Prognosis determination of endocervical adenocarcinomas morphologically reclassified as HPV associated or HPV independent.

OBJECTIVE: To evaluate the prognosis of endocervical adenocarcinomas after reclassification according to the morphologic type based on the 2020 World Health Organization Classification. METHODS: A retrospective longitudinal study with cases admitted at the University of Campinas, Brazil, from 2013 to 2020. The sample included 140 cases morphologically reclassified: 100 cases as adenocarcinoma HPV-associated (HPVA), 17 as HPV-independent (HPVI), and 23 non-HPVA/HPVI. Clinic and pathologic variables were evaluated. Analyses were performed by χ2 , Fisher exact, and Mann-Whitney U tests, Kaplan-Meier curves, Log-rank test, and Cox regression. RESULTS: Compared with the HPVA group, advanced stage (FIGO Stage II+) was more frequent in the HPVI group (P = 0.009), which also showed older patients (P = 0.032), and a higher proportion of deaths (P = 0.006). The median overall survival (OS) differed between groups: 73.3 months in HPVA and 42.4 months in HPVI (P = 0.005). At the multivariate analysis, the risk of death was 6.7 (95% confidence interval 1.9-23.0) times higher in patients diagnosed in advanced stages. CONCLUSION: HPVI cases were more frequent in older patients, presenting at more advanced stages and with worse OS. The morphology-based approach of the new WHO classification appears to be prognostically valuable and applicable in lower- and middle-income settings.

Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors / 中华内科杂志

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Level of Combined Estrogen and Progesterone Receptor Expression Determines the Eligibility for Adjuvant Endocrine Therapy in Breast Cancer Patients.

Hormone receptor (HR)-positive breast cancer has a heterogeneous pattern according to the level of receptor expression. Patients whose breast cancers express low levels of estrogen receptor (ER) or progesterone receptor (PgR) may be eligible for adjuvant endocrine therapy, but limited data are available to support this notion. We aimed to determine whether HR expression level is related to prognosis. Tumors from 6042 patients with breast cancer were retrospectively analyzed for combined HR levels of ER and PgR. Low expression was defined as ER 1-10% and PgR 1-20%. Four HR groups were identified by combining ER and PgR expression levels. Patients whose tumors expressed high levels of a single receptor showed the worst survival outcomes, and their risk continuously increased even after the 10-year follow-up. Endocrine therapy had a significant benefit for patients whose tumors expressed high HR levels and a favorable tendency for patients with tumors expressing low HR levels. We established the possible benefit of endocrine therapy for patients whose breast tumors expressed low HR levels. Thus, HR level was a prognostic factor and might be a determinant of extended therapy, especially for patients with high expression of a single receptor.

[A clinicopathological classification analysis of ocular mass lesions in 7 910 cases].

Objective: To investigate the anatomical region, histopathological classification and histogensis distribution of ocular mass lesions in South China. Methods: Retrospective cases study. The clinical and pathological data of 7 910 samples with ocular (adnexal) tumors or proliferative lesions which were examined from January 2000 to May 2018 were retrospectively retrieved. The constituent ratios of ocular mass lesions in different anatomical regions and histogenesis have been analyzed. Results: There were 3 445 males and 4 465 females aged from 3 months to 106 years. Classification by anatomical region. Eyelid 4 976 cases (62.9%): benign-pigmented nevus (31.7%, 1 342/4 235), squamous cell papilloma (12.3%, 519/4 235), seborrheic keratosis (9.4%, 396/4 235); malignant-basal cell carcinoma (48.5%, 359/741), sebaceous gland carcinoma (34.4%, 255/741), squamous cell carcinoma (12.3%, 91/741). Ocular surface 1 449 cases (18.3%): benign-pigmented nevus (26.6%, 359/1 348), squamous cell papilloma (12.8%, 173/1 348); malignant-lymphoma (34.7%, 35/101), squamous cell carcinoma (30.7%, 31/101).Orbit 1 485 cases (18.8%): benign-hemangioma (28.5%, 332/1 167), lacrimal gland (duct) cyst(13.2%, 154/1 167); malignant-lymphoma (44.7%, 142/318), adenoid cystic carcinoma (10.1%, 32/318). Classification by histogenesis: epithelial 2 145 cases (27.1%), cutaneous appendages 378 cases (4.8%), cystoid 1 068 cases (13.5%), mesenchymal 748 cases (9.5%), lymph-hematopoietic 225 cases (2.8%), neurogenic 31 cases (0.4%), melanocytic 1 765 cases (22.3%), others 1 550 cases (19.6%). Conclusions: Over the past 18 years, the ocular tumors identified at the Second Affiliated Hospital, Zhejiang University School of Medicine most frequently occur in eyelid and originate from epithelium. The most common types are as followings. Benign lesions: pigmented nevus, squamous cell papilloma are the most common types for eyelid and ocular surface, whereas hemangioma, lacrimal gland (duct) cyst and epidermoid cyst are the most common types for orbit. Malignant cancers: basal cell carcinoma is the most prevalent disease in eyelid, whereas lymphoma occurs more frequently in ocular surface and orbit. (Chin J Ophthalmol, 2019, 55: 847-853).

