Dyskeratosis congenita (DKC) is an inherited bone marrow failure syndrome characterized by reticulated skin pigmentation, nail dystrophy, and mucosal leukoplakia. Hoyeraal-Hreidarsson syndrome is considered to be a severe form of DKC. Unconventional forms of DKC (cryptic DKC [cDKC]), which develop slowly in adulthood without the physical anomalies characteristic of DKC, have been reported. The genes responsible for them have been identified as a gene cluster forming a telomerase complex (DKC1, TERC, TERT, NOP10, and NHP2); TINF2, which forms a shelterin complex; TCAB1, which transports the telomerase complex to intranuclear Cajal bodies; and RTEL1, which has a function of the DNA helicase. DKC is thought to occur when a mutation in these genes causes shortening of the telomere, resulting in impaired proliferation in hemopoietic stem cells and other proliferative cells, leading to the symptoms described above. The pathogenesis of DKC involves 3 important factors: 1) telomere-related gene abnormality leading to intracellular molecular biological mutation, 2) generational anticipation, and 3) aging. The mutations of TERC and TERT seen in cDKC produce a haploinsufficiency effect, but the extent of the weakening of telomerase activity is small, so that a certain level of generational anticipation and aging is thought to be required before the DKC phenotype develops. Treatment for DKC and cDKC is either by administering anabolic steroid hormones or by allogeneic hemopoietic stem cell transplant. Anabolic steroid hormones are thought to be converted to estrogen in the cell and to enhance telomerase activity through the estrogen-binding region of the TERT promoter region. So far, this treatment has been reported to be effective in approximately two-thirds of cases of DKC, but the proportion of cases in which results can be achieved is unclear. Meanwhile, allogeneic hemopoietic stem cell transplantation (Allo-HSCT) is an effective treatment for serious bone marrow failure in DKC and HHS, but due to posttransplantation lung complications and other issues, the treatment outcomes have been regarded as disappointing. In the future, with the development of conditioning regimens and supportive therapy of Allo-HSCT, this could therefore be a potentially promising therapeutic approach.

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Terminal cancer patients gradually reduce their oral intake, which can lead to cachexia and metabolic abnormalities. According to Japanese Society of Palliative Medicine guidelines, patients should reduce their fluid intake from one month before projected death. The effectiveness of fluid therapy in these patients should be evaluated by assessing their quality of life (QOL), and not only on the basis of physical symptoms. However, no specific QOL indicators are set out in the guidelines. We have reviewed recent reports on fluid therapy in terminally ill cancer patient in an attempt to identify appropriate indicators of QOL in palliative medicine.

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The role of the pharmacist in diabetes management has grown more prominent with the increased number of patients and diversification of related medical treatment. In addition to pharmacotherapy support, pharmacists also play an important role in self-management education for diabetes patients to ensure optimal quality of life. In this article, we consider the role of the pharmacist in diabetes treatment.

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The digestive system is essential for heterotrophic animals to acquire the energy needed for life. Although the digestive system has been diversified to adapt to the food environment during evolution, molecular mechanisms regulating the system' s organogenesis appear to be highly conserved among vertebrate species. The embryonic gut, which originates from the endoderm, lateral plate mesoderm, and neural crest cells, is first subdivided into the foregut, midgut, and hindgut and is then differentiated into various digestive organs, including the pharynx, esophagus, stomach, and small and large intestines, along the anterior-posterior axis of the embryo. In addition, the liver, pancreas, pharyngeal pouches, and respiratory organs are formed by projections from the foregut. Previous studies have shown that the embryonic gut is regionalized by transcription factors, such as Sox2, Pdx1, Cdx and Hox, which provide positional information along the anterior-posterior axis. Then, organ-specific morphogenesis and cytodifferentiation proceed in each organ. Recently, signaling pathways, including sonic hedgehog (Shh), Wnt, and Notch, have been shown to play important roles in the organogenesis of the gut. Noteworthy, during metamorphosis in the amphibian intestine, thyroid hormones reactivate such pathways and cause pre-existing epithelial cells to dedifferentiate into adult stem cells that generate the absorptive epithelium undergoing cell renewal similar to that in the mammalian intestine. Considering that this amphibian intestinal remodeling during metamorphosis mimics the mammalian intestinal maturation around the time of birth, thyroid hormone-regulated signaling pathways essential for stem cell development are suggested to be evolutionarily conserved among terrestrial vertebrates. Furthermore, in the adult intestine, such pathways are also involved in the regulation of stem cells to maintain epithelial cell renewal. We here review recent progress in this field, focusing on intestinal stem cells, and propose that clarification of molecular mechanisms underlying the development of the digestive system is interesting from the standpoint of evolutionary biology and also provides important information for the regenerative and cancer therapies of human digestive organs.

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Background: Spontaneous pneumothorax is a relatively rare complication of lung cancer. Herein, we report two cases of lung cancer in situ with spontaneous pneumothorax as the initial symptom. Cases: Case 1: A 63-year-old male presented to our outpatient clinic with chest discomfort. He had a collapsed lung, and we inserted a chest drainage tube through the thoracic cavity to re-expand the lung. Computed tomography of the chest showed a large emphysematous bulla at the lung apex. Video-assisted thoracoscopic surgery was used to resect the bulla, and the final pathological diagnosis was an emphysematous bulla with adenocarcinoma in situ. Case 2: A 45-year-old man presented to our outpatient clinic with pain in the left chest and dyspnea. To treat an almost completely collapsed lung, we inserted a chest drainage tube into the thoracic cavity. Air leakage continued for a few days, so we resected the bulla. The final pathological diagnosis was an emphysematous bulla with a squamous cell carcinoma in situ. Conclusion: It is important to consider the possibility of lung cancer in patients with pneumothorax and emphysematous changes, especially in middle-aged or elderly patients.

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