A Novel Preoperative Patient Survey Predicts Adverse Patient Outcomes-Implementation and Preliminary Results of the Tennessee Preoperative Assessment Tool.

BACKGROUND: Accurate preoperative risk stratification remains elusive. Existing tools are often missing important patient-reported and functional factors. We sought to implement a novel tool, with dynamic functional data and comorbidity variables, to define factors which predict postoperative outcomes. MATERIALS AND METHODS: We expanded a previously validated functional questionnaire to create the Tennessee Preoperative Assessment Tool (TPAT). Unique elements included change in functional status, usual and best activity tolerance, and development of new conditions. The survey was administered to all new patients seen in several surgery clinics from July 2021 to June 2022. RESULTS: A total of 1950 patients completed the survey. Of the completed surveys, 197 patients underwent an elective, inpatient, abdominal surgery and were included in the study. Several patient-reported factors were associated with poor postoperative outcomes. For example, decrease in functional activity in the previous 60 days (n = 50; 25.4%) was a strong predictor of poor postoperative outcomes including readmission (30-day: 8.8% vs .0%; P = .034), wound dehiscence (12.0% vs 3.4%; P = .022), blood transfusion (6.0% vs .0%; P = .003), sepsis (4.0% vs .0%; P = .015), and wound infection (18.0% vs 6.8%; P = .076). DISCUSSION: In this preliminary implementation study, patients undergoing elective, inpatient, abdominal surgery, utilization of a novel, patient-reported survey tool proactively identifies patients at risk of clinically relevant postoperative outcomes. Patient-reported decreased activity in the 60 days prior to surgeon evaluation was associated with several adverse postoperative outcomes. Additionally, this study demonstrates that the TPAT can be seamlessly integrated into the usual clinical workflow and is hypothesis generating for future interventional studies.

Primary cutaneous melanoma arising in a long-standing irradiated keloid.

Ionizing radiation has been used therapeutically for a variety of clinical conditions, including treatment of hypertrophic keloids. Keloids may rarely be associated with malignancy, but the use of low-dose ionizing radiation is associated with an increased risk of cutaneous malignancies. We describe a case in which a primary desmoplastic melanoma arose in a long-standing, previously irradiated keloid.

The effect of multiple wire localization in breast conservation.

Variability exists regarding the surgical technique in breast conservation therapy. The purpose of this project was to determine differences between single (SH) or flanking (FH) hooked needle localization wires used for nonpalpable breast lesions. We retrospectively reviewed 201 female patients at a single institution from 2004 to 2008. All patients had biopsy-proven ductal carcinoma in situ or invasive disease. Comparisons were made in regard to margin status, reoperation, completion mastectomy, size of lesion, and breast specimen volume. SH was placed in 122 patients (61%) and FH in 79 patients (39%). In SH, 23 patients (18%) had positive margins and 31 patients (25%) had reoperations as compared with 31 patients (25%) with positive margin and 36 patients (44%) in the FH cohort (P = 0.039 and 0.0037). Average lesion size and volume resected was 1.5 cm and 137 cm(3) in SH and 2.85 cm and 188 cm(3) in FH, respectively (P = 0.0001 and 0.006). Positive margins were associated with lesion size and not volume of tissue excised. The FH technique was associated with more positive margins, reoperation, and completion mastectomy.

Odontogenic ameloblast associated protein as a novel biomarker for human breast cancer.

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using chi2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage (P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy (P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II (P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV (P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage (P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.

The STAT4 and STAT6 pathways in pancreatitis-associated lung injury.

BACKGROUND: The STAT pathways are integral to the inflammatory response and these proteins provide a direct link between the cytokine receptors and cytokine-induced gene transcription. We examined the roles of STAT4 and STAT6 in lung injury after caerulein-induced severe acute pancreatitis. We hypothesized that a modified organ expression of cytokines and chemokines that occurs in transgenic mice may affect the systemic response to severe acute pancreatitis. METHODS: Acute pancreatitis [13-hourly intraperitoneal injections of caerulein (50 microg/kg body weight, 0.2 mL) or the same volume of saline] was induced in wild-type (BALB/c) and transgenic (STAT4 or STAT6) mice of the same background, 7 to 8 weeks old. The pancreatic and lung tissues were collected at 1, 6, 12, and 24 h after the completion of caerulein administration. Tissue leukocyte sequestration was assessed by myeloperoxidase (MPO) activity. Standard histological staining hematoxylin and eosin was performed and blindly scored by a pathologist for evidence of lung injury (pulmonary edema, accumulations of neutrophils and mononuclear cells, thickness of alveolar-capillary membrane, perivascular infiltrate, and hemorrhage). RESULTS: Caerulein-treated wild-type mice exhibited increased lung injury score at 1 through 12 h, as compared to saline controls. As compared to wild-type, STAT6-deficient mice had increased lung injury from 1 to 6 h, with full recovery by 12 h. An opposite pattern was observed in STAT4-deficient mice with mild injury seen at 1 and 6 h, and maximal injury at 12 h. MPO activity was significantly increased at 6 h in caerulein-treated wild-type mice compared to saline-treated controls. Caerulein-treated STAT6 and STAT4 mice had markedly increased MPO activity as compared with their saline controls during the first 6 h. Both caerulein-treated STAT4- and STAT6-deficient mice had significantly increased MPO activity in comparison with wild-type mice with pancreatitis at 6 h. CONCLUSION: We found the maximal lung injury after caerulein-induced pancreatitis occurred at different time-points in STAT4 and STAT6-deficient mice. These temporal differences may suggest alternative roles in the systemic inflammatory response associated with pancreatitis.

