up-regulated macrophage migration inhibitory factor protects apoptosis of dermal fibroblasts in patients with systemic sclerosis.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been demonstrated to regulate the apoptosis of several cell types. Dysregulated apoptosis of fibroblasts has been implicated in a variety of fibrotic diseases, including systemic sclerosis (SSc). In this study, we investigated the role of MIF in the apoptosis of dermal fibroblasts. The concentrations of MIF were measured in sera and in culture supernatants of peripheral blood mononuclear cells (PBMCs) and dermal fibroblasts by enzyme-linked immunosorbent assay. The degree of apoptosis was determined by colorimetric assay, and signalling pathways were examined by Western blot. The results showed that serum levels of MIF were significantly higher in patients with SSc (n = 47) than in healthy controls (n = 56). Stimulation of PBMCs by anti-CD3 and anti-CD28 increased the production of MIF by fourfold over the constitutive levels. SSc dermal fibroblasts produced higher amounts of MIF than normal dermal fibroblasts. When treated with sodium nitroprusside (SNP), SSc dermal fibroblasts showed a lower degree of apoptosis compared with normal dermal fibroblasts. Exogenous MIF (1-100 ng/ml) inhibited SNP-induced apoptosis of dermal fibroblasts dose-dependently. Both extracellular regulated kinase (ERK) inhibitor (PD98059) and protein kinase B (Akt) inhibitor (LY294002) almost completely blocked the inhibitory effect of MIF on apoptosis. Furthermore, MIF increased the expression of Bcl-2, phospho-ERK and phospho-Akt activity in dermal fibroblasts. Taken together, our data suggest that MIF released by activated T cells and dermal fibroblasts decreases the apoptosis of dermal fibroblasts through activation of ERK, Akt and Bcl-2 signalling pathways, which might be associated with excessive fibrosis in SSc.

Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas.

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members. PATIENTS AND METHODS: To clarify the correlations between clinicopathologic profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method. RESULTS: Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour-node-metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors. CONCLUSION: Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas.

Validating risk-adjusted surgical outcomes: chart review of process of care.

OBJECTIVE: The primary purpose of this study was to validate risk-adjusted surgical outcomes as indicators of the quality of surgical care at US Department of Veterans Affairs (VA) hospitals. The secondary purpose was to validate the risk-adjustment models for screening cases for quality review. DESIGN: We compared quality of care, determined by structured implicit chart review, for patients from hospitals with higher and lower than expected operative mortality and morbidity (hospital-level tests) and between patients with high and low predicted risk of mortality and morbidity who died or developed complications (patient-level tests). SUBJECTS: 739 general, peripheral vascular and orthopedic surgery cases sampled from the 44 VA hospitals participating in the National VA Surgical Risk Study. MAIN OUTCOME MEASURES: A global rating of quality of care based on chart review. RESULTS: Ratings of overall quality of care did not differ significantly between patients from hospitals with higher and lower than expected mortality and morbidity. On some of the secondary measures, patient care was rated higher for hospitals with lower than expected operative mortality. At the patient level of analysis, those who died or developed complications and had a high predicted risk of mortality or morbidity were rated higher on quality of care than those with a low predicted risk of adverse outcome. CONCLUSIONS: The absence of a relationship between most of our measures of process of care and risk-adjusted outcomes may be due to an insensitivity of chart reviews to hospital-level differences in quality of care. Site visits to National VA Surgical Risk Study hospitals with high and low risk-adjusted mortality and morbidity have detected differences on a number of dimensions of quality. The patient-level findings suggest that the risk-adjustment models are useful for screening adverse outcome cases for quality of care review.

Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program.

OBJECTIVE: To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy. PATIENTS AND METHODS: A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates. RESULTS: The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay. CONCLUSIONS: Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy.

Overexpression of human telomerase RNA in Helicobacter pylori-infected human gastric mucosa.

