Ideal timing of early cholecystectomy for acute cholecystitis: An ACS-NSQIP review.

BACKGROUND: Current guidelines fail to specify optimal timing of early cholecystectomy for acute cholecystitis. We hypothesized delaying operation past hospital day (HD) 2 would result in increased 30-day morbidity and mortality. METHODS: The ACS-NSQIP database was queried from 2012 to 2015 for all cholecystectomies for acute cholecystitis from HD 1-7. RESULTS: Delay in cholecystectomy to HD 3-7 was observed in 30% of patients with acute cholecystitis. Patients undergoing operation on HD 3-7 were older with higher rates of comorbidities (median 58yrs; 66%) than HD 1 (48yrs; 51%) or HD 2 (51yrs, p < 0.001; 55%, p < 0.001). Operations on HD 3-7 had increased 30-day mortality (1.0%) and morbidity (12%) in comparison to HD 1 (0.3%, 7%) or HD 2 (0.5%, p < 0.001; 8%, p < 0.001). On multivariable analysis, HD was an independent predictor of mortality (OR 1.15, 95% CI [1.04-1.26]). CONCLUSIONS: Acute cholecystitis should be treated with an urgent operation within 2 days of admission due to increased morbidity and mortality when delayed past HD 2.

Population-level outcomes of early versus delayed appendectomy for acute appendicitis using the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: The optimal timing of appendectomy for acute appendicitis has been analyzed with mixed results. We hypothesized that delayed appendectomy would be associated with increased 30-d morbidity and mortality. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients undergoing nonelective appendectomy from 2012 to 2015 with a postoperative diagnosis of appendicitis. Patients were grouped based on hospital day (HD) of operation. Primary outcomes included 30-d mortality and major complications. Logistic regression was performed to determine predictors of major morbidity and mortality. RESULTS: From 2012 to 2015, 112,122 patients underwent appendectomy for acute appendicitis. Appendectomies performed on HD 3 had significantly worse outcomes as demonstrated by increased 30-d mortality (0.6%) and all major postoperative complications (8%) in comparison with operations taking place on HD 1 (0.1%; 3.4%) or HD 2 (0.1%, P < 0.001; 3.6%, P < 0.001). In subgroup analysis, open operations had significantly higher mortality and major postoperative complications, including organ/space surgical site infections (4.6% open versus 2.1% laparoscopic; P < 0.001). Patients with decreased baseline physical status by the American Society of Anesthesiologists Physical Status class had the worst outcomes (1.5% mortality; 14% major complications) when operation was delayed to HD 3. Logistic regression revealed higher American Society of Anesthesiologists Physical Status class and open operations as predictors of major complications; however, HD was not (P = 0.2). CONCLUSIONS: Data from the American College of Surgeons National Surgical Quality Improvement Program demonstrate similar outcomes of appendectomy for acute appendicitis when the operation is performed on HD 1 or 2; however, outcomes are significantly worse for appendectomies delayed until HD 3. Increased complications in this group are likely not attributable to HD of operation, but rather decreased baseline health status and procedure type.

Effects of ketamine on endotoxin and traumatic brain injury induced cytokine production in the rat.

BACKGROUND: Endotoxemia from lipopolysaccharide (LPS) induces systemic cytokine production, whereas traumatic brain injury (TBI) increases intracerebral cytokine production. In anesthetic doses, ketamine has potent anti-inflammatory properties. However, its anti-inflammatory effects at subanesthetic doses and its effects on TBI-induced inflammation have not been fully investigated. We hypothesized that ketamine would attenuate both LPS- and TBI-induced inflammatory responses. METHODS: Male rats received intraperitoneal (i.p.) ketamine (70 mg/kg, 7 mg/kg, or 1 mg/kg) or saline 1 hour before LPS (20 mg/kg i.p.) or saline. Five hours after LPS, rats were killed. Serum was collected for cytokine analysis. In other experiments, male rats were given ketamine (7 mg/kg i.p.) or saline 1 hour before induction of TBI with controlled cortical impact (or sham). One hour and 6 hours after injury, brain was extracted for analysis of cerebral edema and cytokine production. RESULTS: LPS increased the serum concentrations of interleukin (IL)-1α, IL-1ß, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ. Ketamine dose dependently attenuated these changes. TBI caused cerebral edema and increased concentrations of cerebral IL-1α, IL-1ß, IL-6, IL-10, and tumor necrosis factor-α. However, ketamine had minimal effect on TBI-induced inflammation. CONCLUSIONS: Although ketamine did not seem to exert any beneficial effects against TBI in the rat, it did not exacerbate cytokine production or enhance cerebral edema as some studies have suggested.

Ketamine suppresses LPS-induced bile reflux and gastric bleeding in the rat.

