[Malignant peripheral nerve sheath tumor: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

[Validation and modification of AJCC 8th edition staging system for hepatocellular carcinoma--analysis based on SEER database].

Objective: To assess the accuracy of the American Joint Committee on Cancer (AJCC) 8th edition staging system for hepatocellular carcinoma (HCC) and to make an appropriate modification. Methods: Data of patients diagnosed with HCC who underwent surgery were extracted from 2004 to 2015 within the SEER database. Overall survival (OS) and disease-specific survival (DSS) of patients were analyzed. Results: A total of 7 911 patients were included and there were 2 117 females and 5 794 males. The male-to-female ratio was 1.00: 0.36. There were 4 050 patients older than 60 years old. Tumor size ranged from 24 to 65 mm. Tumors with single lobes (80.8%) or single lesions (62.8%) were more common. There were 230 cases and 2 052 cases received radiotherapy and chemotherapy, accounting for 2.9% and 25.9%, respectively. The median follow-up was 42 months. Analysis of the 8th edition of AJCC staging system showed that the survival curves of ⅣA stage and ⅢA stage intersected in both OS and DSS, and the differences were not statistically significant between them (both P>0.05). Analysis of patients in subgroup of ⅣA stage showed that there was no statistically significant difference in the four groups of T1N1M0/T2N0M0, T2N1M0/T3N0M0, T3N1M0/T4N0-1M0 and T3N1M0/T1-4N0-1M1 (all P>0.05). Therefore, the modified 8th edition of the AJCC staging system was proposed after retaining the definition of T/N/M in the old edition: ⅠA and ⅠB stages were retained; ⅣA stage was split: T1N1M0 was included in Ⅱ stage, T2N1M0 in Ⅲ stage, and Ⅳ stage included T3N1M0, T4N0-1M0 and T1-4N0-1M1. Cox proportional risk regression analysis of the modified 8th edition of the AJCC staging showed that significant differences were observed among the four groups, with ⅠB/ⅠA (HR=1.462, 95%CI:1.294-1.651), Ⅱ/ⅠB (HR=1.091, 95%CI:1.003-1.186), Ⅲ/Ⅱ (HR=2.034, 95%CI: 1.793-2.307) and Ⅲ/Ⅳ (HR=1.374, 95%CI: 1.192-1.583) for OS, respectively. The similar findings were seen in DSS, with ⅠB/ⅠA (HR=2.007, 95%CI:1.671-2.411), Ⅱ/ⅠB (HR=1.140, 95%CI:1.023-1.271), Ⅲ/Ⅱ (HR=2.344, 95%CI: 2.018-2.724) and Ⅲ/Ⅳ (HR=1.391, 95%CI:1.180-1.639), respectively. Conclusion: The modified AJCC 8th edition staging system could predict the survival outcome of HCC more accurately.

[Evaluation of prognostic factors for liposarcoma].

Objective: To investigate the relevant prognostic factors of liposarcoma (LPS). Methods: The data of 78 patients with LPS treated in our hospital from July 2009 to March 2017 were reviewed. The 78 patients included 41 males and 37 females, and the average age was (60.5 ±13.4) years (ranged from 18 to 85 years). Among the 78 LPS patients, 27 were well-differentiated LPS, 13 were myxoid LPS, 35 were dedifferentiated LPS and 3 were pleomorphic LPS.The distribution of lesion location included 40 cases of extremities and 38 cases of retroperitoneal. 21 cases were treated with radical excision, 57 cases were treated with marginal resection. 7 patients were treated with postoperative radiotherapy and 9 patients with postoperative chemotherapy. Progression free survival (PFS) and overall survival (OS) of LPS patients were analyzed as clinical outcomes. Prognostic factors were analyzed by univariate and multivariate analyses. Results: 43 patients had local recurrence (9 of extremities/ 34 of retroperitoneal), 18 patients with metastasis (4 of extremities/ 14 of retroperitoneal). The 5-year PFS rate was 31.4% and 5-year OS rate was 44.3%. Univariate analysis showed that the histological subtype and the tumor location were related with PFS (P<0.05), while the histological subtype, the tumor location, the tumor size, the recurrence and metastasis were related with OS (P<0.05). Multivariate cox regression analysis showed that the tumor location was the independent prognostic factor of PFS (P<0.05), while the histological subtype and metastasis were the independent prognostic factors of OS (P<0.05). The median PFS of patients with myxoid LPS treated with radiotherapy was 34.6 months, which was significantly longer than 28.3 months of myxoid LPS patients without radiotherapy (P<0.05). Conclusions: The tumor location is an independent prognostic factor of PFS in LPS patients.Retroperitoneal LPS is more prone to relapse and metastasize. OS is affected by pathological subtype and metastasis. Radiotherapy can improve the PFS of patients with myxoid LPS.

