Identification of novel prognostic markers in relapsing localized resectable neuroblastoma

Patients with localized resectable neuroblastoma (NB) generally have an excellent prognosis and can be treated by surgery alone, but approximately 10% of them develop local recurrences or metastatic progression. The known predictive risk factors are important for the identification of localized resectable NB patients at risk of relapse and/or progression, who may benefit from early and aggressive treatment. These factors, however, identify only a subset of patients at risk, and the search for novel prognostic markers is warranted. This review focuses on the recent advances in the identification of new prognostic markers. Recently we addressed the search of novel genetic prognostic markers in a selected cohort of patients with stroma-poor localized resectable NB who underwent disease relapse or progression (group 1) or complete remission (group 2). High-resolution array-comparative genomic hybridization (CGH) DNA copy-number analysis technology was used. Chromosome 1p36.22p36.32 loss and 1q22qter gain, detected almost exclusively in group 1 patients, were significantly associated with poor event-free survival (EFS). Increasing evidence points to anaplastic lymphoma kinase (ALK) as a fundamental oncogene associated with NB. The immunohistochemical analysis of sporadic NB localized resectable primary tumors (stage 1-2) showed a correlation between aberrant ALK level of expression and tumor progression and clinical outcome. Moreover, other factors that might influence the clinical behavior of these tumors will be reviewed.     

妇科肿瘤患者术后盆腔感染情况调查、 病原菌分布及其危险因素分析

目的调查妇科肿瘤患者术后盆腔感染的情况以及病原菌分布,并探讨术后发生盆腔感染的危险因素。方法回顾性分析自2013年1月到2017年1月在东南大学附属中大医院接受妇科肿瘤手术治疗的384例患者的临床资料。统计妇科肿瘤术后盆腔感染的发生率及病原菌的分布情况。将发生盆腔感染的患者分为感染组,未发生盆腔感染的患者分为未感染组,对比两组的临床资料,并通过多因素Logistic回归分析,归纳妇科肿瘤患者术后发生盆腔感染的危险因素。结果术后发生盆腔感染41例,感染率为10.68%,培养出病原菌54株,其中革兰阳性菌14株,占25.93%,革兰阴性菌35株,占64.81%,真菌5株,占9.26%。感染组患者年龄60岁的比例、手术持续时间2h的比例、合并慢性基础疾病的比例、开放手术的比例、术前化疗的比例、术后留置引流管的比例和术后卧床时间7d的比例均显著高于未感染组(均P0.05);多因素Logistic回归分析结果显示,年龄大、手术持续时间长、合并慢性基础疾病、开放手术、术前化疗、术后留置引流管、术后卧床时间长均是妇科肿瘤患者术后盆腔感染的危险因素(均P0.05)。结论妇科肿瘤患者术后较容易并发盆腔感染,病原菌主要为革兰阴性菌。多种因素可增加术后盆腔感染的风险,临床应加强防控措施,降低妇科肿瘤患者术后盆腔感染的发生率。     

Familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program.     

巨大垂体腺瘤经蝶手术后发生脑脊液鼻漏的危险因素分析

目的：探讨巨大垂体腺瘤经蝶手术脑脊液鼻漏的发病原因,并提出相关的修补措施。方法：选择2009 年2 月-2012年8 月在我院进行诊治的巨大垂体腺瘤患者180 例,所有患者均采用经蝶手术摘除巨大垂体腺瘤。观察预后情况。结果：在接受经蝶手术的180 例患者中,25例发生脑脊液鼻漏,发生率为13.8%。其中男性15例,女性10例。单因素多因素分析都显示肿瘤大小、慢性蝶窦炎与再次手术与脑脊液鼻漏的发生有直接关系,为独立的影响因素（P〈0.05）。对25 例出现脑脊液鼻漏的患者采用鼻内镜手术进行治疗,全部病例经手术修复后获得一次性治愈。随访6个月,无1例复发,无术后并发症。结论：巨大垂体腺瘤经蝶手术脑脊液鼻漏的发病率比较高,肿瘤大小、慢性蝶窦炎与再次手术为主要的独立危险因素,要积极采用鼻内镜下治疗。     

