Chronic ulcerative colitis and colorectal cancer

One of the most important consequences of chronically active ulcerative colitis (UC) or Crohn’s disease (CD) – the two major forms of inflammatory bowel disease (IBD) – is the development of colorectal cancer (CRC). An increased risk for the occurrence of CRC in up to 30% of affected patients after 35 years of UC has been reported. Recent evidence from population based studies indicates a lower risk. Nevertheless the incidence is still significantly increased as compared to individuals without chronic colitis. Colitis-associated CRC (CAC) does not display the adenoma-carcinoma sequence which is typical for sporadic CRC and the pathophysiology appears to be different. Chronic inflammation and the increased turnover of epithelial cells contribute to the development of low- and high-grade dysplasia which may further transform into CAC. Reactive oxygen species (ROS) generated by the inflammatory infiltrate are thought to contribute to the generation of dysplastic lesions. In sporadic CRC the sequence of mutations that finally lead to malignancy involves early activation of Wnt/β-catenin pathway (in 90% of cases) including mutations in adenomatous polyposis coli (APC) tumor suppressor gene, its regulating kinase GSK3β and β-catenin itself. β-catenin mutations are rarer in CAC and mutations in APC occur rather late during the disease progression, whereas there are earlier mutations in p53 and K-ras. Recent data indicate that the intestinal microbiome and its interaction with a functionally impaired mucosal barrier may also play a role in CAC development. CACs frequently show aggressive growth and early metastases. The treatment of CAC in patients with colitis always includes proctocolectomy with ileoanal anastomosis as meta- or synchronic lesions are frequent.     

Breast cancer chemoprevention – a vision not yet realized

Despite recent advances in the surgical and medical treatment of breast cancer, the number of patients dying from the disease is still high. In addition to improvements of early diagnosis and treatment, the overall mortality of breast cancer could be reduced by means of preventive intervention in both women with particularly normal and with high risk. Preventing the potentially deadly disease is presumably more effective than treatment, for life quality issues as well as for the economic perspective. Chemoprevention though is still a research field with results from large prevention trials being discussed controversially. For women with a defined increased risk for breast cancer, tamoxifen may be a choice for chemoprevention, balancing carefully benefits against risks. With promising results in adjuvant settings, aromatase inhibitors may deliver better prevention treatment options in the future, nevertheless, more research is needed to reliably predict risk on an individual basis in the future.     

The Role of Metastasectomy in Urothelial Carcinoma: Where Are We in 2020?

Systemic therapy is the mainstay of treatment for metastatic urothelial carcinoma (UC). Responses to first-line platinum-based therapy tend to be short-lived with potential toxicity. Despite the approval of checkpoint inhibitors, the long-term prognosis for patients with metastatic UC remains dismal. Herein we report the case of a patient with a solitary pulmonary metastatic lesion of urothelial origin as the only site of metastatic disease who remained free of disease for more than 2 years without systemic therapy after metastasectomy. We review the literature discussing the role of combined surgical and medical management of oligometastatic UC. As our case illustrates, a growing body of evidence suggests a potential role for a multimodal approach in patients with oligometastatic UC.     

Unresectable or medically inoperable non-small cell lung cancer: the use of established clinical prognostic factors in making radiation-related treatment decisions

Many physicians consider the prognosis exceptionally poor for patients with localized non-small cell lung cancer who are not eligible for surgery, either because of the extent of their disease or because a coexisting medical condition precludes surgery. Thus, these patients frequently are not offered aggressive curative therapy. However, the disease of many of these patients is potentially curable and should be considered for curative treatment. Although pathologic data from surgical specimens are useful in predicting prognosis, many prognostic factors have also been identified for medically inoperable and locally advanced, unresectable disease. Several of these prognostic factors can and should be used clinically to estimate the risk of lymph node involvement within the clinically uninvolved mediastinum, thereby aiding in the design of radiation therapy fields, and to estimate prognosis, thereby helping to determine which patients should be offered aggressive therapy with curative intent.     

