Risk factors and predictors for surgical site infection after hepatic resection.

Strict control of blood glucose levels with insulin in a surgical intensive care unit reduces postoperative morbidity and mortality. The aim of this study was to identify risk factors and the predictors for the prevention of surgical site infection (SSI) in a consecutive series of hepatectomised cases in a single institution. The association between SSI and various clinical parameters was investigated in 152 patients who underwent hepatic resection at Kochi Medical School from January 2000 through March 2007. The incidence of SSI in these patients was 14.5%. Multivariate analysis identified four independent parameters correlating with the occurrence of SSI: (i) body mass index >23.6 kg/m(2); (ii) estimated blood volume loss >810 mL; (iii) presence of postoperative bile leakage of organ/space SSI; and (iv) use of the sliding scale method for postoperative glucose control. There was no observed SSI after liver resection in the group whose postoperative blood glucose levels were controlled by an artificial pancreas. This study reveals that lack of postoperative glycaemic control is associated with a significantly higher incidence of postoperative infectious complications and longer hospitalisation. Obesity and the level of intraoperative estimated blood loss and bile leakage after hepatic resection are also risk factors with predictive value for SSI. Artificial pancreas is a safe and beneficial device to perform postoperative strict glycaemic control without hypoglycaemia for patients who undergo hepatic resection for liver diseases.

Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer.

Endoscopic submucosal dissection (ESD) has been utilized as an alternative treatment to endoscopic mucosal resection for superficial esophageal cancer. We aimed to evaluate the complications associated with esophageal ESD and elucidate predictive factors for post-ESD stenosis. The study enrolled a total of 42 lesions of superficial esophageal cancer in 33 consecutive patients who underwent ESD in our department. We retrospectively reviewed ESD-associated complications and comparatively analyzed regional and technical factors between cases with and without post-ESD stenosis. The regional factors included location, endoscopic appearance, longitudinal and circumferential tumor sizes, depth of invasion, and lymphatic and vessel invasion. The technical factors included longitudinal and circumferential sizes of mucosal defects, muscle disclosure and cleavage, perforation, and en bloc resection. Esophageal stenosis was defined when a standard endoscope (9.8 mm in diameter) failed to pass through the stenosis. The results showed no cases of delayed bleeding, three cases of insidious perforation (7.1%), two cases of endoscopically confirmed perforation followed by mediastinitis (4.8%), and seven cases of esophageal stenosis (16.7%). Monovalent analysis indicated that the longitudinal and circumferential sizes of the tumor and mucosal defect were significant predictive factors for post-ESD stenosis (P < 0.005). Receiver operating characteristic analysis showed the highest sensitivity and specificity for a circumferential mucosal defect size of more than 71% (100 and 97.1%, respectively), followed by a circumferential tumor size of more than 59% (85.7 and 97.1%, respectively). It is of note that the success rate of en bloc resection was 95.2%, and balloon dilatation was effective for clinical symptoms in all seven patients with post-ESD stenosis. In conclusion, the most frequent complication with ESD was esophageal stenosis, for which the sizes of the tumor and mucosal defect were significant predictive factors. Although ESD enables large en bloc resection of esophageal cancer, practically, in cases with a lesion more than half of the circumference, great care must be taken because of the high risk of post-ESD stenosis.

Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders.

BACKGROUND: Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder. OBJECTIVE: To determine the differences between IgG(4)-related disorders including MD and SS. METHODS: A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared. RESULTS: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement. CONCLUSION: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.

Usefulness of multi-detector row computed tomography for accurate preoperative assessment of pancreatic adenocarcinoma: report of a case.

A 74-year-old female underwent surgical treatment for adenocarcinoma of the pancreatic head. Preoperative multi-detector row computed tomography (MD-CT) demonstrated tumor invasion into the accessory right colic vein and the branch of the middle colic artery (MCA), which was not detected by digital subtraction angiography. MD-CT showed anatomical variants in the left hepatic artery arising from the left gastric artery, and the right posterior hepatic artery arising from the superior mesenteric artery. Three-dimensional reconstruction CT generated a clear picture of the anatomy of the region concerned, which is essential for a safe operation. The MD-CT findings were highly consistent with the intraoperative findings. We have demonstrated that MD-CT is an important and highly accurate modality for pancreatic surgery.

