Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017

Background

Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease.

Methods

These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS ). Of seven allied disorders, isolated hypoganglionosis; megacystis‐microcolon‐intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo‐obstruction were selected as targets of clinical questions (CQ ). In a comprehensive search of the Japanese‐ and English‐language articles in PubMed and Ichu‐Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table.

Results

We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ , the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full‐thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists.

Conclusions

Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ , along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

     

Executive dysfunction in patients with spinocerebellar ataxia type 3

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex–ventral dentate nucleus–thalamus–prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.     

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.     

Association between iron‐deficiency anemia and depression: A web‐based Japanese investigation

Aim

This web‐based survey aimed to examine the relation between iron‐deficiency anemia and depression in 11 876 Japanese participants.

Methods

Participants consisted of 1000 individuals with self‐reported history of depression (mean age, 41.4 ± 12.3 years; 499 women) and 10 876 population‐based controls (mean age, 45.1 ± 13.6 years; 5185 women). The 6‐item Kessler Scale (K6) score was used as a psychological distress scale. The design of the study was cross‐sectional.

Results

The rate of self‐reported lifetime history of iron‐deficiency anemia was higher in the depression group in both men (depression, 7.2%; control, 4.0%; P < 0.001; odds ratio [OR], 1.86; 95% confidence interval [CI], 1.30–2.68) and women (depression, 33.4%; control, 25.8%; P < 0.001; OR, 1.45; 95%CI, 1.19–1.76). The K6 score in participants with self‐reported history of iron‐deficiency anemia was higher in both the depression (P = 0.004) and control (P < 0.001) groups. In addition, in all participants, the rate of individuals who showed a K6 cut‐off score of 13 or more was higher in those with a self‐reported history of iron‐deficiency anemia (P < 0.001; OR, 1.47; 95%CI, 1.31–1.65). Logistic regression analyses revealed that self‐reported history of depression and the K6 score were positively associated with self‐reported history of iron‐deficiency anemia (all P < 0.01).

Conclusion

Self‐reported history of iron‐deficiency anemia was associated with self‐reported history of depression. Furthermore, self‐reported history of iron‐deficiency anemia was associated with higher psychological distress.

     

Early embryonic losses in mice induced by diethylstilbestrol

Estrogens cause embryonic lethality and the disturbance of early placental development in mice. Diethylstilbestrol (DES) at 1, 10, or 100 µg/kg was orally administered to Institute of Cancer Research mice on gestational days (GD) 4 through 8, and the uterus and placenta were examined histopathologically on GD 9. Decidua of DES‐treated mice showed insufficient development, and the uterine lumen at the implantation site did not effectively minimize. The trophoblast giant cell layer was not separated from the uterine lumen by the decidua capsularis, and hemorrhage from the denuded trophoblast giant cell layer into the uterine lumen was noted at the peripheral part of the decidua basalis. The results of the present study suggest that decidual hypoplasia and subsequent placental hemorrhage causes fetal death due to the administration of DES during the early stage of pregnancy.     

Safety and efficacy of S-1 chemotherapy in recurrent/metastatic head and neck cancer

S-1 is an oral 5-fluorouracil (5-FU) anticancer agent and has shown promising effects in the treatment of a wide range of carcinomas, including head and neck cancer. In addition to being used as adjuvant chemotherapy, S-1 is a promising agent for palliative treatment. Its ease of administration makes it an ideal drug to treat patients in the outpatient setting while maintaining adequate quality of life. However, the clinical role of S-1 in patients with recurrent/metastatic head and neck cancer is still uncertain. We retrospectively reviewed 16 patients with recurrent/metastatic head and neck cancer who received S-1 monotherapy. Thirteen patients with squamous cell carcinoma (SCC) and 3 patients with non-SCC who had recurrent/metastatic disease received S-1 monotherapy as outpatients. One patient with nasopharyngeal undifferentiated carcinoma and 1 patient with maxillary adenosquamous carcinoma showed complete response (CR), while all SCC patients showed stable disease (SD) or progressive disease (PD). Median time to progression (TTP) was 12 weeks. Five patients showed grade 3 and 4 adverse reactions, all hematological. Except for one episode of grade 4 leucopenia which required hospitalization and granulocyte colony-stimulating factor (GCSF) treatment, all adverse events resolved with dose reduction or dose omission. S-1 was safely administered in outpatients and showed some efficacy in the treatment of recurrent/metastatic head and neck cancer in patients who had received previous chemotherapy. S-1 could be used as palliative treatment in patients with recurrent/metastatic head and neck cancer.