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PubMed1979

Recommendations for the analysis of the effect of treatment on the development of second malignancies.

Use of the person-years method for evaluating the association between treatment of a primary cancer and subsequent development of a second malignancy is reviewed. For this type of analysis, the risk of developing a second malignancy is implicitly assumed to remain constant during each patient's follow-up period; this assumption is shown to be inappropriate. When the oncogenic potential of two or more treatments is compared, results are biased unfavorably against the use of intensive treatments that prolong life. Misinterpretation of the oncogenic potential of such treatment regimens can therefore occur, and two alternative statistical techniques are proposed, each for use in a commonly encountered experimental situation. These fairly classic methods of survival analysis are recommended to ascertain the relationship between treatment and development of a second cancer.

Antineoplastic Agents↗

PubMed1986

[Malignant melanoma in the area of the head and neck].

The incidence of malignant melanoma is rising worldwide. Recognition of the biological types of malignant melanoma (nodular melanoma, superficial spreading melanoma, lentigo maligna melanoma, and acrolentiginous melanoma) have greatly helped to improve the prognosis in recent years. Determination of the depth of invasion in histological serial sections has proved to be of great prognostic value. Melanomas with minimal invasion have an excellent prognosis. Wide excision of the primary tumour is of utmost importance. The excisional margins should be 3-5 cm, but in superficial melanomas the width of excision may be less. Prophylactic neck dissection is unnecessary for superficial melanomas, it is necessary for lesions between 1 and 3.9 mm in thickness, whereas in tumours with a depth of invasion greater than 4 mm the outcome of the disease is not improved by prophylactic neck dissection. In metastasizing malignant melanoma the tumour mass should be reduced by surgical intervention. Survival is sometimes prolonged by several months or even longer when lymph nodes and metastases are excised. A radical neck dissection is indicated therefore when lymph nodes are clinically involved.

Combined Modality Therapy↗

PubMed2000

Biomarker conservation in primary and metastatic epithelial ovarian cancer.

PURPOSE: The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS: Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied. RESULTS: A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Rare incidence of three consecutive primary tumors in the maxillofacial region: retinoblastoma, leiomyosarcoma, and choriocarcinoma: case report.

Multiple primary tumors occur more commonly in the region of the head and neck than elsewhere in the body. The chance of this is particularly high in patients treated for retinoblastoma, in part because of a genetic predisposition, and in part because of the possibility of irradiation treatment. However, triple tumors occur in only 0.5% of multiple tumors. A rare case of a triple (metachronous) tumor is reported: 12 years after the treatment of bilateral retinoblastoma (enucleation and irradiation), secondary leiomyosarcoma developed in the maxillofacial region, followed 5 years later by choriocarcinoma. Surgery was performed on all three types of tumor. As a result, the female patient (currently 21 years old) is now free of complaints and has married. It is extremely rare for either leiomyosarcoma or choriocarcinoma (CHC) to appear in the maxillofacial region. The long-term, systematic control of such patients is absolutely necessary, for the multiple tumors tend to develop only after a long latency period of 10 to 20 years.

Adolescent↗

PubMed1985

Second primary cancers in patients with gastrointestinal cancers.

The occurrence of multiple primary malignant neoplasms in 9,191 consecutive cases of primary gastrointestinal (GI) tract cancer from 1962 to 1981 at the National Cancer Center was analyzed. The person-years of the cases totaled 28,399.4: 185 second cancers were diagnosed clinically and 85 were first diagnosed at autopsy. The overall frequency was 2.01% for clinically recognizable cancers and 2.94% including those discovered at autopsy. The overall observed/expected ratio was 0.96 for clinical cancers and 1.33 including autopsy cases. However, a significant association between the first and second cancers was present in the oro-pharynx and esophagus; esophagus, stomach and colon; stomach and all other parts of the GI tract; and the colon and rectum. The mode of appearance was also analyzed to clarify the organ relationship.