Long-term follow-up of patients treated with radical surgery for rectal cancer

In developed societies colorectal cancer (CRC) is the second most frequent malignant tumor which causes more than 5000 deaths yearly in Hungary. We have attempted to answer the question how to improve the above mentioned data by the long-term follow-up of patients operated upon for rectal cancer at our department. Of the patients operated on for rectal cancer at our department between March 1990 and April 2006, we have conducted regular follow-up of 297 patients according to a protocol developed by us. We have examined the length of time between the rectum operation and the diagnosis and the number of local recurrences, distant metastases, tumor progression in more than one organ as well as second tumors (independent of the rectal cancer). During this period we found 24 local recurrences, 32 distant metastases, 43 tumor progressions in more than one organ, and 21 second tumors. In two patients, in addition to distant metastases, we found a second CRC independent of the original rectal cancer, and in one patient with tumor progression in more than one organ we also detected breast cancer. In one patient we found 3 second tumors (CR, lung and urinary bladder) independent of the original rectal cancer. Altogether we found tumors in 117 out of 297 patients. During the same period, we performed 69/117 operations and 31/117 patients were alive at the end of our study with a median survival of 60.4 (3-184) months. In summary, we can state that this work is beneficial for curing the recurrence of rectal cancer, making the patients' life longer or making the quality of life better for the patients operated on for rectal cancer.     

p53 serum antibodies as prognostic indicator in head and neck cancer

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The post-therapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer. Received: 5 December 1996 / Accepted: 4 January 1997     

Similar colorectal cancer risk in patients with monoallelic and biallelic mutations in the MYH gene identified in a population with adenomatous polyposis

A large proportion of non-FAP non-HNPCC patients with multiple colorectal adenomas have been reported to carry germline mutations on the MYH gene. Although the number of adenomas appears to be dependent on the number of mutated MYH alleles present in a patient, little is known on the relation of this number with cancer risk. Four hundred fifty-three APC-negative patients with more than five colorectal adenomas were screened for mutations on the entire coding sequence of the MYH gene. Pathogenic mutations were initially found in 74 patients without extradigestive tumors (22.5%) and subsequently in 75 at-risk relatives. Polyposis was more severe in cases with biallelic mutations. However, mutation copy number was correlated neither with the age at diagnosis of adenomas or adenocarcinomas, nor with the presence of a family history of colorectal tumors. Heterozygous and homozygous MYH mutation carriers were both at high risk for synchronous cancers (24% in colorectum and 16% in the upper gastrointestinal tract), but did not demonstrate an increased risk for extradigestive tumors. MYH-associated polyposis is a frequent inherited colorectal cancer predisposition with a strong dominance component. From age 25-30, MYH mutation carriers should be proposed an early screening program, which includes endoscopies of the upper digestive tract and the colorectum every 2 years.     

黑斑息肉综合征临床诊治进展

黑斑息肉综合征（Peutz-Jeghers syndrome,PJS）是一种以皮肤黏膜色素沉着斑、胃肠道多发息肉、家族遗传性为主要特点的常染色体显性遗传病,随着息肉体积增大,患者年龄增加,消化系统及生殖系统等恶性肿瘤发病率明显增加,主要致病基因为19号染色体短臂上的LKB1／STK11（丝氨酸／苏氨酸激酶）基因,是一种肿瘤易感综合征,临床应及早处理胃肠道息肉及密切随访观察,预防恶性肿瘤的发生及早期诊治,减少PJS带来的危害。     

黑斑息肉综合征临床诊治进展

黑斑息肉综合征(Peutz-Jeghers syndrome,PJS)是一种以皮肤黏膜色素沉着斑、胃肠道多发息肉、家族遗传性为主要特点的常染色体显性遗传病,随着息肉体积增大,患者年龄增加,消化系统及生殖系统等恶性肿瘤发病率明显增加,主要致病基因为19号染色体短臂上的LKB1/STK11(丝氨酸/苏氨酸激酶)基因,是一种肿瘤易感综合征,临床应及早处理胃肠道息肉及密切随访观察,预防恶性肿瘤的发生及早期诊治,减少PJS带来的危害。     

