Objectives: The cornerstone of treating colorectal cancer (CRC) is generally a surgical resection with lymph node (LN) dissection. The tools for predicting lymph node metastasis (LNM) in submucosal ...(SM) CRC are useful to avoid unnecessary surgical resection.Methods: Retrospectively, we analyzed 526 consecutive patients with SM CRC who underwent surgical resection at the Osaka International Cancer Institute, Osaka University Hospital, and Minoh City Hospital, Japan, between 1984 and 2012. The Osaka International Cancer Institute group and the Osaka University Hospital group were randomly divided into a training set and a test set of 2:1. The prediction model was validated in Minoh City Hospital.Results: We partitioned patients using three risk factors involved in the presence or absence of LNM in SM CRC: lymphatic invasion (Ly), budding grade (BD) and the depth of submucosal invasion (DSI) (cut-off value 2789 μm) that were significantly different in the multivariate analysis. As a result, a predictive model of "LNM <5%" when "Ly negative and DSI <2789 μm" was evaluated. We similarly partitioned by DSI 3000 μm as easy-to-evaluate values in clinical use. We developed the additional model for predicting LNM is 1.05%, that is, LNM <5%, when there are "Ly negative and DSI <3000 μm." Conclusions: As a limitation, only patients who underwent surgical resection were included in this study. This predictive model could help clinicians and CRC patients decide on the additional surgery required after endoscopic resection.
Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that ...only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.
We investigated two autopsy cases of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) using immunohistochemical staining with an anti‐mitochondrial antibody ...against translocase of the outer membrane 20 (TOMM20). In case 1, the patient was a 42‐year‐old man with a disease duration of 53 days, and in case 2, the patient was a 62‐year‐old woman with a disease duration of 27 months. In both the cases autopsy revealed moderate atrophy of the cerebrum and cerebellum and multifocal necrotizing lesions, irrespective of the vascular territory. Case 1 showed multiple areas with total necrosis in the cortex, accompanied by increases in number of protoplasmic astrocytes and acidophilic neurons as well as axonal swelling, suggestive of acute or subacute stage stroke‐like lesions (SLLs). In case 2, most of the SLLs displayed laminar spongy change in a rarefied cortex, and were considered to be at the chronic stage. In both the cases, capillary proliferation was noted within the SLLs, particularly in the acute phase. Endothelial cells of proliferating capillaries were strongly positive for TOMM20. In the cortex outside the SLLs, microvessels displayed only a fine granular immunoreactivity, as is seen in the controls. Although smooth muscle cells and endothelial cells in pial arteries and arterioles were also strongly positive for TOMM20, the territories of the affected pial arteries and arterioles did not correlate with the distribution of the SLLs. Although MELAS is characterized by recurrent stroke‐like episodes (SLEs), the pathogenetic relationship between SLEs and mitochondrial angiopathy remains unknown. An aberrant increase of mitochondria in the capillary endothelial cells of SLLs may disturb endothelial function, thus playing a role in the formation or development of SLLs.
Cervical occlusion is a rare but serious complication after conization of the uterine cervix. We report on a 69-year-old woman with cervical intraepithelial neoplasia (CIN) 2, who successfully ...underwent follow-up biopsy of an occluded cervical canal after conization using a disposable skin biopsy punch. The disposable skin biopsy punch was inserted into a slight dimple, which was considered a uterine os, in the direction of the cervical canal, and a sample of tissue was obtained from the occluded portion. This procedure was performed without anesthesia and was completed uneventfully. Histological examination of the excised tissue revealed CIN 3. In addition, the procedure resulted in recanalization of the occluded cervical canal. The occlusion was limited in the external portion of the cervical os and attributed to adhesion of scar tissue during the healing process. Our experience suggests that a disposable skin biopsy punch can be used for follow-up biopsy and recanalization in patients with cervical occlusion after conization as a less invasive approach.
Intrapulmonary hematomas are collections of blood within alveolar and interstitial spaces. They occur mainly following thoracic trauma. Typically, intrapulmonary hematomas without bleeding or ...infection spontaneously disappear after several weeks to 6 months. In the current case, the patient presented with an intrapulmonary nodule 17 months after a chest injury. The size of the nodule had not changed at 4 months after the first visit. Consequently, the patient was diagnosed with an intrapulmonary hematoma by surgical resection. To our knowledge, there are no previous studies that described the cause of the persistent intrapulmonary hematoma. This study reports the case of a patient who underwent surgical resection of a persistent traumatic intrapulmonary hematoma.
•Intrapulmonary hematoma occurs with a chest injury, anticoagulants, thrombocytopenia, and congenital diseases.•Differential diagnoses should include intrapulmonary hematoma when considering medical history.•Patients are generally placed under observation when intrapulmonary hematoma is suspected.•This is the first report on the cause of persistent intrapulmonary hematoma.
Background
Approximately 20% of colorectal cancer patients show complete or incomplete bowel obstruction as an early symptom. Preoperative nonsurgical decompression such as placing a self-expanding ...metallic stent for malignant colorectal obstruction has been shown to be effective for reducing perioperative morbidity and mortality. However, there is a lack of published studies reporting robot-assisted laparoscopic surgery (RALS) after self-expanding metallic stent (SEMS) placement for malignant rectal obstruction (MRO). To our knowledge, this is the first report to do so.