Diffusion kurtosis imaging does not improve differentiation performance of breast lesions in a short clinical protocol.

BACKGROUND: Diffusion weighted magnetic resonance imaging (DWI) is known to differentiate between malignant and benign lesions via the apparent diffusion coefficient (ADC). Here, the value of diffusion kurtosis imaging (DKI) for differentiation and further characterization of benign and malignant breast lesions and their subtypes in a clinically feasible protocol is investigated. MATERIAL AND METHODS: This study included 85 patients (with 68 malignant and 73 benign lesions) who underwent 3 T breast DWI using three b values (50, 750, 1500 s/mm2), with a total measurement time < 5 min. ADC maps were calculated from b values 50, 750 s/mm2. The diffusion kurtosis model was fitted to the diffusion weighted images, yielding in each lesion the average kurtosis-corrected diffusion coefficient DK and mean kurtosis K. Histopathology was obtained of radiologically suspicious lesions; follow-up scans were used as a standard of reference for benign appearing lesions. Receiver operating characteristic curves were used to evaluate the parameters' diagnostic performance for differentiation of lesion types and grades. The difference in diffusion parameters between subgroups was analysed statistically using the Wilcoxon rank sum test and Kruskal-Wallis test, applying a Bonferroni correction for multiple testing where necessary. RESULTS: ADC, DK and K showed significant differences between malignant and benign lesions (p < 10-5). All parameters had similar areas under the curve (AUC) (ADC: 0.92, DK: 0.91, K: 0.89) for differentiation of malignant and benign lesions. Sensitivity was highest for ADC (ADC: 0.96, DK: 0.94, K: 0.93), as well as specificity (ADC: 0.85, DK: 0.82, K: 0.82). ADC and DK showed significant differences between tumor histologic grades (p = 6.8⋅10-4, p = 6.6 ·â€¯10-5, respectively), whereas K did not (p = 0.99). All three parameters differed significantly between subtypes of benign lesions (ADC: p < 10-5, DK: p< 10-5, K: p = 4.1·10-4), but not between subtypes of malignant lesions (ADC: p = 0.21, DK: p = 0.25, K: p = 0.08). CONCLUSION: DKI parameters and conventional ADC can differentiate between malignant and benign lesions. Differentiation performance was best for ADC. Different tumor grades were significantly different in ADC and DK, which may have an impact on therapy planning and monitoring. In our study, K did not add value to the diagnostic performance of DWI in a clinical setting.

[Prevalence and attribution of high-risk HPV in different histological types of cervical cancer].