Serum antibodies to carbonic anhydrase IV in patients with autoimmune pancreatitis.

BACKGROUND AND AIMS: Serum antibodies to carbonic anhydrase (CA) II have been reported in patients with autoimmune pancreatitis (AIP) and Sjogren's syndrome (SjS). However, their significance in the pathogenesis of these diseases is controversial. The aim of this study was to identify serum antibodies to CA isozymes, which are expressed in ductal cells of the pancreas. METHODS: Recombinant proteins of human CAs IV, IX, and XII were obtained using a bacterial expression system, and five CA IV peptides with theoretically high antigenicity were synthesised. Western blotting and enzyme linked immunosorbent assay (ELISA) were used to detect serum antibodies to the CA isozymes. RESULTS: The first screening analysis by western blot showed serum antibodies to CA IV among three CA isozymes in patients with idiopathic chronic pancreatitis, including AIP patients. Further analysis by ELISA showed a significantly increased prevalence of serum antibodies to the truncated CA IV protein and the CA IV synthetic peptide (LGS LTT PTC DEK VVW TVF REP I) in patients with definite AIP (4/15 and 6/20, respectively; p<0.01), probable AIP (6/14 and 3/14; p<0.02), and SjS (9/20 and 8/40; p<0.001) compared with normal controls (0/26). There was no significant difference in the antibody prevalence rates between normal controls and patients with alcoholic chronic pancreatitis (2/15 in each) or pancreatic cancer (2/14 and 1/14, respectively). The presence of serum antibodies to the CA IV peptide showed significant correlations with serum gamma-globulin and IgG levels in AIP patients. CONCLUSIONS: These findings suggest that CA IV may be a target antigen that is commonly expressed in epithelial cells of specific tissues involved in AIP and its related diseases.

Developmental expression of carbonic anhydrase-related proteins VIII, X, and XI in the human brain.

Three cDNA homologues of carbonic anhydrase with unknown biological functions have been reported: carbonic anhydrase-related proteins (CA-RP) VIII, X, and XI. In the present study, we produced monoclonal antibodies to these CA-RPs and studied their regional and cellular distributions in the human adult and fetal brains by immunohistochemical analysis. In the adult brain, CA-RP VIII was expressed in the neural cell body spreading to most parts of the brain. CA-RP X was expressed in the myelin sheath and its expression was shown in the cytoplasm of cultured tumor cells by immunocytochemical analysis. CA-RP XI was expressed in the neural cell body, neurites, and astrocytes in relatively limited regions of the brain. In the fetal brain, CA-RP VIII and XI were expressed in the neuroprogenitor cells in the subventricular zone as early as the 84th day of gestation and subsequently detected in the neural cells migrating to the cortex. CA-RP X first appeared in the neural cells in the cortex at the 141st day. In the choroid plexus, the epithelial cells gave CA-RP VIII and XI expressions in both adult and fetal brains. From the findings in the present study on the distribution and the developmental expression of CA-RP VIII, X, and XI in the human brain we suggest that these CA-RPs play roles in various biological process of the CNS.

Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor in patients with pancreatitis.

PURPOSE: We hypothesized that mutations in the pancreatic secretory trypsin inhibitor (PSTI) gene could promote autodigestion, leading to acute or chronic pancreatitis. Our investigation involved mutation analysis of the PSTI gene in patients with acute or chronic pancreatitis. METHODS: Mutation analysis for the PSTI gene was performed in patients with acute or chronic pancreatitis. Unrelated healthy volunteers and family members of a chronic pancreatitis patient with point mutations in the PSTI gene were also analyzed. RESULTS: Two types of single-point mutation in the PSTI gene were observed in one patient with chronic pancreatitis: 34Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and 67Arg (CGC)-to-Cys (TGC) (199 C > T R67C: R67C) in exon 4. No mutations with amino-acid substitution were found in other patients or in the volunteer group. In the patient with the PSTI gene mutations, no additional mutations were observed in the cationic trypsinogen gene. The family study revealed that the mother and a maternal uncle were homozygotes for the N34S mutation, while the father and brother were compound heterozygotes for the N34S and R67C mutations. The uncle (N34S/N34S) showed clinical manifestations of pancreatitis, but the other family members did not. CONCLUSIONS: The N34S mutation may cause a predisposition to pancreatitis, with incomplete penetrance. However, with the limited information available, it is not known whether the R67C mutation promotes pancreatitis.

