Epidemiological aspects of cancer screening in Germany

Purpose Since 1971, a statutory early detection programme has operated in Germany which comprises health-insurance-paid annual examinations of the breast, cervix, prostate, rectum, and the skin. Since the programme is conceptualised as opportunistic screening, the attendance rates have been low and only reached about 50% among females and 13% among males by the end of the 1990s. Based on these figures and present knowledge on the efficacy of screening modalities, we assessed past benefits and the future potential of cancer screening in Germany.Methods We used published data on the efficacy of screening procedures and German attendance rates, and internationally available data on incidence and mortality in Germany and, for cervical cancer, in other countries. Incidence and mortality rates have been standardised to the world standard, and screening benefit has been given as the population preventable fraction given in percentage.Results The past benefits of the statutory early detection programme ranged around 2.0–6.5%. Since the upper limit was due to generous assumptions regarding efficacy or inclusion of treatment effects, the true value might be closer to the estimates of the effect of cervical cancer screening (2.0–4.7%). The achievable future benefit of exploiting the theoretical potential of more exhaustive screening could provide a further mortality reduction of about 3.4% (50% compliance) or 4.7% (70% compliance).Conclusions Screening partially requires an expensive medical infrastructure and is not without risks for the participants. The overall benefit is critically dependent upon the quality of the programme and its in-time control. Any benefit may be annulled by poor quality while costs are overflowing. Well-organised high-quality screening may be a sound basis for cancer control. To preserve or increase the impact of screening and control its expenses: (a) further research efforts are needed towards new or better targeted screening tools or modalities; (b) the efficacy of new modalities has to be evaluated carefully in advance; (c) the programme has to be reconceptualised as organised screening; (d) in-time quality control based on the collection of the basic performance data must be an intrinsic part of the programme.     

Progress against cancer (1971–2011): how far have we come?

'The big C', a common euphemism for cancer, has loomed large on the collective psyche of the mankind for centuries, not least because of the relative dearth of effective treatment against this disease but its ability to relentlessly evade them and come back to haunt us. However, the struggle against cancer took a decisive turn in 1971 when a relentless campaigning by health activists eventually led to signing of the National Cancer Act in the United States, an unprecedented event in the history of diseases. As we commemorate the 40th anniversary of the signing of that historic legislation, an assessment of the progress against cancer would naturally help us understand how we have fared so far in this struggle and guide us in our efforts to re-strategize and re-deploy our limited resources to their best use against this immortal enemy.     

Hereditary factors in pancreatic cancer

The incidence and the mortality rates for pancreatic cancer are the same, indicating its dismal outlook. Its natural history remains elusive. Cigarette smoking appears to be the most significant environmental culprit. Hereditary factors may account for approximately 5% of the total pancreatic cancer burden. However, when its extant heterogeneity and the reduced penetrance of causal germline mutations are considered, the hereditary incidence may significantly exceed this estimate. Even when endoscopic ultrasound (EUS), the gold standard for pancreatic cancer screening, is utilized, early detection with surgical cure has rarely been accomplished. Needed to ameliorate this problem is research into genetic and environmental risk factors and their interaction. The identification of tumor biomarkers which signal early pathogenetic events, thereby enabling pancreatic cancer to be diagnosed at its earliest possible stage before it has spread to regional lymph nodes or to more distant sites, will improve the outlook. We discuss our research approaches to this problem. Members of families with thep16 germline mutation will undergo EUS coupled with the collection of pancreatic juice for the study of a possible gradient for telomerase activity, K‐ras mutations, and cytology. If changes in these putative biomarkers are observed, endoscopic retrograde cholangiopancreatography (ERCP) would be the next diagnostic step. We conclude with a discussion of ethical concerns about this research.     

