Surgical treatment of hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome)

Abstract

The surgical management of the Lynch syndrome patient with colorectal cancer needs to be individualized. Because of the increased incidence of synchronous and metachronous colorectal neoplasms, most favor an extended resection at the time of diagnosis of colorectal cancer. Age of diagnosis, stage of the tumor, co-morbidities, surgical expertise, surgical morbidity, and patient wishes should be taken into account when considering a surgical procedure. There are no prospective randomized trials or retrospective trials suggesting that patients undergoing an extended procedure have a survival advantage compared to those undergoing segmental resection. In retrospective studies it has been demonstrated that patients undergoing extended procedures will develop less metachronous colorectal neoplasms and will undergo less subsequent surgical procedures related to colorectal cancer. In females abdominal hysterectomy and bilateral salpingoophorectomy should be considered at the time of surgery for colorectal cancer.

MDCH- An Update of the Lynch Syndrome in the Quest for Reducing Morbidity and Mortality (note references to ovarian/family history/BRCA/EPCAM...)

Blogger's Note: Dr Lynch's presentation includes what may be higher than anticipated #'s of extracolonic cancers

slides/video

open access: Breast Cancer Research | Abstract | Risk of breast cancer in Lynch syndrome: a systematic review

open access

Introduction
Lynch syndrome, formerly known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC) [1], is an autosomal dominantly inherited disorder of cancer susceptibility caused by germline mutations in the DNA mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and
PMS2. The prevalence of individuals who carry a pathogenic germline mutation in one of these genes in the population is estimated to be, depending on various assumptions, from 1 in 370 to 1 in 3,000 [2-4]. Though rare, mutation carriers have a substantial burden of
increased risks of cancers of the colon, rectum, endometrium, stomach, ovary, ureter, renal pelvis, brain, small bowel, and hepatobiliary tract which generally occur at younger ages than for the general population [5].......

"....There is only one prospective study demonstrating an elevated risk of breast cancer in Lynch syndrome and further independent
evidence is required to confirm the findings. Given the previous epidemiological studies used different selection methods, subjects and statistical methods, a meta-analysis is not appropriate to generate a pooled estimate for breast cancer risk.....

Conclusions

Since breast cancer is relatively common disease in the general population, more precise estimate of risk and gene-specific risks will need to utilize large prospective cohort studies with a long follow-up. While current data is inconclusive at a population level, individual tumor testing results suggest that MMR deficiency is involved with breast cancers in some individuals with Lynch syndrome.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Seth's Blog: Us vs. us

Seth's Blog: Us vs. us

Two In Three Cancer Patients Who Died In Hospital Wanted To Die At Home

 Blogger's Note: while the stats may vary, the presumption of 'dying at home' may be erroneous (see blog for more postings on this issue/debates)

media

open access: Biomarkers for the differentiation of anemia and their clinical useful

open access

Conclusion
Anemia is of multifactorial etiology, but it is to be hoped that by using the biomarkers described in this review, investigators will obtain a fuller understanding of the potential causes of anemia. Automated cell counters provide much useful information to point to potential causes of anemia, but no one method will ever be sufficient to describe the full etiology of anemia. Specific tests may confirm the underlying causes but anemia is the result of a complex interaction of events, which may be difficult to unravel. This review lists the biomarkers that can be used to determine the most likely causes of anemia, but the authors emphasize that anemia is the final stage in a deterioration in red cell synthesis to a point when anemia is defined. At that stage the factors associated with anemia may not fully reflect the circumstances that were responsible for the initial or the progress of deterioration in red cell synthesis.

press release:EGEN, Inc. Announces a Phase I Clinical Trial for Advanced Ovarian Cancer

press release

 March 19, 2013 /PRNewswire/ -- EGEN, Inc. today announced that it has recently initiated a Phase I clinical trial of its novel immunotherapy agent, EGEN-001, in combination with PEGylated liposomal Doxorubicin or Lipodox for the treatment of recurrent ovarian cancer.  The EGEN-sponsored trial is conducted by a network of researchers led by Gynecologic Oncology Group (GOG) at member institutions under an agreement between the GOG and EGEN, Inc.  Dr. Premal Thaker , of Washington University School of Medicine, is the Study Chair for the trial.......

Early Subspecialization and Perceived Competence in Surgical Training: Are Residents Ready?

Abstract

Presented at the Southern Surgical Association 124th Annual Meeting, Palm Beach, FL, December 2012.

Purchase $31.50

    

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Background

In order to understand how current surgical residents feel about their training, a survey focused on perceptions regarding early entry into a subspecialty and the adequacy of training was sent to selected residency programs in general surgery (GS).

