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Although usual interstitial pneumonia (UIP)-like IP has been known as the most serious complication of Hermansky-Pudlak syndrome (HPS), its pathologic features and pathogenesis are poorly understood. We investigated biopsied and autopsied lung tissues from five patients who died of UIP-like IP associated with HPS (HPSIP). The salient histopathologic features of HPSIP observed were: (1) alveolar septa displaying florid proliferation of type-2 pneumocytes (2PCs) with characteristic foamy swelling/degeneration; (2) patchy fibrosis with lymphocytic and histiocytic infiltration centered around respiratory bronchioles, occasionally showing constrictive bronchiolitis; and (3) honeycomb change without predilection for the lower lobes or subpleural area. Those peculiar 2PCs were histochemically characterized by the over accumulation of phospholipid, immunohistochemically by a weak positivity for surfactant protein, and ultrastructurally by the presence of numerous giant lamellar bodies that compressed the nucleus with occasional cytoplasmic disruption, together suggesting a form of cellular degeneration with an over accumulation of surfactant (giant lamellar body degeneration). The present study strongly indicates that there is a basic defect in the formation/secretion process of surfactant by the 2PCs in HPS, which may well be the triggering factor for the HPSIP development. Other factors, such as macrophage dysfunction, may be working synergistically for further acceleration of the inflammatory process. [ABSTRACT FROM AUTHOR]

Abstract Introduction Lung and gastric cancers are the first and second leading causes of death from cancer worldwide, and are especially prevalent in Eastern Asia. Relatively few reports are available in relation to the treatment and outcome of synchronous lung and gastric cancers, although there are increasing numbers of patients with these cancers. Efforts to develop more effective drugs for the treatment of synchronous cancers, without serious adverse effects, have been intensifying. Pemetrexed, a multi-targeted antifolate enzyme inhibitor, was approved by the United States Food and Drug Administration as a first-line chemotherapy for advanced non-squamous non-small cell lung cancer in 2007. Although clinical activity against several tumor types of adenocarcinoma, including gastric cancer, has been demonstrated, the efficacy of pemetrexed for gastric cancer remains to be fully evaluated. Case presentation We report a case involving a 62-year-old Japanese woman with synchronous locally-advanced poorly-differentiated lung adenocarcinoma and poorly-differentiated gastric adenocarcinoma, containing signet-ring cells distinguished by immunohistochemical profiles. She had been treated with carboplatin and pemetrexed as a first-line chemotherapy for lung cancer, and had achieved partial responses for both lung and gastric cancers. These responses led to a favorable 12-month progression-free survival after the initiation of chemotherapy, and the patient is still alive more than 33 months after diagnosis. Conclusions This case suggests a new chemotherapeutic regimen for patients with synchronous multiple primary cancers that have an adenocarcinoma background.

Abstract Background Colorectal cancer is one of the major neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been suggestive to have a suppressive effect on tumorigenesis and cancer cell growth. In a previous study conducted in non-diabetic subjects, we showed that oral short-term low-dose metformin suppressed the development of colorectal aberrant crypt foci (ACF). ACF have been considered as a useful surrogate biomarker of CRC, although the biological significance of these lesions remains controversial. We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps and the safety of this drug in non-diabetic post-polypectomy patients. Methods/Design This study is a multi-center, double-blind, placebo-controlled, randomized controlled trial to be conducted in non-diabetic patients with a recent history of undergoing colorectal polypectomy. All adult patients visiting the Yokohama City University hospital or affiliated hospitals for polypectomy shall be recruited for the study. Eligible patients will then be allocated randomly into either one of two groups: the metformin group and the placebo group. Patients in the metformin group shall receive oral metformin at 250 mg per day, and those in the placebo group shall receive an oral placebo tablet. At the end of 1 year of administration of metformin/placebo, colonoscopy will be performed to evaluate the polyp formation. Discussion This is the first study proposed to explore the effect of metformin against colorectal polyp formation. Metformin activates AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway plays an important role in the cellular protein translational machinery and cell proliferation. Patients with type 2 diabetes taking under treatment with metformin have been reported to be at a lower risk of cancer development than those not taking under treatment with metformin. We showed in a previous study that metformin suppressed the formation of human colorectal ACF. We therefore decided to conduct a study to determine whether metformin might suppress the formation of human colorectal polyps. Trial registration This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000006254