Radiosensitivity of late recurrences following radiotherapy of murine fibrosarcomas

Radiosensitivity of late recurrent tumors which emerged after radiotherapy was investigated. Tumors observed were fibrosarcomas. Recurrences emerged in the irradiated area approximately 200 days after a 50% tumor control dose of radiation of 60Co gamma rays or mixed irradiation with fast neutrons and gamma rays. The recurrent and radiation-induced tumors were differentiated by karyotype analysis. Once transplanted into fresh mice, the recurrent tumors grew more slowly than the original tumor. Tumorigenicity of the late recurrences was lower than that of the original tumor. Radiosensitivity of the late recurrences, which was examined using methods to assess control, tumor growth delay, and colony forming assays, was significantly higher than that of the original tumor. D0 values of hypoxic tumor cells were significantly smaller in two of the three recurrences compared to the original tumor. Oxic cells, when irradiated in vitro, also showed smaller D0 values for the recurrent tumors than the original tumor. Hypoxic cell fractions were between 0 and 14% in the late recurrences and 10% in the original tumor. These results are consistent with the hypothesis that radiotherapy causes mutation of tumor cells which results in increased radiosensitivity of surviving tumor cells.     

肾嗜酸性细胞瘤的诊治体会（附11例报告）

目的：探讨肾嗜酸细胞瘤的诊断和治疗。方法：回顾分析我院2003．2009年间收治11例肾嗜酸细胞瘤的临床资料,结合文献对肾嗜酸细胞瘤的诊断及治疗进行复习讨论。结果：本组11例患者中,年龄为26—75岁,男性7例,女性4例。合并透明细胞癌者1例,术前误诊为肾上腺肿瘤者1例。7例行根治性肾切除术者,4例行肾部分切除术。术后随访11个月-7年未见肿瘤转移或复发。结论：肾嗜酸细胞瘤倾向于良性肾实质性肿瘤,临床表现无特异性,确诊需临床表现、影像学检查与病理学检查相结合。治疗首选保肾手术,但应注意并发恶性肿瘤的可能,加强随访。     

Large Adrenal Incidentalomas Require a Dedicated Diagnostic Procedure

Objective: The management of large nonsecreting adrenal tumors (at least 4 cm) is still a matter of debate as it is unclear whether imaging, especially ¹⁸F-fluorodeoxyglucose (FDG), can be used to characterize their potential malignancy. Moreover, the risk of new hypersecretion in nonoperated tumors is uncertain. Our aim was to better characterize these large adrenal incidentalomas.Methods: Patients followed in our center for a nonsecreting large (at least 4 cm) adrenal incidentaloma, with an initial computed tomography (CT) and ¹⁸F-FDG positron emission tomography (PET) CT, were retrospectively included. Patients who were not operated after initial diagnosis had to be followed with clinical, biological, and imaging evaluations for at least 3 years or until delayed surgery.Results: Eighty-one patients were included in the study: 44 patients (54.3%) had initial surgery while 37 were followed, including 21 (25.9%) who were operated after a mean of 19 months. Among the 65 operated patients, 13 (20%) had a malignant lesion (3 with metastasis, and 10 with adrenocortical carcinoma). Unenhanced CT <10 showed 85.6% sensitivity and 78.8% specificity; all had a ¹⁸F-FDG uptake ratio >1.5. Among the 24 patients who were followed for at least 3 years, 5 (20.8%) finally presented hypercortisolism (4 subclinical).Conclusion: As expected, large adrenal tumors are at a higher risk of malignancy. The combination of unenhanced CT <10 and ¹⁸F-FDG PET ratio <1.5 prove to be reassuring and might lead to a close follow-up rather than immediate surgery. Hormonal follow-up should be focused on the risk of hypercortisolism.Abbreviations: CI = confidence interval; CT = Computed Tomography; ENSAT = European Network for the Study of Adrenal Tumors; ESE = European Society of Endocrinology; FDG = fluorodeoxyglucose; HU = Hounsfield units; PET = positron emission tomography; ROI = regions of interest; SUV = standard uptake value     

DNA and S-phase distribution and incidence of metastasis in human primary lung carcinoma

