The combination of the serum carbohydrate antigen 19-9 and carcinoembryonic antigen is a simple and accurate predictor of mortality in pancreatic cancer patients

Purpose

The aim of this study was to detect high-performance prognostic biomarkers of pancreatic cancer which would enable the identification of high-risk patients.

Methods

The subjects were 324 patients who underwent radical surgery for pancreatic ductal adenocarcinoma without neoadjuvant therapy. We evaluated the prognostic impact of four perioperative serum tumor markers, including carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). We also evaluated the indices by multiplying the values of two tumor markers (e.g., CA19-9 × CEA).

Results

The preoperative CA19-9 × CEA index had a strong correlation with the prognosis of patients with pancreatic cancer, even when the cut-off was set at the median value. CA19-9 × CEA ≥500 was an independent predictor of mortality (hazard ratio: 1.642, p = 0.021). In the ROC curve analysis of early mortality after surgery, the CA19-9 × CEA index had the highest goodness of fit. The presence of CA19-9 × CEA ≥500 had the largest attributable risk proportion because of its combined high predictive performance and prevalence. The postoperative CA19-9 × CEA index was also a significant predictive marker of mortality.

Conclusion

The CA19-9 × CEA index is a strong prognostic biomarker that could help identify pancreatic cancer patients expected to have a poor prognosis so that they can be administered appropriate multidisciplinary treatment.     

Gender differences in prognosis after esophagectomy for esophageal cancer

Purpose

The purpose of this study was to clarify the gender differences in the prognosis, as well as mortality and morbidity, of patients who have undergone esophagectomy for esophageal cancer.

Methods

The clinical results of esophagectomy were compared between 975 male and 156 female patients with esophageal cancer.

Results

The male to female ratios of cervical and thoracic esophageal cancer were 1.87 and 7.38, respectively (P < 0.01). The incidence of preoperative comorbidities was 32.4 and 17.4 %, respectively, and the rates of both tobacco and alcohol abuse were significantly lower in the females than in the males. The mortality rate was lower in the females (3.8 %) than in the males (5.7 %), although the differences were not significant. The overall survival was significantly better in the female than in the male patients (P = 0.039). The 5- and 10-year overall survival rates were 32.6 and 20.5 % in the males and 39.5 and 32.5 % in the females, respectively. A multivariate analysis revealed gender to be an independent prognostic factor. However, no significant differences were recognized in disease-specific survival.

Conclusions

These results suggest that the prognosis of females with esophageal cancer is better than that of males after esophagectomy, most likely due to multiple clinical factors, such as a more favorable lifestyle and general status.     

Three-dimensional kinetic simulation before and after rotational acetabular osteotomy

Background

Some reports indicate that one of major causes of clinical failure after periacetabular osteotomy is development of secondary femoroacetabular impingement (FAI). To assess the impact of range of motion (ROM) on the increase in FAI following rotational acetabular osteotomy (RAO), we performed FAI simulations before and after RAO.

Methods

We evaluated 12 hips that had undergone RAO (study group), and 12 normal hips (control group). The study group was evaluated before and after surgery. Morphological parameters were evaluated to assess acetabular coverage. The acetabular anteversion angle, anterior CE angle, alpha angle, and combined anteversion angle were also measured. Impingement simulations were performed using 3D-CT. The ROM which causes bone-to-bone impingement was evaluated in flexion (flex), abduction, external rotation at 0° flexion, and internal rotation at 90° flexion. The lesions caused by impingement were evaluated.

Results

Radiographic measurements indicated improved postoperative acetabular coverage in the study group. The crossover sign was recognized pre- and postoperatively in every case in the study group and in no cases in the control group. In the simulation study, flexion, abduction, and internal rotation at 90° flexion decreased postoperatively. Impingement occurred within 45° internal rotation at 90° flexion in two preoperative and nine postoperative cases. The impingement lesions were anterosuperior of the acetabulum in all cases. There were correlations between anterior CE angle, CE angle, acetabular anteversion angle, and hip flexion angle. There were also correlations between the anterior CE angle, combined anteversion angle, and angle of internal rotation at 90° flexion.

Conclusions

In the postoperative simulation, there was a tendency to reduce the ROM in flexion, abduction, and internal rotation at 90° flexion due to impingement. Since there were more cases which caused impingement within 45° internal rotation at 90° flexion after RAO, we consider there is a potential for increased FAI after RAO.     

Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes

This paper documents the case of a female Japanese patient with infantile focal epilepsy, which was different from benign infantile seizures, and a family history of infantile convulsion and paroxysmal choreoathetosis. The patient developed partial seizures (e.g., psychomotor arrest) at age 14 months. At the time of onset, interictal electroencephalography (EEG) showed bilateral parietotemporal spikes, but the results of neurologic examination and brain magnetic resonance imaging were normal. Her seizures were well controlled with carbamazepine, and she had a normal developmental outcome. EEG abnormalities, however, persisted for more than 6 years, and the spikes moved transiently to the occipital area and began to resemble the rolandic spikes recognized in benign childhood epilepsy. Her father had paroxysmal kinesigenic dyskinesia, with an onset age of 6 years, and her youngest sister had typical benign infantile seizures. Genetic analysis demonstrated that all affected members had a heterozygous mutation of c.649_650insC in the proline-rich transmembrane protein-2 (PRRT2) gene. This case indicates that the phenotypic spectrum of infantile seizures or epilepsy with PRRT2-related pathology may be larger than previously expected, and that genetic investigation of the effect of PRRT2 mutations on idiopathic seizures or epilepsy in childhood may help elucidate the pathological backgrounds of benign childhood epilepsy.     

An autopsy case of meningeal carcinomatosis with parenchymal invasion through the cranial and spinal nerve roots

Meningeal carcinomatosis is a well‐known complication of malignant neoplasms. We report a case of meningeal carcinomatosis of 2 months' duration in a 22‐year‐old man, in whom the initial symptom was gradually worsening headache. Postmortem examination revealed infiltrating adenocarcinoma of the stomach. Carcinoma cells showed diffuse spread to the subarachnoid space of the brain and spinal cord. In many places, subarachnoid tumor cells had infiltrated to the cranial and spinal nerves. Moreover, carcinoma cells in the nerve roots extended to the parenchyma of the brain and spinal cord beyond the CNS‐peripheral nervous system junction. These findings suggest that cranial and spinal nerve roots can be a possible route of parenchymal invasion in meningeal carcinomatosis.     

Long-Term Results of Seton Placement for Fistula-in-ano in Infants

Background

The present study aimed to assess the long-term results of seton placement for fistula-in-ano (FIA) in infants.

Methods

Data of patients aged <1 year who presented to our department with perianal abscess (PA) between January 2006 and February 2010 were retrospectively reviewed. Our standard initial treatment for PA was incision and drainage. Patients with systemic diseases and inflammatory bowel diseases were excluded.

Results

Ninety-five patients were treated for PA and/or FIA during the 5-year period, and follow-up data were available for 90 patients. The mean follow-up duration in these patients was 49.8?±?11.4 months, and mean age at presentation was 3.1?±?2.7 months. Of the 90 patients, 36 (40 %) developed FIA (39 lesions) and underwent seton placement. The condition healed in a mean period of 6.3?±?4.0 weeks after the placement of a cutting seton. Healing of the fistula was achieved in 35 (97.2 %) of 36 patients after the initial seton procedure, and one patient who showed recurrence underwent a second seton placement, resulting in successful healing of the FIA after 5 weeks.

Conclusions

The long-term success of seton placement indicates that this procedure should be a treatment option for FIA in infants.     

Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy

Background

The primary abnormal manifestation in immunoglobulin A nephropathy (IgAN) is recurring bouts of hematuria with or without proteinuria. Although immunohistochemical analysis of renal biopsy tissue remains the gold standard not only for diagnosis but also for evaluating the activity of IgAN, new sensitive and reasonably specific noninvasive tests are emerging to guide therapeutic strategy applicable to all stages of IgAN. The present study examined serum levels of galactose-deficient IgA1 (Gd-IgA1) and its immune complex (IgA/IgG-IC) as noninvasive markers for the disease activity.

Methods

We enrolled 50 IgAN patients (male 40 %, median age 37 years) showing complete or partial clinical remission after steroid pulse therapy with tonsillectomy (TSP) whose clinical data and serum could be followed up for 3–5 years.

Results

Cross-sectional analysis revealed that the degree of hematuria and proteinuria were significantly associated with levels of Gd-IgA1 and levels of IgA/IgG-IC. Longitudinal analysis further showed that from the group of 44 patients with heavy hematuria before TSP, 31 patients showed complete disappearance of hematuria (group A), but the remaining patients did not (group B). Although the levels of Gd-IgA1 and IgA/IgG-IC in the two groups before TSP were similar, percentage decrease of Gd-IgA1 and IgA/IgG-IC levels in group A was significantly higher than in group B.