Age Factors↗

PubMed2000

Panendoscopy and bronchial washings: role and efficacy in detection of simultaneous primary head and neck cancers.

The phenomenon of multicentricity in head and neck squamous cell carcinoma affects survival rates. We evaluated the use of panendoscopy/triple endoscopy and, in particular, the place of bronchial washings in the initial staging assessment of head and neck tumours. In a prospective panendoscopic study, a second primary rate of 4.8 per cent was discovered. All four bronchial tumours--both index and simultaneous primary cases--were obvious on bronchoscopy and chest X-ray, despite 50 per cent of them being clinically silent. A self-limiting complication rate of 2.4 per cent was encountered. The issue of bronchial washings was debated and our sensitivity (50 per cent) and specificity (97 per cent) results assessed. We advocate the inclusion of bronchoscopy as part of a panendoscopic work-up of head and neck tumours. The rationale for this is discussed. Bronchial washings, although cheap and easy to process, did not change the management of any patient in the study group and contamination could complicate assessment. Overall, panendoscopy is a safe worthwhile procedure.

Adult↗

PubMed1982

Second cancers following radiotherapy for cervical cancer.

Incidence of second primary cancers was evaluated in 7,127 women with invasive cancer of the cervix uteri, diagnosed between 1935 and 1978, and followed up to 38 years (average, 8.9 yr) in Connecticut. Among 5,997 women treated with radiation, 449 developed second primary cancers compared with 313 expected (relative risk = 1.4) on the basis of rates from the Connecticut Tumor Registry. Excess incidence was noticeable 15 years or more after radiotherapy and attributed mostly to cancers of sites in or near the radiation field, especially the bladder, kidneys, rectum, corpus uteri, and ovaries. No excess was found for these sites among the 1,130 nonirradiated women. The ratio of observed to expected cancers for these sites did not vary appreciably by age at irradiation. The data suggested that high-dose pelvic irradiation was associated with increase in cancers of the bladder, kidneys, rectum, ovaries, corpus uteri, and non-Hodgkin's lymphoma but, apparently, not leukemia, Hodgkin's disease, breast cancer, or colon cancer.

Adult↗

PubMed2006

US findings of bilateral primary breast cancer: retrospective study.

BACKGROUND: For women with breast cancer, the contralateral breast is at high risk. The bilateral cancers may be synchronous or metachronous. If the bilateral breast cancers have similar ultrasonography (US) appearances, the US findings of the first breast cancer (index cancer) might lead to early detection of the contralateral cancer. The purpose of this study was to identify the US characteristics of bilateral breast cancer and to determine whether bilateral breast cancers have similar US appearances and whether the US findings for one breast cancer might be predictive of the contralateral breast cancer. METHODS: We retrospectively reviewed the US manifestations of 58 patients with surgically proven bilateral primary breast cancer and compared the contralateral cancer with the index cancer by evaluation the margin, shape, inside echoes, posterior attenuation, calcification and color flow signals of 58 lesion pairs to investigate whether the bilateral breast cancers have similar US appearances. RESULTS: Bilateral primary breast cancers were more located in upper outer quadrant, frequently spiculation, taller than wide shape, with irregular margin, heterogeneous internal echo and acoustic shadowing, containing microcalcification and abundant color flow signals. The most common US appearances were taller than wide shape (75.0%, 87/116), irregular margins (79.3%, 92/116) and heterogeneous internal echo (86.2%, 100/116). Of the total 58 lesion pairs, 18 (31.0%) pairs had similar US characteristics, whereas 40 (69.0%) pairs had different US characteristics. CONCLUSIONS: US signs of the index cancer do not indicate the most likely appearance of the second cancer in the contralateral breast. Evaluation of the contralateral cancer should be performed without regard for the US findings for the index cancer.

Aged↗

PubMedDate not supplied

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer.

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.

Cause of Death↗

PubMed1997

Immunological functions of adult T cell leukemia cells of a patient complicated with synchronous double primary gynecologic cancer.

