Clinical significance of MET in gastric cancer

Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.     

Urinary excretion of an oxidative stress marker, 8-hydroxyguanine (8-OH-Gua), among nickel-cadmium battery workers

The relationship between oxidative stress and carcinogenic metals including nickel and cadmium is a matter of interest. To assess the oxidative stress status of workers exposed to nickel and cadmium simultaneously, we determined urinary excretion of 8-hydroxyguanine (8-OH-Gua), a urinary oxidative stress marker. Our subjects were 66 (64 males and 2 females) nickel-cadmium battery workers. Spot urine and blood samples were collected. The levels of cadmium in blood (Cd-B) and nickel in urine (Ni-U) were determined by graphite furnace atomic absorption spectrophotometry. 8-OH-Gua in urine was analyzed using a high performance liquid chromatography-electrochemical detector (HPLC-ECD) system. Data on age, sex, duration of present work and smoking status were also obtained from each subject. Creatinine-adjusted 8-OH-Gua was significantly correlated with age, Ni-U and Cd-B in univariate analysis, while multivariate analysis revealed that Ni-U and Cd-B were significant independent variables and that these two biological exposure indices were positively correlated with 8-OH-Gua. The data were also analyzed in the context of mixture toxicity. The subjects were divided into groups based on median level of Ni-U and Cd-B (2.86 mug/g creatinine and 0.23 mug/dl, respectively). Workers with high Ni-U/high Cd-B (Group IV) had the highest levels of 8-OH-Gua levels (GM (GSD), 21.7(2.0)), followed by those with high Ni-U/low Cd-B (11.5(1.6) Group III), those with low Ni-U/high Cd-B (8.9(1.9) Group II), and those with low Ni-U/low Cd-B (8.5(1.5) Group I). The p values of Students' t-tests between Group I and Group II, III and IV were 0.847, 0.050 and <0.001, respectively. The combined effect of Cd and Ni on the urinary excretion of 8-OH-Gua departed from additivity.     

Infundibular (follicular) and infundibulocystic squamous cell carcinoma: a clinicopathological and immunohistochemical study

Two types of squamous cell carcinoma (SCC), which are considered to show infundibular differentiation, have been described so far; namely, follicular SCC and infundibulocystic SCC. The latter includes (1) a well-differentiated form, (2) a less-differentiated form, and (3) an infiltrative variant. This study examined the clinicopathological features of 8 cases of SCC with infundibular differentiation, which included follicular SCCs and infundibulocystic SCCs (a less-differentiated form and an infiltrative variant). The present study confirmed that these SCCs with follicular differentiation are clinicopathologically distinct from keratoacanthoma. However, one example of infundibulocystic SCC (less-differentiated form) proved to be difficult to distinguish from keratoacanthoma. The relationship between the follicular SCC and the less-differentiated form of infundibulocystic SCC was investigated. At the periphery of the latter lesions, a focus corresponding to the follicular SCC or advanced follicular SCC lesions was seen. Therefore, these 2 types of SCCs are considered to be similar and thus represent the same neoplastic disease. The less-differentiated form of infundibulocystic SCC is considered to be a more aggressive condition. A unified term, infundibular (follicular) SCC, was used to describe these 2 conditions in this study. The clinicopathological features of the infiltrative variant of infundibulocystic SCCs were unique and distinct from the other 2 types of SCCs. This variant of infundibulocystic SCC is therefore considered to be a distinct entity and therefore has been simply called infundibulocystic SCC in this study. Infundibulocystic SCC may therefore be related to either a microcystic adnexal carcinoma or a malignant counterpart of the trichoadenoma of Nikolowski.     

Two histopathologic patterns of well-differentiated extraocular sebaceous carcinoma

Background: No previous reports on the variation in the histopathological patterns of well‐differentiated sebaceous carcinoma are yet to be published. Methods: We reviewed the histopathology of six examples of well‐differentiated extraocular sebaceous carcinoma. Results: Two distinct histopathological patterns of sebaceous carcinoma, namely a secretory pattern (N = 2) and a non‐secretory pattern (N = 4), were defined. The secretory pattern is typified by sebaceous lobular architecture with focal holocrine secretion, whereas the non‐secretory pattern lacks this organoid quality. Both carcinomas with the secretory pattern showed low‐grade cytological atypia, whereas the four carcinomas with the non‐secretory pattern included three lesions with high‐grade cytological atypia. A sebaceous adenoma‐like area was seen in both secretory pattern carcinomas, whereas a focus of intraepithelial sebaceous carcinoma (sebaceous carcinoma in situ) was seen in two of the non‐secretory pattern carcinomas. Conclusions: The clinicopathological significance of the two histopathological patterns remains unclear, because the number of reported cases is limited. It is possible that these two histopathological patterns of carcinoma have different histogenetic and prognostic implications, but no definitive conclusions can be made until further studies of a larger number of cases can be completed. Misago N, Toda S, Narisawa Y. Two histopathologic patterns of well‐differentiated extraocular sebaceous carcinoma.     