Activation of nuclear factor kappa B and severe hepatic necrosis may mediate systemic inflammation in choline-deficient/ethionine-supplemented diet-induced pancreatitis.

OBJECTIVES: We hypothesized that hepatic injury is associated with severe acute pancreatitis (SAP) and may result in lung injury through nuclear factor kappa B (NF-kappaB)-dependent inflammatory mediators. The study characterizes the timing and determines the involvement of selected cytokines and chemokines in the pathogenesis of hepatocellular injury associated with SAP. METHODS: The SAP was induced in C57BL/6 mice by feeding a choline-deficient/ethionine-supplemented diet. The mice were killed at 12-hour intervals for 96 hours. Terminal deoxynucleotidyl transferase-mediated nick-end labeling staining was used to determine the extent of hepatic apoptosis. The NF-kappaB activation in nuclear protein extracts from liver tissue was measured using a sensitive RelA enzyme-linked immunoadsorbent assay. Tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein (MIP) 2, and keratinocyte-derived chemokine (KC) levels in homogenates of liver and lung tissues were measured by enzyme-linked immunoadsorbent assay. The SAP-associated neutrophil lung inflammation was measured as tissue myeloperoxidase activity. RESULTS: The SAP and subsequent liver injury were confirmed by histological analysis and rises in plasma amylase and transaminase levels. Severe hepatocellular apoptosis was detected at 36 and 48 hours after the diet initiation by terminal deoxynucleotidyl transferase-mediated nick-end labeling staining (P < 0.05) and subsequently progressed to hepatic necrosis. Liver NF-kappaB activation was detected at 36 hours (P < 0.05) and followed by a sharp increase in hepatocellular levels of interleukin 6, MIP-2, and KC at 72 hours and thereafter (P < 0.05). Levels of MIP-2 and KC in lung tissue were also elevated at 72 hours (P < 0.05) and closely correlated with increased myeloperoxidase activity and increased inflammatory cell infiltrate in the lung. CONCLUSIONS: Choline-deficient/ethionine-supplemented diet-induced SAP is accompanied with hepatocellular apoptosis and eventual necrosis. This injury is associated with the hepatic NF-kappaB activation leading to the production of NF-kappaB-dependent cytokines and chemokines in the liver, which may mediate the lung injury.

Do adverse histopathologic findings in colorectal cancer patients explain disparate outcomes?

We have previously reported reduced overall and disease-free survival in black patients from a 10-year retrospective review of 668 patients from tumor registry data. This study of 213 patients reports the analysis of available archived tissue from a city hospital (n=44 patients, 53% black) and from a university medical center (n=169, 10.6% black). Two senior pathologists independently reviewed slides for predetermined histologic criteria reported to correlate with survival: tumor type, stage at diagnosis, character of invasion, vascular or perineural invasion, the presence of residual adenoma, the presence of a Crohn's-like reaction and number of nodes resected. Differences in discrete variables were compared using the Chi-squared test. Differences in continuous variables were analyzed using independent t tests. No statistically significant differences were identified in tumor stage or type by institution or race. In patients treated at the city hospital, there was a higher incidence of infiltrating tumors (85% vs. 61%, p<0.001), vascular invasion (70% vs. 36%, p<0.05) and residual adenoma (84% vs. 39%, p<0.05); however, no differences by race were identified. Blacks at both hospitals had significantly more perineural invasion (81% vs. 30%, p<0.05) and Crohn's-like reaction (64% vs. 30%, p<0.05) when compared to white patients, although there was no difference between hospitals. The total number of lymph nodes resected was higher at the university hospital (17.0 vs. 8.9, p<0.001). There were no differences in number of nodes resected at either institution by race. Histopathologic findings did not explain the apparent disparity in survival. The differences in number of nodes harvested may suggest inadequate resection or insufficient recovery of nodes by the pathologist.

Pulmonary MnSOD is nitrated following hepatic ischemia-reperfusion.

