The dilemma of cystectomy in old-old and oldest-old patients

Bladder cancer (BC) is a disease of the elderly, with a peak incidence at 85 years. If life expectancy continues to increase in such a way that it is, in 20 years nearly half of the population will be considered elderly. The incidence of BC will also dramatically increase in proportion to this and, subsequently, a cure is needed. Currently, only 4–11% of elderly individuals with muscle-invasive BC undergo radical extirpative surgery; a number that is evidently too low when we consider that the cancer-specific mortality rate is highest in the octo- and nona-genarian groups. Advanced age should not in itself be a reason for avoiding radical surgery. Comorbidity is much more important and incisive on complication and mortality rate than age alone. Nevertheless, a complication rate of 24–60% is a realistic expectation, as is a 90-day mortality rate of approximately 10%. Due to the restricted physiological reserve, there is little place for surgical mistakes. This review evaluates all aspects of radical cystectomy in the elderly and gives an overview of upcoming challenges.     

Le contrôle local de la tumeur primitive. Étape indispensable de la guérison des cancers

There is clear evidence for a cancer cure. The hypothesis behind a treatment with curative intent is the ability to eradicate all the cancer cells of a tumour. Out of three cancer deaths, one is related to local failure. In some cancers like breast carcinoma, death is mainly in relation with the development of distant metastases. Even in such a tumour, an improvement in local control can translate as better survival. Radiationtherapy, often in association with surgery, is playing a major role in tumour local control. Such a local control is mandatory if cure is at aim. One of the main goals of clinical research is to find a good compromise between local control of the disease and a non mutilating surgical approach.     

Wnt7a与恶性肿瘤的关系及研究进展

Wnt7a是Wnt信号家族成员中的一种分泌糖蛋白,位于染色体3p25上,极易缺失,主要在胎盘、肾脏、睾丸、子宫、胎肺及人脑中表达,参与人体的胚胎发育及细胞分化。越来越多的研究发现,Wnt7a在很多肿瘤细胞中也有表达,并起着举足轻重的作用。作为一个新的肿瘤治疗靶点或者肿瘤生长通路中重要的因子,Wnt7a开始受到越来越多科学家的注意。     

Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Benefit, risk, and optimization by ROC analysis in cancer radiotherapy

The objective of definitive cancer radiation therapy is cure or control. The attainment of that objective is not without risk of treatment-induced radiation injury. The optimum treatment is, therefore, that level of radiotherapeutic effect with the maximum probability of benefit and the minimum associated probability of injury. An objective of radiotherapy research is the formulation of a model of optimization that is independent of a consensus of what constitutes optimization. Receiver operating characteristic (ROC) analysis is such a model, for it can relate probabilities of benefit and injury yielding a graphical determination of the optimum level of radiotherapeutic effect. ROC analysis is explained, an example taken from the contemporary radiotherapy literature is presented, and clinical research requirements for a general application of ROC analysis to the optimization of definitive cancer radiotherapy are developed.     

A feasibility study for non-invasive thermometry using non-linear ultrasound

Purpose: High intensity focused ultrasound (HIFU) is used during hyperthermia cancer treatment to increase the tumour temperature. For an adequate and safe application it is important to measure the temperature in the heated region, preferably in a non-invasive manner and by the same modality as used for heating. The goal of this feasibility study is two-fold; first, it is investigated whether the acoustic non-linearity parameter B/A is most suitable for measuring temperature changes, second, a non-invasive thermometry method based on B/A is proposed and demonstrated.

Material and methods: Water is used to confirm that B/A is a sensitive acoustic medium parameter that is practically applicable for non-invasive thermometry. Next, a thermometry method is proposed that employs the ratios between the fundamental and the higher harmonic frequency components of a non-linear acoustic wave. The method determines these ratios for a measured acoustic pulse that has traversed a certain medium, and compares these with temperature dependent reference ratios for the same medium. The method is demonstrated using simulated measurements of an acoustic plane wave propagating in glycerol.

Results: Results obtained for water show that B/A is more sensitive for temperature changes than other practical acoustic parameters. For a combination of 16 simulated measurements, it is demonstrated that temperature can be predicted non-invasively with zero bias and a standard deviation of 2°C if the noise level does not exceed ?40?dB.

Conclusion: The suitability of B/A as a basis for non-invasive thermometry is confirmed, and a non-invasive thermometry method based on B/A is proposed and successfully demonstrated.     

