Immunohistochemistry or Molecular Analysis : Which Method Is Better for Subtyping Craniopharyngioma?

Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining and one PCP showed membranous β-catenin expression and negative for BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features between, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice

Growth hormone-producing pituitary adenomas in childhood and young adulthood : clinical features and outcomes

Purpose Growth hormone (GH)-producing pituitary adenomas (PAs) in childhood or young adulthood are rare, and the details surrounding these tumors remain enigmatic. We present the clinical, pathological and genetic features of this disease. Methods We identified 25 patients aged 20 years or younger with GH-producing PAs who underwent surgery between 2003 and 2016 at Toranomon Hospital in Tokyo. We retrospectively reviewed the clinical data, treatment outcomes and pathological features of these patients to shed light on childhood acromegaly. Results The cohort comprised 14 male and 11 female patients whose average age at the time of surgery was 17.3 years. Germline AIP mutations were present in 5 of 13 patients examined, and Carney complex was identified in 2 of 25 patients. The mean maximum tumor diameter was 26.7 mm, and total resection assessed during surgery was achieved in 17 patients. Based on their respective pathological findings, patients were divided into the following 4 groups: sparsely granulated adenomas (5), densely granulated (DG) adenomas (6), plurihormonal adenomas (9), and silent subtype 3 (SS3) adenomas (5). During the mean follow-up period of 50.3 months, complete endocrinological remission was achieved in 14 of 25 patients (56%) by surgery alone and in 19 patients (76%) after postoperative adjuvant therapy. Conclusions GH-producing PAs in young patients are intriguing and difficult to treat due to their distinct tumor characteristics, including a lower incidence of the DG subtype and a higher incidence of SS3 adenomas and genetic abnormalities. Therefore, multi-modal therapies are essential to achieve optimal clinical outcomes

Hope in Adult Patients with Chronic Disease: Qualitative Study.

To identify the sources of hope for patients with chronic disease, a semi - structured interview was conducted with patients middle-aged and older, whose disease types and levels of activities of daily living limitations varied. Six patience - three with chronic kidney disease, one with rheumatoid arthritis, one with spinal cord injury, and another with lumbar spinal canal stenosis - were interviewed by a psychologist and an internist. It was determined that their sources greatly differed depending on individual circumstances, such as types and severity of disease, sources of joy and happiness, family structure, employment status, relationship with friends, etc. However, it also showed a stylization of hope dependent on individual experience; in other words, there was a tendency for patients to redefine their source of hope by setting attainable goals to match their limitations, or acknowledging what they have achieved and finding hope in maintaining their current state. We have determined that the sources of hope are comprised of two categories: ［foundation and process of finding hope］ and ［specific goals and sources］. The former consists of: ［stylization dependent on experience］, ［method and will］, ［use of external information］, ［intrinsic foundation］, and ［extrinsic foundation］. The latter consists of: ［health］, ［source of joy and happiness］, ［family］, and ［social connections］

Update in Pathogenesis, Diagnosis, and Therapy of Prolactinoma

Prolactinomas comprise 30–50% of all pituitary neuroendocrine tumors, frequently occur in females aged 20 to 50, and cause hypogonadism and infertility. In typical cases, female patients exhibit galactorrhea and amenorrhea due to serum prolactin (PRL) elevation, and patients during pregnancy should be carefully treated. During diagnosis, other causes of hyperprolactinemia must be excluded, and an MRI is useful for detecting pituitary neuroendocrine tumors. For treating prolactinoma, dopamine agonists (DAs) are effective for decreasing PRL levels and shrinking tumor size in most patients. Some DA-resistant cases and the molecular mechanisms of resistance to a DA are partially clarified. The side effects of a DA include cardiac valve alterations and impulse control disorders. Although surgical therapies are invasive, recent analysis shows that long-term remission rates are higher than from medical therapies. The treatments for giant or malignant prolactinomas are challenging, and the combination of medication, surgery, and radiation therapy should be considered. Regarding pathogenesis, somatic SF3B1 mutations were recently identified even though molecular mechanisms in most cases of prolactinoma have not been elucidated. To understand the pathogenesis of prolactinomas, the development of new therapeutic approaches for treatment-resistant patients is expected. This review updates the recent advances in understanding the pathogenesis, diagnosis, and therapy of prolactinoma

Vehicle configurations associated with anatomical-specific severe injuries resulting from traffic collisions.

