Gastric granulomas and Helicobacter pylori: An incidental relationship.

AIMS: Studies investigating the relationship between granulomatous gastritis (GG) and Helicobacter pylori infection have been largely inconclusive. This study was designed to determine whether the analysis of a very large number of patients would provide clearer answers evaluate the association between H. pylori infection and gastric granulomas. METHODS: We used a large national database of clinicopathological data to extract 1,673,086 patients who underwent esophagogastroduodenoscopy with gastric biopsies between 2008 and 2020. In a case-control study, we evaluated the occurrence of H. pylori infection in patients with and without gastric granulomas. We also explored other clinical and histopathological associations. RESULTS: H. pylori infection was present in 44 of 496 (8.9%) patients with gastric granulomas, compared to 158,949 (9.5%) in the control group (OR = 0.93, 95% CI = 0.68-1.26). Of the 129 patients with gastric granulomas, 50 had documented inflammatory bowel disease. CONCLUSIONS: The results of this study show that the prevalence of H. pylori infection in patients with gastric granulomas is essentially identical to that of controls with no evidence of granulomas or granulomatous disease. When patients with and without a plausible-known association for gastric granulomas were analyzed separately, the prevalence of H. pylori infection remained remarkably similar in GG patients and controls. Considering the very large numbers of patients with gastric biopsies analyzed in this study, we submit that there is no basis for suggesting that H. pylori is etiologically related to GG.

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

Inverse association of esophageal eosinophilia and Barrett esophagus.

BACKGROUND: The high frequency of gastroesophageal reflux symptoms reported in patients with eosinophilic esophagitis has suggested that the two disorders may be associated; however, few studies have systematically addressed this issue. GOALS: To determine the frequency of the simultaneous occurrence of esophageal eosinophilia and Barrett esophagus and define the clinical characteristics of patients with both conditions. STUDY: From a national pathology database of patients who had esophagogastroduodenoscopy with mucosal biopsies we extracted patients with a diagnosis of Barrett mucosa, eosinophilic esophagitis pattern of injury [(≥15 eosinophils/high-power field (HPF)], or both. We then evaluated their respective clinicopathologic associations. RESULTS: Among 233,662 unique patients evaluated during the study period, Barrett mucosa without increased eosinophils was diagnosed in 29,733 patients (12.7%; median age 63 y; 67.6% male); eosinophil counts of ≥15/HPF were recorded in 9509 patients without Barrett mucosa (4.1%; median age 44 y; 63.9% male). A simultaneous diagnosis of Barrett mucosa and ≥15 eosinophils/HPF in the squamous epithelium and was made in 404 unique patients (0.17%; median age 56 y; 79.5% male). The observed prevalence of the simultaneous occurrence of the two conditions was one third of that expected if they occurred independently (odds ratio 0.29; 95% confidence interval, 0.27-0.33; P<0.0001). CONCLUSIONS: These data suggest a strong inverse relationship between Barrett metaplasia and eosinophilic infiltrates in the esophageal mucosa. Although the influence of diagnostic bias cannot be excluded, the possibility that eosinophilic infiltrates in the esophageal mucosa prevent subsequent metaplastic changes may deserve to be explored.

Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive sarcomas with variable patient survival and few known prognostically relevant genomic biomarkers. To identify survival-associated genomic biomarkers, we performed high-resolution array-based comparative genomic hybridization (aCGH) on a large set of MPNSTs. EXPERIMENTAL DESIGN: Candidate gene alterations identified by aCGH in 38 MPNSTs were validated at the DNA, RNA, and protein levels on these same tumors and an independent set of 87 MPNST specimens. RESULTS: aCGH revealed highly complex copy number alterations, including both previously reported and completely novel loci. Four regions of copy number gain were associated with poor patient survival. Candidate genes in these regions include SOX5 (12p12.1), NOL1 and MLF2 (12p13.31), FOXM1 and FKBP1 (12p13.33), and CDK4 and TSPAN31 (12q14.1). Alterations of these candidate genes and several others of interest (ERBB2, MYC and TP53) were confirmed by at least 1 complementary methodology, including DNA and mRNA quantitative real-time PCR, mRNA expression profiling, and tissue microarray-based fluorescence in situ hybridization and immunohistochemistry. Multivariate analysis showed that CDK4 gain/amplification and increased FOXM1 protein expression were the most significant independent predictors for poor survival in MPNST patients (P < 0.05). CONCLUSIONS: Our study provides new and independently confirmed candidate genes that could serve as genomic biomarkers for overall survival in MPNST patients.