Thromboprophylaxis with low‐molecular‐weight heparin in medical patients with cancer

Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment and is associated with multiple clinical consequences, including recurrent VTE, bleeding, and an increase in the risk of death. Although the risks associated with VTE have been well recognized in surgical cancer patients, there is also considerable and increasing risk in medical cancer patients. VTE risk factors in medical cancer patients include the type and stage of cancer, major comorbid illnesses, current hospitalization, active chemotherapy, hormone therapy, and antiangiogenic agents. Low‐molecular‐weight heparins (LMWHs) are recommended commonly for the prevention of VTE in hospitalized cancer patients and in higher risk ambulatory cancer patients because of their favorable risk‐to‐benefit profile. These agents have demonstrated effectiveness in both the primary and secondary prevention of VTE in medical cancer patients. Extended‐duration anticoagulant therapy is often recommended to reduce the risk of VTE recurrence in patients with cancer. LMWHs are often used for long‐term prophylaxis because of a reduced need for coagulation monitoring, few major bleeding episodes, and once‐daily dosing. Despite clinical and practical benefits, a substantial proportion of medical cancer patients do not receive VTE prophylaxis. To improve the appropriate prevention and treatment of VTE in cancer patients, guidelines have been published recently by the American Society of Clinical Oncology and the National Comprehensive Cancer Network. Widespread dissemination and application of these guidelines are encouraged to improve the appropriate use of these agents and to improve clinical outcomes in medical cancer patients at risk for VTE and its complications. Cancer 2009. © 2009 American Cancer Society.     

子宫内膜癌的治疗

子宫内膜癌患者在较早期时即出现了症状,所以多数可以通过内膜的活检得以诊断。根据本病的生物学行为和病理特点可以将其分为子宫内膜样癌和非子宫内膜样癌。手术治疗是首选的治疗手段。目前,对子宫内膜样癌患者主要采用全面的手术分期,术后根据病理的结果即有无高危因素决定是否给予辅助治疗;对非子宫内膜样癌的手术方式更倾向于类似卵巢癌的肿瘤细胞减灭术。放射治疗虽然可以明显减少手术后的局部复发,但却不能改善患者的生存。化疗主要用于特殊的病理类型、肿瘤组织分化差、晚期或复发的患者。大剂量孕激素对子宫内膜癌有肯定疗效。     

胃癌腹膜转移的外科诊治观

随着诊断性腹腔镜的普及、晚期胃癌转化治疗概念的兴起,以及腹腔化疗港、腹腔热灌注化疗等技术的应用,胃癌腹膜转移的诊断与治疗取得新的进展。然而,胃癌腹膜转移预后差,治疗依旧缺乏高级别证据,在实践过程中应注意规范化诊断与评效,在患者筛选、手术指征、术后化疗等重要问题上进行多学科讨论决策。药物治疗的进展仍是未来提高胃癌腹膜转移预后的关键。     

Ⅲa期肺鳞癌生存因素分析

目的 分析Ⅲa期肺鳞癌的治疗模式.方法 回顾性分析102例Ⅲa期肺鳞癌患者的病历资料,并对临床信息及治疗情况等因素对患者生存的影响进行分析.结果 102例Ⅲa期肺鳞癌患者中,行根治性手术患者65例(63.7%),非根治性手术患者37例(36.3%).根治性手术组与非根治性手术组患者的中位OS分别为27.9个月和19.0个月,差异有统计学意义(P=0.005).单因素分析结果显示:N2淋巴结转移个数和N2淋巴结转移组数对行根治性手术的Ⅲa/N2期肺鳞癌患者的OS有影响(P<0.05),而N2淋巴结转移个数≥3个的患者术后死亡风险更高(RR=3.342).结论 对于Ⅲa期肺鳞癌患者,如果患者体力情况较好,建议行手术治疗.纵隔N2淋巴结转移个数是影响患者术后生存率的主要因素.     

Reaching out to undeserved populations. Highlights from programs to improve cancer disparities

As the number of cancer survivors continues to increase, oncologists are faced with the challenge of providing cancer therapy to patients who may 1 day want to have children. Yet, gonadotoxic cancer treatments can compromise future fertility, either temporarily or permanently. There are established means of preserving fertility before cancer treatment; specifically, sperm cryopreservation for men and in vitro fertilization and embryo cryopreservation for women. Several innovative techniques are being actively investigated, including oocyte and ovarian follicle cryopreservation, ovarian tissue transplantation, and in vitro follicle maturation, which may expand the number of fertility preservation choices for young cancer patients. Fertility preservation may also require some modification of cancer therapy; thus, patients' wishes regarding future fertility and available fertility preservation alternatives should be discussed before initiation of therapy. This commentary provides an overview of the range of fertility preservation options currently available and under development, using case‐based discussions to illustrate ways in which fertility preservation can be incorporated into oncology care. Cases involving breast cancer, testicular cancer, and rectal cancer are described to illustrate fertility issues experienced by male and female patients, as well as to provide examples of strategies for modifying surgical, medical, and radiation therapy to spare fertility. Current guidelines in oncology and reproductive medicine are also reviewed to underscore the importance of communicating fertility preservation options to young patients with cancer. Cancer 2011. © 2010 American Cancer Society.     