Telomerase, an enzyme associated with cellular immortality and malignancy, plays an important role in cellular immortalization and tumorigenesis. Furthermore, overexpression of the RNA component of the telomerase, called human telomerase RNA (hTR), has been demonstrated in various human cancers as an early event. The pattern of hTR expression following Helicobacter pylori (H. pylori) infection in human gastric mucosa was investigated by a radioactive in situ hybridization (ISH) assay. Paraffin-embedded sections of 50 biopsy specimens taken from the gastric antrum of individual patients infected to different extents with H. pylori, as well as normal gastric mucosa, were studied. In normal gastric mucosa, only weak hTR expression was noted and the expression was limited to basal cells of the gastric glands. However, the degree of hTR expression gradually increased in parallel with the degree of H. pylori infection. The mean scores of gastric mucosa with mild, moderate and severe degrees of H. pylori infection were 2.3, 2.8, and 3.7 times higher than that of normal gastric mucosa, respectively. The results of this study suggested that up-regulation of hTR expression is a frequent and early event associated with H. pylori infection in the gastric mucosa and may play some role in gastric carcinogenesis. Sufficient synthesis of hTR during this early stage may be a prerequisite for telomerase reactivation to occur in gastric cancer.

Potentiation of early necrotic death of glucose-starved pheochromocytoma 12 cells by nerve growth factor.

Recently suggested is an arguable hypothesis that neurotrophins can induce necrosis but suppress apoptosis of target cells in some pathological conditions. We examined this hypothesis by tracing the type of NGF-promoted cell death occurring in a hypoglycemic condition at various angles, such as kinetic analyses, histological examinations of membrane alterations, morphological observations in ultra-structural changes, and determinations of DNA fragmentation. Glucose-starved cell death consisted of two kinetically different stages, suggesting that it be mixed with early and delayed death. Several lines of evidence revealed that NGF prominently enhanced the early death with necrotic characters. By contrast, apoptotic characters of glucose-starved delayed death were not much affected by NGF. Nifedipine, a voltage-gated calcium channel blocker, could completely compensate for the enhancement of the early glucose-starved death by NGF. Interestingly, the NGF-promoted cell death was also blocked by cycloheximide that did not keep PC12 cells alive from glucose starvation. Therefore, all the data in this study suggest that NGF accelerates the early necrosis of glucose-starved cell death probably through the alterations of intracellular calcium ions and protein syntheses.

Transforming growth factor-beta induces apoptosis in activated murine T cells through the activation of caspase 1-like protease.

Transforming growth factor-beta (TGF-beta) has been known as a potent immunosuppressive cytokine that can induce apoptosis in lymphoid cells. We established an IL-2-independent cell line, CTLL-2A, from murine T cell line CTLL-2. CTLL-2A expressed higher levels of CD95, CD69, and CD18 molecules than CTLL-2 did, suggesting a more activated state in CTLL-2A than in the CTLL-2 by phenotype. Exposing both CTLL-2 and CTLL-2A to TGF-beta results in differential apoptosis patterns defined by DNA fragmentation and plasma membrane alteration. Among the bcl-2 family members, bcl-2, bcl-w, and bcl-x(L) were also differently expressed in these two cell lines. In CTLL-2A, bcl-x(L) was amplified as a major anti-apoptotic molecule, and TGF-beta-induced cell death was more enhanced than in the original cell line. Caspase 1-like protease was activated by TGF-beta treatment and consequently it cleaved bcl-x(L) in CTLL-2A. TGF-beta-induced DNA fragmentation and cleavage of bcl-x(L) were inhibited by pretreatment with tetra peptide caspase 1 inhibitor, YVAD.cmk. These findings suggest that TGF-beta induces cell death in activated murine T cells through cleavage of bcl-x(L) via activated caspase 1-like protease, which may act as an important executor in that process.

Platelet-derived growth factor-induced H(2)O(2) production requires the activation of phosphatidylinositol 3-kinase.

