Pediatric subhepatic appendicitis with elevated lipase.

Appendicitis is the most common surgical emergency in children, of which most are located in the retrocecal space or pelvis. Appendicitis occurring in the subhepatic space is uncommon and may present with atypical features such as right upper quadrant pain, leading to delayed diagnosis and complications. We present a rare case of subhepatic appendicitis in an 11-year-old female, who presented with a three-day history of both right upper quadrant (RUQ) and right lower quadrant (RLQ) abdominal pain and serum lipase elevated four times the upper normal limit. The abdominal ultrasound was normal, except for prominent RLQ abdominal lymph nodes. Hours later, a computed tomography scan revealed a non-ruptured subhepatic appendicitis and normal pancreas. Our patient encounter demonstrates the need to be aware of the atypical presentations of pediatric appendicitis in general and subhepatic appendicitis in particular. Moreover, to our knowledge, this is the first reported case of elevated lipase (with a radiographically normal pancreas) in association with subhepatic appendicitis. Providers should be aware elevated serum lipase levels may be due to conditions other than pancreatitis and further evaluation should be considered if the elements of the clinical picture are incongruent.

Tissue proteolysis in appendicitis with perforation.

BACKGROUND: Matrix metalloproteinases (MMPs) and serine proteases are able to degrade the extracellular matrix (ECM) and modulate immune responses in the gastrointestinal tract. The purpose of this study was to investigate local proteolysis in perforated appendicitis and its association with the appendix perforation. MATERIALS AND METHODS: Biopsies were taken at the sites of perforation (n = 15) and with a gradually increased distance from it. The expression and distribution of MMP-1, -2, and -9, the tissue inhibitor of metalloproteinases type (TIMP-1), plasminogen activator inhibitor type1 (PAI-1), and urokinase plasminogen activator (uPA) were measured by ELISA. The distribution of MMP-9, TIMP-1, uPA, and PAI-1 in perforated, nonperforated, and uninflamed appendix was investigated by immunohistochemistry with monoclonal antibody technique. RESULTS: MMP-1 expression was highest close to the perforation and was gradually decreased in biopsies in more distal locations (P < 0.01). MMP-9 showed a similar pattern being highest at the sites of perforation (P < 0.05), while MMP-2 expression showed a trend in the opposite direction without statistically significance. The expression of TIMP-1 trended lower at the sites of perforation. PAI-1 was highest at the sites of perforation (P < 0.01) and the uPA expression was similarly elevated close to and at the perforation. CONCLUSIONS: These data indicate a key role of MMP in the pathogenesis of appendix perforation. A local imbalance between MMP-9 and the inhibitor TIMP-1 could potentially contribute to the tissue injury leading to an appendix perforation. The overexpression of PAI-1 at the sites of perforation may also contribute to tissue damage.

Immunohistochemical analysis of granzyme B in non-perforated appendicitis--short communication.

The aim of the present study was to determine the expression ofgranzyme B in non-perforated appendicitis. Appendix biopsies were obtained from the patients with clinically diagnosed as acute appendicitis and subjects admitted for elective abdominal surgery. All biopsies from the patients were non-perforated and histologically divided into acute and non-acute appendicitis. Granzyme B expression was assessed immunohistochemically. The results showed that granzyme B expression in both acute and non-acute appendicitis was significantly lower than that in the control appendix tissues (P < 0.05). The expression of this cytotoxic protein in acute and non-acute appendicitis was comparable (P > 0.05). Therefore, the results of the present study suggest that reduced expression of granzyme B in non-perforated appendicitis may reflect low cytotoxic activities which may prevent tissue damage.

Perforated appendicitis masquerading as acute pancreatitis in a morbidly obese patient.

Diagnosis and treatment of common conditions in morbidly obese patients still pose a challenge to physicians and surgeons. Sometimes too much reliance is put on investigations that can lead to a misdiagnosis. This case demonstrates an obese woman admitted under the medical team with a presumed diagnosis of pneumonia, who was later found to have an acute abdomen and raised amylase, which led to an assumed diagnosis of pancreatitis. She died within 24 h of admission and post mortem confirmed the cause of death as systemic sepsis due to perforated appendicitis, with no evidence of pancreatitis. Significantly elevated serum amylase level may occur in non-pancreatitic acute abdomen.