A patient with triple malignancies is reported, who presented cervical cancer, vulvar cancer and adult T cell leukemia (ATL). ATL was diagnosed as a smouldering type, because antibody to human T cell leukemia virus associated antigen (ATLA) was positive with a titer of 1:160. Although her malignant cells had an OKT 4+8-3+Tac+ phenotype, the cells did not display helper T cell functions. Namely they showed no response to Phytohemagglutinin (PHA) and Interleukin 2 (IL-2) and suppressed the PWM driven IgG synthesis of B cells obtained from healthy donor. They did not produce IL-2 by stimulation with PHA and phorbol myristate acetate (PMA). Furthermore, these ATL cells were producing IL-2 inhibitor like factors. As synchronous triple malignancies are extremely rare, two gynecologic cancers seem to ascribe to the suppressing state of the immunosurveillance mechanism by viral infection.

Aged↗

PubMed1993

Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology.

OBJECTIVE: To outline the preferable approach to the management of patients with nonfamilial colorectal polyps. DATA SOURCES: The human subject English language literature for the past 15 years, searched using MEDLINE and the terms "polyp-," "adenoma-," and "polypectomy-colorectal." STUDY SELECTION: The titles and abstracts of all pertinent articles were reviewed. All randomized controlled trials and large case-control and cohort studies related to colorectal polyps were reviewed in depth. DATA SYNTHESIS: Evidence was evaluated along a hierarchy with randomized controlled trials receiving the greatest weight. Conclusions and recommendations were reviewed by a large group of experts in gastroenterology, radiology, and pathology and were circulated for comment to primary care medical societies. CONCLUSIONS: Most patients with polyps should undergo colonoscopy to excise the polyp and search for synchronous neoplasms. Small polyps (< 0.5 cm) require individualization. A hyperplastic polyp found during proctosigmoidoscopy is not an indication for colonoscopy. Large sessile polyps require careful follow-up to ensure complete resection. The need for further treatment of a resected polyp with invasive carcinoma depends on several well-defined clinical and pathologic criteria. Follow-up surveillance after polypectomy should be tailored to the individual risk assessment for each patient. Initial follow-up should be performed at 3 years for most postpolypectomy patients. After one negative result of a 3-year examination, the interval can be increased to 5 years. Patients with one small tubular adenoma do not have an increased risk for cancer, and therefore follow-up surveillance may not be indicated. Adoption of these recommendations should substantially reduce the cost of postpolypectomy surveillance and of screening for colorectal cancer.

Colonic Polyps↗

PubMed2000

Second primary malignancies associated with renal cell carcinoma: influence of histologic type.

OBJECTIVES: This study was performed to determine which histologic types of renal cell carcinoma have an association with a second primary malignancy. METHODS: Seven hundred sixty-three patients underwent an operation for renal cell carcinoma between July 1989 and January 1999. The incidence of antecedent, synchronous, or subsequent second malignancies was determined. Statistical tests based on the Poisson model were used to compare the observed number of subsequent malignancies developing after a diagnosis of renal cell carcinoma with the expected number calculated using the 1973 to 1994 U.S. Surveillance, Epidemiology, and End Results age, race, gender, and calendar-year specific incidence rates. RESULTS: Second primary malignancies were present in 209 of 763 (27.4%) patients, with prostate, breast, colon, and bladder cancer and non-Hodgkin's lymphoma being the five most common second malignancies. The other malignancies were antecedent in 118 cases (44.5%), synchronous in 104 cases (39.2%), and subsequent in 43 cases (16.2%). Patients with papillary renal cell carcinoma were at increased risk of developing bladder cancer (standardized incidence ratio [SIR] 6.5, P = 0.038). Men with papillary renal cell carcinoma were also at increased risk of developing prostate cancer (SIR 2.8, P = 0.035). CONCLUSIONS: There is an increased risk of subsequent bladder and prostate cancer in patients with papillary renal cell carcinoma.

