Psychological and endocrine factors and pain after mastectomy.

BACKGROUND: This prospective study was designed to examine the associations of demographic, clinical, psychological and neuroendocrine factors with acute and chronic post-operative pain following partial mastectomy. METHODS: Sixty-four female patients scheduled for partial mastectomy were enrolled. Pre-operative anxiety/depression was assessed, using the Hospital Anxiety and Depression Scale (HADS). Pre-operative 24-h urinary cortisol levels were measured 2 days before surgery. Post-operative pain was examined using a visual analog scale (VAS) for acute pain on 0-2 post-operative day (POD), and a short-form McGill Pain Questionnaire for chronic pain at 6 months after surgery. In the last 29 subjects, post-operative 24-h urinary cortisol levels were also measured on 0 POD and were subjected to correlation analysis. RESULTS: Multivariate logistic regression analysis revealed that lower pre-operative cortisol secretion and greater pre-operative anxiety were significantly associated with an increased risk of moderate to severe acute post-operative pain [Odds Ratio (95% Confidence Interval); 0.96 (0.92-0.98), and 1.24 (1.04-1.54)], and that patients with greater pre-operative anxiety and moderate to severe acute pain were more likely to develop chronic post-operative pain [OR (95% CI); 1.63 (1.23-2.40), and 5.07 (1.30-24.6)]. Correlational analysis demonstrated that the post-operative cortisol level was inversely correlated with pre-operative anxiety and the intensity of acute post-operative pain (r = -0.40, p < 0.05, and r = -0.50, p < 0.01), but not with the intensity of chronic pain. CONCLUSIONS: This study confirms that pre-operative anxiety is associated with both acute and chronic post-operative pain after partial mastectomy. It also suggests that lower perioperative cortisol secretion might be associated with greater acute post-operative pain. SIGNIFICANCE: Although the associations between psychological stress/stress hormone levels and chronic post-operative pain remain to be determined, pre-operative psychological stress and perioperative cortisol levels are correlated with acute post-operative pain.

Intra- and postoperative low-dose ketamine for adolescent idiopathic scoliosis surgery: a randomized controlled trial.

BACKGROUND: In this randomized controlled trial, we examined whether intra- and postoperative infusion of low-dose ketamine decreased postoperative morphine requirement and morphine-related adverse effects as nausea and vomiting after scoliosis surgery. METHODS: After IRB approval and informed consent, 36 patients, aged 10-19 years, undergoing posterior correction surgery for adolescent idiopathic scoliosis, were randomly allocated into two groups: intra- and postoperative ketamine infusion at a rate of 2 µg/kg/min until 48 h after surgery (ketamine group, n = 17) or infusion of an equal volume of saline (placebo group, n = 19). All patients were administered total intravenous anesthesia with propofol and remifentanil during surgery and intravenous morphine using a patient-controlled analgesia device after surgery. The primary outcome was cumulative morphine consumption in the initial 48 h after surgery. Pain scores (Numerical Rating Scale, NRS, 0-10), sedation scales, incidence of postoperative nausea and vomiting (PONV), and antiemetic consumption were recorded by nurses blinded to the study protocol for 48 h after surgery. RESULTS: Patient characteristics did not differ between the two groups. Cumulative morphine consumption for 48 h after surgery was significantly lower in the ketamine group compared to the placebo group (0.89 ± 0.08 mg/kg vs. 1.16 ± 0.07 mg/kg, 95% confidence interval for difference between the means, 0.03-0.48 mg/kg, P = 0.019). NRS pain, sedation scales, and incidence of PONV did not differ between the two groups. Antiemetic consumption was significantly smaller in ketamine group. CONCLUSIONS: Intra- and postoperative infusion of low-dose ketamine reduced cumulative morphine consumption and antiemetic requirement for 48 h after surgery.

Clinical evaluation of reduced field-of-view diffusion-weighted imaging of the cervical and thoracic spine and spinal cord.

BACKGROUND AND PURPOSE: DWI has the potential to improve the detection and evaluation of spine and spinal cord pathologies. This study assessed whether a recently described method (rFOV DWI) adds diagnostic value in clinical patients. MATERIALS AND METHODS: Consecutive patients undergoing clinically indicated cervical and/or thoracic spine imaging received standard anatomic sequences supplemented with sagittal rFOV DWI by using a b-value of 500 s/mm(2). Two neuroradiologists blinded to clinical history evaluated the standard anatomic sequences only for pathology and provided their level of confidence in their diagnosis. These readers then rescored the examinations after reviewing the rFOV DWI study and indicated whether this sequence altered findings or confidence levels. RESULTS: Two hundred twenty-three patients were included in this study. One hundred eighty patient scans (80.7%) demonstrated at least 1 pathologic finding. Interobserver agreement for identifying pathology (κ = 0.77) and in assessing the added value of the rFOV DWI sequence (κ = 0.77) was high. In pathologic cases, the rFOV DWI sequence added clinical utility in 33% of cases (P < .00001, Fisher exact test). The rFOV DWI sequence was found to be helpful in the evaluation of acute infarction, demyelination, infection, neoplasm, and intradural and epidural collections (P < .001, χ(2) test) and provided a significant increase in clinical confidence in the evaluation of 11 of the 15 pathologic subtypes assessed (P < .05, 1-sided paired Wilcoxon test). CONCLUSIONS: rFOV diffusion-weighted imaging of the cervical and thoracic spine is feasible in a clinical population and increases clinical confidence in the diagnosis of numerous common spinal pathologies.

Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma.

BACKGROUND AND AIM: Recent studies indicated that hepatic stem cells in the bone marrow could differentiate into mature hepatocytes, suggesting that bone marrow cells could be used for replacement of damaged hepatocytes in a variety of liver diseases. Hepatocellular carcinoma (HCC) is thought to arise from hepatic stem cells. In this study, we investigated the malignant potential of hepatic stem cells derived from the bone marrow in a mouse model of chemical hepatocarcinogenesis. METHODS: Bone marrow cells were obtained from the male beta-galactosidase (beta-gal) transgenic mouse and transplanted into female recipient mice. Hepatocarcinogenesis was induced by a year of treatment with diethylnitrosamine and phenobarbital (NDEA/PB). One year later, the liver was removed from each treated mouse and evaluated by x-gal staining, immunohistochemistry, and fluorescence in situ hybridisation (FISH). RESULTS: Forty per cent of recipient mice survived and developed multiple HCC. Clusters of beta-gal positive mature hepatocytes were detected sporadically in the entire liver of NDEA/PB treated mice who underwent bone marrow transplantation (BMT) with while no such hepatocytes were identified in the liver of BMT mice that were not treated with NDEA/PB. The Y chromosome was detected with the same frequency as the donor male liver in clusters of beta-gal positive mature hepatocytes by FISH. However, no HCC was positive for beta-gal or the Y chromosome. Immunohistochemically, beta-gal positive mature hepatocytes did not express CD34 or alpha-fetoprotein. CONCLUSIONS: Our results suggest that hepatic stem cells derived from the bone marrow have low malignant potential, at least in our model.

Real-time black-blood MRI using spatial presaturation.

A real-time interactive black-blood imaging system is described. Rapid blood suppression is achieved by exciting and dephasing slabs outside the imaging slice before each imaging excitation. Sharp-profiled radio frequency saturation pulses placed close to the imaging slice provide good blood suppression, even in views containing slow through-plane flow. In vivo results indicate that this technique improves endocardial border definition during systole in real-time cardiac wall-motion studies. Phantom and animal results indicate that this technique nearly eliminates flow artifacts in real-time intravascular studies. J. Magn. Reson. Imaging 2001;13:807-812.

Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor.

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.

Long-term follow-up of sustained responders to interferon therapy, in patients with chronic hepatitis C.

Interferon (IFN) therapy has been proven to induce the normalization of serum alanine aminotransferase (ALT) levels and to eradicate the hepatitis C virus (HCV) in some patients with chronic hepatitis C, and these patients are usually defined as 'sustained responders'. However, there have been some reports of hepatocellular carcinoma (HCC) in these patients, and the development of HCC remains life-threatening in patients who clear HCV. We analysed the long-term prognoses of patients with chronic hepatitis C in whom HCV was eradicated with IFN. We investigated 392 sustained responders to IFN therapy, from 1,277 patients with chronic HCV infection who received IFN treatment at one of our institutions between April 1989 and March 1999. We analysed the medical records and looked for the development of HCC. About 30% of the sustained responders had been lost to follow-up 3 years after the end of IFN therapy, and the follow-up rate of sustained responders was significantly lower than that of non-sustained responders (P < 0.0001). HCC were found in eight patients: in seven patients HCC developed within 5 years after completion of IFN therapy; but in one patient, a single HCC less than 3 cm in diameter was detected between 7 and 8 years after completion of IFN. Of the five patients who had regular medical follow-up, the HCC was solitary, and the patients survived without any evidence of recurrence. Of the three patients who had not been followed-up, two died from HCC and HCC recurred in the third. These results suggest that HCC can develop in sustained responders and that sustained responders should be followed-up closely after completion of IFN so that HCC may be detected at an early stage. The optimal duration of the follow-up period of the sustained responders remains unclear. Additional prospective studies are required in order to establish an appropriate follow-up protocol for sustained responders to IFN.

Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins.

beta-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two beta-defensins have been identified. Here, we report the identification of two genes encoding beta-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human beta-defensin-1 (HBD-1) gene and mouse beta-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat beta-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of beta-defensins. The beta-defensin genes mapped closely on rat chromosome 16 and were closely linked to the alpha-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were approximately 0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel beta-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of beta-defensins to host defense in the lung, kidney, and other tissues.

Patent ductus venosus.

BACKGROUND: Patent ductus venosus is extremely rare with only 14 cases reported in the world literature. We present a case of patent ductus venosus. METHODS AND RESULTS: A 29-year-old male was admitted with melaena stool caused by gastric haemorrhagic ulcers. Laboratory data disclosed severe anaemia; however, liver function tests were normal. Serum ammonia was also within the normal range. Serological viral markers for hepatitis B or C were all negative. The abdominal ultrasonography and computed tomography indicated a 12 mm diameter shunt located in the left lobe of the liver, which connected the portal vein with the left hepatic vein. After treatment for gastric ulcers, percutaneous transhepatic portography was performed and an enormous shunt connecting the umbilical portion of the portal vein with the left hepatic vein was revealed. CONCLUSIONS: Histological findings of the liver biopsy showed that portal venules could not be observed in the portal areas and that no fibrosis or inflammatory cell infiltration were shown. Because of the anatomical position of the shunt, the case was diagnosed as patent ductus venosus.

[Chronic pancreatitis, acute pancreatitis].

MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

Gastric antral vascular ectasia successfully treated by endoscopic electrocoagulation.

We report two cirrhotic patients with gastric antral vascular ectasia (GAVE) in whom chronic blood loss presented a major problem. Case 1, a 69-year-old man, had alcoholic liver cirrhosis, and case 2, a 75-year-old woman, had liver cirrhosis associated with hepatitis C virus. The patients required repeated blood transfusions but still exhibited persistent anemia. On upper gastrointestinal endoscopy, both patients showed esophageal varices without stigmata of bleeding or red color signs and presented with a characteristic antral appearance so distinctive as to be diagnostic; diffuse erythemas consisting of ectatic and tortuous capillaries throughout the antrum. Endoscopic electrocoagulation treatment with a monopolar probe was effective for controlling blood loss from GAVE. The patients tolerated the procedure well and there were no resultant complications. Several sessions of the treatment resulted in eradication of almost all the vascular lesions, negative fecal occult blood test results, and marked alleviation of their anemia without further treatment. Endoscopic electrocoagulation is suggested to be a safe, non-invasive, and effective treatment for blood loss from GAVE, especially in patients with liver cirrhosis in whom surgery carries an increased risk.

A gene for familial juvenile polyposis maps to chromosome 18q21.1.

Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study was to perform a focused genome screen in a large family segregating FJP. No evidence for linkage was found with markers near MSH2, MLH1, MCC, APC, HMPS, CDKN2A, JP1, PTEN, KRAS2, TP53, or LKB1. Linkage to FJP was established with several markers from chromosome 18q21.1. The maximum LOD score was 5.00, with marker D18S1099 (recombination fraction of .001). Analysis of critical recombinants places the FJP gene in an 11.9-cM interval bounded by D18S1118 and D18S487, a region that also contains the tumor-suppressor genes DCC and DPC4. These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP.

Extrahepatic portosystemic venous shunt without portal hypertension.

A 72-year-old woman was admitted for recurrent episodes of encephalopathy. Laboratory data showed mild liver dysfunction and hyperammonemia, while she had neither anemia nor splenomegaly. The dilated inferior mesenteric vein (IMV) was opacified retrogradely from the superior mesenteric vein by superior mesenteric arteriography, and IMV was found to connect with the inferior vena cava (IVC) through a torturous shunt. No obstruction of the extrahepatic portal vein or hepatic vein was observed by arteriography. Histological evaluation of the liver biopsy indicated remarkable fatty change without cirrhosis. Finally, we diagnosed this case as extrahepatic portosystemic venous shunt without portal hypertension.

Case report: multiple systemic lymph node metastases from a small hepatocellular carcinoma.

Extrahepatic lymph node metastases from hepatocellular carcinoma (HCC) are usually observed in patients with advanced and poorly differentiated HCC. We encountered a patient with multiple, systemic lymph node metastases from a small HCC (18 mm in diameter), which was nodular and had a capsule at the time of resection (a partial hepatectomy of the postero-inferior subsegment of the right lobe of the liver). Widespread lymphadenopathy resembling malignant lymphoma developed 2 months after surgery. A biopsy specimen from a supraclavicular lymph node revealed metastatic HCC. The patient died 2.5 months after the detection of the lymphadenopathy. Lymph node metastases can occur in small HCC less than 2 cm in diameter and may adversely affect the long-term prognosis of patients with these curatively resectable small HCC.

Pseudoaneurysm of the cystic artery associated with upper gastrointestinal bleeding.