Significance of thymidine phosphorylase expression in stromal cells around invasive front of rectal cancer.

BACKGROUND/AIMS: Thymidine Phosphorylase (TP) expression in the tumor cells correlates with postoperative recurrence, but the significance of its expression in the stromal cells around the invasive front of the tumor is not clarified. METHODOLOGY: This study was conducted on 95 patients with T2 (n=34) or T3 (n=61) rectal cancer for whom curative surgical resection was performed between 1998 and 2002. As a control, appendix vermiform of twenty patients excised for acute appendicitis during the same period was analyzed. Paraffin-embedded sections of their surgical specimens were immunostained for TP and Vascular Endothelial Growth Factor (VEGF). Relationship between expression level of the binary angiogenic factors and malignant potential were evaluated. RESULTS: There was a strong relationship between TP expression in the malignant cells at the invasive front of the tumor and depth of tumor invasion. TP expression in the stromal cells was very high regardless of the status of the depth of tumor invasion. TP expressions in the stromal cells in the appendix with inflammation were also very high, which was detectable both in the nucleus as well as in the cytoplasm. CONCLUSION: TP expression in the stromal cells may seem to reflect local immunoreactions, rather than tumor anginogenesis.

Validade da amilasemia e da lipasemia no diagnóstico diferencial entre pancreatite aguda/crônica agudizada e outras causas de dor abdominal aguda / Validity of serum amylase and lipase for the differential diagnosis between acute/acutized chronic pancreatitis and other causes of acute abdominal pain

RACIONAL: Várias doenças abdominais podem cursar com aumento de amilasemia e lipasemia. OBJETIVO: Avaliar a validade da amilasemia e lipasemia para os diagnósticos diferenciais entre pancreatite aguda/pancreatite crônica agudizada, doenças das vias biliares, úlcera gastroduodenal perfurada e apendicite aguda. PACIENTES E MÉTODOS: Foram avaliados, prospectivamente, 38 pacientes com pancreatite aguda/pancreatite crônica agudizada, 35 com doenças das vias biliares, 17 com úlcera gastroduodenal perfurada e 44 com apendicite aguda, com idade média (desvio padrão) de 42,4 ± 17,7, 46,7 ± 18,3, 47,8 ± 12 e 33,7 ± 17,8 anos, respectivamente. A amilasemia e a lipasemia foram determinadas à admissão no pronto-socorro. RESULTADOS: Para o diagnóstico de pancreatite aguda/pancreatite crônica agudizada, quando o nível de corte da amilasemia variou entre o limite superior de referência e 5 vezes este limite, a sensibilidade diminuiu de 92 por cento para 74 por cento, a especificidade aumentou de 85 por cento para 99 por cento, o valor preditivo positivo aumentou de 71 por cento para 97 por cento e o valor preditivo negativo diminuiu de 96 por cento para 91 por cento. Para a lipasemia valores semelhantes foram obtidos para sensibilidade e valor preditivo negativo, mas a especificidade e o valor preditivo positivo foram mais baixos. Quando se considerou amilasemia ou lipasemia elevadas, houve pequeno aumento na sensibilidade e no valor preditivo negativo. CONCLUSÕES: Para o diagnóstico de pancreatite aguda/pancreatite crônica agudizada, 1) o melhor nível de corte para ambos os testes foi o de duas vezes o limite superior de referência; 2) as sensibilidades da amilasemia e da lipasemia foram semelhantes; 3) a especificidade e o valor preditivo positivo da amilasemia foram ligeiramente maiores do que as da lipasemia; 4) a sensibilidade, mas não a especificidade, aumentou quando pelo menos uma das enzimas estava elevada.

Expression of cyclooxygenase-2 in biopsies obtained from human transplanted kidneys undergoing rejection.

