Curative Criteria After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinomas.

BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.

Diagnosis of superficial esophageal squamous cell carcinoma invasion depth before endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.

Metastatic patellar bone tumor due to gastric cancer resembling a primary or secondary aneurysmal bone cyst: A case report.

INTRODUCTION AND IMPORTANCE: Patellar bone tumors are very rare, and most are benign or of intermediate type. In this report, we describe our experience of a metastatic patellar bone tumor caused by gastric cancer, which resembled a very rare primary or secondary aneurysmal bone cyst and review the literature. CASE PRESENTATION: A 65-year-old man presented with severe pain in the patellar region and marked limitation of the knee joint range of motion. He had a history of gastric cancer; however, epidemiological, clinical, and imaging findings led us to strongly suspect an aneurysm-like bone cyst. Thus, we performed bone tumor curettage and autologous artificial bone grafting without biopsy because of the severe pain. Pathology results showed gastric cancer metastasis; hence, patellectomy and patellar tendon augmentation with femoral fascia were performed. The Musculoskeletal Tumor Society (MSTS) score was taken postoperatively to assess pain and function. CLINICAL DISCUSSION: We experienced a very rare gastric cancer-related metastatic patellar bone tumor, which resembled a primary or secondary aneurysmal bone cyst in frequency and imaging findings. Patellectomy was ultimately performed, and the patient's MSTS score improved markedly. CONCLUSION: Despite its very low frequency, patellar metastatic bone tumors must be taken into account without being misled by the frequency or imaging findings and a biopsy should necessarily be performed.

New special approach for shoulder stability after Malawer type IVB shoulder girdle resection: A case report.

INTRODUCTION AND IMPORTANCE: Scapular prostheses are useful in shoulder stability after shoulder girdle resection for malignant bone tumors; however, they are difficult to obtain in Japan. Therefore, other methods must be considered, depending on the extent of resection. We report a case in which a clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis were used to ensure shoulder stability and preserve stable upper limb function. CASE PRESENTATION: A 56-year-old man presented with a large mass and edema over the entire right scapula, which caused severe pain, limited the shoulder's range of motion, and impaired function of the entire upper extremity. Clinical imaging and pathological findings indicated a diagnosis of conventional chondrosarcoma. Using the Malawer technique type IVB, we resected the shoulder girdle and secured shoulder stability with a clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis. To evaluate the patient, we obtained his Musculoskeletal Tumor Society (MSTS) and Disabilities of Arm, Shoulder, and Hand (DASH) scores 3 months postoperatively. CLINICAL DISCUSSION: To preserve the function of the patient's elbow and hand, the stability of his shoulder was important. We could achieve this stability by using a prosthesis available in Japan. The patient's MSTT and DASH scores improved remarkably. CONCLUSION: A clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis can be used to ensure shoulder stability after scapular girdle resection and can preserve or improve upper limb function.

Synchronous and subsequent lesions of serrated adenomas and tubular adenomas of the colorectum.

The characteristics of synchronous and subsequent lesions of serrated adenomas (SAs) of the colorectum are still unclear. This study aimed to clarify the characteristics of synchronous and subsequent lesions of SAs compared with tubular adenomas (TAs) of the colorectum. Patients were divided into 2 groups: SA (127 patients) and TA (158 patients). The mean follow-up durations in the SA and TA groups were 39.7 and 42.7 months, respectively. The number and clinical features of the synchronous and subsequent lesions of both groups were examined. In the SA group, 19 (15%) patients had synchronous lesions and 3 (2%) patients had subsequent lesions. In the TA group, 68 (43%) patients had synchronous lesions and 14 (9%) patients had subsequent lesions. The frequencies of patients with synchronous and subsequent lesions in the SA group were significantly lower than those in the TA group (p < 0.0001 and p = 0.02, respectively). The most frequent synchronous lesion was SA (67%) in the SA group and TA (95%) in the TA group. The most subsequent lesion was SA (62%) in the SA group and TA (100%) in the TA group. The histology of the index polyp and synchronous and subsequent lesions tended to be identical. No invasive colorectal carcinomas were observed in either group. Our data suggest that the colonic tumorigenesis potential of patients with SA may differ from that of patients with TA.

Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. PATIENTS AND METHODS: 96 patients with esophageal SCC who had been treated by EMR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. RESULTS: 10 patients (10 %) had synchronous multiple SCCs, and 12 (13 %) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4 %. The incidence of a speckled pattern of LVLs was 20/74 (27 %) in patients with solitary SCC, 5/10 (50 %) in synchronous multiple SCC, and 10/12 (83 %) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68 % vs. 27 %, P = 0.0004). CONCLUSIONS: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.

Expression of hypoxia-inducible factor-1alpha and its relationship to tumour angiogenesis and cell proliferation in cartilage tumours.

We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1alpha, HIF-2alpha, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1alpha and HIF-2alpha staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1alpha and HIF-2alpha expression was 40% and 25%, respectively. The tumour size (> or = 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1alpha expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1alpha and the MVD and a strong trend towards a correlation between HIF-1alpha and the PCNA index or histological grade. Our findings suggest that HIF-1alpha protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.

Acute Graft Rejection and Formation of De Novo Donor-Specific Antibodies Triggered by Low Cyclosporine Levels and Interferon Therapy for Recurrent Hepatitis C Infection After Liver Transplantation: A Case Report.

BACKGROUND: We report a case of acute rejection of a liver graft, together with the occurrence of de novo donor-specific antibodies (DSAs), in a 53-year-old Japanese man who had undergone deceased-donor liver transplantation. METHODS: The graft rejection was triggered by low cyclosporine levels and pegylated interferon treatment for the recurrence of hepatitis C virus (HCV) infection 18 months after transplantation. Although the graft was ABO-compatible, pre-formed DSA B51 was detected; therefore, total plasma exchange was performed and intravenous rituximab (500 mg/body) was administered before transplantation. RESULTS: DSA was absent 6 months after transplantation. HCV recurrence was treated with pegylated interferon-α-2a. Renal function deteriorated with this anti-HCV therapy, with serum cyclosporine levels decreasing to 50 ng/mL. A rapid virologic response was achieved, but liver function deteriorated after 3 months of anti-HCV therapy, with histologic evidence of acute cellular rejection and formation of de novo DSAs. Anti-thymocyte globulin was administered for 5 days, which led to immediate improvement in liver function. However, renal function declined, warranting hemodialysis. The patient recovered 2 months after acute rejection, although de novo DSAs persisted. CONCLUSIONS: Careful immunologic monitoring may be required for patients receiving interferon therapy for HCV infection to maintain sufficient blood levels of immunosuppressive agents and to prevent acute liver graft rejection.

The role of apoptotic or nonapoptotic cell death in determining cellular response to anticancer treatment.

AIMS: Apoptosis, an early response cell death, is a useful marker for predicting tumour response after anticancer treatment; however, late-response cell death or nonapoptotic cell death, autophagy, can also be observed. This article reviews a rational model for predicting tumour response by assessing the influence of nonapoptotic cell death, and thereby developing a more efficient strategy for enhancing the therapeutic effect of anticancer treatment. METHOD: Literature search of clinical and experimental studies on "cell death and cancer" using established databases, including PUBMED. FINDINGS: Although induction of apoptosis may not contribute to overall tumour response, nonapoptotic cell death such as autophagy, which may be triggered by apoptosis, still occurs. Anticancer treatment-induced apoptosis is regulated by the balance of proapoptoic and antiapoptoic proteins through mitochondria, and resistance to apoptosis is mediated by Bcl-2-dependent and Akt-dependent pathways. Bcl-2 partially inhibits nonapoptotic cell death as well as apoptosis, whereas Akt inhibits both apoptotic and nonapoptotic cell death through several target proteins. CONCLUSIONS: Drug sensitivity is likely correlated with the accumulation of apoptotic and nonapoptotic cell deaths, which may influence overall tumour response in anticancer treatment. The ability to predict overall tumour response from the modulation of several important cell death-related proteins may result in a more efficient strategy for improving the therapeutic effect.