Gastric cancer, Helicobacter pylori infection and other risk factors

Gastric cancer incidence is declining. However, it is too early to consider this neoplastic disease as rare and the worldwide mortality rate still remains high. Several risk factors have been identified for non-cardia gastric cancer and primary prevention is feasible since most of the risk factors can be removed. Helicobacter pylori eradication treatment reduces but does not abolish gastric cancer risk. Indeed, gastric cancer is a multifactorial disease and removing one factor does not therefore prevent all cases. Endoscopic surveillance is still needed, especially in subjects at higher risk. The definition of high-risk patients will be the future challenge as well as identifying the best surveillance strategy for such patients.     

Interpretation of the development of neoadjuvant therapy for gastric cancer based on the vicissitudes of the NCCN guidelines

Gastric cancer is one of the most common digestive system tumors in China, and locally advanced gastric cancer (LAGC) accounts for a high proportion of newly diagnosed cases. Although surgery is the main treatment for gastric cancer, surgical excision alone cannot achieve satisfactory outcomes in LAGC patients. Neoadjuvant therapy (NAT) has gradually become the standard treatment for patients with LAGC, and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate, but it also significantly improves the long-term prognosis of patients. Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies, and the regimens have also been evolved in the past decades. Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide, here, we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019, and also discuss the future of NAT.     

Surgical treatment of colorectal cancer metastasis

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of thermal ablation. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas administration of systemic or regional chemotherapy rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens. Modern surgical treatment of colorectal liver metastases can be performed safely with low mortality and transfusion rates, and surgical treatment should be considered in patients with disease confined to their liver.     

男性乳腺癌的临床研究进展

男性乳腺癌发病罕见,过去25年问发病率呈上升趋势.目前对男性乳腺癌生物学、自然病程以及治疗策略的研究大部分是基于对女性乳腺癌的研究成果.男性乳腺癌的发病风险因素包括BRCA2基因突变和职业因素,而职业因素又包括高温工作环境、燃料和尾气;此外,性激素失衡,如生殖腺功能失调、肥胖、辐射等均可增加患病风险.临床病情进展可缓慢或快速转移.病理类型绝大多数为导管癌,10%为导管原位癌.常采取的手术是乳房切除术和腋窝淋巴结清扫或前哨淋巴结活检术.放疗步骤和方法同女性乳腺癌.由于90%的男性乳腺癌患者雌激素受体阳性,因此他莫昔芬是标准的辅助内分泌治疗药物,个别病例也可从化疗中获益.本文对近年有关男性乳腺癌的流行病学、生物学和治疗方面的相关内容进行总结.     

Practical considerations in the re-irradiation of recurrent and second primary head-and-neck cancer: who, why, how, and how much?

Despite progress in surgical and reconstructive techniques, as well as advances in radiotherapy delivery methods, a significant proportion of patients irradiated for head-and-neck cancer develop locoregional recurrence. These patients are also at high risk of developing new second primary cancers of the head and neck. Because of the heterogeneity of this population with respect to disease-related and patient-related factors, such as previous treatment, tumor recurrence site, disease extent, and performance status, the optimal treatment of locoregionally recurrent or second primary cancers of the head and neck remains to be defined. Although surgical resection typically constitutes the mainstay of treatment, effective salvage therapy is often precluded by anatomic inaccessibility and the risk of perioperative complications. Although chemotherapy alone has traditionally been considered an alternative to surgery, the response rates have been poor, with nearly all patients dying of disease progression within months. Similarly, salvage therapy using re-irradiation has historically been avoided because of concerns regarding toxicity. Although the results of more recent studies using contemporary treatment techniques and conformal delivery methods have been somewhat more promising, the role of re-irradiation after previous full-course radiotherapy is still considered investigational by many. Numerous questions remain unanswered, and practical guidelines for clinical decision-making are sparse.     