BACKGROUND: The inducible cyclooxygenase (COX)-2 is a target of immunosuppressive drugs routinely administered to patients after transplantation. This study investigates a potential involvement of COX-2 in transplant rejection. Therefore, we examined the expression of COX-2 in biopsies obtained for diagnostic purposes. METHODS: COX-2 was detected by immunohistochemistry and in situ hybridization. Congruent staining was obtained by both methods: in specimens of a kidney explanted as the result of vascular rejection, tubular epithelial cells and endothelial cells stained positively for COX-2. Furthermore, in appendiceal specimens obtained at surgery, epithelial cells of the crypts, interstitial cells, and mesothelial cells were positive by both methods, affirming the specificity of the antibody. RESULTS: Compared with healthy control subjects, intensive staining of COX-2 was observed in most of the 28 biopsies obtained from patients diagnosed with vascular rejection combined with cellular interstitial rejection and tubulitis. Glomeruli and the macula densa area were essentially negative compared with prominent staining in cortical and medullary epithelial cells of the tubuli. Staining was distinct with individual positive cells in the tubular cross sections. Few arteries expressed COX-2 in intimal cells. Less prominent expression of COX-2 was detected in the biopsies of six kidneys obtained from patients diagnosed with acute tubular necrosis. CONCLUSION: This is the first report to show the up-regulation of COX-2 in human transplanted kidneys, despite ongoing immunosuppressive treatment. It remains to be established whether the up-regulation of COX-2 is part of the rejection process or has to be considered implicated in renal preservative mechanisms.

Nitrergic hyperinnervation in appendicitis and in appendices histologically classified as normal.

CONTEXT: The pathogenesis of appendicitis remains poorly understood. Despite new diagnostic techniques, appendices removed from patients with suspected appendicitis often appear histologically normal on conventional examination. There is increasing evidence of involvement of the enteric nervous system in immune regulation and in inflammatory responses in the gastrointestinal system. OBJECTIVE: To investigate the nitrergic innervation of (a) acutely inflamed appendices, (b) appendices classified as histologically normal from patients with a clinical diagnosis of appendicitis, and (c) normal control appendix specimens, using the whole-mount preparation technique. PATIENTS AND DESIGN: Full-thickness specimens were collected from 28 acutely inflamed appendices (age range, 3.2-13.4 years), 31 histologically normal appendices removed from patients (age range, 5.7-13.6 years) with suspected appendicitis, and 23 histologically normal appendices from patients (age range, newborn to 12.1 years) undergoing elective abdominal surgery (controls). Whole-mount preparation using nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and neuronal nitric oxide synthase immunohistochemistry were performed. The density of myenteric plexus was measured with a computerized analysis system. RESULTS: The density of myenteric plexus in normal appendix specimens was similar to that of large bowel from the newborn period up to 3 years of age; this density decreased significantly thereafter. The myenteric plexus of normal appendix specimens from patients older than 4 years demonstrated smaller ganglia connected by thin nerve bundles, compared to larger ganglia and nerve bundles in large bowel. Significant neuronal hypertrophy was found in 55% of acutely inflamed and 41% of histologically classified normal appendix specimens. The myenteric plexus of these appendix specimens had even thicker nerve bundles connecting an increased number of ganglion cells. CONCLUSIONS: Differences in the architecture of the myenteric plexus in patients older than 3 years suggest an altered function and motility of appendix in the early years of life. The significant increase in neuronal components of the myenteric plexus in a high proportion of acutely inflamed and histologically normal appendix specimens is unlikely to have developed during a single acute inflammatory episode. This suggests an underlying chronic abnormality as a secondary response to chronic luminal obstruction or repeated inflammatory episodes in the histologically normal appendix.

Plasma superoxide dismutase activity and malondialdehyde level correlate with the extent of acute appendicitis.

Although the mechanism of acute appendicitis (AA) is partly understood, the progression following the onset of inflammation has not yet been clarified. To determine oxidative activities in the plasma of patients with AA, superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels were measured in samples from 31 patients diagnosed as having AA and 10 otherwise healthy children with inguinal pathologies. The patients with AA were divided into three subgroups: acute focal (AFA) (n = 8), acute suppurative (ASA) (n = 9), and acute perforated appendicitis (APA) (n = 14), according to the intraoperative findings and histopathologic examination. SOD and MDA were compared statistically between these subgroups and between them and the control group. Additionally, mean leukocyte counts of each group were determined and the differences between the groups were evaluated. Both SOD and MDA were significantly higher in the ASA and APA groups compared to controls and AFA group. The mean leukocyte numbers of the ASA and APA groups were significantly higher compared to the AFA group. Based to these results, it may be speculated that oxygen free radicals (OFR) may play an important role in the extent of AA. To prevent the hazardous effects of OFR, the organism may increase SOD and other antioxidant enzyme levels and/or activities.