Adherence to biopsy guidelines for Barrett's esophagus surveillance in the community setting in the United States.

BACKGROUND & AIMS: Current surveillance guidelines for Barrett's esophagus (BE) recommend extensive biopsies to minimize sampling error. Biopsy practice patterns for BE surveillance in the community have not been well-described. We used a national community-based pathology database to analyze adherence to guidelines and to determine whether adherence was associated with dysplasia detection. METHODS: We identified 10,958 cases of established BE in the Caris Diagnostics pathology database from January 2002-April 2007. Demographic, pathologic, and endoscopic data were recorded. Dysplasia was categorized as low grade, high grade, or adenocarcinoma. Adherence was defined as > or =4 esophageal biopsies per 2 cm BE or a ratio > or =2.0. Generalized estimating equation multivariable analysis was performed to assess factors associated with adherence, adjusted for clustering by individual gastroenterologist. RESULTS: A total of 2245 BE surveillance cases were identified with linked endoscopy reports that recorded BE length and could be assessed for adherence. Adherence to guidelines was seen in 51.2% of cases. In multivariable analysis, longer segment BE was associated with significantly reduced adherence (3-5 cm, odds ratio [OR] 0.14, 95% confidence interval [CI] 0.10-0.19; 6-8 cm, OR 0.06, 95% CI 0.03-0.09; > or =9 cm, OR 0.03, 95% CI 0.01-0.07). Stratified by BE length, nonadherence was associated with significantly decreased dysplasia detection (summary OR 0.53, 95% CI 0.35-0.82). CONCLUSIONS: Adherence to BE biopsy guidelines in the community is low, and nonadherence is associated with significantly decreased dysplasia detection. Future studies should identify factors underlying nonadherence as well as mechanisms to increase adherence to guidelines to improve early detection of dysplasia.

A case of herpes esophagitis after fluticasone propionate for eosinophilic esophagitis.

BACKGROUND: A 19-year-old white woman presented with a 6-month history of progressively worsening dysphagia. INVESTIGATIONS: Esophagogastroduodenoscopy, esophageal biopsies followed by histological evaluation of biopsy samples including immunohistochemical staining for herpes simplex virus. DIAGNOSIS: Herpes esophagitis with concurrent eosinophilic esophagitis. MANAGEMENT: Valaciclovir and fluconazole.

Time course of nicotinamide adenine dinucleotide diaphorase staining after renal radiofrequency ablation influences viability assessment.

BACKGROUND AND PURPOSE: Nicotinamide adenine dinucleotide (NADH) diaphorase staining has been used to confirm cell viability or death after radiofrequency ablation (RFA) of renal tissue. The time course over which NADH staining status converts from viable to non-viable after a lethal insult has not been defined for renal RFA, but the change may not be immediate. Our objective was to assess porcine renal tissue for viability using NADH diaphorase staining at various times after RFA. MATERIALS AND METHODS: Seven pigs underwent monopolar RFA of both kidneys followed by needle biopsy of the ablation zone before and immediately after ablation and at 15-minute intervals thereafter. Initially, a single kidney was treated, and the contralateral kidney was treated 2 weeks later. Biopsies were taken from untreated renal parenchyma in a similar time course after nephrectomy to examine the effect of ischemia. All biopsy specimens, as well as representative sections of the ablation zone, were subjected to NADH staining and reviewed by a pathologist who was blinded to the tissue treatment. RESULTS: Most of the post-RFA biopsy specimens (86%) showed non-viable tissue. However, 14% of the specimens revealed viable tissue as late as 150 minutes after RFA. Therefore, none were positive. In the nephrectomy parenchyma, 92% of the biopsy specimens showed viable tissue as late as 4 hours after the onset of ischemia. CONCLUSION: Staining for NADH can establish tissue non-viability after RFA, but the timing of staining after treatment must be considered when interpreting results to avoid false positive tests. Tissue that is apparently viable by NADH staining within 2.5 hours of RFA may in fact have been ablated.