Matched-pair analysis of patients with advanced hypopharyngeal cancer: surgery versus concomitant chemoradiotherapy

Background

The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer.

Methods

This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates.

Results

The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P < 0.01), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups. For T4a patients with cartilage invasion, the matched-pair analysis included 46 patients. The 5-year overall survival, disease-specific, and locoregional control rates were 56.5% and 26.0% (P = 0.092), 56.5% and 41.3% (P = 0.629), and 43.0% and 42.5% (P = 0.779), respectively, for patients in the total pharyngolaryngectomy and chemoradiotherapy groups.

Conclusions

The data from this large-scale multi-institutional joint research program of hypopharyngeal cancer in Japan suggest that chemoradiotherapy may provide adequate survival benefit for hypopharyngeal cancer patients with the distinct advantage of larynx preservation. Our data also suggest that chemoradiotherapy is as beneficial as total pharyngolaryngectomy for the local control of locally advanced hypopharyngeal cancer.

     

Early detection of nonperitoneal recurrence may contribute to survival benefit after curative gastrectomy for gastric cancer

Background

There is no evidence that strict follow-up using cross-sectional imaging after curative gastrectomy benefits survival; however, nonperitoneal recurrence detected early might be treated with additional surgery. The present study examined whether early detection of recurrence by imaging modalities could increase survival, particularly in patients with nonperitoneal recurrence.

Methods

We retrospectively analyzed 218 patients with recurrent gastric cancer after curative gastrectomy performed from 2002 to 2014. The patients were divided into an asymptomatic group (n = 117) and a symptomatic group (n = 101), according to the presence of symptoms at the time of recurrence, to compare clinicopathological characteristics and long-term survival.

Results

Peritoneal recurrence was less frequent in the asymptomatic group (22.2%) than in the symptomatic group (62.4%), the median time to recurrence was shorter (12.7 months vs 18.9 months; P < 0.001), and the median survival time after recurrence was longer (18.7 months vs 7.5 months; P < 0.001). In the asymptomatic group, 10 of 117 patients (8.5%) received additional curative surgery after recurrence. Median overall survival after gastrectomy was not significantly different between the groups (30.1 months for the asymptomatic group vs 30.0 months for the symptomatic group; P = 0.132); however, it was significantly longer among asymptomatic patients with nonperitoneal recurrence compared with symptomatic patients (35.9 months vs 24.0 months; P = 0.039).

Conclusions

The presence of symptoms at recurrence did not affect survival in patients with recurrent gastric cancer. However, detection of nonperitoneal recurrence before the appearance of symptoms may provide survival benefit. Therefore, regular follow-up, including use of imaging modalities, is recommended.

     

Beyond the midbrain atrophy: wide spectrum of structural MRI finding in cases of pathologically proven progressive supranuclear palsy

Purpose

Recently, it has been recognized that pathologically proven progressive supranuclear palsy (PSP) cases are classified into various clinical subtypes with non-uniform symptoms and imaging findings. This article reviews essential imaging findings, general information, and advanced magnetic resonance imaging (MRI) techniques for PSP and presents these MRI findings of pathologically proven typical and atypical PSP cases for educational purposes.

Methods

With the review of literatures, notably including atypical pathologically proven PSP cases, MRI and clinical information of 15 pathologically proven typical and atypical PSP cases were retrospectively evaluated.

Results

In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia. As well as clinical symptoms, the degree of midbrain atrophy, a well-known imaging hallmark, is not consistent in atypical PSP cases. This fact has important implications for the limitation of midbrain atrophy as a diagnostic imaging biomarker of PSP pathology. Additional evaluation of other imaging findings including various regional atrophies of the globus pallidus, frontal lobe, cerebral peduncle, and superior cerebellar peduncle is essential for the diagnosis of atypical PSP cases.

Conclusion

It is necessary for radiologists to recognize the wide clinical and radiological spectra of typical and atypical PSP cases.