Case presentation
An 80-year-old man with incomplete paralysis of the lower limbs as well as bladder–rectal disorder due to a spine fracture sustained in a fall accident 26 years ago presented with lower abdominal pain and vomiting. Abdominal multi-detector computed tomography revealed an obstructive rectal tumor with distended bowel on the oral side. Emergency colonoscopy was performed, and an SEMS placed. The patency of SEMS and decompression of the distended bowel was confirmed, and elective RALS was performed 29 days after SEMS placement. To our knowledge, this is the first report of RALS after decompression with SEMS placement for MRO.
Conclusions
RALS after SEMS placement is a safe and feasible therapeutic strategy for MRO.
A 78‐year‐old man with a history of open sigmoidectomy for sigmoid cancer presented with abdominal pain and vomiting. Abdominal multi‐detector CT revealed an obstructive ileocecal tumor with ...distended small bowel on the oral side. We performed emergency drainage using a transnasal decompression tube, and 2 days later, we conducted a colonoscopic examination, which lead to a provisional diagnosis of obstruction with a malignant tumor invading the ileocecal valve. We then placed a self‐expanding metallic stent (SEMS) through the ileocecal valve. We confirmed patency of the ileocecal valve and removed the transnasal decompression tube 2 days after SEMS placement. We then performed elective laparoscopic colectomy 8 days after SEMS placement. To the best of our knowledge, there has been only one previous report of laparoscopic colectomy after decompression with SEMS placement through the ileocecal valve for right‐sided malignant colonic obstruction.
AKT is a serine/threonine kinase which is important in tumorigenesis. Several molecules involved in AKT pathway are dysregulated in various kinds of human cancers.
Ninety-three patients (53 males and ...40 females), ages ranging from 19 to 77 years (median, 57 years), with localized soft-tissue sarcomas arising in the trunk and extremities, were analyzed. Immunoperoxidase procedure (avidin-biotin complex method) was done on paraffin-embedded sections with anti-phosphorylated AKT (Thr308), anti-phosphorylated p44/42 extracellular signal-regulated kinase 1 and 2 (ERK1/2) (Thr202/Tyr204), anti-phosphorylated forkhead in rhabdomyosarcoma (FKHR) (Ser256), and anti-Ki 67 antibodies. Expression levels of phosphorylated AKT (p-AKT), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated FKHR (p-FKHR) were categorized as either weaker (level 1) or equal to or stronger (level 2) compared with those in the endothelial cells of the same specimens. Percentage of cells showing intranuclear staining with Ki-67 was shown as the Ki-67 labeling index (LI). Cases were divided into two groups: level 1, Ki-67 LI < 20%; level 2, Ki-67 LI > or = 20%.
Twenty-six (28.0%), 6 (6.5%), and 46 (44.1%) of the tumors showed level 2 expression for p-AKT, p-ERK1/2, and Ki-67 LI, respectively. Tumors with level 2 p-AKT expression showed a higher ratio of level 2 p-FKHR expression (P < 0.01). Multivariate analysis revealed p-AKT expression and Ki-67 LI to be independent prognosticators for overall survival, and p-AKT expression for disease-free survival.
p-AKT expression level is a significant prognosticator in soft-tissue sarcoma.
The efficacy of hematopoietic stem cell transplantation (HSCT) for Hunter disease (deficiency of iduronate-2-sulfatase, IDS) remains unclear. We treated a 6-year-old male suffering from a severe type ...of Hunter disease with cord blood stem cell transplantation (CBSCT); however, he died at 10
months post-therapy due to a laryngeal post-transplantation lymphoproliferative disorder. During the follow-up period after CBSCT, his hyperactivity, estimated mental age, and brain MR findings had not improved. We assessed the efficacy of CBSCT by biochemical and pathological analyses of the autopsied tissues. There were many distended cells with accumulated substrate in the brain, but not in the liver. IDS enzyme activity in the cerebrum remained very low, although that in the liver reached about 40% of the normal control level. However, a variable number of tandem repeats analyses demonstrated a weak donor-derived band not only in the liver but also in the cerebrum. Furthermore, IDS-immunoreactivity in the liver was recognized broadly not only in Kupffer cells but also in hepatocytes. On the other hand, IDS-immunoreactivity was recognized exclusively in CD68-positive microglia/monocytes in the patient’s brain; whereas that in the normal brain was also detected in neurons and oligodendrocytes. These donor-derived IDS-positive cells were predominantly localized in perivascular spaces and some of them were evidently present in the brain parenchyma. The efficacy of CBSCT was judged to be insufficient for the brain at 10
months post-therapy. However, the pathological detection of donor-derived cells in the brain parenchyma suggests the potential of HSCT for treatment of neurological symptoms in Hunter disease. This is the first neuropathological report documenting the distribution of donor-derived cells in the brain after CBSCT into a Hunter disease patient.
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