Large-volume laparoscopic partial nephrectomy using the potassium-titanyl-phosphate (KTP) laser in a survival porcine model.

OBJECTIVES: Laparoscopic partial nephrectomy (LPN) remains a technically challenging procedure primarily because of difficulties with hemostasis. In an attempt to develop a hemostatic cutting instrument for laparoscopic partial nephrectomy, we evaluated the potassium-titanyl-phosphate (KTP) laser for use during large-volume laparoscopic partial nephrectomy in a porcine model. METHODS: Transperitoneal lower pole laparoscopic partial nephrectomy was performed in six pigs. Two nonsurvival animals were used initially to develop the laser technique. Four animals underwent a right-sided laparoscopic laser partial nephrectomy followed by an identical left-sided procedure 2 weeks later. Renal hilar occlusion was used in all cases. A novel 365-mum end-firing laser fibre and 80-W KTP laser were used for resection and hemostasis. All renal remnants underwent retrograde pyelography and histologic examination. RESULTS: Laser resection and hemostasis was successfully completed in all cases, and no perioperative complications occurred. Mean estimated blood loss was 80 ml (25-250 ml). Mean laser and warm ischemia times were 35 and 34 minutes, respectively. Resection speed was limited by smoke formation but not by cutting or hemostatic efficiency of the laser. Mean resected kidney mass was 30 g or 25% of total kidney mass. There were no urinomas, but, on retrograde pyelogram, extravasation was noted in seven of eight kidneys (87.5%). CONCLUSIONS: The KTP laser provides hemostasis during large-volume resection in the porcine kidney. This technique appears promising for laparoscopic partial nephrectomy in humans.

Expression and function of somatostatin receptors in peripheral nerve sheath tumors.

Although somatostatin receptors have been detected in many normal and neoplastic tissues, little is known of their expression and function in peripheral nerve tumors. In the present study, we examined the expression of all 5 somatostatin receptor subtypes (sst1-5) in 3 normal peripheral nerves, 3 traumatic neuromas, 27 schwannomas, 18 neurofibromas, and 177 malignant peripheral nerve sheath tumors (MPNSTs) by immunohistochemistry as well as by Western blot and reverse transcriptase-polymerase chain reaction investigations in 2 normal peripheral nerves, one neurofibroma, 5 schwannomas, and 5 MPNSTs. Immunoreactive somatostatin receptors were not detectable in normal peripheral nerve and in nonneoplastic Schwann cell proliferations. In contrast, sst2A mRNA and protein was present in 89% of schwannomas. This receptor subtype was less frequently detected in neurofibromas (22%) and MPNSTs (15%). Interestingly, sst4 was seen in 32% of MPNSTs and was almost exclusively expressed in this malignant tumor type. In support of a role in Schwann cell tumor growth control by somatostatin was the observation of induced internalization of sst2A and inhibition of cell proliferation in an NF1-associated MPNST cell line. Moreover, administration of an sst2A-selective agonist resulted in induction of MPNST cell apoptosis. We conclude that peripheral nerve sheath tumors often express at least one functional somatostatin receptor. Furthermore, our findings suggest a potential clinical role for somatostatin receptor agonists in tumor imaging and/or treatment of schwannomas and MPNSTs.

Laparoscopic choledochojejunostomy via PTFE-covered stent successfully achieves internal drainage of common bile duct obstruction.