The aim of the study was to investigate the relationship between DNA and S-phase distribution in primary non-small-cell lung carcinomas with the incidence of metastasis. Patients with non-small-cell lung carcinomas were divided into two groups depending on whether at time of surgery there were metastases or not, and these groups were correlated with the data obtained by flow cytometry or autoradiography. As expected from other studies, survival time was significantly longer for those patients without metastases at time of surgery (P = .0002) and the incidence of metastasis was significantly higher when the primary tumor was greater than or equal to 70 cm3 (P = .026). In this study, a total of 185 fresh specimens of lung carcinomas were investigated by flow cytometry. Patients with aneuploid tumors had a higher tendency to have metastases (P = .016). Patients with tumors with a higher proportion of S-phase cells measured by either flow cytometry or autoradiography demonstrated significant increase in the formation of metastases (P = .02 and P = .05). We feel that these results warrant further investigation with other primary tumors. A comparison of primary tumors that are known to rapidly metastasize vs. those that either slowly or rarely metastasize may prove to yield valuable insight into the important factors associated with metastatic potential.     

Anti-CEA and other antibodies in the study of gastrointestinal tumors.

Localization of gastrointestinal tumors by means of labeled monoclonal antibodies is a new, sensitive and suitable technique currently used in several centers. Encouraging results have been documented with several monoclonal antibodies by different authors. This article reviews our experience with radioimmunoscintigraphy in 59 patients with colorectal cancer in follow-up, using 131I and 111In labeled B72.3, and in 16 patients with primary gastrointestinal tumors using 99mTc anti-CEA monoclonal antibody (type F023C5). The sensitivity of both B72.3 and anti-CEA was greater than 70% either for primary tumors and abdominal recurrences or distant metastases except hepatic ones. A significant gradient in antibody uptake was measured on surgical biopsies between tumors and normal tissues allowing a good in vivo contrast for gamma detection. We have defined the impact of some factors affecting in vivo tumor targeting. In fact, pharmacodynamics of MAbs, percentage of injected dose bound to tissues were measured, and in particular antigenic content in tumor nodules was quantified. Furthermore, the results of RIS were compared to those obtained by CT and other imaging modalities.     

End results in parotid tumors

Management of parotid tumors can be based on a clinical classification of these lesions as being either "encapsulated" or infiltrating. The Warthin tumor (papillary cystadenolymphomatosum) is a benign encapsulated tumor, often occurring multicentrically or bilaterally especially in the lower pole area of the parotid. It is characterized clinically by its softness and fluctuation in size and a high incidence in elderly men. The so-called "capsule" of well demarcated mixed and mucoepidermoid tumors is represented by a condensation of host fibrous stroma, in the interstices of which tumor cells may be present. The "encapsulated" tumors should be excised with a "shell" of uninvolved parotid tissue. To do this safely, the facial nerve should first be isolated. Total parotidectomy is necessary only if the size of the tumor, the multiplicity of recurrences, or the infiltrating nature of the tumor are such that complete eradication of the primary site must be done. Radical neck dissection is never performed electively except in the small group of nonencapsulated infiltrating primary lesions. In a series of cases of previously untreated parotid tumors treated by the method outlined, the local parotid recurrence rate was less than 1 per cent.     

Low Incidence of Synchronous or Metachronous Tumors after Endoscopic Submucosal Dissection for Early Gastric Cancer with Undifferentiated Histology

Background

Gastric cancer with undifferentiated histology has different clinicopathologic characteristics compared to differentiated type gastric cancer. We aimed to compare the risk of synchronous or metachronous tumors after curative resection of early gastric cancer (EGC) via endoscopic submucosal dissection (ESD), according to the histologic differentiation of the primary lesion.

Methods

Clinicopathological data of patients with initial-onset EGC curatively resected via ESD between January 2007 and November 2014 in a single institution were reviewed. We analyzed the incidence of synchronous or metachronous tumors after ESD with special reference to the differentiation status of the primary lesion.