Study Design

A 36-item online anonymous survey was sent to the program directors of 55 GS programs. The national sample consisted of 1,515 PGY 1 to PGY 5 categorical residents.

Results

The response rate was 45%. Overall, 80% were planning on pursuing a fellowship. The majority (63%) believed that the Residency Review Committee for Surgery and the American Board of Surgery should consider the shift to early subspecialty training. Almost 70% of respondents preferred a 3-year basic track followed by a 3-year subspecialty track. In response to the survey item, “Do you think a 5-year GS residency fully prepares you to practice GS?”, 38% of residents overall responded “no” or “unsure.”

Practical Issues in Palliative and Quality-of-Life Care

Abstract

"Although palliative care is not new to health care or to oncology, oncologists still struggle to maximize the value of this type of care across the entire care continuum and across the patient's trajectory of illness. When we don't use what may be the best tools for the job, at the right times in the care path, we miss opportunities to optimize patient and family coping, to limit suffering, and to ensure that our care plans are patient centered. In this article, we look at how we define palliative care and how the tools of palliative medicine can be used to enhance patient care in the outpatient oncology practice setting."

open access: Second primary cancers after adjuvant radiotherapy in early breast cancer patients

open access

Impact of beta blocker medication in patients with platinum sensitive recurrent ovarian cancer- a combined analysis of 2 prospective multicenter trials by the AGO Study Group, NCIC-CTG and EORTC-GCG

Abstract

CONCLUSIONS:

In this series of recurrent platin-sensitive ovarian cancer patients it could not be confirmed that beta blocker treatment was associated with better or worse outcome.

OBJECTIVE:

Retrospective analyses suggest that the treatment with beta blocker improves survival in patients with breast cancer and melanoma. The aim of this study was to investigate the impact of medication with beta blocker in patients with recurrent ovarian cancer.

METHODS:

Included patients received treatment within two prospective clinical trials: AGO-OVAR 2.4 phase I trial (Carboplatin/ Gemcitabine; N=25, protocol AGO-OVAR 2.4) and AGO led Intergroup phase III trial (Carboplatin vs Carboplatin/ Gemcitabine; N=356, protocol AGO-OVAR 2.5, EORTC-GCG, NCIC CTG). Concurrent medication was documented after every cycle and thorough monitoring was conducted.

RESULTS:

During the studies 38 patients (9.97%) received a beta blocker as co-medication. Patients treated with beta blockers were significant older than patients not treated with beta blockers. Response rates to chemotherapy were not different between patients treated with beta blockers and those who were not.

open access: A Case of Stage III c Ovarian Clear Cell Carcinoma: The Role for Predictive Biomarkers and Targeted Therapies

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  Ovarian cancer treatment presently does not reflect molecular differences in histologic subtype. Ovarian clear cell carcinoma (OCCC) exhibits several differences in terms of molecular pathogenesis and tumor behavior from the more common, chemosensitive, serous carcinomas, which makes OCCC a candidate for targeted therapies. A 53-year-old Japanese woman was diagnosed with stage IIIc ovarian clear cell adenocarcinoma with marked chemoresistance to conventional regimens. She demonstrated a partial response to a multikinase inhibitor. The tumor was resistant to PI3K/mTOR pathway inhibitors despite harboring a PIK3CA mutation. The present case suggests a role for targeted therapies in the treatment of OCCC and a need for the identification of biomarkers that will predict response to targeted therapies. 

Ovarian epithelial tumors and reproductive factors: a systematic review

Abstract

PURPOSE:

The aim of this systematic review is to summarize the current knowledge about the etiology and pathogenesis of borderline tumors ovarian cancer with special emphasis on the role of endocrine treatments and reproductive factors to establish a foundation for future studies.

The Acceleration in Papillary Thyroid Cancer Incidence Rates is Similar Among Racial and Ethnic Groups in the United States

Abstract

CONCLUSIONS:

Although the lowest rates of thyroid cancer are observed in blacks, the greatest rate of acceleration is occurring in black females. Our data also show that the rate of papillary thyroid cancer will continue to surpass rates of ovarian cancer, and in white women: it is projected to be more incident than colorectal cancer as well; and in Hispanic and Asian/Pacific Islander women, rates of papillary thyroid cancer are projected to be higher than lung, colorectal, and ovarian cancers in the near future.

Cytoreductive Surgery and Hyperthermic Intrap... [Ann Surg Oncol. 2013] - PubMed - NCBI

Abstract

CONCLUSIONS:

CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.

BACKGROUND:

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients.

METHODS:

Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS.