Abstract Introduction Gastrointestinal stromal tumor is the most frequent nonepithelial tumor found in the gastrointestinal tract. One important clinical problem is that gastrointestinal stromal tumors, especially the extramural growth type, can be difficult to distinguish from other organ tumors. The case of a patient with an extramural gastrointestinal stromal tumor of the duodenum that mimicked a pancreatic head tumor has previously been reported. Here, we report a rare case of a patient with a duodenal gastrointestinal stromal tumor with extramural growth that mimicked a pancreatic neuroendocrine tumor. In this case, the gastrointestinal stromal tumor was also associated with neurofibromatosis type 1 (also known as von Recklinghausen's disease). To the best of our knowledge, this is the first report to describe the case of a patient with a duodenal gastrointestinal stromal tumor with neurofibromatosis type 1 in which the radiological findings resembled those of a pancreatic neuroendocrine tumor. Case presentation A 60-year-old Japanese woman with a history of neurofibromatosis type 1 was admitted to our hospital for the treatment of a tumor of her pancreas. She had no symptoms, but an abdominal ultrasonography screening examination had revealed a hypoechoic mass in the head of her pancreas. Laboratory data, including tumor markers, were within the normal ranges, and her insulin and glucagon levels were also within the normal ranges. However, her plasma gastrin level was elevated at 580 pg/mL (30 to 150 pg/mL). A computed tomography examination revealed a hypervascular tumor measuring 14 mm in diameter in the head of her pancreas. We diagnosed the patient as having a pancreatic neuroendocrine tumor and performed a tumor resection with a duodenal wedge resection. Microscopic analysis revealed spindle cell tumors in a trabecular pattern. The patient was finally diagnosed as having a duodenal gastrointestinal stromal tumor of the uncommitted type. Conclusion Extramural growth-type gastrointestinal stromal tumors can be difficult to distinguish from other organ tumors. In our case, a duodenal gastrointestinal stromal tumor was difficult to distinguish from a pancreatic neuroendocrine tumor based on radiological findings. When patients are identified as having hypervascular lesions that have adhered to the gastrointestinal tract, the possibility of an extramural growth-type gastrointestinal stromal tumor as a differential diagnosis should be considered in patients with neurofibromatosis type 1.

Abstract Introduction Standard endoscopic mucosal resection or endoscopic submucosal dissection is a procedure for patients with minute cancers, complicated with esophageal varices that puts them at high risk of bleeding. Case presentation We present the case of a 77-year-old Japanese man with alcoholic cirrhosis who underwent a routine endoscopy examination as a screening procedure for esophageal varices and was incidentally diagnosed as having minute cancer of the esophagogastric junction with esophageal varices. Endoscopic ultrasonography findings suggested that the minute cancer was a non-invasive carcinoma (carcinoma in situ) and a 2 mm in diameter blood vessel, feeding the esophageal varices, pierced the lesion. Following the examination, we carried out endoscopic treatment of the minute cancer and esophageal varices. Endoscopic variceal ligation was performed using a pneumo-activated device (Sumitomo Bakelite, Tokyo, Japan). Two years after the treatment, during the follow-up endoscopic examination on the patient, recurrence of carcinoma was not detected endoscopically or histologically. Conclusion Endoscopic therapy using an endoscopic variceal ligation device for minute cancer of the esophagogastric junction, complicated with esophageal varices, may be an acceptable and easily applicable method.

Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM) complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day) of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.