Quantitative trait locus analysis for chronic pancreatitis and diabetes mellitus in the WBN/Kob rat.

A causative gene mutation is still undefined in approximately half of patients with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancreatitis-associated gene, we performed a quantitative trait locus (QTL) analysis for the traits of chronic pancreatitis and diabetes mellitus in WBN/Kob rats. We identified two highly significant QTLs for chronic pancreatitis and/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on completely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a genetic analysis in WBN/Kob rats might be useful for gene targeting for human chronic pancreatitis.

cDNA sequence of human carbonic anhydrase-related protein, CA-RP X: mRNA expressions of CA-RP X and XI in human brain.

A full-length cDNA clone of human carbonic anhydrase-related protein (CA-RP) X was obtained and sequenced. The 2720 bp long cDNA sequence was predicted to encode a 328 amino acid polypeptide. The deduced amino acid sequence showed an overall similarity of 25-57% to other CA isozymes and the highest % similarity to a CA-RP XI. Similar to CA-RP XI, CA-RP X lacked two out of three zinc-liganded histidine residues, suggesting no biological activity of CA. Northern blot analysis demonstrated an approx. 2.8 kb transcript in the human brain and kidney. RNA dot blotting showed significant signals for CA-RP X and XI mRNA expressions in the adult total brain and almost all parts of the central nervous system, but no expression in the fetal brain. These results suggest that CA-RP X and XI play some role in human brain, especially in brain development.

Carbonic anhydrase isozymes in the human pancreas.

Recently, an increasing number of carbonic anhydrase (CA) isozymes have been discovered in the human pancreas. These isozymes are classified as the CA family with various molecular structures and different subcellular localizations: cytoplasmic CA II, mitochondrial CA VB, secretory CA VI, membrane-bound CA IV, and transmembrane CA IX and XII. However, there is little evidence concerning their pathophysiological roles. Here, we reviewed the expression of CA isozymes in the human pancreas and proposed hypotheses related to their physiological and pathological roles.

The fine form of Helicobacter pylori on the metaplastic duodenal mucosa is associated with recurrent duodenal ulcers.

BACKGROUND/AIM: It is well known that Helicobacter pylori changes its shapes according to various environmental conditions. The aim of this study was to examine the morphological differences between H. pylori in the duodenum and that in the stomach. METHODS: Duodenal biopsy specimens were obtained from patients with duodenal mucosal lesions, and these specimens were then histopathologically examined. Morphological and genetic properties of cultured H. pylori isolates were analyzed. RESULTS: H. pylori was identified in 16 out of 50 duodenal biopsy specimens. Along with the regular form, we found a fine form of H. pylori in the gastric metaplastic mucosa of ten duodenal specimens that was shorter in length and thinner in diameter than the regular helical form. There were no detectable differences between the ureA-ureB polymorphism of the duodenal fine form and that of gastric regular form in a single patient. As compared with patients without H. pylori in the duodenum, the prevalence of recurrent duodenal ulcers significantly increased in patients with the fine form (p < 0.05), but not in patients with the regular form. CONCLUSION: The fine form of H. pylori in the metaplastic duodenal mucosa could result from its adaptation to the duodenal environment and may be associated with the recurrence of a duodenal ulcer.

Hereditary pancreatitis in Japan: a review of pancreatitis-associated gene mutations.

Pancreatitis-associated gene mutations have been reported in patients with hereditary pancreatitis and idiopathic pancreatitis in the Caucasian population and involve the cationic trypsinogen gene, the pancreatic secretory trypsin inhibitor gene and the cystic fibrosis transmembrane conductance regulator gene. In the Japanese population, mutational screening analyses of these genes have shown several mutations. The present study reviews previous reports from Japan in order to evaluate the racial specificity of pancreatitis-associated gene mutations.