D2 lymphadenectomy can disseminate tumor cells into peritoneal cavity in patients with advanced gastric cancer.

We sought to determine the dissemination of gastric cancer cells before and after radical D2 surgery and to determine the effectiveness of EIPL in preventing post-operative peritoneal metastasis. 64 patients were recruited with advanced gastric cancer for our final analysis. Complete curative gastrectomy with D2 lymphadenectomy was performed on the 64 patients. Before surgery, peritoneal lavage fluid was collected for cytological analysis by cell smearing and immunohistochemistry to detect disseminated cancer cells (S1). Following tumor and lymph node resection, peritoneal lavage fluid was collected for cytological examination (S2). The patients were treated by extensive intra-operative peritoneal lavage (EIPL) with normal saline (n = 31) or distilled water (n = 33). The peritoneal lavage fluid was collected for cytological examination (S3). At S1 stage, 18 patients (28.1%) were positive for disseminated cancer cells in their abdominal fluid. After D2 lymphadenectomy, 34 patients (53.1%) had disseminated cancer cells in their abdominal fluid at stage S2, which indicated that the D2 lymphadenectomy caused in an additional 16 (16/46, 34.8%) patients positive for disseminated cancer cells. After EIPL with either normal saline or distilled water at the S3 stage), all the patients were negative for disseminated cancer cells in their abdominal fluid. A total of six patients died, and four patients had recurrencent cancer. These findings indicate that D2 lymphadenectomy can disseminate gastric cancer cells, and post-operative lavage of the abdominal cavity can eliminate cancer cell dissemination and decrease the risk of peritoneal metastasis.

["See fine world" -copy experience and thinking of membrane anatomy in laparoscopic radical gastrectomy (D2+CME)].

Primary lesion removal and lymph node dissection are the main constituents of radical gastrectomy. However, the high recurrence rate after D2 radical gastrectomy for advanced gastric cancer has not improved. Recently, studies have found that discrete tumor deposits in the mesogastrium may be an important factor affecting the prognosis of gastric cancer after surgery. With the development of laparoscopic equipment, the ever-expanding "submicroscopic vision" makes it possible to completely remove the mesogastrium. Professor Gong Jianping advocated "membrane anatomy" to optimize the concept of radical gastrectomy: D2- based complete mesenteric resection (CME), namely D2+CME procedure. To prevent the leakage of tumor cells into the surgical field, as histological barrier, the intact mesogastrium should be located. The essential difference between D2+CME and previous D2/D2+systematic mesogastrium excision (SME), en-bloc mesogastric excision (EME) is as follow: double-factor guiding (lymph nodes and discrete tumor deposits) vs. single factor guiding (lymph nodes only). After practicing dozens of radical gastrectomy (D2+CME) authors believe that its conceptual connotation (double factor guiding) and operational extension (above mesentery bed) cover D2. In D2+CME surgery, depending on the anatomical identification under the magnified field of view, the conformal space between gastric mesentery and mesenteric beds is unique operational plane with repeatability. These findings and considerations address one problem: where is the precise boundary of en bloc principle in radical gastrectomy? In author's opinion, with laparoscopy and "sub-microsurgery" progression and detection of discrete tumor deposit metastasis, survival benefit from definition of en bloc boundary in radical gastrectomy will be widely recognized. Meanwhile, D2+CME procedure is an appropriate way for study. Although the development of the "membrane anatomy" concept for gastric cancer still requires many further clinical and basic researches, it is reasonable to foresee that D2+CME surgery will guide a concept-optimized era for gastric cancer surgery.