Renal fungus ball in a patient with retroperitoneal fibrosis: Unique complication in a rare disease

Candida fungus ball is a rare presentation of urinary tract infections among adult patients and is associated with considerable morbidity. Because clinical signs are not specific, diagnosis is often delayed. Furthermore, treatment is occasionally difficult, and the approach to such cases varies widely among different centers. In this report, we describe a patient with retroperitoneal fibrosis who developed a renal fungus ball. Management of this challenging case is discussed, and review of the literature is presented.     

The genetics of gestational trophoblastic disease: a rare complication of pregnancy

Gestational choriocarcinoma is usually a rapidly spreading fatal disease, but it is curable if diagnosed early and treated. It is a unique malignancy that is a partial or complete allograft with a genotype that is not the same as the host genotype. It is most often preceded by an abnormal molar pregnancy. The surprising and unique androgenetic origin of complete hydatidiform molar pregnancies was first revealed by Kajii and Ohama in 1977. We describe the current understanding of the morphology, epidemiology and genetics of gestational trophoblastic disease that followed the milestone findings by Kajii and Ohama.     

Iatrogenic tumor implantation

Iatrogenic tumor implantation is a condition that results from various medical procedures used during diagnosis or treatment of a malignancy. It involves desquamation and dissemination of tumor cells that develop into a local recurrence or distant metastasis from the tumor under treatment. The main clinical feature of the condition is nodules at the operation＇s porous channel or incision, which is easily diagnosed in accordance with the case history. Final diagnosis can be made based on pathological examination. Tumor implantation may occur in various puncturing porous channels, including a laparoscopic port, abdominal wall incision, and perineal incision, etc. Besides a malignant tumor, implantation potential exists with diseases, such as a borderline tumor and endometriosis etc. Once a tumor implantation is diagnosed, or suspected, surgical resection is usually conducted. During the diagnosis and treatment of diseases, avoiding and reducing iatrogenic implantation and dissemination has been regarded as an important principle for surgical treatment of tumors. In a clinical practice setting, if possible, excisional biopsy should be employed, if a biopsy is needed. Repeated puncturing should be avoided during a paracentesis. In a laparoscopic procedure, the tissue is first put into a sample bag and then is taken out from the point of incision. After a laparoscopic procedure, the peritoneum, abdominal muscular fasciae, and skin should be carefully closed, and/or the punctured porous channel be excised. In addition, the sample/tissue should be rinsed with distilled water before surgical closure of the abdominal cavity, allowing the exfoliated tumor cells to swell and rupture in the hypo-osmolar solution. Then surgical closure can be conducted following a change of gloves and equipment. The extent of hysteromyomectomy should as far as possible be away from the uterine cavity. The purpose of this study is to make clinicians aware of the possibility of tumor implantation and to give special attention to avoid, or re     

肥胖与结直肠癌的相关性研究

现今生活和饮食结构的改变,导致肥胖在正常人群中的患病比重不断增加,同时结直肠癌（colorectal cancer,CRC）在肥胖患者中又具有高发病率,虽然现已明确肥胖是结直肠癌发生的重要因素,但其具体的作用机制尚不明了。对于肥胖患者患结直肠癌的预后尚无定论,而肥胖悖论的提出引发了我们新的探索,对于患有结直肠癌的肥胖患者其中是否存在一定特异性相似以及其行新辅助治疗的必要性仍需要进一步研究。本文就肥胖与结直肠癌的临床关系以及一些特异性联系作一综述。     

Hypertension and targeted therapy

Angiogenesis is essential for tumor growth and metastasis and is an important target for new antineoplastic agents. Vascular endothelial growth factor (VEGF) is one of the best characterized of the proangiogenic growth factors that regulate angiogenesis and is a logical target for cancer therapy. Bevacizumab, a humanized monoclonal antibody directed at VEGF, has shown promising results in a range of solid tumors. To maximize the potential of this agent further research is needed to clarify a number of important issues including dose, schedule, possible combinations, and management of toxicities. Hypertension is the most commonly identified toxicity and has been reported in all studies involving bevacizumab. It is important that blood pressure is monitored before, during and after treatment, and that medical therapy is instigated appropriately. Most patients with bevacizumab-associated hypertension require drug treatment and standard oral antihypertensives control virtually all episodes. Hypertensive crises are rare but require discontinuation of treatment. Bevacizumab represents a successful example of targeted therapy for cancer treatment. As these new therapies are introduced into current practice it is important that oncologists not only recognize a new set of toxicities, such as hypertension, but also learn how to recognize and manage them effectively.     