Conclusion

Disease activity of IgAN assessed by hematuria and proteinuria correlated with serum levels and changes of Gd-IgA1 and IgA/IgG-IC. These new noninvasive disease activity markers can be useful for future activity scoring system and guiding therapeutic approaches.     

Lumbar spinal fusion with β-TCP granules and variable Escherichia coli–derived rhBMP-2 dose

Background contextThe ideal tissue-engineered solution for any bone graft substitute is to assist in the rapid formation of bone and facilitate fusion.PurposeThe present study aims to evaluate this E-BMP-2 (Escherichia coli–derived human bone morphogenetic protein-2) in ovine posterolateral lumbar fusion (PLF) to examine the influence of dose and overall performance in a model with similar graft size and diffusive challenges to the human.Study design/settingIn vivo large animal model study.MethodsAn adult ovine PLF was performed in 30 animals with groups of E-BMP-2 with a beta-tricalcium phosphate (β-TCP) carrier at three different dosages, β-TCP alone, and autograft from the iliac crest. The fusions were assessed by radiography (X-ray and microcomputed tomography), mechanical testing, and hard-tissue histology with bone labels at 6, 8, and 10 weeks along with routine paraffin histology at 12 weeks.ResultsResults showed increasing new bone and fusion rate with E-BMP-2 dose, whereas β-TCP alone was largely resorbed and did not achieve fusion in this model at 12 weeks. Autograft showed similar grading for the amount of bone between the transverse processes but a lower fusion rate than β-TCP/E-BMP-2 groups. Bone labels revealed new bone formation at all time points for the E-BMP2 groups, whereas the autograft group showed active bone formation at 10 weeks. Beta-tricalcium phosphate displayed reliable incorporation into the decorticated host bone, whereas limited new bone was found between the transverse processes. At the center of the fusion mass, increased E-BMP-2 dose led to increased incorporation of β-TCP by new bone.ConclusionsThese results suggest that E-BMP-2 was capable of producing posterolateral fusion in the ovine model that is equal to or superior to autologous graft in terms of fusion rate and mechanical strength. E-BMP-2 dose had considerable influence on β-TCP granule resorption.     

Morphological evaluation of the distal interosseous membrane using ultrasound

Evidence from a recent cadaveric study has revealed that the thickness of the distal interosseous membrane (DIOM) of the forearm shows substantial individual variations, and a thick fibrous tissue known as the distal oblique bundle (DOB) was found in 40 % specimens in the study. Another cadaveric study revealed that greater stability of the distal radioulnar joint (DRUJ) was obtained in a group with DOB following ulnar shortening than in a group without DOB. Thus, the presence of DOB influences the condition of DIOM and the ability of DIOM to provide stability to the compromised DRUJ. In the present study, we carried out a preoperative morphological evaluation of DIOM using ultrasound (US) and compared the US findings with intraoperative findings in order to investigate the efficacy and the meanings of this US evaluation. A total of 14 patients with various diseases or injuries of the distal forearm requiring corrective surgery were enrolled. The mean values of DIOM thickness as measured by US evaluation correlated well with those measured intraoperatively. The sensitivity of US evaluation in confirming presence of DOB was 80 % when the presence of DOB bundle was judged by DIOM thickness. In addition, 4 of 5 patients with chronic DRUJ instability showed no DOB. This study suggested that US can be a useful tool in evaluating DIOM and for detecting the presence of DOB and may provide helpful information regarding DRUJ instability.     

Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors

Differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine H₁ receptors. In this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human H₁ receptors and their structural determinants. The binding enthalpy and entropy of 20 antihistamines were estimated with the van’t Hoff equation using their dissociation constants obtained from their displacement curves against the binding of [³H]mepyramine to membrane preparations of Chinese hamster ovary cells expressing human H₁ receptors at various temperatures from 4 °C to 37 °C. Structural determinants of antihistamines for their thermodynamic binding properties were assessed by quantitative structure–activity relationship (QSAR) analyses. We found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy–entropy compensation between the binding forces of first- and second-generation antihistamines. QSAR analyses indicated that enthalpy–entropy compensation was determined by the sum of degrees, maximal electrostatic potentials, water-accessible surface area and hydrogen binding acceptor count of antihistamines to regulate their affinity for receptors. In conclusion, it was revealed that entropy-dependent hydrophobic interaction was more important in the binding of second-generation antihistamines, even though the hydrophilicity of second-generation antihistamines is generally increased. Furthermore, their structural determinants responsible for enthalpy–entropy compensation were explored by QSAR analyses. These findings may contribute to understanding the fundamental mechanisms of how the affinity of ligands for their receptors is regulated.