Gastric cancer patients at high-risk of having synchronous cancer

AIM: To identify patients with a high-risk of having a synchronous cancer among gastric cancer patients. METHODS: We retrospectively analyzed the prospective gastric cancer database at the National Cancer Center, Korea from December 2000 to December 2004. The clinicopathological characteristics of patients with synchronous cancers and those of patients without synchronous cancers were compared. Multivariate analysis was performed to identify the risk factors for the presence of a synchronous cancer in gastric cancer patients. RESULTS: 111 of 3291 gastric cancer patients (3.4%) registered in the database had a synchronous cancer. Among these 111 patients, 109 had a single synchronous cancer and 2 patients had two synchronous cancers. The most common form of synchronous cancer was colorectal cancer (42 patients, 37.2%) followed by lung cancer (21 patients, 18.6%). Multivariate analyses revealed that elderly patients with differentiated early gastric cancer have a higher probability of a synchronous cancer. CONCLUSION: Synchronous cancers in gastric cancer patients are not infrequent. The physicians should try to find synchronous cancers in gastric cancer patients, especially in the elderly with a differentiated early gastric cancer.     

Endocrine-related cancers and the role of AMPK

AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis involved in the regulation of a number of physiological processes including β-oxidation of fatty acids, lipogenesis, protein and cholesterol synthesis, as well as cell cycle inhibition and apoptosis. Important changes to these processes are known to occur in cancer due to changes in AMPK activity within cancer cells and in the periphery. This review aims to present findings relating to the role and regulation of AMPK in endocrine-related cancers. Obesity is a known risk factor for many types of cancers and a number of endocrine factors, including adipokines and steroid hormones, are regulated by and regulate AMPK. A clear role for AMPK in breast cancer is evident from the already impressive body of work published to date. However, information pertaining to its role in prostate cancer is still contentious, and future work should unravel the intricacies behind its role to inhibit, in some cases, and stimulate cancer growth in others. This review also presents data relating to the role of AMPK in cancers of the endometrium, ovary and colon, and discusses the possible use of AMPK-activating drugs including metformin for the treatment of all endocrine-related cancers.     

他汀类药物在消化系统癌症中的使用研究进展

随着经济的快速发展、人民饮食结构的改变及环境污染,消化系统癌症的发病率及死亡率呈逐年上升趋势,对于早期癌症可行内镜下治疗,进展期可采用外科手术、放疗、化疗、免疫治疗及靶向治疗等方法。近年来,多项研究显示,他汀类药物在消化系统癌症中的使用可一定程度上降低癌症患者的死亡率及患癌风险。本文主要探讨他汀类药物在消化系统癌症中的应用研究进展,有望为癌症的治疗发现新的辅助用药。     

口腔菌群与消化道肿瘤相关性的研究进展

口腔是全身寄居微生物密度最高,种类最多的部位之一。口腔幽门螺杆菌与胃部肿瘤关系的研究引发了对口腔微生物与肿瘤之间关系的研究热潮。本文从消化道肿瘤影响口腔菌群的组成,以及口腔菌群影响消化道肿瘤的发生与发展两个方面对口腔菌群与消化道肿瘤之间的关系进行综述,为口腔菌群与消化道肿瘤关系的进一步研究提供参考,并对相关研究在临床工作中的应用前景进行阐述,为消化道肿瘤的早期检测,早期预防及临床治疗提供新思路。     

HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists

Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.     