Autophosphorylation of the platelet-derived growth factor (PDGF) receptor triggers intracellular signaling cascades as a result of recruitment of Src homology 2 domain-containing enzymes, including phosphatidylinositol 3-kinase (PI3K), the GTPase-activating protein of Ras (GAP), the protein-tyrosine phosphatase SHP-2, and phospholipase C-gamma1 (PLC-gamma1), to specific phosphotyrosine residues. The roles of these various effectors in PDGF-induced generation of H(2)O(2) have now been investigated in HepG2 cells expressing various PDGF receptor mutants. These mutants included a kinase-deficient receptor and receptors in which various combinations of the tyrosine residues required for the binding of PI3K (Tyr(740) and Tyr(751)), GAP (Tyr(771)), SHP-2 (Tyr(1009)), or PLC-gamma1 (Tyr(1021)) were mutated to Phe. PDGF failed to increase H(2)O(2) production in cells expressing either the kinase-deficient mutant or a receptor in which the two Tyr residues required for the binding of PI3K were replaced by Phe. In contrast, PDGF-induced H(2)O(2) production in cells expressing a receptor in which the binding sites for GAP, SHP-2, and PLC-gamma1 were all mutated was slightly greater than that in cells expressing the wild-type receptor. Only the PI3K binding site was alone sufficient for PDGF-induced H(2)O(2) production. The effect of PDGF on H(2)O(2) generation was blocked by the PI3K inhibitors LY294002 and wortmannin or by overexpression of a dominant negative mutant of Rac1. These results suggest that a product of PI3K is required for PDGF-induced production of H(2)O(2) in nonphagocytic cells, and that Rac1 mediates signaling between the PI3K product and the putative NADPH oxidase.

Differentiation of hamster liver oval cell following Clonorchis sinensis infection.

Oval cells which appear in the liver after hepatic injuries are suspected to be progenitor cells for both hepatocytes and bile duct cells. Oval cell isolated from the livers of the hamsters treated with diethylnitrosamine and 2-acetylaminofluorene and infected with Clonorchis sinensis (CS). cultured for 2 weeks and evaluated for differentiation and plasticity by electron microscopy and immunohistochemistry. In the CS-uninfected group, glycogen granules and peroxisomes were noted in the cells that were cultured for 2 weeks. Starting at 1 week postculture, immunoreactivity of the cells to cytokeratin 19 markedly decreased but that to albumin and alpha-fetoprotein gradually increased. This means that oval cells isolated from hamsters that were not infected with CS differentiated toward hepatocyte lineage. However, in the CS-infected group, cultured cells contained numerous rough endoplasmic reticulum and showed immunoreactivity that was generally in reverse to that of CS-uninfected group, meaning that cells isolated following CS infection were primed by CS and differentiated toward bile duct cell lineage. The results of this study suggested that oval cells are indeed bipolar progenitor cells for hepatocytes and bile duct cells and can differentiate toward either lineage depending upon the priming factor.

Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis.

Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). The mRNA level of cyclin D1 was increased 1.2-fold in adenocarcinomas but not significantly in adenomas, when compared with normal rat colonic mucosa (p<0.05). The cyclin E mRNA level was increased 2.7-fold in adenomas and 3.3-fold in adenocarcinomas (p<0.05). The PCNA mRNA level was also increased 1.9-fold in adenomas and 1.8-fold in adenocarcinomas (p<0.05). Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression.

Telomerase RNA expression during progression of gastric cancer.

Telomerase, an enzyme associated with cellular immortality and malignancy, is stringently repressed in most normal somatic cells but is reactivated in malignant tumor cells and immortal cell lines, indicating that activation of telomerase may play an important role in tumorigenesis and immortalization. The pattern of human telomerase RNA (hTR) expression during progression of gastric cancer was investigated by a radioactive in situ hybridization (ISH) assay. Paraffin-embedded sections of 85 archival samples from Korean patients with benign and various malignant stages of gastric carcinomas as well as normal and regenerative tissues were studied. In normal gastric mucosae and regenerative lesions such as chronic peptic ulcer and hyperplastic polyps, only a weak degree of hTR expression was noted, and the expression was limited to basal cells of the gastric glands. Also, a moderate degree of hTR expression was present in the germinal centers of lymphoid follicles present in the submucosa. In tubular adenomas, the degree of hTR expression was also generally weak, but, unlike normal gastric mucosa, the expression was rather diffuse and occasionally focal in distribution. However, moderate to intense and usually diffuse hTR expression was present in all cancerous tissues at different stages. Although some heterogeneity of hTR expression was noted, there was a tendency for intensity of hTR expression to increase gradually as the cancer progressed to a more advanced stage. Our results indicate that upregulation of telomerase expression is associated with gastric cancer development or plays some role in gastric carcinogenesis. Upregulation of hTR expression detected by ISH assay may be a useful marker or tool for the early detection of gastric cancer.