Anticoagulation therapy for prevention and treatment of venous thromboembolic events in cancer patients: A review of current guidelines

Cancer patients in general have a high risk of venous thromboembolic events (VTE) driven not only by patient-related risk factors, but also risk factors related to the disease and anti-cancer therapies. Cancer patients with documented VTE have a notably worse outcome than non-cancer VTE patients. Since VTE is a highly preventable condition, it is striking that large surveys have shown significant underuse of VTE prophylaxis in surgical cancer patients and in medical cancer patients in particular. Recently, guidelines have been issued from European and American medical oncology societies and organizations for identification of cancer patients at risk, and the guidelines give recommendations for treatment of individual groups of cancer patients.     

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.     

Usefulness and positioning of MAB therapy for prostate cancer

Prostate cancer is a relatively slow-growing disease compared to other cancers, and the patients tend to be older. Taking into consideration therefore life expectancy of the patients and risks of recurrence and progression, conservative treatments (mainly hormonal therapy) are often applied for early cases, as well as radical treatments (total prostatectomy and radiotherapy). Particularly in Japan, many patients start treatment with hormonal therapy alone, in both early and advanced cases. Hence, Maximal Androgen Blockade (MAB) therapy, in which surgical or medical castration (such as LH-RH agonist treatment) and anti-androgen treatment are combined, is widely exercised with the hope to enhance treatment effects. The usefulness of MAB therapy has been assessed in a number of randomized comparative studies, covering mainly metastatic cases. The efficacy of the therapy with the use of flutamide as non-steroidal anti-androgen has been confirmed in some of the studies, although the magnitude of the efficacy cannot be said major. In Phase III clinical studies of MAB therapy with bicalutamide being conducted in Japan for patients in Stages C and D, however, the patient group treated with MAB therapy demonstrated more favorable results compared to the group treated with LH-RH agonist alone, particularly in terms of time to progression (TTP) of the patients in Stage C. These are relatively new findings on the usefulness and adaptability of MAB therapy. In this Panel Discussion, views and experiences are exchanged on a wide variety of topics covering the real usefulness of MAB therapy, its adaptability, possible outcomes of hormonal therapy in early cases, and the future of MAB therapy, taking into account the prevailing opinions and current practices on prostate cancer in both the United States and Japan.     

Cancer risks in ulcerative colitis patients

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.     

Advances in the management of testicular cancer

Although testicular cancer is currently a rare disease, the incidence is rising. The most important risk factor remains cryptorchism and there is a variable association with testicular microlithiasis. Serum tumor markers remain important for diagnosis, and they have prognostic value and can be used to monitor therapy and follow-up. Conventional imaging can only be improved in specific categories of patients with positron emission tomography scanning. The optimal therapy after orchiectomy should be individualized based on the histology of the primary specimen, the presence or absence of metastasis, and marker levels. An optimal definition of risk factors will likely spur the development of risk-adjusted treatment modalities and subsequently lead to better results and less toxicity. Extensive research into the molecular biology of testicular cancer is ongoing and will hopefully offer new targets for the diagnosis, staging, and treatment of testicular cancer in the future.     

Surgical management of primary thyroid tumours

The majority of patients who present with well differentiated thyroid cancer will require surgery, but decisions on the appropriate primary procedure will depend on information relating to patient, tumour and surgical factors. As the incidence of thyroid cancer continues to rise, it is critical that clinicians involved in the management of these cases understand the factors which underpin surgical decision making for individual patients. Reporting outcomes in well differentiated thyroid cancer (WDTC) has always been challenging due to the low recurrence and mortality rate of the disease. Although early data supported total thyroidectomy for all patients with >1 cm WDTC, more recent evidence has supported lobectomy in selected, low risk patients. As a result we have seen a change in the approach of international guidelines from a blanket statement that total thyroidectomy should be the treatment for all patients towards a more selective approach to therapy. When selecting the most appropriate surgical approach to WDTC, the primary aim is to minimize the chance of death from disease or further recurrence. Additionally the impact of potential side effects of treatment (laryngeal nerve injury and hypocalcaemia) must also be weighed in the balance. In this review of surgical management of WDTC we aim to present a historical perspective on this subject and explore the arguments for and against total thyroidectomy and thyroid lobectomy in the low-risk patient group.