paywalled: Diathermy-Induced Injury May Affect Detection of Occult Tubal Lesions at Risk-Reducing Salpingo-Oophorectomy

Diathermy: In the natural sciences, the term diathermy means "electrically induced heat" and is commonly used for muscle relaxation. It is also a method of heating tissue electromagnetically or ultrasonically for therapeutic purposes in medicine.

Diathermy-Induced Injury May Affect Detection of Occult Tuba... : International Journal of Gynecological Cancer

Background: Electrosurgery-induced tubal thermal injury obscures cellular detail and hampers histomorphological assessment for occult pathology.

Objective: 

The objectives of this study were to report on diathermy-related thermal injuries to the fallopian tube observed at RRSO and explore its potential impact on the detection of occult tubal epithelial lesions.

Design: 

This study was composed of high-risk women from breast and/or ovarian cancer families attending a tertiary high-risk familial gynecologic cancer clinic. This was a retrospective case-control analysis of high-risk women who underwent RRSO. Cases were all women detected to have occult lesions (tubal atypia/carcinoma in situ/cancer) between January 2005 and December 2010. Control subjects were all women with normal tubal/ovarian histology between August 2006 and December 2007.

Conclusions: This report highlights the potential impact of electrosurgical thermal injury on detection of occult tubal pathology following RRSO. It is important for surgeons to avoid thermal injury to the distal end of the tube.

Epigenetic modification and cancer: mark or stamp? (BRCA/fallopian tube....)

Epigenetic modification and cancer: mark or stamp?

Abstract

Hypotheses are built upon data, but data require hypotheses before they can be understood. The development of the ‘two-hit’ hypothesis of carcinogenesis was a key event in cancer genetics because it provided a testable model of how tumours develop. In this commentary on ‘Promoter hypermethylation patterns in Fallopian tube epithelium of BRCA1 and BRCA2 germline mutation carriers’ by Bijron et al. published in the February 2012 issue of Endocrine-Related Cancer, the need for new grammar and some new hypotheses in epigenetics is discussed. Meanwhile, data suggesting an important role of epigenetic modification in the cause, progression and treatment of cancer continues to accumulate............

Introduction

In hereditary tumours, the first hit occurs in the germ line, whereas in non-hereditary tumours, the first hit occurs in the cell from which the tumour arises. The second hits are always somatic, and can inactivate the second allele in various different ways. The development of the ‘two-hit’ hypothesis of carcinogenesis was a key event in cancer genetics because it provided a testable model of how tumours develop (Knudson 1971, 1978). Although there have been extensions and revisions to the basic model (Tomlinson et al. 2001), the essential elements of the basic hypothesis remain intact, 40 years on. In the original ‘test case’ of RB-1 mutations in retinoblastoma, these events were physical alterations in the structure of the chromosome or gene (Cavenee et al. 1983), and the perception was such that physical changes put a ‘stamp’ on the tumour that could be detected by examination of genomic DNA.............

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abstract: Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma.

Validation of an Algorithm for the Diagnosis of Serous Tubal Intraepithelial Carcinoma

Abstract

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The κ value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting.

abstract: Clinicopathologic Characteristics and Survival in BRCA1- and BRCA2-Related Adnexal Cancer: Are They Different?

Abstract

Objective:  

Our aim was to examine the clinicopathologic characteristics and survival of ovarian, tubal, and peritoneal (further denoted "adnexal") cancer in BRCA1 compared with BRCA2 carriers.

Methods: A consecutive series of adnexal cancers in BRCA1/2 mutation carriers diagnosed in 1980 to 2010 at the University Medical Center Groningen was analyzed.

Results: 

We evaluated 55 BRCA1- and 16 BRCA2-related adnexal cancers, consisting of 51 ovarian, 13 tubal, and 7 peritoneal cancers. Peritoneal cancer was restricted to BRCA1 carriers. Ovarian and tubal cancer was equally present in both carrier groups. Median age at diagnosis was younger in BRCA1 compared with BRCA2 carriers (50 vs 54 years; P = 0.03). No other clinicopathologic differences were found. Regarding survival, a nonsignificant trend was noted for BRCA2 carriers to have fewer relapses, a longer time to first relapse, and a longer disease-free and overall survival.

Conclusions: Except for age at diagnosis and prevalence of peritoneal cancer, no significant clinicopathologic differences were found between BRCA1- versus BRCA2-associated adnexal cancer. On survival, it might be suggested that BRCA2 carriers have a more favorable outcome than BRCA1 carriers, marked by fewer relapses, a longer time to first relapse, and a longer disease-free and overall survival.

abstract: Phase I clinical trial of alternating belotecan and oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer (total 6 patients/phase 1)

Abstract: 
This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer.

"....Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses."

"Primary peritoneal" high-grade serous carcinoma is very likely metastatic from serous tubal intraepithelial carcinoma: Assessing the new paradigm of ovarian and pelvic serous carcinogenesis and its implications for screening for ovarian cancer.

CONCLUSIONS: At least half the cases of primary peritoneal high-grade serous carcinoma are associated with intraepithelial carcinoma of the fallopian tube, usually involving the fimbriae. These findings support the view that, like "primary ovarian carcinoma," what has been traditionally classified as "primary peritoneal carcinoma" is probably derived from occult high-grade serous carcinoma in the fallopian tube. These findings have important implications for ultrasound screening trials for ovarian cancer which are based on the assumption that an enlarged ovary is a very early manifestation of disease.