Expression of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer.

Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.

Elevated serum levels of antibodies to carbonic anhydrase I and II in patients with chronic pancreatitis.

An immune-mediated reaction to pancreatic structures has been postulated for the pathogenesis of chronic pancreatitis (CP). Several reports demonstrate the presence of antibodies to the pancreatic ductal epithelium in some patients suffering from CP. Serum antibodies to carbonic anhydrase I (anti-CA I) and II (anti-CA II) are present in patients affected by idiopathic CP. The aim of this study was to evaluate the presence of anti-CA I and anti-CA II in a series of patients with CP. We studied 78 consecutive CP patients (62 male, 16 female; mean age 48.6 +/- 10.2 years) referred to the Verona University Center for the Study of the Pancreas. As a control group, we studied 26 healthy subjects recruited from among the medical and nursing staff of the center. Serum anti-CA I and anti-CA II levels were quantified by enzyme-linked immunosorbent assay using a standard method with minor modifications. The mean absorbance of antibodies was higher in CP patients than in control subjects (anti-CA I: 0.064 +/- 0.042 vs. 0.047 +/- 0.015, p = 0.051; and anti-CA II: 0.038 +/- 0.02 vs. 0.029 +/- 0.014, p = 0.033). Positive results were arbitrarily defined as absorbance values >0.067 for anti-CA I and 0.047 for anti-CA II. We found anti-CA I and anti-CA II positivity in 21 of 78 (27%) and 20 of 78 (26%) of CP patients, respectively, and in only two of 26 control subjects (7.7%) (p = 0.032 and 0.039). Twenty-two of 26 subjects in the control group (84.6%) and 48 of 78 patients (61.5%) in the CP group tested negative for both antibodies (p = 0.03). None of the control subjects and 12 of 78 (16.6%) of the CP patients tested positive for both anti-CA I and anti-CA II. We observed a significant correlation between anti-CA I and anti-CA II serum levels in control subjects (R = 0.423; p = 0.016) and in CP patients (R = 0.584; p < 0.0001). No correlation was found between serum antibody levels and any of the following variables: length of disease, alcohol consumption, smoking habits, pancreatic surgery, pancreatic calcifications, diabetes, and steatorrhea. Serum levels of anti-CA I and anti-CA II are elevated in some patients suffering from CP.

A discrepant finding between magnetic resonance imaging and other imaging modalities suggests a microcystic serous cystadenoma of the pancreas.

BACKGROUND: Serous cystadenoma of the pancreas is generally considered as having no malignant potential. Thus, of clinical importance is a differential diagnosis of this neoplasm from other solid tumors that are often malignant. RESULTS: We report a case of microcystic serous cystadenoma of the pancreas. Abdominal ultrasonography, computed tomography, and endoscopic ultrasonography showed a solid mass in the body of the pancreas with a diameter of 15 mm, but magnetic resonance imaging revealed it as a unilocular cystic lesion. Histological examinations on the surgically resected tissue specimen showed a honeycombed tumor with innumerable tiny cysts appearing grossly as a solid mass. The discrepant finding between magnetic resonance imaging and other imaging modalities observed in this case is suggestive of and might be specific to microcystic serous cystadenoma of the pancreas. CONCLUSIONS: Magnetic resonance imaging is a mandatory modality to identify pancreatic serous cystadenoma that contains no visible cystic compartments on computed tomography and ultrasonography.

Idiopathic calcifying pancreatitis in a Japanese pediatric patient.

We recently experienced a rare case of chronic pancreatitis in a 13-year-old Japanese boy. Recently, in hereditary pancreatitis patients, some mutations have been identified in the trypsinogen gene. The purpose of this study was to investigate whether the same mutations could also be found in this patient. Polymerase chain reaction (PCR)-amplified products of his cationic and anionic trypsinogen genes were examined by direct sequence analysis. The gene analysis failed to show any mutation in any exons and their flanking intronic sequences of his trypsinogen genes. These findings indicate that the chronic calcifying pancreatitis in the present patient is "idiopathic", and thus a rare case of juvenile pancreatitis.

