A Brief Overview of the WHO Classification of Breast Tumors, 4th Edition,Focusing on Issues and Updates from the 3rd Edition

Zusammenfassung

Die vierte Auflage der WHO Klassifikation der Tumoren der Mamma ist ein Update der 2003 erschienenen dritten Auflage und behandelt alle neoplastischen und präneoplastischen Läsionen der Mamma. Die Änderungen der vierten Auflage betreffen neue Aspekte und Änderungen der Terminologie, und spiegeln unser gegenwärtiges Verständnis dieser Läsionen wider. Die histopatholo-gischen Definitionen werden ergänzt um Beschreibungen der klinischen Charakteristika, der Makroskopie, Genetik und prognostischer und prädiktiver Informationen. In dieser Übersicht wird ein Überblick über die invasiven Karzinome, die Vorläuferläsionen und einige benigne Epithelproliferaionen gegeben.     

Carcinoembryonic antigen in serum,urine and cells of patients with bladder carcinoma

Summary A raised level of CEA-like substance has been demonstrated by radioimmunoassay in the urine of patients with bladder carcinoma, in concentrations which increase with a more advanced stage, and in serum of patients with advanced disease. In a 2-year follow-up of patients receiving chemotherapy, a correlation of raised urinary CEA to local recurrence was seen, as well as rising and high serum values with metastases. In the patients who responded to treatment, CEA values became normal. CEA was also located in carcinoma cells from bladder washings in 24–61 % of the cases. Combined studies of CEA in serum, urine and cells may be used to study the biology of the tumor and perhaps also in the monitoring of patients with urothelial carcinoma.     

Melanoma Metastases in Regional Lymph Nodes Are Accurately Detected by Proton Magnetic Resonance Spectroscopy of Fine-Needle Aspirate Biopsy Samples

Background Nonsurgical assessment of sentinel nodes (SNs) would offer advantages over surgical SN excision by reducing morbidity and costs. Proton magnetic resonance spectroscopy (MRS) of fine-needle aspirate biopsy (FNAB) specimens identifies melanoma lymph node metastases. This study was undertaken to determine the accuracy of the MRS method and thereby establish a basis for the future development of a nonsurgical technique for assessing SNs. Methods FNAB samples were obtained from 118 biopsy specimens from 77 patients during SN biopsy and regional lymphadenectomy. The specimens were histologically evaluated and correlated with MRS data. Histopathologic analysis established that 56 specimens contained metastatic melanoma and that 62 specimens were benign. A linear discriminant analysis–based classifier was developed for benign tissues and metastases. Results The presence of metastatic melanoma in lymph nodes was predicted with a sensitivity of 92.9%, a specificity of 90.3%, and an accuracy of 91.5% in a primary data set. In a second data set that used FNAB samples separate from the original tissue samples, melanoma metastases were predicted with a sensitivity of 87.5%, a specificity of 90.3%, and an accuracy of 89.1%, thus supporting the reproducibility of the method. Conclusions Proton MRS of FNAB samples may provide a robust and accurate diagnosis of metastatic disease in the regional lymph nodes of melanoma patients. These data indicate the potential for SN staging of melanoma without surgical biopsy and histopathological evaluation.     

Next-generation sequencing technology in prostate cancer diagnosis,prognosis, and personalized treatment

Next-generation sequencing (NGS) of the genetic information of cancer cells has revolutionized the field of cancer biology, including prostate cancer (PCa). New recurrent alterations have been identified in PCa (e.g., TMPRSS2-ERG translocation, SPOP and CHD1 mutations, and chromoplexy), and many previous ones in well-established pathways have been validated (e.g., androgen receptor overexpression and mutations; PTEN, RB1, and TP53 loss/mutations). With its highly heterogeneous nature, PCa continues to pose a tremendous challenge in terms of diagnosis and prognosis. Combining the information gained through NGS studies with clinicopathological and radiological data will help diagnose the aggressiveness of the cancer with greater accuracy. Furthermore, understanding the heterogeneity of tumor through single-cell or single-molecule sequencing technology will also strengthen the prognosis and provide better, patient-specific drug identification. As this research becomes more prominent, it is important that urologic oncologists become familiar with the various NGS technologies and the results generated using them. We highlight the commonly used NGS tools and summarize recent discoveries relevant to PCa.     