[Contesting Remedies: The Debate on STD Treatment Therapies in the early PRC].

During the early years of the People's Republic of China, sexually transmitted diseases (STD) were almost eliminated nationwide for a period. In the STDs eradication campaign, "political correctness" became a ruling policy. During the prevention and treatment of the STDs, the choice of therapy depended on the "political correctness" policy rather than medical effectiveness. With this political background, three competing treatments of STDs emerged (especially for syphilis): penicillin treatment, arsenic and bismuth mixed and intermittent treatment, and traditional Chinese medicine treatments. The argument between treatments was a vivid microcosm of the love-hate political relationship between China and the Union of Soviet Socialist Republics (USSR). The traditional Chinese medicine treatments for syphilis were used as a tool by the authorities to prevent the national medical system becoming more and more westernized. The penicillin treatment, the winner of this battle, won because it catered to the political themes of the time, the "Great Leap Forward" . Overwhelming state power had a strong influence and control over the medical system and medical practice, with the initiative and independence of doctors being limited in an unprecedented fashion.

[A study on the burden and causes of hospitalization and deaths in Shenzhen, between 1995 and 2014].

Objective: Data from the surveillance program was collected, to analyze the situation of hospitalization and cases of death with recorded causes, in Shenzhen, from 1995 to 2014. Situation of hospitalization and causes of deaths were studied in Shenzhen which had been a fast-developing city with growing number of immigrants so as to provide reference for decision-making on related prevention and control strategies. Methods: Data on hospitalizations and deaths collected from the surveillance program, were classified by both International Classification of Diseases (ICD)- 9 and ICD-10. A database was constructed with methods on related descriptive and trend analysis. Results: Around 6.3 million inpatients were seen in the past two decades in Shenzhen. The top five diseases for hospitalization were pregnancy childbirth and puerperium complications, respiratory diseases, injury and poisoning, digestive system diseases and circulatory system diseases, that accounting for 68.4% of all the hospitalization burden. The number of inpatients increased annually, with an 11 times increase during the past two decades. Proportions for pregnancy childbirth and puerperium complications, circulatory system diseases and urinary system diseases all showed increasing (χ(2)=53 806.94, 6 893.95 and 15 383.14, P<0.01), while proportions for injuries and poisoning, respiratory diseases, digestive system diseases showed a declining trend (χ(2)=131 480.09,1 711.84 and 11 367.66, P<0.01). Number of cumulative inpatient deaths exceeded 60 000, with the top five causes as malignant tumor, circulatory system diseases, injury and poisoning, respiratory system diseases and digestive system diseases, that accounting for 82.28% of all the inpatient deaths. Deaths due to circulatory system diseases, injury and poisoning increased and then decreased. Malignant tumor and respiratory diseases-induced deaths showed an increasing trend (χ(2)=1 546.48, 309.55, P<0.01), while induced deaths from disease of the other systems showed slight changes. The overall case fatality rate showed an annual decline (χ(2)=4 378.63, P<0.01), from 2.23% in 1995 to 0.74% in 2014, with mortality attribute to tumor, circulatory system disease decreased significantly. Conclusions: Shenzhen had been under an ageing transition, with relatively young population living in the city. Chronic diseases such as tumor gradually had become the major causes for heavy hospitalization burden on the population of Shenzhen.

[Advances in osteoradionecrosis of nasopharynx after radiotherapy for nasopharyngeal carcinoma].

Radiation therapy is the first choice for the treatment of nasopharyngeal carcinoma. However, it is inevitable that nasopharyngeal mucosa and tissue will be damaged after radiotherapy of nasopharyngeal carcinoma, which will cause corresponding complications. Nasopharyngeal osteonecrosis is a serious complication. Up to now, there are few reports about nasopharyngeal osteonecrosis, and the underlaying pathological mechanism remains unclear. The potential theories include radiotherapy damage, infection and trauma, but also the " three H" principle of hypoxic hypocellular hypovascular tissue, as well as the theory of radio induced fibrosis. It is controversial about the treatment of nasopharyngeal osteonecrosis. It takes comprehensive treatment, including local treatment, systemic treatment, surgical treatment and other treatments. Among them, local treatment as nasopharyngeal debridement usually is first choice. We reviewed the pathological mechanism and treatment methods of nasopharyngeal osteonecrosis, in order to provide a reference for better prevention and treatment of it.