BACKGROUND: Although ketamine has many beneficial effects in a rat model of noninfectious inflammation with lipopolysaccharide (LPS), its effects on gut ileus are unknown. We hypothesized that ketamine would improve LPS-induced ileus and therefore examined its effects on gastric emptying and intestinal transit as well as duodenogastric bile reflux and associated gastric bleeding. METHODS: Male rats received saline or ketamine (7 mg/kg ip) 1 hour before saline or LPS (20 mg/kg ip) for 5 hours. Thirty minutes before killing, rats received orogastric rhodamine B isothiocyanate-labeled dextran and 5 minutes later fluorescein isothiocyanate-labeled dextran via a duodenal catheter. GI contents were collected for dye, bile acid, and hemoglobin (index of bleeding) determinations. RESULTS: LPS significantly impaired intestinal transit and increased duodenogastric bile reflux and gastric luminal hemoglobin content. Ketamine improved intestinal transit, prevented LPS-induced bile reflux, and diminished gastric bleeding. In mechanistic studies, ketamine also attenuated LPS-induced upregulation of the proinflammatory genes inducible nitric oxide synthase and cyclo-oxygenase-2 in the stomach but preserved expression of the anti-inflammatory gene heme-oxygenase-1 (Western blot). CONCLUSIONS: These data suggest that ketamine may prevent LPS-induced gastric bleeding by decreasing bile reflux through improved intestinal transit or by local changes in nitric oxide, prostaglandin, and carbon monoxide metabolism.

Laparotomy attenuates lipopolysaccharide-induced gastric bleeding in the rat.

Lipopolysaccharide (LPS) increases systemic inflammation and causes duodenogastric reflux of bile and gastric bleeding. Laparotomy prevents gastric injury from the luminal irritant bile, but its effects on LPS-induced gastric injury are unknown. We hypothesized that laparotomy would diminish inflammation and attenuate gastric bleeding caused by LPS. In the rat, laparotomy, done either before or after administration of LPS, attenuated LPS-induced bile reflux, gastric bleeding, and cyclooxygenase-2, but not inducible nitric oxide synthase, expression when compared to controls given LPS. Laparotomy also blunted LPS-induced changes in serum cytokine production. These data suggest that laparotomy has gastroprotective effects by preventing LPS-induced bile reflux and gastric bleeding and by a mechanism mediated, at least in part by cyclooxygenase-2.

Ketamine-induced hepatoprotection: the role of heme oxygenase-1.

Lipopolysaccharide (LPS) causes hepatic injury that is mediated, in part, by upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Ketamine has been shown to prevent these effects. Because upregulation of heme oxygenase-1 (HO-1) has hepatoprotective effects, as does carbon monoxide (CO), an end product of the HO-1 catalytic reaction, we examined the effects of HO-1 inhibition on ketamine-induced hepatoprotection and assessed whether CO could attenuate LPS-induced hepatic injury. One group of rats received ketamine (70 mg/kg ip) or saline concurrently with either the HO-1 inhibitor tin protoporphyrin IX (50 micromol/kg ip) or saline. Another group of rats received inhalational CO (250 ppm over 1 h) or room air. All rats were given LPS (20 mg/kg ip) or saline 1 h later and euthanized 5 h after LPS or saline. Liver was collected for iNOS, COX-2, and HO-1 (Western blot), NF-kappaB and PPAR-gamma analysis (EMSA), and iNOS and COX-2 mRNA analysis (RT-PCR). Serum was collected to measure alanine aminotransferase as an index of hepatocellular injury. HO-1 inhibition attenuated ketamine-induced hepatoprotection and downregulation of iNOS and COX-2 protein. CO prevented LPS-induced hepatic injury and upregulation of iNOS and COX-2 proteins. Although CO abolished the ability of LPS to diminish PPAR-gamma activity, it enhanced NF-kappaB activity. These data suggest that the hepatoprotective effects of ketamine are mediated primarily by HO-1 and its end product CO.

Neurothekeoma.

OBJECTIVES: The purpose of this study was to investigate and share the experiences at The University of Texas M. D. Anderson Cancer Center in diagnosing, treating, and following patients with neurothekeoma. We report 13 cases. STUDY DESIGN: Case series. The clinical, surgical, and pathology records of the 7 patients with neurothekeoma treated at M. D. Anderson Cancer Center were retrospectively reviewed. In addition, the pathology records of 6 patients reviewed by the Department of Pathology for diagnosis only were retrospectively reviewed. RESULTS: Nine patients were women. Their mean age was 30 years (median, 24 years). Six of the lesions were on the head or neck, 4 were on extremities, and 2 were on the trunk, and the location of 1 was not recorded. Two lesions had been previously diagnosed, histologically, as leiomyosarcomas, 1 as a malignant nodular hidradenoma, and 1 as a clear cell hidradenoma. All the lesions had the characteristic nested pattern of growth, with various degrees of myxoid background. Mitotic figures and marked cellular pleomorphism were not common. Six cases were treated with wide local excision. A lesion of the nasal ala was excised by using Mohs micrographic surgery. Most cases were limited to the dermis, but 2 lesions infiltrated subcutaneous tissue and skeletal muscle. All patients were without evidence of disease at 8 months median follow-up range (0 to 35 months). CONCLUSION: Neurothekeoma is a benign neoplasm occurring usually in women and commonly in the head and neck. Because it may be locally invasive, treatment with wide local excision using frozen section control of margins is recommended. Care must be taken in the pathologic diagnosis of cutaneous neoplasms, and neurothekeoma should be considered in the differential diagnosis for spindle cell lesions. SIGNIFICANCE: Neurothekeoma is commonly misdiagnosed, pathologically and clinically, and it can be treated successfully with surgical excision. EBM RATING: C.