RESULTS:

Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n = 39), colorectal cancer (n = 28), primary peritoneal (n = 6), appendiceal cancer (n = 20), and mesothelioma (n = 7).

Proteomic analysis of differential protein expression by brain metastases of gynecological malignancies

Abstract

Brain metastases of gynecological malignancies are rare, but the incidence is increasing. Patients with brain metastases have a poor prognosis, therefore early detection and optimal management is necessary. In order to determine a new biomarker, we aimed to identify proteins that associated with brain metastases. We investigated proteins associated with brain metastases of gynecological malignancies in three patients who underwent surgical resection (stage IIb cervical cancer, stage Ib endometrial cancer, and stage IIIb ovarian cancer). Proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples of the primary tumors and brain metastases, which were analyzed by liquid chromatography with tandem mass spectrometry.

Clinical Trials of Neoadjuvant Chemotherapy for Ovarian Cancer: What Do We Gain After an EORTC Trial and After Two Additional Ongoing Trials Are Completed?

Abstract

 The aim of neoadjuvant chemotherapy is to reduce the tumor volume or spread of the disease before the main treatment, and it could possibly make the main procedures easier or less invasive. Although the standard therapeutic strategy for advanced ovarian cancer is a maximum primary debulking surgery followed by chemotherapy, a European Organisation for Research and Treatment of Cancer (EORTC) prospective randomized trial demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to the standard procedure. This study raised a number of controversies, particularly regarding the quality of debulking surgery. To solve the questions, we need to wait for the results of two additional ongoing randomized trials. However, the results of those two trials must be carefully assessed, because the quality of debulking surgery would significantly affect survival, and may make the interpretation of the trial results more confusing and difficult.

Sonographic predictors of ovarian malignancy

Abstract

PURPOSE.: To identify a combination of sonographic features that best predicts ovarian malignancy.
METHODS.: Subjects included 249 women who had a transvaginal sonogram for a pelvic mass at Brigham and Women's Hospital between December 2005 and February 2010. Subjects underwent surgery for removal of the mass and pathologic diagnosis was available. Images were reviewed retrospectively by one sonologist blinded to diagnosis and clinical information. Twelve sonographic features were scored for each mass. The dataset was divided into training (n = 149) and testing (n = 100) sets. Within the training set, a stepwise logistic regression was used to weigh each variable and combination of features to identify those associated with malignancies. Using the results from the logistic regression analyses, we created a three-level risk stratification that was applied to the sonograms of subjects in the testing set to assess its ability to distinguish benign lesions from invasive and borderline cancers. RESULTS.: High risk lesions included all masses with internal vascularity. In our testing set, this feature was present in 9 out of 12 (75%) invasive cancers, 1 out of 6 (16.7%) borderline lesions, and 9 out of 82 (11%) benign masses. The intermediate risk level included lesions with a thick wall or thick septa without internal blood flow. This combination of features identified one additional invasive cancer and 5 out of 6 (83.3%) borderline tumors. Masses with low risk features had a 2/49 (4.0%) incidence of malignancy.
CONCLUSIONS.: In the absence of high or intermediate risk sonographic features, the risk of malignancy is low.

Journal of Ovarian Research | Full text | Longitudinal health-related quality of life assessment: implications for prognosis in ovarian cancer

Full text

Registration Now Open for OCNA's 16th Annual Conference - Discussion - Ovarian Cancer National Alliance Support Community - Inspire

Register by June 7th for preferred rate

Expert Says Diet Rules Can Fight Cancer — But Use Reason

Media

(U.S.) Study Criticizes Policy Penalizing Nonemergency ED Visits

Medscape

Access : Reply to '|Comment on Cancer incidence in the United Kingdom: projections to the year 2030'

no abstract

Comment on 'cancer incidence in the United Kingdom: projections to the year 2030'

Access

"We agree with Mistry et al. (2011) that quantification of the future burden of cancer incidence is vital in health-care planning and that where risk factors are not well understood (as is the case for the majority of haematological cancers) projections from observed trends provide the best available evidence to achieve this. However, we are concerned that the projections they have recently published for haematological cancers, and which are widely disseminated via the Cancer Research UK CancerStats website (Cancer Research UK, 2012), are not credible and are likely to be based on incomplete data."

Avastin Recalled Over Eye Infections - Physician's First Watch

media

Avastin (bevacizumab) unit dose syringes have been recalled after five intraocular infections were reported to the manufacturer. The cancer drug was used off-label to treat macular degeneration.
The syringes were sent to physicians' offices in Georgia, Louisiana, South Carolina, and Indiana beginning December 18, 2012.

LINK(S):

Manufacturer's news release (Free)