Adenocarcinoma arising in mature cystic teratoma: a case report

Benign cystic teratoma is recognized as one of the most common tumors in women during the reproductive age and frequently is treated by pelviscopic operation. Malignant transformation of a benign cystic teratoma is a rare event, and adenocarcinoma is extremely rare, and distinguishing this malignant change from benign disease preoperatively is nearly impossible even by the use of radiological imaging or various tumor markers. Therefore, patients should be informed that if a laparoscopic cystectomy is undertaken, a prompt second staging operation should be performed if the definitive pathology reveals an unexpected malignancy. We present a case with thyroid papillary carcinoma of follicular variant arising from mature cystic teratoma removed by laparoscopic salpingo-oophorectomy followed by staging laparotomy. We briefly reviewed literatures with regard to malignant transformation of a benign cystic teratoma.     

CyclinD1表达与泌尿系统肿瘤关系的研究进展

D型细胞周期蛋白（Cyclin）是目前已知的细胞周期蛋白（Cyclins）中的亚型之一,与肿瘤的关系最为密切,D型Cyclin中的CyclinD1是细胞周期中起关键作用的正向调节因子,主要作用于细胞增殖及细胞分裂过程,CyclinD1特异性过表达于多种肿瘤细胞。研究发现,在泌尿系恶性肿瘤中也存在Cy-clinD1过表达现象,且与肿瘤细胞的侵袭、转移和复发有关。因此,以CyclinD1作为泌尿系肿瘤的研究靶点,有可能为泌尿系恶性肿瘤的预防及治疗等提供新的思路。     

MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin

Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.     

The potential benefits of the use of regional anesthesia in cancer patients

Cancer is a leading cause of morbidity and mortality worldwide. In light of demographic changes among other factors, it is anticipated this trend will continue. Surgical resection is the primary method of treating solid tumours. Unfortunately, even with the use of adjunct therapies, metastatic disease is a leading cause of death in people with cancer. Recent evidence suggests choice of anesthetic technique may influence cancer outcome. This review considers the latest evidence regarding local and regional anesthesia in the context of cancer biology. There is a focus on the indirect and direct mechanisms involved. An integrated approach is used such that diverse areas of research are explored; ranging from epigenetics to cell death pathways. With a better understanding of how regional anesthesia and/or local anesthetics interact with cancer cells, these techniques can be trialed and evaluated to ascertain potential clinical benefits in cancer patients. Thus far, there is insufficient evidence to warrant a change in clinical practice.     

Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery

Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion.     

Definition and Diagnostic Implications of Gemistocytic Astrocytomas: A Pathological Perspective

Summary Gemistocytic astrocytoma still continues to be enigmatic; both in terms of definition and prognostic implications. The major issue of contention has been the clinical relevance of this pathological entity. The currently accepted definition of gemistocytic astrocytoma requires 20% or more gemistocytes, and considers the neoplasm as a diffuse astrocytoma, which is a WHO grade II tumor. Some suggest that gemistocytic morphology should be considered as evidence of a higher grade astrocytoma. However, there is no consensus on the percentage of gemistocytes associated with a worse prognosis than otherwise expected. Given the reported cases and series, it is not clear that this morphology portends a more aggressive biology when all else is equal. There is still a need for studies with sufficient numbers of well-matched gemistocytic and non-gemistocytic astrocytic neoplasms to decide whether upgrading a tumor with ‘significant’ number of gemistocytes is justifiable. This article presents a critical review of the existing studies and a brief mention of our experience from a pathological perspective.     

早期发现和筛选鼻咽癌的EB病毒血清学检测

鼻咽癌是中国人,特别是中国南方人的一种常见癌症;世界上除其他少数族群具有中等程度的发病率以外,它是一种罕见的癌症。鼻咽癌多见于男性,男女发病率之比约为3∶1,且好发于中年人。现今已有令人信服的证据,支持EB病毒(国际癌症研究协会归属为第一类人体肿瘤病毒)是鼻咽癌的致病因子,肯定参与鼻咽癌的多阶段、多因素发生过程。本文简要地复阅了EB病毒在鼻咽癌发病机理中的作用,重点地介绍了EB病毒抗体和EB病毒DNA作为鼻咽癌标志的主要应用;根据由鼻咽癌导致的EB病毒抗体反应的现代知识,并考虑到目前可采用的检测技术,提出了促进有效地早期发现鼻咽癌的血清学筛选策略。