The purpose of this study was to develop a method of laparoscopic biliary bypass utilizing a PTFE-covered biliary stent. An animal model of common bile duct obstruction was developed. Three days before the planned choledochojejunostomy, the common duct in 10 female pigs was ligated using mini-laparoscopy instrumentation (2 mm) to create an obstruction model. A laparoscopic choledochojejunostomy was then performed using intracorporal suturing (n=5) or stented (n=5) techniques. In the sutured group, a side-to-side two-layer anastomosis was performed. In the stented group, a Seldinger technique was used to deliver the stent into the abdomen through the small bowel and into the anterior wall of the common bile duct for deployment across both the duct and bowel to create an anastomosis (under fluoroscopic guidance). After the surgery, the animals were followed for 7 days, and then sacrificed to examine the anastomosis grossly and histologically. Statistical analysis was used to compare the two groups. Although the difference was not statistically significant, the mean anastomosis time in minutes was shorter for the stented group (37.8; range 15-74 minutes) than in the sutured group (52.8; range 28-70 minutes). All animals survived for 7 days after the procedure with no detectable biliary leaks or biliary obstruction at autopsy. These gross findings were confirmed by pathologic examination of the anastomoses. Laparoscopic choledochojejunostomy using a PTFE-covered metallic biliary stent can be performed to relieve common bile duct obstruction. In addition, the stent method was as safe and effective as sutured laparoscopic choledochojejunostomy.

T-cell prolymphocytic leukemia presenting as an ear canal mass.

OBJECTIVE: We discuss the first reported case of a chronic leukemia involving the external auditory canal. STUDY DESIGN: Case report and review of the literature (Medline, 1962-2003). METHODS AND RESULTS: An adult man in good health came to receive medical attention because of a sensation of aural fullness. Radiologic and physical examination demonstrated an ovoid soft tissue mass of the lateral external auditory canal that, after biopsy and flow cytometry studies, was found to be T-cell prolymphocytic leukemia. The patient presented with minimal disease in a highly symptomatic location, allowing early initiation of therapy and extending his life by nearly four times the average life expectancy for this aggressive chronic leukemia. CONCLUSION: Lymphomas of the external auditory canal are extremely rare neoplasms. Only a few cases have previously been reported, and all of the previous reports involve acute leukemias. This report indicates that chronic leukemias can present with otologic manifestations such as an external auditory canal mass.

Prevalence of malignancy within cytologically indeterminate thyroid nodules.

BACKGROUND: The optimal management of cytologically indeterminate thyroid nodules is controversial given the variable malignancy rates reported in this patient population. We examined the prevalence of malignancy within cytologically indeterminate follicular thyroid lesions in an attempt to predict malignancy based on cytologic features. METHODS: Cytopathology reports obtained after fine-needle aspiration biopsy (FNAB) examination of indeterminate follicular thyroid lesions were examined over a 4-year period. The prevalence of malignancy on final histology was determined in 4 indeterminate cytologic categories. RESULTS: A total of 107 records were available (91 women, 16 men). The mean patient age was 45.4 +/- 16 years. Forty-eight patients (45%) underwent surgery and had histopathologic diagnosis, while 57 patients did not have surgery. The prevalence of malignancy in patients who underwent thyroidectomy was 42% (20 of 48). CONCLUSIONS: The high prevalence of malignancy within indeterminate follicular lesions may necessitate thyroidectomy for patients with indeterminate follicular lesions on FNAB examination.

Acute histologic effects of temperature-based radiofrequency ablation on renal tumor pathologic interpretation.