Results

Of 1,560 patients with EGC who underwent curative resection via ESD, 1,447 had differentiated type cancers, and 113 had undifferentiated type cancers. The cumulative incidence of metachronous or synchronous tumor after ESD was higher in the differentiated cancer group than in the undifferentiated cancer group (P = 0.008). Incidence of metachronous or synchronous tumor was 4.8% and 1.2% per person-year in the differentiated and undifferentiated cancer groups, respectively. The Cox proportional hazard model revealed that undifferentiated cancers were associated with a low risk of synchronous or metachronous tumors after adjusting for confounding variables (hazard ratio [95% confidence interval] = 0.287 [0.090–0.918]).

Conclusions

The rate of synchronous or metachronous tumors after curative ESD was significantly lower for undifferentiated cancers compare to differentiated cancers. These findings suggest that ESD should be actively considered as a possible treatment for undifferentiated type EGCs.     

Immunopotentiation with levamisole in resectable bronchogenic carcinoma: a double-blind controlled trial; Study Group for Bronchogenic Carcinoma.

A long-term multicentre double-blind study was designed to test the immunotropic effects of levamisole in patients undergoing operation for primary bronchial carcinoma. They received levamisole 50 mg three times a day by mouth or placebo for three days every fortnight, starting three days before surgery. Unless there was clinical evidence of recurrence, cytostatic drugs, corticosteroids, and radiotherapy were prohibited. In the 111 patients who have been followed up for one year the incidence of side effects was similar in both groups. Recurrences occurred in 10 out of 51 patients (seven deaths) receiving levamisole and in 20 out of 60 (12 deaths) receiving placebo. Further analysis showed that there were fewer recurrences on levamisole in patients with squamous cell carcinomas and medium and large primary tumours and fewer suspected and proved recurrences and deaths from metastases on levamisole in patients with extended tumours. Distant recurrences tended to be less common with levamisole, whereas the disease-free interval in relapsing patients was almost identical in the two groups. These interim results show that levamisole seems to exert its beneficial effect by preventing immunosuppression due to surgery.     

Carcinoid tumor of the kidney: case report and review of the literature

Carcinoid tumors are low-grade malignant tumors that arise from neuroendocrine cells. Primary renal carcinoid tumors are extremely uncommon. They seem to be more indolent than renal cell carcinomas, although metastases to regional lymph nodes, liver, and bone have been described. The presence of metastases seems to indicate a more malignant course; however, even with metastases a patient might live for 3 or 4 years. Renal carcinoid tumors should be managed by radical or partial nephrectomy, and good outcomes have been obtained for organ-confined disease after radical excision. Conventional methods of imaging are inadequate for detecting smaller carcinoids, so somatostatin receptor scintigraphy should complement computed tomography and magnetic resonance imaging when searching for occult or metastatic disease. Close follow-up after surgery is necessary.     

Prognosis of sentinel node staged patients with primary cutaneous melanoma

Background

This study investigated survival probabilities and prognostic factors in sentinel lymph node biopsy (SLNB) staged patients with cutaneous melanoma (CM) with the aim of defining subgroups of patients who are at higher risk for recurrences and who should be considered for adjuvant clinical trials.

Methods

Patients with primary CM who underwent SLNB in the Department of Dermatology, University of Tuebingen, Germany, between 1996 and 2009 were included into this study. Survival probabilities and prognostic factors were evaluated by Kaplan-Meier and multivariate Cox proportional hazard models.

Results

1909 SLNB staged patients were evaluated. Median follow-up time was 44 months. Median tumor thickness was 1.8 mm, ulceration was present in 31.8% of cases. The 5-year Overall Survival (OS) was 90.3% in SLNB negative patients (IB 96.2%, IIA 87.0%, IIB 78.1%, IIC 72.6%). Patients with micrometastases (stage IIIA/B) had a 5-year OS rate of 70.9% which was clearly less favorable than for stages I–II. Multivariate analysis revealed tumor thickness, ulceration, body site, histopathologic subtype and SLNB status as independent significant prognostic factors.

Conclusion

Survival rates of patients with primary CM in stages I–II were shown to be much more favorable than previously reported from non sentinel node staged collectives. For future clinical trials, sample size calculations should be adapted using survival probabilities based on sentinel node staging.