Comparative study on dielectric constants and conductivities of invasive ductal carcinoma tissues.

Measurements of dielectric constants and conductivities of invasive ductal carcinoma (IDC) tissues such as scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma were made by use of microwave dielectric spectroscopy. Dielectric constants of inhomogeneous breast tumor tissues were analyzed by use of Bruggeman's effective medium approximation theory. It is found that the dielectric constants of scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma of IDC tissues have correlation to the volume fractions of the cancer cells in the stroma tissues.

Loss of KAI1/CD82 expression in bone and soft tissue tumors is not associated with lung metastasis.

The KAI1 gene has been identified as a metastasis suppressor gene in human prostate cancer. Decrease or loss of KAI1/CD82 expression has been shown to be associated with poorer prognosis and metastasis in carcinomas of various organs. The purpose of this study was to examine whether KAI1/CD82 is expressed in bone and soft tissue tumors, and whether it is associated with metastasis to the lungs. Immunohistochemically, KAI1/CD82 expression in benign and malignant soft tissue tumors was noted in 83% and 37% of cases, respectively. KAI1/CD82 was- also expressed in benign bone tumors and osteosarcomas in 67% and 36% of the cases, respectively. Four (40%) of 10 osteosarcoma cases with no lung metastasis and one (25%) of four osteosarcoma cases with lung metastasis were positive for KAI1/CD82, respectively. Metastasis of osteosarcoma cells to the lungs was not correlated with the loss of KAI1/CD82 in osteosarcoma cells.

Cytokines facilitate chemotactic motility of breast carcinoma cells.

BACKGROUND: Both growth and motility of various tumor cells have been shown to be influenced by surrounding cells such as lymphocytes, histiocytes and fibroblasts through various cytokines, growth factors and extracellular matrices. The role of cytokines and extracellular matrices produced by lymphocytes, histiocytes and fibroblasts on migration and invasion of breast carcinoma cells has not been fully investigated METHODS: We investigated the effect of hepatocyte growth factor (HGF), interleukin (IL)-6, IL-8, IL-11, soluble type IV collagen and soluble laminin on the migration of 3 human breast carcinoma cell lines, MDA-MB-231, MCF-7 and T-47D, using a cell culture insert and a biocoat matrigel invasion chamber to assess migration across a matrigel-coated polyethylene telephtalate membrane. RESULTS: HGF, IL-6, IL-11 and IL-8 induced significant migration of MDA-MB-231 cells depending on the dose of each cytokine. However, type IV collagen and laminin inhibited migration of MDA-MB-231 cells. In contrast, IL-8 inhibited migration of MCF-7 cells and IL-6 induced significant migration of T-47D cells, while no other cytokine or extracellular matrix induced significant migration of MCF-7 and T-47D cells. Only HGF induced significant invasion of MDA-MB-231 cells depending on the dose. MCF-7 and T-47D cells did not invade in response to any of the cytokines and extracellular matrices tested. CONCLUSIONS: These results suggest the possibility that the potency of chemotaxis or chemoinvasion differs according to the breast carcinoma cell line and that various cytokines and extracellular matrices secreted by lymphocytes, histiocytes and fibroblasts in the stroma of breast carcinoma can affect the invasion of breast carcinoma cells.

Significance of alpha 9 beta 1 and alpha v beta 6 integrin expression in breast carcinoma.