Objective: To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods: A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results: (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and ≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions: SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Prevalence and attribution of high-risk HPV in different histological types of cervical cancer / 中华妇产科杂志

Objective To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Clinicopathological features and prognosis of patients with triple-negative special types of breast cancer / 肿瘤

Objective: To examine the clinicopathological features and prognosis of triple-negative special types of breast cancer (SBC). Methods: The clinical data of 240 patients with triple-negative SBC who were treated in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2014 were collected. The clinicopathological features and survival time of patients were retrospectively analyzed. The univariate analysis of survival factors was performed by log-rank test, and the multivariate analysis of survival factors was performed by COX proportional hazard model. Results: Among the 240 patients, there were 38 cases of medullary carcinoma, 84 cases of metaplastic carcinoma, 19 cases of adenoid cystic carcinoma, 31 cases of invasive lobular carcinoma, 30 cases of apocrine carcinoma, and 38 cases of mixed lobular-ductal carcinoma. The histological grade, tumor T stage, lymph node metastasis, Ki-67 expression, chemotherapy or not and chemotherapy regimens had statistically significant differences among the different histological types of triple-negative SBC patients (all P < 0.05). The 5-year disease-free survival (DFS) and 5-year overall survival (OS) rates in patients with mixed lobular-ductal carcinoma, metaplastic carcinoma or invasive lobular carcinoma were lower than those in patients with adenoid cystic carcinoma, medullary carcinoma or apocrine carcinoma (all P < 0.01). The 5-year DFS and OS rates of patients with triple-negative SBC were correlated with histological grade, tumor T stage, lymph node metastasis, chemotherapy and histological type (all P < 0.05). Tumor T stage, lymph node metastasis, chemotherapy and histological type were independent prognostic factors on the 5-year DFS and OS in the triple-negative SBC patients (all P < 0.05). The metaplastic carcinoma patients after platinumbased chemotherapy (P = 0.044) and the mixed lobular-ductal carcinoma patients after anthracycline combined with taxane-based chemotherapy (P = 0.008) obtained longer DFS time. Conclusion: Triple-negative SBC patients with different histological types have different clinicopathological features and prognosis. The patients with adenoid cystic carcinoma, medullary carcinoma and apocrine carcinoma have a better prognosis, while the patients with metaplastic carcinoma, invasive lobular carcinoma and mixed lobular-ductal carcinoma have a poor prognosis. Platinum-based chemotherapy can be used in the treatment of patients with triple-negative metaplastic carcinoma.

[Clinicopathologic features of gastric adenocarcinoma based on the revised Lauren's classification].

Objective: To compare the clinicopathologic features and prognosis of the subtypes in a consecutive series of gastric cancers (GC) patients basing on the revised Lauren's classification so as to better understand the biological behavior of GC. Methods: The surgically resected GC from Peking Union Medical College Hospital during 2003-2005 were reviewed for patients' age, gender, tumor size, location, Borrman classification, depth of invasion, lymph node metastasis, vascular invasion, and tumor growth pattern (Ming classification). Results: One hundred and sixty-six GC cases were enrolled and classified into four groups: intestinal GC (30, 18.1%), diffuse GC (56, 33.7%), solid GC (9, 5.4%), and mixed GC (71, 42.8%). Intestinal GC patients were older[ (63.2±11.3) years], with a male predominance, and were more frequently found in the antrum. Intestinal GC was the most common subtype for early GC, and tend to develop liver metastases. Diffuse GC patients were youngest [(52.2±12.7) years], with no gender difference, and were usually found in the antrum. Microscopically, diffuse GC were more likely infiltrative (51/56, 91.1%), and tended to metastasize by lymphatic pathway. Solid GC were usually large[ (6.4±2.2) cm], with a male predominance, and the most frequent site was the body/fundus. Solid GC were more likely to show expansile growth pattern with greater depth of invasion (8 of 9 cases were T3/4), but lower rate of lymphatic metastasis. Mixed GC also showed a male predominance, usually found in the antrum, and showed an infiltrative growth pattern (49/71, 69.0%). Though there was fewer T3/4 than solid and diffuse GC, mixed GC were more likely to show lymph nodes, vascular metastases and liver metastases (13/71, 18.3%). TNM staging, lymph nodes metastasis, lymphovascular invasion and revised Lauren's classification were four independent prognostic factors on multivariate analysis(P<0.05). The survival of patients with mixed GC were significantly worse than patients with other histological types. Conclusion: Revised Lauren's classification for GC has four distinct subgroups and can be used as independent prognostic factors.

Surgical treatment of pulmonary metastasis: report from a tertiary care center.