Human carbonic anhydrase XIV (CA14): cDNA cloning, mRNA expression, and mapping to chromosome 1.

A full-length cDNA clone of a human carbonic anhydrase XIV (HGMW-approved gene symbol CA14) was obtained and sequenced. The cDNA sequence was 1757 bp long and was predicted to encode a 337-amino-acid polypeptide with a molecular mass of 37.6 kDa. The deduced amino acid sequence of CA XIV showed an overall similarity of 29-46% to other active CA isozymes. The highest percentage similarity was with a transmembrane CA isoform, CA XII. As observed for CA XII, CA XIV has hydrophobic segments at both termini of the deduced protein for a putative signal sequence and a transmembrane domain. CA XIV showed low activity and was sensitive to acetazolamide, but not to sulfonamide. Northern blot analysis demonstrated an approximately 1.7-kb transcript in the adult human heart, brain, liver, and skeletal muscle. RNA dot-blot analysis for CA XIV mRNA expression showed a strong signal in all parts of the human brain and a weaker signal in the colon, small intestine, urinary bladder, and kidney. RT-PCR analysis showed an intense signal in the liver and spinal cord and a faint signal in the kidney. No CA XIV mRNA was seen in the salivary gland and pancreas. In contrast, CA XII mRNA was expressed in the kidney, salivary gland, and pancreas, but not in the liver or spinal cord. The CA XIV gene was localized to human chromosome 1q21. These findings indicate genetically distinct but closely related isoforms of human transmembrane CAs, CA XII and CA XIV, which have different patterns of tissue-specific expression.

Cholecystokinin A and B receptor mRNA expression in human pancreas.

Little information is available on the expression of cholecystokinin (CCK) receptors in the human pancreas, especially in the developing pancreas. We evaluated expression patterns for the CCK receptors in human pancreas at three different ages: fetus, infant, and adult. Expressions of CCK-A and CCK-B receptor messenger RNA (mRNA) were studied in human midtrimester fetus (14-15 weeks' gestation), infant (50 days old), and adult pancreas by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Expression levels of mRNA for both receptors also were evaluated by Northern blot analysis of adult pancreas. Northern blot analysis showed a strong signal for CCK-B receptor mRNA in adult pancreas, but no detectable signal for CCK-A receptor mRNA. However, RT-PCR/Southern blotting showed the presence of CCK-A receptor mRNA in adult pancreas. This was confirmed by sequencing of the complementary DNA (cDNA). RT-PCR/Southern blot analysis also showed CCK-A and CCK-B receptor mRNA expression in fetal and infant pancreas. These results show that the both CCK receptor types are expressed in human pancreas at stages of early gestation, but there is predominant expression of CCK-B receptor in adult pancreas.

The ability of anti-carbonic anhydrase II antibody to distinguish autoimmune cholangitis from primary biliary cirrhosis in Japanese patients.

Serum antibody against carbonic anhydrase (CA) II has been described as a serological marker for distinguishing autoimmune cholangitis (AIC) from primary biliary cirrhosis (PBC). To validate this finding in a Japanese population, we evaluated sera from patients with PBC and AIC for antibody to human CA II. An enzyme-linked immunosorbent assay was employed to quantify serum antibody against CA II in patients with PBC (n = 40), AIC (n = 23), autoimmune hepatitis (n = 10), and extrahepatic obstructive jaundice (n = 10). Compared with the finding of a 4% prevalence of anti-CAII antibody in healthy subjects (n = 24), a significantly higher prevalence of anti-CA II antibody was detected in patients with PBC (35%) and AIC (30%) (P < 0.05), but not in patients with autoimmune hepatitis and patients with obstructive jaundice. No significant difference was observed between PBC and AIC patients. These results showed that AIC and PBC would be indistinguishable by anti-CA II antibody testing in Japanese patients. However, the finding of serum anti-CA II antibody in patients with PBC and AIC supports the disease concept of autoimmune exocrinopathy.