Nitric oxide synthetase and Helicobacter pylori in patients undergoing appendicectomy.

BACKGROUND: This study was designed to determine whether Helicobacter pylori forms part of the normal microenvironment of the appendix, whether it plays a role in the pathogenesis of acute appendicitis, and whether it is associated with increased expression of inducible nitric oxide synthetase (iNOS) in appendicular macrophages. METHODS: Serology for H. pylori was performed on 51 consecutive patients undergoing emergency appendicectomy. Appendix samples were tested for urease activity, cultured and stained for H. pylori, graded according to the degree of inflammatory infiltrate, and probed immunohistochemically for iNOS expression. RESULTS: The mean age of the patients was 21 (range 7-51) years. Seventeen patients (33 per cent) were seropositive for H. pylori but no evidence of H. pylori was found in any appendix specimen. However, an enhanced inflammatory cell infiltration was observed in seropositive patients (P < 0.04) and the expression of macrophage iNOS in the mucosa of normal and inflamed appendix specimens was increased (P < 0.01). CONCLUSION: H. pylori does not colonize the appendix and is unlikely to be a pathogenic stimulus for appendicitis. Priming effects on mucosal immunology downstream from the foregut may occur after infection with H. pylori.

Macroamylasemia in a patient with acute appendicitis: a case report.

Macroamylasemia is a condition of persistent, elevated serum amylase activity with no apparent clinical symptoms of a pancreatic disorder. In Korea, however, no such case has been reported to date. We report a case of a 17-year-old female diagnosed with macroamylasemia and acute appendicitis. One day earlier, she developed epigastric and right lower quadrant abdominal pain. She was characterized by high level of serum amylase, but normal lipase. Amylase isoenzyme analysis demonstrated increased fraction of salivary type and follow-up amylase level was persistently increased. Immunofixation disclosed the macroamylase binding with an immunoglobulin, consisting of IgA and kappa chain. The patient was treated by appendectomy, and the abdominal pain subsided.

Macroamylasemia in a patient with acute appendicitis: a case report

Macroamylasemia is a condition of persistent, elevated serum amylase activity with no apparent clinical symptoms of a pancreatic disorder. In Korea, however, no such case has been reported to date. We report a case of a 17-year-old female diagnosed with macroamylasemia and acute appendicitis. One day earlier, she developed epigastric and right lower quadrant abdominal pain. She was characterized by high level of serum amylase, but normal lipase. Amylase isoenzyme analysis demonstrated increased fraction of salivary type and follow-up amylase level was persistently increased. Immunofixation disclosed the macroamylase binding with an immunoglobulin, consisting of IgA and kappa chain. The patient was treated by appendectomy, and the abdominal pain subsided.

The effect of acute ligation of the rabbit appendix on antioxidant enzymes.

The role of oxygen free radicals (OFR) in the pathogenesis of many diseases is known. This experimental study was planned to investigate the role of OFR in acute abdominal inflammation. In this study, 20 adult rabbits were used. They were divided into two groups with 10 rabbits in each. In the study group, blood samples were taken from peripheral and mesenteric veins and then their appendices were ligated; after 24 h, blood samples were taken again and the appendices were resected. The same procedures were carried out in the control group, except for ligation of the appendices. Superoxide dismutase,catalase and glutathione peroxidase (GPX) activities were measured in all blood samples. The activities of catalase and GPX were increased postoperatively in peripheral and mesenteric blood samples in the experimental group. The catalase activity was increased in the control group. These results suggest that OFR increased sufficiently to activate the enzymatic defense system in acute appendicitis.

Maternal serum creatine kinase as a biochemical marker of tubal pregnancy.

OBJECTIVE: To evaluate the role of serum creatine kinase as a possible marker for diagnosis of tubal pregnancy. METHODS: Five groups of patients were included in this prospective study: group A, 20 patients with tubal pregnancies; group B, 20 patients with missed abortions; group C, 20 patients with pelvic inflammatory disease; group D, 10 patients with acute appendicitis; group E (controls), 20 patients with normal pregnancies matched for age and gestation. Total creatine kinase levels were measured in the serum of all five groups. RESULTS: Creatine kinase levels were found to be > or =75 IU/l in all patients with tubal pregnancies, which was significantly higher than in the other four groups (P < 0.0001). CONCLUSION: Our results indicate that maternal serum creatine kinase can be an important biochemical marker in suspected tubal pregnancy.