OBJECTIVES: To describe the histopathologic changes and evaluate the interpretability of human renal tumor specimens obtained after temperature-based radiofrequency ablation (RFA). METHODS: RFA of 119 solid kidney tumors was performed percutaneously under computed tomography guidance, laparoscopically or during open surgery, using a temperature-based system. Of the 119 tumors, 70 were biopsied (two or more samples) after RFA, 39 immediately before ablation, and 10 were not biopsied. All specimens were pathologically classified, and for those specimens obtained after RFA, analysis of the acute histologic changes secondary to RFA was performed by a single pathologist using standard hematoxylin-eosin staining. RESULTS: Ablated tumor specimens maintained their tissue architecture and had predictable changes (cytoplasmic eosinophilia, nuclear elongation, cytoplasmic dissolution) easily recognizable by our pathologists. The diagnostic rate of renal cell carcinoma after RFA (72%) was comparable to the diagnostic rate reported for tumors less than 4 cm in other non-RFA biopsy series. Only 2.6% of specimens obtained before and 5.7% obtained after RFA were nondiagnostic secondary to the paucity of tissue obtained. In 8.3% of all tumors (regardless of RFA treatment), the distinction between oncocytoma and low-grade oncocytic renal cell carcinoma could not be made because of insufficient tissue. CONCLUSIONS: Acutely, RFA of renal tumors causes predictable histologic changes and preserves the tissue architecture. Obtaining two or more incisional biopsies after RFA provided sufficient tissue for reliable pathologic diagnosis.

Innate immunity genes influence the severity of acute appendicitis.

OBJECTIVE: Using acute appendicitis as a model, we tested the hypothesis that polymorphisms in genes involved in host defense can be associated with the severity of local infection-inflammation in humans. SUMMARY BACKGROUND DATA: Innate immunity is the body's front-line system for antimicrobial host defense. Local inflammation is a major innate immune mechanism for containing and destroying microbes, but it may also contribute to tissue injury. METHODS: We studied 134 patients with acute appendicitis treated at an urban hospital. We looked for associations between the severity of appendicitis (uncomplicated vs. perforated or gangrenous), plasma and peritoneal cytokine concentrations, and single nucleotide polymorphisms in genes involved in recognizing bacterial molecules [CD14 (-159 C-->T); TLR4 (896 A-->G)] and in mounting an inflammatory response [IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), IL-1beta (-31 C -->T)]. RESULTS: Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1beta, and TNF-alpha genes were not associated with the severity of appendicitis. A strong association was found between C-allele carriage at -174 in the IL-6 gene and decreased risk of complicated disease (adjusted odds ratio = 0.24, 95% CI = 0.07-0.76). Lower plasma and peritoneal fluid IL-6 concentrations in the IL-6 -174 C-carriers than in the GG homozygotes suggest that this polymorphism contributes to decreased IL-6 production in vivo. CONCLUSIONS: Polymorphism in the IL-6 gene was associated with the severity of appendicitis, even after adjustment for duration of symptoms. The risk for developing appendiceal perforation or gangrene may be determined, in part, by variation in the IL-6 gene.

Ureteral replacement using small-intestinal submucosa and a collagen inhibitor in a porcine model.

PURPOSE: Small-intestinal submucosa (SIS) has been successful as an onlay graft in ureteral repair, but tubularized segment interposition of SIS has been unsuccessful. Our objective was to evaluate whether a type I collagen inhibitor, halofuginone, would prevent stricture formation in tubularized SIS interposition. MATERIALS AND METHODS: We performed either laparoscopic partial ureteral excision followed by an SIS onlay graft (N = 5) or complete laparoscopic ureteral excision followed by an SIS interposition graft (N = 7) in domestic pigs. Animals received either no (N = 3), low-dose (N = 5), or high-dose (N = 4) halofuginone. Animals had ureteral stenting for 2 weeks after surgery and were permitted to survive for 6 or 9 weeks. An intravenous urogram (IVU) was performed prior to sacrifice. Kidneys were examined grossly and histologically. RESULTS: One animal that received an onlay graft died of an unrelated illness. The remaining four ureteral onlay animals, including one control and two low-dose and one high-dose pig, had grossly normal kidneys at harvest. The IVU was normal in the control and high-dose animal but showed delayed excretion with mild hydroureteronephrosis in the low-dose animals. Pathologic examination of the SIS site revealed circumferential reepithelialization with inflammation and mild fibrosis. All seven tubularized interposition graft kidneys demonstrated either severe hydroureteronephrosis (N = 5) or renal atrophy (N = 2), and all had complete obstruction on IVU. Pathologic examination revealed a stenotic ureteral lumen with extensive surrounding inflammation and fibrosis. CONCLUSIONS: An SIS onlay graft was successful in the porcine model of ureteral injury. Halofuginone, a type I collagen inhibitor, did not demonstrate a significant beneficial effect in this technique. Ureteral tubularized interpositions with SIS are unsuccessful and not improved by halofuginone.