Mucosal carcinoma of the fallopian tube coexists with ovarian cancer of serous subtype only: a study of Japanese cases

Abstract
Previous studies in Western countries have revealed that mucosal carcinoma of the fallopian tube frequently coexists with pelvic (ovarian, tubal, and peritoneal) serous carcinomas, and early tubal carcinoma is now regarded as a possible origin of these tumors. However, the relationship between early tubal carcinoma and non-serous ovarian cancer, such as clear cell adenocarcinoma, has not been studied in detail. In this study, we sought to examine the coexistence of mucosal carcinoma of the fallopian tube in Japanese ovarian cancer cases. We submitted the fallopian tubes in toto for histological examination in 52 ovarian carcinoma cases and three peritoneal serous carcinoma cases. The ovarian tumors included 12 serous adenocarcinomas, 23 clear cell adenocarcinomas, nine endometrioid adenocarcinomas, three mucinous adenocarcinomas, and four mixed epithelial carcinomas. Mucosal carcinoma of the fallopian tube did not coexist with non-serous adenocarcinoma (n = 40). In contrast, mucosal carcinoma of the fallopian tube was observed in six cases of ovarian serous adenocarcinoma and one case of peritoneal serous adenocarcinoma. In these cases, the p53 immunophenotypes were similar in tubal lesions and invasive ovarian or peritoneal carcinomas. Tumors were negative for p53 in four of seven cases, and one of the p53-negative serous adenocarcinomas showed low-grade morphology. We believe that some ovarian and peritoneal serous adenocarcinomas develop from early tubal carcinomas. However, it should be noted that early tubal carcinomas are not always p53-positive immunohistochemically. Finally, it is unlikely that early tubal lesions are involved in the carcinogenesis of clear cell adenocarcinoma and other non-serous adenocarcinomas.

media - Ovarian cancer researchers request practice changes to protect against ovarian cancer: deaths could be reduced 50 percent over 20 years

"They are asking all BC gynecologists to change surgical practice to fully remove the fallopian tube when performing hysterectomy or tubal ligation. Current practice leaves the fallopian tube in place for many types of hysterectomy and tubal ligation. This is a matter of convention, not need."

Fallopian tube removal cuts ovarian cancer risk - Yahoo! Canada News

"...But Dr. Sarah Finlayson, a gynecological oncologist at Vancouver General, said recent research has shown that at least half of the cases of the deadliest form of ovarian cancer originate in the fallopian tubes — not the ovaries.
That malignancy, called a high-grade serous tumour, represents about 70 per cent of all ovarian cancers. And because there is no screening test and symptoms can be non-existent or vague, diagnosis too often occurs once the cancer is at an advanced stage and has spread to other tissues.
"Something that we had thought of in the past as an ovarian cancer is really, in fact, a fallopian tube cancer," said Finlayson. "Removing the fallopian tube becomes a way of preventing these cancers."...cont'd

Objective To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation (abstract)

Objective

To identify risk factors for the presence of a non-invasive lesion of the fallopian tube in women with a BRCA1 or BRCA2 mutation.

Conclusion

The prevalence of tubal p53 signature and TIC (tubal intra-epithelial carcinoma)  increases with age at salpingectomy and with BMI. Oral contraceptive use is associated with a decrease in the prevalence of TICs.

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutation

Reminder on stats: < 1.0 is decreased risk; > 1.0 is increased risk; OR=overall risk; edited some stats for ease of reading - see abstract/read more:

Conclusions

Parity and oral contraceptive use are associated with reduced risks of fallopian tube cancer. In contrast, hormone replacement therapy may be associated with an increase in the risk of fallopian tube cancer.

Abstract/full free access | Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival

Background

Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.

 Conclusions

AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.

"While several immunohistochemistry (IHC)-based studies have confirmed widespread AR (androgen receptor)expression in EOC, data describing it as a prognostic biomarker are relatively sparse. One study describing a large series of tumors (n=322), found no association between AR protein expression and clinical outcome, however individual histological subtypes were not examined. Increased levels of AR mRNA
have been described in cells from normal ovarian surface epithelium as compared to ovarian cancer cells, the majority of which were derived from serous tumors. We are, however, unaware of any studies describing AR expression in fallopian tubes, from which a substantial but not yet not fully appreciated proportion of serous ovarian carcinomas are thought to arise.."

Risk factors for carcinoma of the fallopian tube in women with and without a germline BRCA mutationBRCA,mutation

free full access: A phase-I trial of pemetrexed plus carboplatin in recurrent ovarian cancer.

for full free access click on 'pdf'

Abstract: Risk factors for epithelial ovarian cancer by tumor dominance, a surrogate for cell of origin -Cancer Prevention Research

"Although limited by small case numbers, our results suggest that tubal ligation may be more strongly associated with tumors of ovarian origin, while family history of ovarian cancer primarily increases risk of tumors of tubal origin. Characterizing risk factor relationships by tumor dominance may elucidate how these exposures alter risk and help to improve prevention efforts."