Adolescent↗

PubMed2003

Papillary carcinoma of the extrahepatic bile duct: characteristic features and implications in surgical treatment.

BACKGROUND: Papillary carcinoma of the extrahepatic bile duct presents clinically and histologically distinct features relevant to surgical decision-making. STUDY DESIGN: Serial sections of 15 specimens of resected papillary carcinoma of the bile duct were histologically examined to determine mode of spread, possibility of multicentric tumor origins, and coincidence with other neoplastic lesions. The presence of anomalous pancreaticobiliary ductal union was also investigated. These characteristics were considered with regard to surgical treatment. RESULTS: Three patients displaying pancreaticobiliary maljunction and one of three patients with a long common channel (> or = 8 mm) exhibited multicentric tumors. Eight patients (53%) demonstrated superficial spread along a mean length of 37.8 mm (range, 5 to 67 mm) of bile duct mucosa. Multicentric tumors developed synchronously in 4 patients, while metachronous tumors were identified in three patients displaying tumor histology similar to the primary lesions. Two of these three underwent successful repeated resection. Concomitant neoplastic lesions in the biliary tract were identified as mucosal dysplasia in four patients and cholangiocellular carcinoma of the liver in two. All tumors but one were removed via hepatic lobectomy or pancreatoduodenectomy, or both, resulting in a 5-year survival rate of 60%. CONCLUSIONS: Aggressive resection offers clear survival benefits for patients presenting with tumors displaying extensive superficial spread or multicentric origins. Closer attention should be paid to long common channels in relation to carcinogenesis of the bile duct, in addition to pancreaticobiliary maljunction. The risk of secondary tumor development remains, particularly in patients with pancreaticobiliary maljunction even after excision of the tumor-bearing extrahepatic bile duct.

Adult↗

PubMed1990

Second primary cancer after treatment of invasive carcinoma of the uterine cervix, compared with those arising after treatment for in situ carcinomas. An effect of irradiation? A cancer registry study.

A cancer registry cohort of 16,704 cases of invasive carcinoma of the uterine cervix and 56,116 cases of in situ carcinomas of the uterine cervix was followed up and second new primary cancers were recorded. The invasive carcinomas contributed 127,118 woman-years at risk and the in situ carcinomas contributed 453,362 woman-years at risk. The main treatment for the invasive carcinomas had been radiotherapy and for the in situ carcinomas, conization and other types of surgical intervention. 767 new primaries occurred after treatment of invasive carcinoma of the uterine cervix, compared with 644.5 expected. O/E is 1.19. After the in situ carcinomas, 1,421 malignant tumors were observed, vs. 1,188.0 expected (O/E 1.19). If, however, cases of invasive carcinoma of the uterine cervix after in situ carcinomas are excluded, the ratio observed/expected is 1.10. For some sites the increased observed/expected ratios were found after both invasive and in situ carcinomas, which speaks for some common carcinogenic effect other than irradiation (for instance, in bronchus and trachea, pharynx, nose, sinus and larynx, but also in rectum, urinary bladder, other female genital organs, pancreas, lymphosarcoma, as well as acute and non-lymphatic leukemia). A lower risk than expected--after both in situ and invasive carcinoma of the uterine cervix--is observed for breast cancer, cancer of the corpus uteri and for multiple myeloma. However, analyses based on time since treatment provide evidence of a carcinogenic effect of irradiation, especially in intensively irradiated organs such as bladder, rectum, corpus uteri and ovary, and also for acute and non-lymphatic leukemia.

Adult↗

PubMed1990

Second malignancies following radiotherapy for testicular seminoma.