Objective This retrospective analysis aimed to determine the factors influencing prognosis in adult patients who presented to our thoracic surgery service with lung metastases and were eligible for pulmonary metastasectomy. Methods We retrospectively reviewed the data of 296 patients who underwent resection of 575 lung metastases from January 2000 to January 2016. Univariate and multivariate analyses were performed based on age, sex, histology of the primary tumor, disease-free interval, number and size of metastases. Results Sixty-eight (22.97%) patients developed lung metastases from bone sarcoma, 68 (22.97%) from soft-tissue sarcoma, 56 (18.9%) from head and neck cancers, 46 (15.5%) from colorectal cancer, and 58 (19.6%) from other epithelial tumors. The mean size of the lung nodules was 2.48 cm. Open surgical resection was performed in 217 (73.3%) patients. After a mean follow-up of 43 months, 120 (40.7%) patients had died or were lost to follow-up. Univariate analysis confirmed that patients with bone cancer, soft tissue sarcoma, or colorectal carcinoma had a worse prognosis ( p = 0.0003). Moreover, those with a disease-free interval >24 months had a better 5-year survival ( p = 0.0001). The number and size of metastases, age, and sex had no effect on prognosis. The actuarial survival after complete metastasectomy was 71.6% (95% confidence interval: 66-75) at 2 years and 59.3% (95% confidence interval: 56-64) at 5 years. Conclusions Pulmonary metastasectomy provides good long-term survival. The type of primary tumor and disease-free interval are independent prognostic factors for survival.

Research of ultrasound vascular effects and drug delivery to tumor / 中华医学超声杂志（电子版）

Objective To improve the chemotherapy drug delivery to tumor by enhancing the tumor vascular perfusion induced by diagnostic ultrasound combined with microbubbles.Methods Ten healthy male sprague-dawley(SD)rats with total twenty walker-256 tumors implanted in the two back legs were randomized to the two paired groups: controlled group(C,n=10)and treatment group(T,n=10).Tumors in the controlled group were ultrasonic sham operated,while in the treatment group were treated by diagnostic ultrasound combined with microbubbles.The treatment group were taken contrast-enhanced ultrasound(CEUS)before and after treatment and analyzed the quantitative parameters.The microbubbles used in the treatment and CEUS was a kind of self-made lipid microbubbles called Zhifuxian.The 0.02 ml microbubbles were bolus injected at CEUS,while during treatment,0.04 ml microbubbles diluted into 1 ml saline solution were injected slowly at constant speed.Flushed by saline solution after treatment,the rats' tumors were harvested into three parts: one for chemotherapy drug concentration detected by high performance liquid chromatography(HPLC),one for HE detection,and one for Dox fluorescence intensity detected by confocal laser scanning microscopy(CLSM).The peak intensity(PI)values,the area under curve(AUC)values and the Dox concentration of each group were analyzed by pared-samples t test.Results(1)The contrast enhanced ultrasound quantitative analysis of the T group: PI value of the tumors before and after treatment were 66.22±16.25 and 75.74±17.67.The AUC values were 2937.52±677.51 and 3354.91±796.15.There was significant statistical difference between them(t=-5.212,-5.259,all P ＜ 0.05).(2)The Dox concentration of the T and C groups were(1.15±0.25)ug/g and(0.96±0.21)ug/g.There was significant statistical difference between them(t=2.403,P＜0.05).The Dox concentration of the treatment group was 1.2 times of the controlled group.(3)The pathology results of T and C groups: the tumor cells were arranged in cords,with big round deep-stained nucleus.No pathological changes were observed in the controlled group,and there was no significant difference between the two groups.But in the treatment group,tumor vascular congestion and inflammatory cell infiltration could be observed.(4)The confocal laser scanning microscopy(CLSM)detection of the T and C groups: the Dox red fluorescence was distributed in the tumor tissue interstitial,and the fluorescence intensity and distribution area of the treatment group were significant higher than the controlled group.Conclusions Diagnostic ultrasound combined with microbubbles treatment could significantly increase the blood perfusion in the walker-256 tumors of SD rats.Taking advantage of this vascular effect,the chemotherapy drug Dox could be delivered much more to the tumor tissue along with circulating bloodstream.With the addition of the sonoporation effect induced by the cavitation of the microbubbles,the chemotherapy drugs could be released much more to the tumor interstitial tissue.