Changes of protein gene product 9.5 (PGP 9.5) immunoreactive nerves in inflamed appendix.

The existence of chronic appendicitis is controversial. In this prospective study, we investigated possible changes in the innervation of the appendix under different pathological conditions and correlated histological findings with clinical observation. Thirty appendectomy specimens and 14 appendices obtained from organ donors or patients who underwent right hemicolectomy were immediately fixed in Bouin's solution and processed for immunocytochemistry using an antiserum directed against the panneuronal marker protein gene product 9.5 (PGP 9.5). The density of PGP 9.5 immunostaining was evaluated by digitized morphometry. Significant differences in the density of the PGP 9.5-immunoreactive area were detected in the mucosal layer. In the nonacute appendicitis group, PGP 9.5 was increased (10.99 +/- 3.15%) as compared to acute appendicitis (3.89 +/- 1.77%) and controls (4.98 +/- 1.25%). The significant increase of PGP 9.5 in nonacute appendicitis may suggest axonal sprouting leading to hyperinnervation of the mucosa. This may be a neuronal factor in the pathophysiology of the disease and pain symptoms.

Phospholipase A2, C-reactive protein, and white blood cell count in the diagnosis of acute appendicitis.

We compared the predictive value of determining group II phospholipase A2 (PLA2) in serum for diagnosing acute appendicitis with the predictive values of white blood cell count (WBC) and measurement of C-reactive protein (CRP). In this prospective study, we included 186 patients who were undergoing appendectomy after clinical diagnoses of acute appendicitis. The performance of each test was measured by receiver-operating characteristic curves. WBC was the test of choice in diagnosing uncomplicated acute appendicitis. However, in contrast to CRP and PLA2, which increased in patients with protracted inflammation, there was not a concomitant increase in WBC. Therefore, especially CRP, but also PLA2, were better indicators of appendiceal perforation or abscess formation than was WBC. Increased WBC, CRP, and PLA2 values did not unequivocally corroborate the clinical suspicion of appendicitis, but if all three values were within normal limits, acute appendicitis could be excluded with a 100% predictive value. PLA2 values showed a highly significant correlation with CRP but not with WBC values, which supports the view that PLA2 represents an acute-phase reactant.

[The prognostic significance of natural killers and dehydrogenases of the peripheral blood lymphocytes in patients with a suppurative inflammation]. / Prohnostychne znachennia pryrodnykh kileriv i dehidrohenza limfotsytiv peryferichnoï krovi u khvorykh z hniinym zapalenniam.

In patients with purulent inflammation foci of various location, reduction in the number of natural killers (NK) and in the activity of alpha-glycerophosphatedehydrogenase (alpha-GPDH) and adenosinetriphosphatase (ATP-ase) of lymphocytes was revealed. Maximum reduction in indices of NK, alpha-GPDH and ATP-ase was noted in patients with diffuse peritonitis, phlegmonous-gangrenous cholecystitis, destructive appendicitis. After treatment, the mentioned indices increased, but by the time of discharge of the patients from the hospital they were lower than the normal ones.

Serum alanine aminotransferase (ALT) elevation in asymptomatic US Air Force basic trainee blood donors.

The purpose of this study was to determine the etiology of elevated alanine aminotransferase (ALT) in a population of asymptomatic volunteer blood donors. Subjects with an ALT value > 2.25 sd above norm (> 55 IU/liter) from the donated unit, were prospectively evaluated over a six-week interval. The subjects consisted of blood donors (78% male, 22% female) beginning basic military training at Lackland Air Force Base. Of 44,160 individuals screened, 19,877 (45%) voluntarily donated blood, 99 (0.5%) of which had confirmed ALT elevation. Of these (90 male/9 female), an associated condition or explanation was made in 12%: four with acute hepatitis B, four positive for anti-HCV, two with autoimmune disease, one with cholelithiasis and one associated with acute appendicitis. In 87 the ALT elevation could not be explained using available testing methods but may represent individual variation from a non-Gaussian distribution, be of nonhepatic origin (muscle), or of hepatic disease not detected by the diagnostic algorithm used. To increase the diagnostic yield, it is suggested that at least two elevated ALT values be established in this population over a period of time (yet undefined), before an extensive hepatic investigation is pursued.