Traditional treatment for testicular seminoma produces excellent survival. We report five, second non-testicular malignancies which occurred in a group of seminoma patients. A total of 79 men with primary testicular seminoma were available for analysis. All underwent a radical inguinal orchiectomy. Those with Stage I disease received adjuvant radiation therapy to the para-aortic and ipsilateral iliac nodes. The usual dose was 2500 cGy in 15 treatments. Stage II patients also received prophylactic mediastinal radiation therapy to a dose of 2500 cGy. None of the 51 Stage II patients died of tumour, whereas four of the 28 Stage II patients died of their disease. The median follow-up was ten years (range 4-25 years). The second malignancies seen were melanoma (2), myeloma, caecal adenocarcinoma, and retroperitoneal fibrosarcoma. All but one tumour developed within the radiation fields. Based on US SEER data for white males, only 1.5 cancers were expected, giving significantly greater (P = 0.04) relative risk. This observation lends support to observation, rather than elective treatment, in patients with Stage I testicular cancer.

Dysgerminoma↗

PubMed1995

Treatment of multiple primary squamous cell carcinomas of the lung.

BACKGROUND: The prevalence of multiple primary bronchogenic cancers, especially squamous cell carcinoma, has been increasing as a result of improvements in early detection and cancer therapy. MATERIALS: We treated 14 patients with multiple squamous cell carcinoma of the tracheobronchial tree and lung, which corresponded to 2.3% of all squamous cell carcinoma patients undergoing resection. RESULTS: Two patients had peripheral secondary tumors and underwent segmentectomy or partial resection of the lung with good results. The secondary lesions were superficial and minute (less than 5 mm) in 3 patients, and treated with neodymium-yttrium aluminum garnet laser ablation. Five patients had endobronchial tumors of the nodular or polypoid type with suspected deep invasion or invasion extending beyond the bronchial wall based on the bronchoscopic findings. They underwent parenchymal-sparing limited bronchoplasty with excellent results. Three patients had more advanced tumor with massive invasion outside the bronchial wall without lymph node metastases, 1 patient underwent sleeve lobectomy with long survival, and the other 2 patients without operation died of bleeding or had recurrence. One patient with stage IIIA (T2 N2) secondary cancer who underwent lobectomy died 14 months after the second operation. CONCLUSIONS: The surgical treatment of multiple squamous cell carcinoma is justified and limited operation using bronchoplastic techniques provides superior results.

Aged↗

PubMed1999

Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas.

OBJECTIVE: Intraductal papillary mucinous tumor (IPMT) of the pancreas has a favorable prognosis. Non-pancreatic primary neoplasms have potential prognostic significance in patients with IPMT. This study focused on the incidence and characteristics of nonpancreatic neoplasms in IPMT patients. METHODS: Forty-two patients (mean age, 64 yr) with IPMT underwent surgery; 16 had adenoma and 26 adenocarcinoma. Preoperative and postoperative, nonpancreatic neoplasms were investigated. The mean postoperative follow-up period was 4.2 yr (range, 0.2-13 yr). Furthermore, 46 patients with pancreatic ductal adenocarcinoma were analyzed for nonpancreatic neoplasms. RESULTS: Five-year survival rates were 100% for benign and 82% for malignant IPMT. Twenty patients (48%) had nonpancreatic neoplasms, before (n = 11), at (n = 4), and after (n = 10) surgery for IPMT. Fifteen patients (32%) had nonpancreatic malignancies. Nonpancreatic neoplasms included colorectal adenomas (21%) and adenocarcinomas (12%), and gastric carcinomas (10%). One patient died of subsequent bile duct carcinoma. Development of nonpancreatic neoplasms was related to age but not to gender, family history, adjuvant chemotherapy, or IPMT pathology. The incidences of nonpancreatic neoplasms and malignancies were significantly higher in patients with IPMT than in those with pancreatic ductal adenocarcinoma (11% and 7%, respectively). CONCLUSIONS: IPMT is associated with a high incidence of nonpancreatic neoplasms, particularly colorectal neoplasms. In IPMT patients, systemic surveillance may allow early detection of second tumors. In preoperative screening and postoperative follow-up of patients with nonpancreatic neoplasms, the possibility of IPMT should be considered.

Adenocarcinoma, Mucinous↗

PubMed1999

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Adult↗