Clinicopathologic features of gastric adenocarcinoma based on the revised Lauren′s classification / 中华病理学杂志

Objective@#To compare the clinicopathologic features and prognosis of the subtypes in a consecutive series of gastric cancers (GC) patients basing on the revised Lauren′s classification so as to better understand the biological behavior of GC.@*Methods@#The surgically resected GC from Peking Union Medical College Hospital during 2003-2005 were reviewed for patients′ age, gender, tumor size, location, Borrman classification, depth of invasion, lymph node metastasis, vascular invasion, and tumor growth pattern (Ming classification).@*Results@#One hundred and sixty-six GC cases were enrolled and classified into four groups: intestinal GC (30, 18.1%), diffuse GC (56, 33.7%), solid GC (9, 5.4%), and mixed GC (71, 42.8%). Intestinal GC patients were older[ (63.2±11.3) years], with a male predominance, and were more frequently found in the antrum. Intestinal GC was the most common subtype for early GC, and tend to develop liver metastases. Diffuse GC patients were youngest [(52.2±12.7) years], with no gender difference, and were usually found in the antrum. Microscopically, diffuse GC were more likely infiltrative (51/56, 91.1%), and tended to metastasize by lymphatic pathway. Solid GC were usually large[ (6.4±2.2) cm], with a male predominance, and the most frequent site was the body/fundus. Solid GC were more likely to show expansile growth pattern with greater depth of invasion (8 of 9 cases were T3/4), but lower rate of lymphatic metastasis. Mixed GC also showed a male predominance, usually found in the antrum, and showed an infiltrative growth pattern (49/71, 69.0%). Though there was fewer T3/4 than solid and diffuse GC, mixed GC were more likely to show lymph nodes, vascular metastases and liver metastases (13/71, 18.3%). TNM staging, lymph nodes metastasis, lymphovascular invasion and revised Lauren′s classification were four independent prognostic factors on multivariate analysis(P<0.05). The survival of patients with mixed GC were significantly worse than patients with other histological types.@*Conclusion@#Revised Lauren′s classification for GC has four distinct subgroups and can be used as independent prognostic factors.

Effect of Nonurothelial Histologic Variants on the Outcomes of Radical Cystectomy for Nonmetastatic Muscle-invasive Urinary Bladder Cancer.

INTRODUCTION: Knowledge of the comparative oncologic outcomes of histologic variants after radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) relies on small case series. We compared the effect of pure squamous cell carcinoma, adenocarcinoma, and neuroendocrine carcinoma compared with pure urothelial carcinoma (PUC) on overall survival (OS) and pathologic tumor, lymph node, and surgical margin status after RC. PATIENTS AND METHODS: Using the National Cancer Database, we retrospectively examined patients undergoing RC for MIBC from 2003 to 2011. Our cohort was stratified according to histologic type and included only pure variants: squamous cell, adenocarcinoma, neuroendocrine, and PUC. Inverse probability weighting-adjusted and facility-clustered Cox and logistic regression analyses were used to assess the effect of histologic variants versus PUC on OS and pathologic outcomes. RESULTS: Overall, 475 (4.4%), 224 (2.1%), 155 (1.4%), and 10,033 (92.2%) patients underwent RC for MIBC with pure squamous cell carcinoma, adenocarcinoma, neuroendocrine carcinoma, and PUC, respectively. In inverse probability weighting-adjusted analyses, squamous cell (hazard ratio, 1.26; 95% confidence interval [CI], 1.07-1.49; P = .006) and neuroendocrine (hazard ratio, 1.53; 95% CI, 1.21-1.95; P < .001) types were associated with worse OS relative to PUC. Squamous cell carcinoma (odds ratio [OR], 1.58; 95% CI, 1.23-2.04; P < .001), adenocarcinoma (OR, 1.49; 95% CI, 1.04-2.14; P = .030), and neuroendocrine carcinoma (OR, 2.37; 95% CI, 1.58-3.55; P < .001) at diagnosis were associated with greater odds of ≥ pT3 disease. The squamous cell and neuroendocrine variants were associated with decreased (OR, 0.66; 95% CI, 0.48-0.91; P = .012) and increased (OR, 1.58; 95% CI, 1.06-2.37; P = .026) odds of pN+ disease, respectively. Adenocarcinoma was associated with greater odds of positive margins (OR, 2.14; 95% CI, 1.39-3.30; P = .001). CONCLUSION: Pure squamous cell and neuroendocrine carcinoma histologic types were associated with worse OS relative to PUC. However, no difference was found between adenocarcinoma and PUC. All histologic variants were associated with higher tumor stage at surgery compared with PUC.