[Spectrum and case fatality of inpatients with malignant tumors from 1995 to 2014 in Shenzhen city].

Objective: To analyze the epidemiological features, spectrum and case fatality of malignant tumor patients in Shenzhen city, to provide evidence for the development of prevention and treatment strategies on malignant tumor in Shenzhen. Methods: All the hospitalized malignant tumor patients including deaths, were monitored from 1995 to 2014 in Shenzhen, and data was analyzed by SPSS 20.0 software. Results: There were 160 988 inpatients of malignant tumors between 1995 and 2014 in Shenzhen. The top three hospitalized tumors were lung (13.64%), liver (11.13%) and breast (7.86%) cancers. Numbers of the malignant tumor inpatients had been rapidly increasing during the past 20 years, 12.3 times in 2014 higher than in 1995. The total number of deaths due to malignant tumors was 19 460. Deaths of the top three malignant tumors were lung (24.40%), liver (19.84%) and colorectal (8.63%) cancers and the number of deaths was increasing, 12.5 times higher in 2014 than in 1995. The overall case fatality rate was 12.09%. The annual percent change (APC) of malignant tumors case fatality rate was 9.7%(95%CI: 2.0%-18.0%), during 1995-2003, with an increasing trend (t=2.72, P<0.05). The APC of case fatality rate during 2003-2014 was -3.4%(95%CI: -7.6%-1.1%), but the decreasing trend (t=-1.63, P>0.05) was not statistically significant. The top three major malignant tumors related to case fatality rate were lung cancer (21.62%), liver cancer (21.39%), and esophageal cancer (16.50%). The case fatality rates of leukemia and liver cancer had decreased during the past 20 years. The case fatality rates of cancers in lung, esophagus, stomach, breast, colorectal and nasopharyngeal, had all increased. The number of male patients was significantly exceeding the females (χ(2)=41.691, P<0.01), with sex ratio as 1.65∶1. From age 35 and on, the number of deaths due to malignant tumors increased significantly, with the peak after 60 years of age. Conclusions: The number of malignant tumor inpatients had an annual increase as well as the case fatality rate. Cancers in lung, liver appeared the leading causes of death among the malignant tumor patients, with elderly in particular. Strategies related to the prevention and treatment of cancers in lung, liver should be strengthened.

Separation of polyethylene glycols and amino-terminated polyethylene glycols by high-performance liquid chromatography under near critical conditions.

The separation and characterization of polyethylene glycols (PEGs) and amino-substituted derivatives on common silica-based reversed-phase packing columns using isocratic elution is described. This separation is achieved by liquid chromatography under the near critical conditions (LCCC), based on the number of amino functional end groups without obvious effect of molar mass for PEGs. The mobile phase is acetonitrile in water with an optimal ammonium acetate buffer. The separation mechanism of PEG and amino-substituted PEG under the near LCCC on silica-based packing columns is confirmed to be ion-exchange interaction. Under the LCCC of PEG backbone, with fine tune of buffer concentration, the retention factor ratios for benzylamine and phenol in buffered mobile phases, α(benzylamine/phenol)-values, were used to assess the ion-exchange capacity on silica-based reversed-phase packing columns. To the best of our knowledge, this is the first report on separation of amino-functional PEGs independent of the molar mass by isocratic elution using common C18 or phenyl reversed-phase packing columns.

[Clinical application of a digital method in mammographic image processing]. / Application clinique d'une technique de traitement numérique de l'image en mammographie.

The authors describe digital processing of mammographic images based on simulation of the procedure performed by radiologists to analyse radiographs. Image processing allows automatically enhancing contrasts and expressing them as a range of different light intensities and colors. Minimum contrast differences that are difficult to perceive with the bare eye are thus highly enhanced. This processing of mammographic images has proved useful not only to detect discrete lesions, but also to differentiate benign and malignant lesions.

Serotonin regulates osteoblast proliferation and function in vitro.

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1B receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

Serotonin regulates osteoblast proliferation and function in vitro

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1B receptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.