External validation of Chun,PCPT, ERSPC,Kawakami, and Karakiewicz nomograms in the prediction of prostate cancer: A single center cohort-study

Objectives

The aim of our study was to analyze the performance of 5 different risk calculators for prostate cancer diagnosis: Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC), European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSP-RC), Karakiewicz nomogram, Chun nomogram, and Kawakami Nomogram.

The Safety and Efficacy of Laparoscopic Surgical Staging and Debulking of Apparent Advanced Stage Ovarian, Fallopian Tube, and Primary Peritoneal Cancers

Objectives:

To describe our experience with laparoscopic primary or interval tumor debulking in patients with presumed advanced ovarian, fallopian tube, or peritoneal cancers.

Methods:

This is a retrospective analysis of a prospective case series. Women with presumed advanced (FIGO stage IIC or greater) ovarian, fallopian tube, or primary peritoneal cancers deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited.

Results:

The study comprised 32 patients who underwent laparoscopic evaluation. Seventeen underwent total laparoscopic primary or interval cytoreduction, with 88.2% optimal cytoreduction. Eleven underwent diagnostic laparoscopy and conversion to laparotomy for cytoreduction, with 72.7% optimal cytoreduction. Four patients had biopsies, limited cytoreduction, or both. In the laparoscopy group, 9 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 2 have died of disease (DOD), with mean follow-up time of 19.7 months. In the laparotomy group, 3 patients are NED, 5 are AWD, and 3 are DOD, with mean follow-up of 25.8 months. Estimated blood loss and length of hospital stay were less for the laparoscopy group (P=0.008 and P=0.03), while operating time and complication rates were not different. Median time to recurrence was 31.7 months for the laparoscopy group and 21.5 months for the laparotomy group (P=0.3).

Conclusions:

Laparoscopy can be used for diagnosis, triage, and debulking of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer and is technically feasible in a well-selected population.     

mTOR,Cancer and Transplantation

One of the most clinically important molecular signalling networks to emerge over the past decade is the mammalian target of rapamycin (mTOR) pathway. mTOR, the protein kinase at the core of this intricate and continually evolving pathway, controls cellular growth and behavior, impacting vital processes from immune reactivity to cancer progression. As researchers, surgeons and physicians in the field of organ transplantation, we have acquired a keen interest in regulating mTOR activity, because this molecule is not only able to block IL‐2 signalling in T cells, and thus alloimmune reactivity, it is a critical part of the cellular circuitry which is often constitutively activated in neoplastic cells, leading to the all‐too‐often occurrence of cancer. Since allograft rejection and the development of cancer lead most lists for causing excess morbidity and mortality in our organ transplant population, a thorough and current understanding of the mTOR pathway becomes essential. In this review, we endeavor to unravel the latest molecular developments in mTOR signalling and use this basic knowledge to generate perspectives on how pharmacologic mTOR intervention may form a balance to impact long‐term antidonor immune responses and the development of malignancy in transplant recipients.     

晚期卵巢癌、输卵管癌及原发性腹膜癌腹腔镜肿瘤细胞减灭术的安全性及有效性研究

目的总结晚期卵巢癌、输卵管癌和腹膜癌患者行腹腔镜初次或间歇性肿瘤细胞减灭术的临床经验。方法回顾分析接受腹腔镜肿瘤细胞减灭术的晚期卵巢癌(FIGOⅡc期以上)、输卵管癌和原发性腹膜癌患者临床资料。结果 32名患者接受腹腔镜评估手术。17例接受全腹腔镜肿瘤细胞减灭术,其中88.2%为满意的肿瘤细胞减灭术;11例腹腔镜评估后转开腹肿瘤细胞减灭术,其中72.7%为满意的肿瘤细胞减灭术;4例仅进行活检和(或)姑息手术。腹腔镜组平均随访时间19.7月9,例无瘤生存6,例带瘤生存2,例因肿瘤死亡。开腹组平均随访时间25.8月,3例无瘤生存,5例带瘤生存,3例因肿瘤死亡。腹腔镜组术中失血量较少,术后住院时间较短(P=0.008和P=0.03),但手术时间及并发症发生率与开腹组相比无统计学差异。中位复发时间,腹腔镜组为31.7月,开腹组为21.5个月(P=0.3)。结论对于经过精心挑选的晚期卵巢癌、输卵管癌和原发性腹膜癌病例,采用腹腔镜进行诊断、分期和肿瘤细胞减灭术,在技术上是可行的。     

Epidemiology, presentation, diagnosis, and outcomes of choledochal cysts in adults in an urban environment