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

BACKGROUND: Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. METHODS: Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. RESULTS: Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [P<.001]), micropapillary differentiation (OR, 0.30; 95% CI, 0.10-0.95 [P=.041]), sarcomatoid urothelial carcinoma (OR, 0.40; 95% CI, 0.17-0.94 [P=.035]), and adenocarcinoma (OR, 0.24; 95% CI, 0.06-0.91 [P=.035]) were less likely to harbor non-organ-confined disease at the time of RC when treated with neoadjuvant chemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). CONCLUSIONS: Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society.

Histologic subtype needs to be considered after partial nephrectomy in patients with pathologic T1a renal cell carcinoma: papillary vs. clear cell renal cell carcinoma.

PURPOSE: We compared the oncological outcomes of papillary renal cell carcinoma (pRCC) with clear cell renal cell carcinoma (ccRCC) after partial nephrectomy (PN) in patients with pathologic T1a RCC. METHODS: After excluding patients with synchronous multiple renal tumors, familial RCC, and pathologic stage T1b or above, 759 patients with ccRCC and 84 patients with pRCC were included. We assessed the impact of histologic subtypes on oncologic outcomes after PN in patients with pathologic T1a RCC (median follow-up duration, 67 months). RESULTS: There was no difference in patient and tumor characteristics between the 2 groups, except Fuhrman grade (p = 0.006). Kaplan-Meier analysis identified 5-year recurrence-free survival of 98.7 and 95.6% in patients with ccRCC and pRCC, respectively. However, 10-year recurrence-free survival in patients with ccRCC and pRCC was 96.1 and 73.0%, respectively (p < 0.001). Recurrence ≥5 years post surgery was more common in patients with pRCC compared with those with ccRCC (0.3 vs. 4.8%; p < 0.001). In multivariate analysis, pRCC [hazard ratio (HR) 5.309; p = 0.001] was a significant risk factor for recurrence after PN in patients with pathologic T1a RCC, in addition to larger tumor size (HR 1.861; p = 0.038) and Fuhrman grade ≥3 (HR 5.176; p = 0.003). CONCLUSIONS: In patients with pathologic T1a RCC, recurrence after PN occurred more commonly in pRCC compared with ccRCC. As over half of the recurrence cases in patients with pRCC occurred ≥5 years post surgery, a longer follow-up time is required, even for those with pathologic stage T1a disease.

Research progress of tumor markers in pancreatic cancer tissue / 国际外科学杂志

Pancreatic cancer is a hidden disease,rapid progress,treatment and poor prognosis of the digestive tract malignant tumor,in recent years,the incidence rate has increased significantly.At present,surgical resection is the only effective way to long-term survival of pancreatic cancer patients,however,once the clinical diagnosis of the disease patients mostly in late or distant metastases occur,often lost the best chance of operation.The development of modem biomedical science and technology provides a new technique for the study of high sensitivity pancreatic cancer markers,which can improve the early diagnosis rate of pancreatic cancer,thus improving the surgical resection rate and improving the prognosis of patients.The study of tumor markers in pancreatic cancer tissues has always been a hot topic in the early diagnosis of pancreatic cancer.This paper reviews the progress of pancreatic cancer tumor markers in pancreatic cancer tissues.

Associations between childhood height and morphologically different variants of melanoma in adulthood.