Relation of surgical volume to outcome in eight common operations: results from the VA National Surgical Quality Improvement Program.

OBJECTIVE: To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity. SUMMARY BACKGROUND DATA: In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial. METHODS: The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA). RESULTS: Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found. CONCLUSIONS: In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

Prognostic models of thirty-day mortality and morbidity after major pulmonary resection.

BACKGROUND: A part of the prospective, multi-institutional National Veterans Affairs Surgical Quality Improvement Program was developed to predict 30-day mortality and morbidity for patients undergoing a major pulmonary resection. METHODS: Perioperative data were acquired from 194,319 noncardiac surgical operations at 123 Veterans Affairs Medical Centers between October 1, 1991, and August 31, 1995. Current Procedural Terminology code-based analysis was undertaken for major pulmonary resections (lobectomy and pneumonectomy). Preoperative, intraoperative, and outcome variables were collected. The 30-day mortality and morbidity models were developed by means of multivariable stepwise logistic regression with the preoperative and intraoperative variables used as independent predictors of outcome. RESULTS: A total of 3516 patients (mean age 64 9 years) underwent either lobectomy (n = 2949) or pneumonectomy (n = 567). Thirty-day mortality was 4.0% for lobectomy (119/2949) and 11.5% for pneumonectomy (65/567). The preoperative predictors of 30-day mortality were albumin, do not resuscitate status, transfusion of more than 4 units, age, disseminated cancer, impaired sensorium, prothrombin time more than 12 seconds, type of operation, and dyspnea. When the intraoperative variables were considered, intraoperative blood loss was added to the preoperative model. In the presence of these intraoperative variables in the model, do not resuscitate status and prothrombin time more than 12 seconds were only marginally significant. Thirty-day morbidity, defined as the presence of 1 or more of the 21 predefined complications, was 23.8% for lobectomy (703/2949) and 25.7% for pneumonectomy (146/567). In multivariable models, independent preoperative predictors (P <.05) of 30-day morbidity were age, weight loss greater than 10% in the 6 months before surgery, history of chronic obstructive pulmonary disease, transfusion of more than 4 units, albumin, hemiplegia, smoking, and dyspnea. When intraoperative variables were added to the preoperative model, the duration of operation time and intraoperative transfusions were included in the model and albumin became marginally significant. CONCLUSIONS: This analysis identifies independent patient risk factors that are associated with 30-day mortality and morbidity for patients undergoing a major pulmonary resection. This series provides an initial risk-adjustment model for major pulmonary resections. Future refinements will allow comparative assessment of surgical outcomes and quality of care at many institutions.

Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study.

OBJECTIVE: To improve the precision and reliability of estimates of the association between preoperative serum albumin concentration and surgical outcomes. DESIGN: Prospective observational study. Patients were followed up for 30 days postoperatively. Multiple logistic regression models were developed to evaluate serum albumin level as a predictor of operative mortality and morbidity in relation to 61 other preoperative patient risk variables. SETTING: Forty-four tertiary care Veterans Affairs (VA) medical centers. PATIENTS: A total of 54215 major noncardiac surgery cases from the National VA Surgical Risk Study. MAIN OUTCOME MEASURES: Thirty-day operative mortality and morbidity. RESULTS: A decrease in serum albumin from concentrations greater than 46 g/L to less than 21 g/L was associated with an exponential increase in mortality rates from less than 1% to 29% and in morbidity rates from 10% to 65%. In the regression models, albumin level was the strongest predictor of mortality and morbidity for surgery as a whole and within several subspecialties selected for further analysis. Albumin level was a better predictor of some types of morbidity, particularly sepsis and major infections, than other types. CONCLUSIONS: Serum albumin concentration is a better predictor of surgical outcomes than many other preoperative patient characteristics. It is a relatively low-cost test that should be used more frequently as a prognostic tool to detect malnutrition and risk of adverse surgical outcomes, particularly in populations in whom comorbid conditions are relatively frequent.