BACKGROUND: Choledochal cysts (CDC) are rare congenital cystic lesions of the biliary tract. In North America the incidence of CDC is estimated as 1/150,000; it is not clear that the disease pattern in North America is similar to that in Asia. METHODS: Retrospective chart review. Statistical analysis was under taken using Fisher's exact test. RESULTS: Presentation, epidemiology, diagnosis, and outcome were evaluated in 51 patients with CDC. Malignant transformation was identified in 4 patients presenting uniformly with jaundice (P = .027). Type 4a cysts (54.9%) were the most common cyst identified. Four (14%) type IVa and two (13%) type I cysts developed postoperative stricture. No patient developed cholangiocarcinoma after complete resection of their cyst. CONCLUSIONS: Types I and IVa cysts can be treated similarly with excellent outcome. However, our observation of a high proportion of type 4a cysts may represent a specific North American pattern of this disease requiring a re-evaluation of the classification system.     

Diagnosis,prognosis and management of incidentally found prostate cancer

Summary Incidentally discovered cancer of the prostate may be divided into focal and diffuse disease. The focal tumour tends to be of low grade and low-volume and in the majority of patients runs a clinically benign course. In 10–15% of untreated patients, however, progression occurs by 10 years after diagnosis. At the same stage of follow-up 30–63% of the patients have died of other causes, with no evidence of recurrence. In patients with low-grade focal cancer of the prostate, radical prostatectomy may be curative. An alternative management option is to closely observe these patients. Digital rectal examination, prostatic specific antigen, transrectal prostatic ultrasound and repeated prostatic biopsies can all make contributions to the follow-up of these patients.     

睾丸癌组织中P21、P53蛋白以及增殖细胞核抗原的表达研究

应用免疫组织化学方法研究5例正常睾丸组织和27例睾丸癌组织中增殖细胞核抗原(PCNA)、P21和P53的表达,表达阳性的PCNA和P53均定位于肿瘤细胞核内,P21蛋白定位于肿瘤细胞膜上,27例睾丸癌组织中PCNA、P21和P53的阳性表达率分别为51.9％、44.4％和48.2％。并且PCNA、P21和P53阳性表达率与睾丸癌的病理分级和临床分期关系密切。提示PC-NA、P21和P53可作为评估睾丸癌预后的生物学指标。     

Analgesic effects of nonsteroidal antiinflammatory drugs, acetaminophen, and morphine in a mouse model of bone cancer pain

Purpose Bone metastasis is one of the major causes of cancer-related pain, and not all bone cancer pain can be effectively treated. Recently, a mouse model of bone cancer pain was introduced. To test the analgesic effects of nonsteroidal antiinflammatory drugs on bone cancer pain, the authors examined the effects of oral administration of a cyclooxygenase-1 (COX-1) selective inhibitor (SC560), a COX-2 selective inhibitor (celecoxib), and a nonselective COX inhibitor (indomethacin) on bone cancer pain and compared these effects to the effect of orally administered acetaminophen and morphine.Methods An animal model of bone cancer pain was induced by injecting osteolytic murine sarcoma cells in the mouse femur. Drugs were administered orally 2 weeks after tumor-cell implantation, and the level of bone cancer pain was assessed 30, 60, 90, 120, and 180 min after drug administration.Results Oral administration of acetaminophen, indomethacin, and morphine, but not of SC560 or celecoxib, produced an analgesic effect on bone cancer pain. Co-administration of a subanalgesic does of morphine with acetaminophen enhanced the analgesic effect of acetaminophen.Conclusion These data suggest that bone cancer pain is effectively treated by oral administration of indomethacin, acetaminophen, and morphine and that the co-administration of acetaminophen and an opioid provides a beneficial effect when treating of bone cancer pain.     

Facial pain I. A prospective survey of 1052 patients with a view of: Definition,delimitation, classification,general data,genetic factors,and previous diseases

Summary 1052 patients with facial pain have been examined and followed up by the author for an 18-year period. The patients are classified according to type of attack into: Typical Trigeminal Neuralgia (brief pain paroxysms with pain-free intervals), Atypical Trigeminal Neuralgia (pain paroxysms with intervals of pain or paroxysms lasting for minutes), Non-neuralgiform Facial Pain (pain lasting or occurring for long periods). The material was equally distributed between patients with Neuralgia and Non-neuralgiform Facial Pain. In the majority of cases Trigeminal Neuralgia occurred after the age of 50, Non-neuralgiform Pain mainly between 30 and 50. There is a majority of women with Non-neuralgiform Pain. No genetic factors could be demonstrated. A detailed registration of previous diseases in the central nervous system, the peripheral nerves, and the facial structures revealed no relation to important aetiological factors.Financial support has been given by the Foundation for the Advancement of Medical Research.     