AIM OF THE STUDY: Melanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants. METHOD: A cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7-13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed. RESULTS: A total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13-1.27) for SSM, 1.19 (95% CI: 1.09-1.29) for melanoma NOS, and 1.21 (95% CI: 1.04-1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM. CONCLUSION: Childhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.

Epidemiological characterization of oral cancer: literature review / Caracterización epidemiológica del cáncer oral: revisión de la literatura

Oral cancer is a disease of high impact globally. It ranks as the sixth more frequent one among all types of cancer. In spite of being a widely known pathology and easy access to the diagnosis, the lack of epidemiological data reported in the last 10 years in Chile called attention to. At the global level, the World Health Organization (WHO) has developed a project called “GLOBOCAN” in order to collect epidemiological data of the global cancer, between its data, highlights the high incidence and high rate of mortality in the male sex, parameter that shows tendency to replicate in both America and Chile. In consequence to these data, a narrative review of the literature concerning the epidemiological profile of the different forms of oral cancer in the past 15 years was done. The diagnosis of oral cancer crosses transversely the Dental Science, forcing us to establish triads of work between oral and maxillofacial surgeons, pathologists and dentists of the various specialties, so as to allow a timely research, appropriate biopsies and histopathological studies finishes with the purpose of, on the one hand, obtain timely and accurate diagnostics, in addition, maintaining the epidemiological indicators...

El cáncer oral es una patología de alto impacto a nivel mundial, ocupando el sexto lugar más frecuente entre todos los tipos de cáncer. A pesar de unapatología ampliamente conocida y de fácil acceso al diagnóstico, llama la atención la falta de datos epidemiológicos reportados en los últimos 10 años en Chile. A nivelmundial, la Organización Mundial de Salud (OMS) ha desarrollado un proyecto denominado “GLOBOCAN”con el fin de recolectar datos epidemiológicos mundiales del cáncer, entre sus datos, destaca la gran incidencia y elevada tasa de mortalidad en el sexo masculino, parámetro que muestra tendencia a replicarse en tanto América como en Chile. En consecuencia a estos datos, se realizóuna revisión narrativa de la literatura, referente al perfil epidemiológico de las diferentes formas de cáncer oral enlos últimos 15 años. El diagnóstico del cáncer oral cruza de manera transversal a la Odontología, obligándonos a establecer triadas de trabajo entre cirujanos orales y maxilofaciales,patólogos y odontólogos de las diversas especialidades, para permitir así una oportuna pesquisa, biopsias adecuadas y estudios histopatológicos acabados con la finalidad de, por una parte, obtener diagnósticos oportunos y certeros, además, mantener actualizados los indicadores epidemiológicos...

Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.

PURPOSE: We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old. MATERIALS AND METHODS: Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses. RESULTS: Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models. CONCLUSIONS: Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.

Liquid-based cytology improves preoperative diagnostic accuracy of the tall cell variant of papillary thyroid carcinoma.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is the most common among the aggressive variants of the disease. We aimed to investigate the clinicopathologic characteristics of TCV, and evaluate the diagnostic efficacy of liquid-based cytology (LBC) in TCV detection compared with conventional smear in thyroid fine needle aspiration (FNA). A total of 266 consecutive patients (220 women and 46 men) with PTC were enrolled. We analyzed tumor characteristics according to histologic growth patterns as classic, classic PTC with tall cell features, and TCV. The cytomorphologic features of these subtypes were investigated according to the preparation methods of conventional smear and LBC. TCV and classic PTC with tall cell features comprised 4.9% and 6.0% of all tumors, respectively, and were significantly associated with older age at presentation, larger tumor size, high frequency of extrathyroid extension, and BRAF mutation in comparison with classic PTC. However, there was no statistically significant difference in clinicopathologic features between TCV and classic PTC with tall cell features. Tall cells were more easily detected by LBC than by conventional smear. The percentage of tall cells identified using LBC was well correlated with three histologic subtypes. Our results demonstrate that TCV is more common than previously recognized in Korea and any PTC containing tall cells may have identical biological behavior regardless of the precise proportions of tall cells. It is possible to make a preoperative diagnosis of TCV using LBC.