Vehicles can be classified by configuration as either bonnet-type or cab-over type according to engine location. Compared to bonnet-type, the front compartment of cab-over type vehicles is considerably shorter; thus, it may be less likely to absorb the energy generated in a collision, and in turn be unable to prevent deformation of the occupant space and protect occupants from injury. This study was a cohort study involving 943 occupants of mini-vehicles who were injured in frontal collision accidents between 2001 and 2015 and transferred to Ohta Nishinouchi Hospital. The vehicle configuration was divided into bonnet-type and cab-over type (i.e., truck-type and wagon-type). The tested outcomes were anatomical-specific severe injury of the pelvis and extremities, the head and neck, the abdomen, and the chest. To estimate adjusted odds ratios (AOR) for associations between vehicle configuration and anatomical-specific severe injury, we fitted generalized estimating equations for each outcome. Compared with bonnet-type vehicles, a greater risk of serious pelvis and extremities injury was found for both truck (AOR: 2.21; 95% Confidence Interval [95% CI]: 1.22-4.00) and wagon-type vehicles (AOR: 3.43; 95%CI 1.60-7.39). For serious head and neck injury, truck-type vehicles were associated with greater risk (AOR: 2.04; 95% CI: 1.10-3.79) than bonnet-type vehicles, whereas wagon-type vehicles were not. Compared with the occupants of bonnet-type vehicles, cab-over type vehicle occupants were more likely to have serious pelvis and extremities injury during frontal collisions. Additionally, truck-type vehicle occupants were more likely to have serious head and neck injury than bonnet-type vehicle occupants. These findings are expected to promote safer behaviors for vehicle occupants and the automobile industry

Effectiveness of combined thoracoscopic-laparoscopic esophagectomy: comparison of postoperative complications and midterm oncological outcomes in patients with esophageal cancer.

[Background ] : During esophagectomy, laparoscopy can be used together with thoracoscopy, but it is not known whether a combined thoracoscopic–laparoscopic procedure is associated with fewer postoperative complications than open esophagectomy, and without compromising oncological outcome. [Methods ] : This was a longitudinal cohort study that included 185 esophageal cancer patients, including 72 who underwent combined thoracoscopic–laparoscopic esophagectomy (TLE), 34 who underwent thoracoscopic esophagectomy (TE), and 79 who underwent open esophagectomy (OE) between January 2002 and May 2010. The main outcome measures were postoperative respiratory and overall complications. The secondary outcome was 2-year relapse-free survival (RFS). [Results ] : Respiratory complications occurred in 9 patients who underwent TLE, 13 who underwent TE, and 31 who underwent OE. TLE was associated with fewer respiratory complications (TLE vs. OE: odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09–0.53 and TE vs. OE: OR, 0.71; 95% CI 0.29–1.76). Overall complications occurred in 34 patients who underwent TLE, 20 who underwent TE, and 54 who underwent OE. TLE was associated with fewer overall complications (TLE vs. OE: OR, 0.47; 95% CI 0.23–0.94 and TE vs. OE: OR, 0.51; 95% CI 0.21–1.25). The 2-year RFS rates were similar among the three groups: 71.6% for TLE, 57.7% for TE, and 58.3% for OE (TLE vs. OE: hazard ratio, 0.65; 95% CI 0.35–1.20 and TE vs. OE: hazard ratio, 0.91; 95% CI 0.45–1.82). [Conclusion ] : Unlike TE, TLE was associated with fewer postoperative complications than was OE, with no compromise of 2-year RFS. A randomized controlled trial with longer follow-up is needed

Incorporation of apical lymph node status into the seventh edition of the TNM classification improves prediction of prognosis in stage III colonic cancer.