Cell fate regulation by gelsolin in human gynecologic cancers

Chemoresistance is a major hurdle in cancer treatment. Down-regulation of apoptosis pathways is one of the key determinants for chemoresistance. Here, we report higher gelsolin (GSN) levels in chemoresistant gynecological cancer cells compared with their sensitive counterparts. cis-Diammine dichloroplatinium (II) (CDDP)-induced GSN down-regulation is associated with its cleavage and apoptosis. Although the C-terminal GSN fragment (C-GSN) sensitized chemoresistant cells to CDDP, intact GSN and its N-terminal fragment (N-GSN) attenuated this response. GSN silencing also facilitated CDDP-induced apoptosis in chemoresistant cells. In contrast, intact GSN (I-GSN) was prosurvival in the presence of CDDP through a FLICE-like inhibitory protein (FLIP)-Itch interaction. This interaction was colocalized in the perinuclear region that could be dissociated by CDDP in sensitive cells, thereby inducing FLIP ubiquitination and degradation, followed by apoptosis. In resistant cells, GSN was highly expressed and CDDP failed to abolish the I-GSN-FLIP-Itch interaction, resulting in the dysregulation of the downstream responses. In addition, we investigated the association between GSN expression in ovarian serous adenocarcinoma and progression free survival and overall survival, as well as clinical prognosis. GSN overexpression was significantly associated with more aggressive behavior and more cancer deaths and supported our hypothesis that high GSN expression confers chemoresistance in cancer cells by altering the GSN-FLIP-Itch interaction. These findings are in agreement with the notion that GSN plays an important role in the regulation of gynecological cell fate as reflected in dysregulation in chemosensitivity.Cell-fate decision is the underpinning of cancer-therapy effectiveness, which is dependent on chemosensitivity. cis-Diammine dichloroplatinum (II) (cisplatin or CDDP) is a widely used chemotherapeutic agent (1) for gynecological, testicular, lung, and head-and-neck cancer. Clinical evidence supports that the platinum-taxane combination for ovarian cancer (OVCA) remains the standard regimen of choice (2). CDDP-based cancer chemotherapy, however, is often limited by acquired or intrinsic chemoresistance. OVCA patients are clinically divided into “resistant,” “partially sensitive,” and “sensitive” to platinum according to the progression-free interval (PFI) of <6 mo, 6–12 mo, and >12 mo (3, 4). This concept is supported by evidence of lower response rates to subsequent platinum retreatment in patients with PFI < 12 mo compared with those with PFI > 12 mo.Cellular mechanisms potentially contributing to CDDP resistance include changes in cellular drug uptake and accumulation, drug detoxification, apoptosis inhibition, and repair of the DNA adducts. Inability of the cells to undergo apoptosis is critical in CDDP resistance (5), and dysregulation of proapoptotic (6) and antiapoptotic (7–9) pathways plays an important role in chemoresistance.Gelsolin (GSN) controls actin dynamics and plays a role as a multifunctional regulator for cell metabolism and survival (10, 11). GSN participates in multiple important cellular signaling for motility, apoptosis, proliferation, differentiation, epithelial mesenchymal transition (12), and carcinogenesis phenotypes (13, 14). GSN plays roles as both effecter and inhibitor of apoptosis, which underlines its association in a wide variety of cancer types.We screened potential proteins interacting with GSN using a yeast-two-hybrid system combined with site-directed mutagenesis. A panel of proteins involving drug resistance and antiapoptosis pathways was found to potentially interact with GSN. These interactions could render a mobile docking hypothesis to affect critical functional pathways in chemoresistance. Elucidation of GSN cross-talks with intracellular intermediates is important to better understand the molecular and cellular mechanisms of chemoresistance in gynecological cancer.We have demonstrated the role of Fas-associated death domain-like interleukin-1β–converting enzyme (FLICE)-like inhibitory protein (FLIP) in CDDP resistance in cervical cancer cells (8). FLIP, a Fas-associated death domain (FADD)-binding inhibitor of apoptosis, exists as 55-kDa (FLIP_L) and 28-kDa (FLIP_S) splice variants. CDDP-induced FLIP degradation in chemosensitive cells involves FLIP-p53-Itch interaction and its translocation to the cell membrane for Itch-mediated FLIP ubiquitination and proteasomal degradation (15, 16).To date, there has been no clinical investigation to examine the relationship between GSN and cancer progression in OVCA. In the present study, we investigated GSN expression in human ovarian cancerous tumors, its influence on patient survivals, and its association with PFI. Moreover, we compared the GSN expression between chemosensitive and chemoresistant cell lines of ovarian and cervical cancer. The molecular mechanisms governing the role of GSN and FLIP in modulating cancer chemosensitivity were also examined. Our clinical results are complemented with in vitro findings illustrating the important role GSN plays in the regulation of gynecological cell fate as reflected in dysregulation in chemosensitivity. They support the hypothesis that GSN forms a complex with FLIP and Itch and stabilizes FLIP in a nonstress state whereas CDDP dissociates GSN from the complex in chemosensitive cells, thereby facilitating FLIP ubiquitination and degradation, caspase-3 activation, and GSN cleavage.     

Pancreatic cancer in 2021: What you need to know to win

Pancreatic cancer is one of the solid tumors with the worst prognosis. Five-year survival rate is less than 10%. Surgical resection is the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage of the disease and surgery could be performed in a very limited number of patients. Moreover, surgery is still associated with high post-operative morbidity, while other therapies still offer very disappointing results. This article reviews every aspect of pancreatic cancer, focusing on the elements that can improve prognosis. It was written with the aim of describing everything you need to know in 2021 in order to face this difficult challenge.     

