Diagnosis of gastroesophageal reflux disease using a new questionnaire

BACKGROUND AND AIM: An early and accurate evaluation by a general practitioner is needed to screen out non-gastroesophageal reflux disease (GERD) patients. A recent questionnaire (QUEST) highlighted problems with specificity and complexity, so the aim of the present study was to design a simplified questionnaire. METHODS: When admitted to hospital to undergo an upper gastrointestinal endoscopy for suspected GERD, 333 patients completed a 50-item questionnaire requiring 'yes/no' answers to different combinations of questions relating to symptoms of upper gastrointestinal tract conditions (e.g. GERD, ulcers and functional dyspepsia) and psychosomatic symptoms. The endoscopic diagnosis was then correlated with the rate of positive answers to each question. RESULTS: Based on the analysis of the 50 items, the 8-10 questions most often answered affirmatively by each of the GERD and non-GERD groups were chosen for the simplified questionnaire. Three draft questionnaires were compiled. After calculating the sensitivity, specificity and accuracy in relation to the diagnosis of GERD and other conditions, it was found that questionnaire B (selection of persons answering 'yes' to at least one of questions 1-5 and exclusion of persons answering 'yes' to at least three of questions 7-10) had a high sensitivity, high specificity and low false positive rate. CONCLUSION: A novel questionnaire was developed. It was designed to detect the symptoms of GERD while simultaneously excluding non-GERD patients. This simplified nine-item simplified questionnaire had a sensitivity of 79.8%, a specificity of 53.6% and an accuracy of 63.4%.     

Intra-aortic balloon pumping is effective for hemodynamic management of catecholamine resistant ampulla (Takotsubo) cardiomyopathy

Ampulla (Takotsubo) cardiomyopathy resembles acute myocardial infarction, with absent coronary stenosis. We report a case of catecholamine resistant ampulla cardiomyopathy, successfully managed using intra-aortic balloon pumping (IABP). After laparotomy, the patient developed circulatory collapse. T wave inversion was observed on electrocardiogram. In spite of circulatory support using high dose cathecholamines, the hemodynamics of the patient showed no improvement. Upon starting IABP, the patient's hemodynamics were improved and the dose of catecholamines could be reduced. Because the ampulla cardiomyopathy is considered a subtype of 'stunned myocardium' and the hemodynamic disorder is temporary and reversible, IABP appears effective for hemodynamic management.     

Ki-67 expression and prognosis for smokers with resected stage I non-small cell lung cancer

BACKGROUND: The cigarette smoking status of patients before surgery is an important prognostic factor in evaluation of stage I non-small cell lung cancer, and the proliferative activity of lung tumors is also related to the patient's prognosis. This study evaluates relationships between various clinicopathologic factors, including tumor proliferative activity and smoking status, and the patient's prognosis in stage I non-small cell lung cancer. METHODS: One hundred eighty-seven stage I adenocarcinoma and squamous cell carcinoma cases were evaluated. The patients underwent complete resection between 1988 and 1993 at Chiba University Hospital. Expression levels of Ki-67 nuclear antigen, p53 protein, and retinoblastoma protein were determined immunohistochemically, and postoperative survival rates for patients in the categories of clinicopathologic factors were estimated. RESULTS: The mean Ki-67 labeling index (LI) for all cases was 19.3%. Labeling index values were significantly higher in squamous cell carcinoma than in adenocarcinoma (p < 0.0001). Postoperative survival of adenocarcinoma patients was significantly related to the LI values and to the patient's smoking status (p = 0.0164 and 0.0268, respectively). The LI values were also related to smoking status and the extent of histologic differentiation (p = 0.0112 and p < 0.0001, respectively). For non-smoking adenocarcinoma patients, higher LI values were associated with abnormalities in p53 expression (p = 0.0048). Retinoblastoma protein abnormalities were not related to LI values. CONCLUSIONS: In smokers with stage I pulmonary adenocarcinoma, tumor proliferative activity and smoking status before surgery were important prognostic determinants. The LI values were related to several clinicopathologic factors.     

Neuroendocrine small cell carcinoma of the uterine cervix showing polypoid growth and complicated by pregnancy

BACKGROUND: Neuroendocrine small cell carcinoma of the uterine cervix is an aggressive disease, and it rarely is complicated by pregnancy. CASE: A polypoid tumor was found in the uterine cervix in a 27-year-old Japanese woman at 27 weeks of gestation. No polyp had been detected at 14 weeks of gestation. The polyp was excised and diagnosed as neuroendocrine small cell carcinoma by histological examination, including Grimelius, neuron-specific enolase, and chromogranin staining. A healthy infant was born by cesarean section at 29 weeks of gestation: this was followed by radical hysterectomy with pelvic lymphadenectomy. After surgery, four cycles of combination chemotherapy with cisplatin and etoposide were administered, and the patient is disease-free as of 13 months after surgery. CONCLUSION: When a polypoid lesion is found, especially when it demonstrates rapid growth, it may be necessary to excise and histologically examine the polyp even during pregnancy.     

Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology

BACKGROUND: Large cell carcinoma has been classified as four potential types based on its neuroendocrine morphology and evidence of neuroendocrine differentiation discernible by immunohistochemistry or electron microscopy. However, the clinical relation among these four categories has not been clearly defined. In 1999, the World Health Organization (WHO) categorized large cell neuroendocrine carcinoma as a variant of large cell carcinoma. MATERIAL AND METHODS The authors analyzed 119 cases of large cell carcinoma from a total of 2070 primary lung carcinoma cases resected surgically between 1969-1999. Using light microscopy, electron microscopy, and immunohistochemical staining, the authors reclassified these cases into large cell neuroendocrine carcinoma (LCNEC), large cell carcinoma with neuroendocrine differentiation (LCCND), large cell carcinoma with neuroendocrine morphology (LCCNM), and classic large cell carcinoma (CLCC). RESULTS: In multivariate analyses, the authors found that large cell carcinoma with neuroendocrine features, which combined LCNEC, LCCND, and LCCNM, impacted both the overall survival and disease-free survival of patients. The clinical behavior of LCCNM was similar to that of LCNEC. CONCLUSIONS: Large cell carcinomas with neuroendocrine features appear to be more clinically aggressive than CLCCs. The authors' findings suggest that the histologic identification of neuroendocrine features in tumor tissue from patients diagnosed with large cell carcinoma of the lung may have clinical relevance.     

The effect of cyclooxygenase-2 inhibitor FK3311 on ischemia-reperfusion injury in a canine total hepatic vascular exclusion model

BACKGROUND: Liver grafts from non-heart-beating donors inevitably suffer from warm ischemic injury. In these grafts, large quantities of inflammatory cytokines and arachidonic acid metabolites are induced, further aggravating injury. Cyclooxygenase (COX) is an intracellular enzyme that converts arachidonic acid into prostaglandin (PG)G2 and PGH2. COX has two isoforms: constitutive COX-1 and inducible COX-2. The aim of this study was to evaluate the effects of COX-2 inhibition by FK3311 (FK) on warm ischemic injury in a canine total hepatic vascular exclusion (THVE) model. STUDY DESIGN: Sixteen mongrel adult dogs were studied. The portal triad of the hilum and the inferior vena cava above and below the liver was clamped for 1 hour. Splanchnic decompression was achieved by active splenofemorojugular bypass. The animals were divided into two groups. FK (1 mg/kg) was administered in the FK group (n = 8), and saline was administered in the control group (n = 8). Hepatic venous blood was collected to measure serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase (LDH), and hyaluronic acid levels. Serum thromboxane (Tx)B2 and 6-keto-PGF1alpha levels were also measured. Hepatic tissue blood flow was estimated simultaneously. Liver specimens were harvested for histologic study and polymorphonuclear neutrophils were counted. RESULTS: Alanine aminotransferase, aspartate aminotransferase, and hyaluronic acid 2 and 6 hours after reperfusion and LDH 30 minutes and 2 and 6 hours after reperfusion were significantly (p < 0.05) lower in the FK group than in the control group. Hepatic tissue blood flow remained significantly (p < 0.05) higher in the FK group than in the control group 1, 2, and 6 hours after reperfusion. Histologic tissue damage was mild and polymorphonuclear neutrophil infiltration was significantly lower (p < 0.05) in the FK group than in the control group 1 and 6 hours after reperfusion. Thirty minutes after reperfusion, TxB2 was significantly reduced (p < 0.05) in the FK group, and 6-keto-PGF1alpha was not significantly lower. CONCLUSIONS: FK protected against hepatic warm ischemia-reperfusion injury by marked inhibition of TxA2.     

Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to university of wisconsin solution on reperfusion injury in liver transplantation

BACKGROUND: Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of ischemia/reperfusion injury in nonhepatic organs, such as the heart. However, the role of p38 MAPK activation in the liver is unclear. We examined the effects of FR167653, a novel p38 MAPK inhibitor, as an additive to University of Wisconsin (UW) solution in rat liver transplantation. METHODS: Rat orthotopic liver transplantation was performed after 30 hr of cold storage using UW solution with or without FR167653. Ten-day survival rates, serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels, liver tissue blood flow, histological findings, and activities of p38 MAPK and p46/p54 c-Jun N-terminal kinase (JNK) in liver grafts were evaluated. RESULTS: The addition of FR167653 significantly increased animal survival rates. FR167653 significantly suppressed serum ALT and LDH levels and improved liver tissue blood flow after transplantation. FR167653 also ameliorated histological damage to the liver graft. Neither p38 MAPK nor p46/p54 JNKs was activated during cold storage, whereas both were markedly activated within 30 min of reperfusion and remained activated until 60 min after reperfusion. FR167653 inhibited the activation of p38 MAPK both 30 and 60 min after reperfusion, but it did not affect the activation of p46/p54 JNKs. CONCLUSIONS: The addition of FR167653 to UW solution improved liver graft viability and animal survival rates associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting the activation of p38 MAPK may attenuate ischemia/reperfusion injury in liver transplantation.     

Living-related liver transplantation for type II citrullinemia using a graft from heterozygote donor

BACKGROUND: Type II citrullinemia (CTLN2) characterized by a liver-specific argininosuccinate synthetase deficiency is an adult onset genetical disorder caused by the mutation of SLC25A13 gene, which results in fulminant hyperammonemia often with poor prognosis. METHODS: A 16-year-old Japanese boy presented fulminant hyperammonemia and encephalopathy and recovered after aggressive medical treatment. The patient was diagnosed as CTLN2 by plasma amino acid pattern and detection of the mutated SLC25A13 gene. We performed living-related liver transplantation (LRLT) using a graft from the genetically proven heterozygote father. RESULTS: Serum amino acid concentration was normalized within a day after transplantation without protein restriction and medication. The patient's postoperative course was natural. The patient is back in school 6 months after surgery. CONCLUSIONS: Living-related liver transplantation using a graft from genetically proven heterozygote donors might be a permissible treatment modality for CTLN2. Long-term observation may be necessary to make a definite conclusion possible.     

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.