BACKGROUND: Both alpha 9 beta 1 and alpha v beta 6 integrins have been newly identified from the tracheal epithelium of guinea pig. It has been pointed out that alpha 9 beta 1 functions as a receptor for tenascin-C and osteopontin. As for the ligands of alpha v beta 6, fibronectin and tenascin-C have been identified. It has not been ascertained whether alpha 9 beta 1 and alpha v beta 6 are expressed in normal breast tissue, benign breast lesion or breast carcinoma. METHODS: Immunohistochemical staining for alpha 9 beta 1 and alpha v beta 6 was performed in benign breast lesion and breast carcinoma specimens. Western blotting was carried out on 11 breast carcinoma cases. RESULTS: alpha 9 beta 1 was expressed in the cytoplasm of carcinoma cells in 23 of 90 cases (26%) and alpha v beta 6 in the membrane of carcinoma cells in 16 of 90 cases (18%). However, these findings of alpha 9 beta 1 and alpha v beta 6 did not correlate with any clinicopathological factors including the patients' age, tumor size, histological type of carcinoma, location of carcinoma cells and hormone receptor status. With regard to the histological grade of carcinoma, alpha v beta 6 and alpha 9 beta 1 expression did not statistically correlate, although no expression of alpha v beta 6 was observed in 14 cases of Grade I. On Western-blott analysis strong and weak bands consistent with alpha v beta 6 were noted in the membrane fraction extracted from breast carcinoma cells. On the other hand weak bands consistent with alpha 9 subunit were noted in the whole cell lysates of breast carcinoma cells and very weak or no bands consistent with alpha 9 subunit were noted in the membrane fraction extracted from the breast carcinoma cells. CONCLUSIONS: Significance of alpha 9 beta 1 and alpha v beta 6 integrins expression in breast carcinoma was still unknown on clinicopathological examination. The findings of Western blot analysis may indicate that the transportation system of glycoproteins such as integrins to the cell membrane of carcinoma cells is disturbed, although these integrins can be produced.

[Early-onset parkinsonism with diurnal fluctuation--clinical and pathological studies].

The literature regarding parkinsonism of early-onset indicates that it encompasses several diseases differing in their clinical and pathological features. Since 1968 we have reported cases of early-onset parkinsonism with diurnal fluctuation of symptoms (abbrev. as EPDF). Attention has been focused on its similarities to or differences from Parkinson's disease (PD), juvenile parkinsonism of Yokochi, and hereditary progressive dystonia (HPD) of Segawa et al. In this paper we report the clinical and pathological characteristics of EPDF to facilitate its nosological identification. We examined the pathological features of EPDF in two cases. Case 1 was a 52-year-old female with consanguineously related parents and two other affected sisters. The disease began at the age of 20, and she had marked diurnal fluctuation of symptoms. With the assistance of L-dopa and bromocriptine, she was able to enjoy relatively satisfactory daily life activity until the age of 50. In the last two years she was bed-ridden with advanced parkinsonism. Case 2 was a 56-year-old man without any contributing family history. His disease started at age 26 and his symptoms showed slight fluctuation during the earlier stages of the disease. Treatment with L-dopa and bromocriptine was associated with marked up-and-down phenomenon and choreatic dyskinesia. Pathological study in the two cases revealed marked cell loss in the substantia nigra zona compacta, especially in the area A9, while the neuronal cell population of the ventral tegmental area (A10), locus caeruleus, superior raphae nucleus, and substantia innominata was relatively well preserved. There were no Lewy bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Elastosis in breast--correlation with epithelial proliferation in benign disease and carcinomatous growth.