Neoadjuvant Chemotherapy and Radiation for Patients with Locally Unresectable Pancreatic Adenocarcinoma: Feasibility, Efficacy, and Survival

Abstract Background We evaluated the feasibility and efficacy of neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic cancer. Materials and Methods From October 2000 to August 2006, 245 patients with pancreatic adenocarcinoma underwent surgical exploration at our institution. Of these, 78 patients (32%) had undergone neoadjuvant therapy for initially unresectable disease, whereas the remaining patients (serving as the control group) were explored at presentation (n = 167). All neoadjuvant patients received gemcitabine-based chemotherapy, often in conjunction with docetaxal and capecitabine in a regimen called GTX (81%). Seventy-five percent of neoadjuvant patients also received preoperative abdominal radiation (5,040 rad). Results Neoadjuvant patients were younger than control-group patients (60.8 vs 66.2 years, respectively, p < 0.002). Seventy-six percent of neoadjuvant patients were resected as compared to 83% of control patients (NS). Concomitant vascular resection was required in 76% of neoadjuvant patients but only 20% of NS (p < 0.01). Complications were more frequent in the neoadjuvant group (44.1 vs 30.9%, p < 0.05), and mortality was higher (10.2 vs 2.9%, p < 0.03). Among the neoadjuvant patients, all but one of the deaths were in patients that underwent arterial reconstruction. Mortality for patients undergoing a standard pancreatectomy without vascular resection was 0.8% in this series. Of patients resected, negative margins were achieved in 84.7% of neoadjuvant patients and 72.7% of NS. Within the cohort of neoadjuvant patients, radiation significantly increased the complication rate (13.3 vs 54.6%, p < 0.006), but did not affect median survival (512 vs 729 days, NS). Median survival for patients who received neoadjuvant therapy (503 days) was longer than NS that were found to be unresectable at surgery (192 days, p < 0.001) and equivalent to NS that were resected (498 days). Conclusions Resection rate, margin status, and median survivals were equivalent when neoadjuvant patients were compared to patients considered resectable by traditional criteria, demonstrating equal efficacy. Surgical resection with venous reconstruction following neoadjuvant therapy for patients with locally advanced pancreatic cancer can be performed with acceptable morbidity and mortality. This approach extended the boundaries of surgical resection and greatly increased median survival for the “inoperable” patient with advanced pancreatic cancer. This work was presented at the American Hepato-Pancreato-Biliary Association Conference in Las Vegas, NV, April 2007.     

A single-institution study of 117 pregnancy-associated breast cancers (PABC): Presentation,imaging, clinicopathological data and outcome

BackgroundThis retrospective single-institution study was designed to describe the main clinical, radiological and histological features, as well as the outcome of pregnancy-associated breast cancer (PABC), with a special emphasis on imaging and diagnostic difficulties.Material and methodsWe reviewed all breast cancers diagnosed during pregnancy or during the 12 months following delivery at our institution, between 1993 and 2009. Out of a total of 16,555 new cases of breast cancer observed during this period, 117 PABC (0.7%) were diagnosed.ResultsMean age at diagnosis was 33.7 years. Most cancers (81.2%) were diagnosed after delivery. Intermediate or high family risk was frequent (27.5%). The most common mode of presentation was a palpable mass (89.7%). Mean time to diagnosis was 5.8 months. Sensitivity for mammography was 80.9% and for ultrasound 77%. Most prognostic factors were unfavourable: frequent lymph node involvement (51.8%), high-grade tumours, hormone receptor negativity (45.9%) and HER2 positivity (38.7%). Treatments generally included surgery (61.7% mastectomies), radiotherapy (96%) and chemotherapy (79.6%). Overall 5-year survival was 81.8%.ConclusionPABC is an uncommon but aggressive form of breast cancer and must be considered in the presence of any breast abnormality during pregnancy or the months following delivery. Mammography and ultrasound should both be performed at the slightest clinical suspicion. Radiologists must be aware that masses may lack typical malignant ultrasound characteristics. Biopsies should be largely performed.