[Background]The node classification outlined in the seventh edition of the TNM classification is based solely on the number of metastasized lymph nodes. This study examined the prognostic value of apical lymph node (ALN) metastasis and the additional value of incorporating ALN status into a risk model based on the seventh edition. [Methods]This was a cohort study of patients with stage III colonic cancer who underwent tumour resection with dissection of regional (including apical) lymph nodes at 71 hospitals across Japan between 2000 and 2002. The main exposure was pathologically confirmed ALN metastasis, and the primary endpoint was cancer-specific death. [Results]ALN metastasis was present in 113 (8·3 per cent) of 1355 patients. During 5356 patient-years of follow-up (median 5·0 years), 221 instances (16·3 per cent) of cancer-specific death were observed. After adjustment for tumour and node classification (as described in the seventh edition of the TNM classification) and other prognostic factors, ALN metastasis was found to be independently associated with cancer-specific death (hazard ratio 2·29, 95 per cent confidence interval (c.i.) 1·49 to 3·52). Incorporation of ALN metastasis into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for cancer-specific death (difference in concordance index 0·0146, 95 per cent c.i. 0·0030 to 0·0262) and risk reclassification for cancer-specific death at 5 years (category-free net reclassification improvement 19·4 (95 per cent c.i. 5·0 to 33·4) per cent). [Conclusion]Assessment of ALN metastasis provided independent prognostic information beyond that achievable with the seventh edition of the TNM classification in patients with stage III colonic cancer

Preferences of young physicians at community hospitals regarding academic research training through graduate school: a cross-sectional research.

[Background] Desire to attend graduate school for academic research training following the mandatory two-year clinical internship is unknown among young Japanese physicians who work at community hospitals after their internship. The aim of this study is to determine opinions and factors regarding pursuing higher education through graduate school among young physicians who work at community hospitals after their two-year internship. [Methods] This cross-sectional survey was conducted among young physicians working at community hospitals after their two-year internship. We examined the percentage of young physicians considering higher education through graduate school, the planned timing and field of enrollment among those wanting to enroll, and reasons for not continuing their education among those with no such plans. The association between desire to enroll in graduate school and background characteristics was examined using modified least-squares regression to estimate proportion difference. [Results] Among 127 (73.2 % internal medicine specialists, median age 30 years) physicians in 33 hospitals, 71 (55.9 %) stated that they wished to enroll in graduate school. The most frequently reported timing was 7–8 years after graduation from medical school. Those who stated no desire to attend graduate school cited concerns about the quality of training or not having enough knowledge to choose an appropriate laboratory or field, among other reasons. Increased number of years since graduating medical school [adjusted proportion difference (PD) −6.0 %, 95 % confidence interval (95 % CI) −9.8 to −2.3 %], being a woman with children [adjusted PD −53.4 %, 95 % CI −87.3 to −19.5 % (vs. a man not having children)], and completing their two-year internship at both university and community hospitals [adjusted PD −40.3 %, 95 % CI −72.5 to −8.0 % (vs. internship only at community hospitals)] were associated with a reduction in desire to enroll in graduate school. [Conclusions] We identified a growing trend in desire among young physicians to attend graduate school. Attracting those young physicians who express no desire to attend graduate school, however, will require establishment of more flexible graduate school programs which address their concerns

Effectiveness of cinacalcet treatment for secondary hyperparathyroidism on hospitalization: Results from the MBD-5D study

Objectives: To elucidate the effect of cinacalcet use on all-cause and cause-specific hospitalization outcomes using a prospective cohort of maintenance hemodialysis patients. Methods: We used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism and examined baseline characteristics as well as longitudinal changes. All patients were cinacalcet-naïve at study enrollment. Further, we used a marginal structural model to account for time-varying confounders on cinacalcet initiation and hospitalization outcomes, and an Andersen-Gill–type recurrent event model to account for any recurring events of hospitalization in the outcome analysis using the weighted dataset. Results: Among the 3, 276 patients, cinacalcet treatment was initiated in 1, 384 patients during the entire follow-up. Cinacalcet users were slightly younger, included more patients with chronic glomerulonephritis and fewer patients with diabetes, were more likely to have a history of parathyroidectomy, and were more often used receiving vitamin D receptor activator, phosphate binders, and iron supplements. The overall hospitalization analysis yielded a hazard ratio (HR) of 0.97 (95% confidence interval [CI]: 0.80, 1.18). A trend toward a mild protective association was observed for cardiovascular-related hospitalizations (HR: 0.85; 95% CI: 0.64, 1.14). In the subgroup analysis, a protective association was seen due to cinacalcet use for infection-related hospitalizations in the lowest intact parathyroid hormone group (HR: 0.36; 95% CI: 0.14, 0.95). Conclusions: Cinacalcet initiation in patients on maintenance hemodialysis had no effect on all-cause and cause-specific hospitalizations. Although the overall association was statistically not significant, cinacalcet may have a protective association on cardiovascular-related hospitalization in all patients and infection-related hospitalization in patient with low intact parathyroid hormone