Elastosis in the breast is an unusual phenomenon and its morphogenesis has not yet been fully ascertained. The degree of elastosis in the breast associated with benign diseases, including fibroadenoma and fibrocystic disease as well as with breast carcinoma, was examined with special reference to the correlation between the degree of epithelial proliferation and elastosis. Using the immunohistochemical method, the presence of elastase (EL) and alpha 1-antichymotrypsin (ACT), one of the protease inhibitors, in these epithelial cells was also investigated to elucidate the role of an imbalance in these enzymes in the morphogenesis of the elastosis. Consequently, it was shown that there is a tendency in fibroadenoma and fibrocystic disease, for epithelial proliferation to be related to the degree of elastosis, and that the lack of EL in proliferated epithelial cells might play a role in the occurrence of elastosis, although ACT has no significant correlation. On the contrary, in our study noninvasive carcinoma showed marked periductal elastosis but no stromal elastosis, while invasive carcinoma showed various degrees of periductal and stromal elastosis. In invasive carcinoma, especially scirrhous carcinoma, the degree of ACT in cancer cells correlated well with stromal elastosis, although there was no correlation with EL. These findings suggest that an imbalance of the protease-antiprotease system, produced by epithelial cells of the breast, contribute to the morphogenesis of elastosis, although the physiological event, aging, is only marginally related to elastosis. Further investigation of the cells producing elastin and regulatory factors may be necessary.

Microsatellite instability in breast cancers with special reference to patients' age and bilaterality.

We examined breast cancers from 67 female patients to ascertain the possible correlation between RER or LOH status, age and bilaterality using eight microsatellite markers on chromosomes 2p, 3p, 16q, 17p and 17q. The frequencies of RER in young patients (25-35 years old), patients with double primary disease (43-77 years old) and patients with contralateral metastases (46-72 years old) were 35%, 63%, and 80%, respectively, while that in elderly patients (60-81 years old) was 0%. In contrast, there were no statistically significant differences in the frequency of LOH between these groups. Our results suggest that RER might play an important role in the occurrence of breast cancer at a younger age and in bilateral breast cancer.

Granular cell tumor of the breast: report of a case.

A case of granular cell tumor of the breast in a 43-year-old woman is described. The patient presented with a painless mass in the upper-outer quadrant of her right breast. Mammography showed a spiculated tumor and ultrasonography demonstrated a hypoechoic mass with an irregular border. Magnetic resonance (MR) mammography revealed a homogeneous enhanced mass in T1-weighted images using Gd-DTPA and a ringed high-intensity area around the mass in T2-weighted images. Fine-needle aspiration cytology failed to show any malignant cells. A partial resection of the breast was performed and histological examination revealed a granular cell tumor. Granular cell tumors are generally always benign, but they may be misdiagnosed as malignant tumors because of their mammographic and ultrasonographic findings. MR mammography did not reveal a typical breast cancer in either T1- or T2-weighted images in the present case. This case illustrates the need for care in preoperative examinations in order to avoid overdiagnosis of breast cancer.

[The proliferative activity in epithelial hyperplasia of the breast].

Epithelial hyperplasia of the breast has been recognized as an indicator of the risk for occurrence of invasive ductal carcinoma. In the future, however, its biological nature as well as precancerous potency remains unclear. Therefore, in order to elucidate a part of its biological nature, we attempted to evaluate proliferative activity in 62 lesions of epithelial hyperplasia of the breast, by means of immunohistochemistry of Ki-67 and silver stain of nuclear organizer region (NOR). Consequently, the labelling index (LI) of Ki-67 and the number of AgNOR became larger according to the increased grade of stratification, but cellular atypia without significant stratification also showed large LI of Ki-67 and number of AgNOR. Moreover, it was suggested from the discrepancy in the results of Ki-67 and AgNOR that AgNOR and Ki-67 reflected different phenomena.

[Inflammatory pseudotumor of the lung with infiltration identified radiographically and hemoptysis].

The patient was a 53-year-old man whose chief complaint was a dry cough and hemoptysis. Chest X-ray films and computed tomographic scans revealed a hazy shadow with unclear margins in the left middle lobe. A diagnosis of inflammatory pseudotumor was made because transbronchial lung biopsy specimens showed proliferation of plasma cells and lymphocytes. Initially, in response to steroid therapy, his clinical condition and pulmonary infiltration improved, but about 30 days after the start of steroid therapy, hemoptysis occurred and the shadow increased, and therefore left segmentectomy was performed. Histology revealed not only proliferation of acute and chronic inflammatory cells but also changes in the vessels. These pathologic findings were considered to be related to the infiltration shadows and the hemoptysis.