Laparoscopic partial nephrectomy using holmium laser in a porcine model.

OBJECTIVE: To evaluate the utility of the holmium laser for partial nephrectomy in a porcine model. METHODS: Transperitoneal lower pole laparoscopic partial nephrectomy was performed in 5 farm pigs. All animals underwent a left-sided laparoscopic partial nephrectomy and were kept alive for 2 weeks (survival group). Subsequently, a right laparoscopic partial nephrectomy was performed (acute group), and the animals were sacrificed. A 1000-microm (n=6) or 550-microm (n=4) end-fire holmium laser fiber set at 0.2 joules and 60 pulses per second was used to transect the lower pole of the kidney 1 cm below the level of the hilum. The cut parenchymal surface was then sealed with fibrin glue in the survival animals. The operated on kidneys were inspected grossly and evaluated microscopically. RESULTS: Laser transection was successfully completed in all cases, and hemostasis proved adequate without any adjunctive measures. No perioperative complications occurred. Estimated blood loss was less than 50 cc for each laparoscopic partial nephrectomy. The acute and survival pigs showed no statistically significant differences in specimen size or weight. Serum creatinine levels were normal in all survival animals. Extravasation was noted on retrograde pyelograms of 2 animals in the survival group. CONCLUSIONS: The Holmium:YAG laser provides an efficacious modality for transecting the kidney in a porcine model. Clinical trials are necessary to determine its role in laparoscopic partial nephrectomy in humans.

Interpretive disparity among pathologists in breast sentinel lymph node evaluation.

BACKGROUND: Immunohistochemical staining on breast sentinel lymph nodes (SLN) is controversial. METHODS: Twenty-five SLN cases were reviewed by 10 pathologists (three academic, seven private) including 5 negative by both hematoxylin and eosin (H&E) and immunohistochemistry, 11 micrometastases (<2 mm) negative by H&E but positive by immunohistochemistry, and 8 micrometastases and 1 macrometastasis (>2 mm) positive for both H&E and immunohistochemistry. Answers included "positive," "negative," and "indeterminate" for each slide. RESULTS: The mean number of incorrect responses was 6.6 for immunohistochemistry and 5 for H&E. Twelve percent of cases were correct by all 10 pathologists; 80% of positive IHC cases had at least one pathologist score it incorrectly. As tumor cells decrease in number, incorrect responses increase. When tumor cells numbered less than 10, more than 30% of pathologists answered incorrectly. CONCLUSIONS: As tumor cells decrease in number pathologists' ability to recognize them decreases. We propose adding "indeterminate" to "positive" and "negative" when tumor cells number less than 10.

Infection by gram-negative organisms via the biliary route results in greater mortality than portal venous infection.

Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD(50)) for E. coli injected into the bile duct was 50 CFU/animal; the LD(50) for E. coli injected into the portal vein was 5 x 10(7) CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.

Infrared thermography and thermocouple mapping of radiofrequency renal ablation to assess treatment adequacy and ablation margins.