Flat-Type Early Colorectal Cancer Preferentially Develops in Right-Sided Colon in Older Patients

BACKGROUND Flat-type colorectal cancer is frequently reported in Japan and Europe, but its clinical features remain obscure. Thus, we investigated the clinical features of flat-type early colorectal cancer with respect to tumor location and patient age and compared them with those of polypoid-type early and advanced cancer.METHODS Between January 1999 and June 2001, total colonoscopy was performed in 6,178 patients (mean age, 61 years; 4,290 males and 1,888 females). Of these patients, 402 patients with 429 colorectal cancers were found: 202 at advanced stage (invading beyond muscularis propria) and 227 at early stage (carcinoma in situ or invading within submucosa). Early-stage cancer was classified into two macroscopic subgroups: flat-type and polypoid-type.RESULTS Out of 227 early cancers, 44 were flat type and 183 were polypoid. Flat-type early cancer was more frequently located in the right colon (57 percent, 25/44) than polypoid-type cancer (19 percent, 35/183; P < 0.001). Adenomatous component in flat-type early cancer was less frequent than in polypoid-type cancer (23 percent vs. 92 percent, P < 0.001). The proportion of right-sided colon in flat-type early cancer increased with age (33 percent in patients 59 years, 50 percent in patients between 60 and 69 years, and 72 percent in patients 70 years), whereas polypoid-type early cancer showed minimal change (16 percent, 18 percent, and 25 percent, respectively). An increase in the proportion of right-sided colon with age was also found in advanced cancer (20 percent, 38 percent, and 52 percent, respectively).CONCLUSION The incidence of flat-type early cancer in right-sided colon increased with age, similar to the pattern of advanced cancer. This suggests that flat-type early cancer may be a precursor of advanced cancer in the right colon, especially in older people.Presented in part at the meeting of the American Gastroenterological Association, San Diego, California, May 14 to 17, 2000.     

Choroidal and skin metastases from colorectal cancer

Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine(1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from rightsided colorectal cancer.     

结肠、肝脏及膀胱三原发癌1例

临床上三原发癌少见,其中结肠、肝脏和膀胱三种原发癌的组合更为罕见,本文报告1例.通过介绍本例1994-10/2009-12临床资料及查阅相关文献,总结了多原发性恶性肿瘤相关临床知识,以提高临床医生对多原发性恶性肿瘤的进一步认识.及时诊断和治疗,避免误诊或漏诊所致病情延误,对改善患者的生存及预后是至关重要的.     

Metachronous double cancer of the gallbladder and common bile duct

We report a rare case of metachronous double cancer of the biliary tract. At age 59 years, a man had undergone a cholecystectomy and resection of the liver bed for gallbladder cancer pathologically diagnosed as papillary adenocarcinoma, in 1997. Four years later, he was admitted to our hospital with jaundice. At first, we suspected lymph node metastasis of the gallbladder cancer along the common bile duct. But abdominal computed tomography demonstrated circular wall thickness of the common bile duct, so primary bile duct cancer was strongly suspected. Thus, extended right hepatectomy and pancreaticoduodenectomy were performed after right portal vein embolization. The pathological diagnosis of the resected specimen was well-differentiated tubular adenocarcinoma, and this case was clarified to be metachronous double cancer. A review of the literature regarding double cancer of the biliary tract is presented following this case report. We showed that half of 30 cases of double cancer of the biliary tract were not associated with pancreaticobiliary maljunction, including all 6 metachronous cases.     

Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell carcinoma of the stomach

Adenocarcinoma of the small intestine is uncommon. Due to this paucity and the lack of specificity of symptoms, patients are usually seen late in the course of their illness, when curative therapy, mainly represented by extensive surgical resection, is unlikely. The authors report a case of primary well-differentiated tubular adenocarcinoma (T4N0M0) arising in the duodenal limb of a reconstructed Billroth I gastroduodenostomy, 9 years after a distal gastrectomy for signet-ring cell carcinoma of the stomach (T4N0M0). Evidence for excluding the possibility of a recurrence of the primary gastric cancer was based on the different histologic pattern, the long disease-free interval, and other features of the second neoplasm. Relatively early diagnosis of the neoplasm, followed by curative surgical therapy was made possible by the early onset of the obstructive symptoms and the favorable anatomical location of the tumor.