Pseudoaneurysm of the cystic artery is a cause of hemobilia, and is extremely rare, with only eight cases having been reported in the world literature. We report a case of pseudoaneurysm of the cystic artery in a 72-year-old Japanese man. The patient experienced epigastric pain and melena, and was found to have jaundice and liver dysfunction. Repeated gastroendoscopy did not reveal the cause of the alimentary tract bleeding; however, color-Doppler ultrasonography detected an aneurysm of the cystic artery in the gallbladder. Selective hepatic arteriography demonstrated that the posterior branch of the cystic artery was markedly dilated and that an aneurysm had formed in the midst of the artery. We diagnosed hemobilia due to the pseudoaneurysm of the cystic artery, and associated gastrointestinal bleeding. Cholecystectomy was performed immediately. Pathologically, the gallbladder showed acute calculous cholecystitis. This case emphasizes the importance of including hemobilia in the differential diagnosis whenever gastrointestinal bleeding is associated with signs of biliary disorder; color-Doppler imaging is a favorable modality for the diagnosis of pseudoaneurysm of the cystic artery.

Case report: multiple cancers: hepatocellular carcinoma and adenocarcinomas of the common bile duct and the gall-bladder in a woman with primary biliary cirrhosis.

We present a case of primary biliary cirrhosis associated with simultaneous triple cancers: a hepatocellular carcinoma and adenocarcinomas of the common bile duct and gall-bladder. A 70 year old Japanese woman, who had been diagnosed with primary biliary cirrhosis (stage 2 by Scheuer) 15 years before, was admitted to Koseiren Kamo Hospital in a comatose state. Laboratory data were as follows: the ammonia level was high (164.0 micrograms/dL), the antimitochondrial antibody showed a 320-fold increase, a high level of alpha-fetoprotein was indicated (2677 ng/mL), hepatitis B surface antigen was negative and hepatitis C antibody by enzyme immunoassay was negative, although a test for the RNA of hepatitis C virus by polymerase chain reaction was positive (10(3.5) copies/50 microL). The patient's condition gradually worsened and the patient died of liver failure. Autopsy showed triple cancers in the liver (hepatocellular carcinoma; trabecular type, moderately differentiated), the common bile duct (well-differentiated papillary adenocarcinoma) and the gall-bladder (well-differentiated papillary adenocarcinoma) with primary biliary cirrhosis (stage 4). Primary biliary cirrhosis has been believed to be a low risk for the development of hepatocellular carcinoma, despite the high risk of extrahepatic malignancy. The simultaneous occurrence of triple cancers with primary biliary cirrhosis, to the best of our knowledge, has never been reported. The present case may provide additional evidence for a predisposition to malignancy in primary biliary cirrhosis.

Case report: fibrolamellar hepatocellular carcinoma in a Japanese woman: a case report and review of Japanese cases.

Fibrolamellar hepatocellular carcinoma (FLHCC) is an entity distinct from ordinary hepatocellular carcinoma and is very rare in Oriental countries. We present here a Japanese case of FLHCC in a 25 year old woman, and review Japanese cases of FLHCC. The patient had mild abdominal pain when the hepatic tumour was revealed by ultrasonography. Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody were negative and serum alpha-fetoprotein (AFP) was within the normal limit. Ultrasound-guided fine needle biopsy was performed and the tumour was histologically diagnosed as FLHCC. A right lobectomy of the liver was then performed. Macroscopically, the tumour (10 x 10 x 8 cm) was circumscribed, rather hard and yellowish white. Microscopically, neoplastic hepatocytes were polygonal and large with eosinophilic cytoplasm, which contained pale bodies. A number of fibrous stroma were arranged in thin parallel bands. Consequently, the case was diagnosed as FLHCC. In Japan, approximately 18,000 people die of ordinary hepatocellular carcinoma annually, while only nine cases (including the present case; six males, three females) of FLHCC in Japanese subjects have been reported previously. The mean age of the Japanese cases of FLHCC is 20.9 years old. One case with positive HBsAg, liver cirrhosis and high level of AFP was observed of nine cases. The nature of FLHCC in Japanese subjects may not be significantly different from that in Caucasians, except for male predominance.

Inhomogeneity correction using an estimated linear field map.

A fast and robust method for correcting magnetic resonance image distortion due to field inhomogeneity is proposed and applied to spiral k-space scanning. The method consists of acquiring a local field map, finding the best fit to a linear map, and using it to deblur the image distortions due to local frequency variations. The linear field map is determined using a maximum likelihood estimator with weights proportional to the pixel intensity. The method requires little additional computation and is robust in low signal regions and near abrupt field changes. Additionally, it can be used in combination with other deblurring methods. The application of this method is illustrated in conjunction with a multislice, T2-weighted, breath-held spiral scan of the liver.