OBJECTIVES: The primary disadvantage of renal tumor RF ablation is the inability to monitor the intraoperative propagation of the RF lesion with real-time imaging. We sought to assess whether adequately lethal temperatures are obtained at the margins of the intended ablation zone using laparoscopic thermography to monitor radiofrequency (RF) lesions in real time, thermocouple measurements, and histopathologic evaluation. METHODS: Renal RF lesions were created under direct laparoscopic vision in the upper (1 cm diameter) and lower (2 cm) poles of the right kidney in 5 female pigs. The RF lesions were produced with the RITA generator and probe, set at 105 degrees C for 5-minute ablations. During RF treatment, a laparoscopic infrared (IR) camera measured the surface parenchymal temperatures, as did multiple thermocouples. The pigs were then either immediately killed (n = 3) or allowed to live for 2 weeks (n = 2). The kidneys were removed to correlate the temperature measurements with histologic analysis of the ablated lesion. RESULTS: Using a threshold temperature of greater than 70 degrees C for visual "temperature" color change, the IR camera identified the region of pathologic necrosis of the renal parenchyma during RF ablation. Thermocouple measurements demonstrated that the temperatures at the intended ablation radius reached 77.5 degrees C at the renal surface and 83.7 degrees C centrally, and temperatures 5 mm beyond the set radius reached 52.6 degrees C at the surface and 47.7 degrees C centrally. The average diameter of the gross lesion on the surface of the kidney measured 17.1 mm and 22.4 mm for 1-cm and 2-cm ablations, respectively. These surface measurements correlated with an average diameter of 16.1 mm and 15.9 mm (1-cm and 2-cm ablations, respectively) as measured with the IR camera. All cells within these ablation zones were nonviable by nicotinamide adenine dinucleotide diaphorase analysis. The average depth of the lesions measured 19 mm (1-cm ablation) and 25 mm (2-cm ablation) on gross histologic examination. CONCLUSIONS: The laparoscopic IR camera is able to monitor the surface renal temperatures during RF treatment. Thermocouple measurements during RF ablation confirmed the thermographic findings and demonstrated that lethal temperatures at the margin of the intended treatment zone are routinely obtained and that a rapid decline in temperature occurs beyond the predicted ablation margin.

Regional and systemic cytokine responses to acute inflammation of the vermiform appendix.

OBJECTIVE: To measure local (peritoneal fluid) and systemic (plasma) cytokine profiles in patients with infection-inflammation of the vermiform appendix, a relatively mild, localized inflammatory process. SUMMARY BACKGROUND DATA: The systemic host response to invading microorganisms, often termed the systemic inflammatory response syndrome (SIRS), includes changes in heart rate, respiratory rate, body temperature, and circulating white blood cell numbers. Although these changes can be induced experimentally by administering proinflammatory cytokines, the mediators that appear in the bloodstream during early, localized infection in humans have not been defined. METHODS: The authors studied 56 patients with pathologically proven appendicitis. Blood was obtained before the induction of anesthesia, when 82% of the patients met the criteria for SIRS. Peritoneal fluid (PF) was obtained by intraoperative lavage. Cytokines were measured by immunoassay. To assess the net impact of the mediators within plasma, the authors studied the ability of patient plasma to augment or suppress bacterial lipopolysaccharide (LPS) stimulation of monocytes in vitro. RESULTS: Of the proinflammatory cytokines, tumor necrosis factor-alpha was present in PF but not in plasma, interleukin (IL)-1beta and interferon-gamma were found in low concentrations in both PF and plasma, and IL-12 (p70) was detectable in plasma but not PF. In contrast, IL-6 and IL-1 receptor antagonist (IL-1ra) were the most abundant cytokines in the PF and plasma, and the concentrations of IL-4 and IL-10 were also elevated in both compartments. Patients with more severe appendicitis had higher plasma levels of IL-6 and IL-10 and lower plasma levels of IL-12 and interferon-gamma than did those with uncomplicated disease. Patient plasma inhibited LPS-induced stimulation of a monocyte cell line, and this inhibition was accentuated by complicated disease. CONCLUSIONS: As judged from the pattern of soluble cytokines in plasma and the effect of the plasma on monocyte activation by LPS, mild, localized infection can induce a systemic response that is predominantly anti-inflammatory.