BACKGROUND: Ischemia-reperfusion (I/R) of remote organs is a common cause of lung injury. We observed that lung injury after partial hepatic I/R in mice coincides with the appearance of 3-nitrotyrosine (NT) in the lung tissue, a marker of peroxynitrite involvement and oxidant stress. Peroxynitrite can cause mitochondrial dysfunction by inactivation of manganese superoxide dismutase (MnSOD), the major antioxidant enzyme in mitochondria. Our aims were to examine whether pulmonary MnSOD is a target of nitration following hepatic I/R and whether nitrated MnSOD (N-MnSOD) correlates with acute lung injury. METHODS: Five 20-25-g male C57BL/6 mice underwent laparotomy, and atraumatic occlusion of the portal and arterial blood supply to the upper three lobes of the liver for 90 min. This warm ischemic period was followed by 4 h of reperfusion, and the animals were then euthanized. Lung injury was assessed by LDH and protein levels in bronchoalveolar lavage (BAL) fluid. Pulmonary MnSOD activity in pulmonary homogenates was measured by the cytochrome c reduction method. The presence of N-MnSOD was determined by immunoprecipitation (IP) and Western Blot analysis. Controls (N = 5) underwent sham operation. RESULTS: Elevated plasma transaminases confirmed hepatic injury. Lung injury was demonstrated by elevation in BAL protein and LDH levels (495.7 (48.4) versus 644.9 (37.3) [p < 0.05] and 56.5 (11.8) versus 345.2 (80) [p < 0.01], respectively). Immunoprecipitation and Western blot demonstrated N-MnSOD in the lung tissue of I/R animals but not controls. MnSOD activity decreased following I/R (8.1 (0.7) versus 10.8 (0.3) [p < 0.05]). CONCLUSIONS: Pulmonary MnSOD is both nitrated and inactivated following hepatic I/R and is associated with acute lung injury. These findings suggest that MnSOD incapacitance may contribute to I/R-induced lung injury and provide a therapeutic target in attenuating multisystem injury following hepatic I/R.

Endotoxin potentiates lung injury in cerulein-induced pancreatitis.

BACKGROUND: In this study we examine the effect of endotoxin (lipopolysaccharide) on lung injury in the setting of acute pancreatitis (AP). METHODS: Twelve hourly injections of cerulein (50 microg/kg/h) were used to induce pancreatitis in mice. Intraperitoneal lipopolysaccharide (LPS [6 mg/kg]) was administered 24 hours after the initial cerulein injection. Twenty-four hours after LPS injection, myeloperoxidase (MPO) activity, nuclear factor (NF)-kappaB activation, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and chemokines MIP-2 and KC levels were measured in pancreas, liver, and lung tissues. Four groups of mice were studied: cerulein-LPS, cerulein-saline, saline-LPS, and saline-saline treated mice. RESULTS: Elevated serum lipase confirmed pancreatitis in cerulein treated mice. Lung MPO activity was significantly increased in the cerulein-LPS group. NF-kappaB was activated in the liver but not in pancreas and lung tissue. Chemokines MIP-2 and KC were elevated in pancreatic tissue only. CONCLUSIONS: These findings suggest that gram-negative infections may be an important predisposition for the development of adult respiratory distress syndrome in the setting of AP and that hepatic NF-kappaB may mediate multisystem injury.

Systemic nf-kappaB activation in a transgenic mouse model of acute pancreatitis.

BACKGROUND: Transcription factor NF-kappaB has been implicated in numerous human inflammatory diseases. Acute pancreatitis can result in remote tissue injury, but the involved mechanisms are unknown. This study evaluates the role of systemic NF-kappaB activation in the pathogenesis of lung inflammation in a transgenic pancreatitis model. MATERIALS AND METHODS: Using transgenic mice expressing photinus luciferase controlled by an NF-kappaB-dependent promoter, luciferase activity was measured in pancreas, liver, and lung tissues as a surrogate marker of NF-kappaB activity. Luciferase activity was measured by in vivo bioluminescence and correlated to an in vitro luciferase assay of organ homogenates. Following measurement of luciferase activity in uninjured animals, these animals were fed a choline-deficient, ethionine supplemented diet for 48 h to induce pancreatitis, and luciferase activity was then measured at 48, 60, 72, and 96 h. Lung inflammation was determined by total nucleated cell counts in bronchoalveolar lavage (BAL) fluid. RESULTS: Bioluminescence detected increased luciferase activity over the upper abdominal region at 48 and 60 h (P < 0.05), and over the thorax at 60 and 72 h (P < 0.05). Luciferase assays showed significantly increased luciferase activity in both liver and lung tissue at 48 (liver = P < 0.005, lung = P < 0.05) and 60 h (liver = P < 0.05, lung = P < 0.05) compared to activity in uninjured controls. Total nucleated cell counts in BAL fluid were significantly increased at 72 h (P < 0.05) compared with controls. CONCLUSION: In this model, NF-kappaB binding activity is increased in the liver and lung. These data suggest that the liver modulates pancreatitis-induced systemic inflammatory response syndrome (SIRS) and suggest strategies to reduce multisystem injury.