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Thursday, September 22, 2016

Dr. Matthew Yurgelun on Pathogenic Mutations in CRC (Lynch+BRCA) video 2:03



Dr. Matthew Yurgelun (video)

 Matthew B. Yurgelun, MD, Targeted Oncology, Yurgelun, Instructor in Medicine, Harvard Medical School, discusses a recent study which uncovered BRCA1 and BRCA2 mutations as possible risk markers for colorectal cancer.

The study examined 1000 individuals with colorectal cancer who were seen at the Dana Farber Cancer Institute. The goal of the study was to try and understand what the prevalence of hereditary cancer susceptibility syndromes was in this patient population.

It was determined that 10% of patients in the cohort had pathogenic mutations in one or more cancer susceptibility genes. There was a 3.1% prevalence of Lynch syndrome, which fits with what has been seen in established literature, says Yurgelun. Virtually all of the patients who had Lynch syndrome had tumors with high-level microsatellite instability and mismatch repair deficiency, illustrating that the current processes for identifying Lynch syndrome among colorectal cancer patients seems to work

What was novel about the study however, was that 7.1% of patients with colorectal cancer had a mutation in the non-Lynch syndrome cancer susceptibility gene, says Yurgelun. These are patients who wouldn't be picked up by typical tumor testing, as tumor testing really just looks for evidence of Lynch syndrome. The most common high-penetrance finding in the cohort beyond Lynch syndrome was, surprisingly, mutations in BRCA1 and BRCA2, says Yurgelun.  These are genes that are not traditionally linked to risks of colorectal cancer. 

(connections to ovarian cancer noted) Genetic Predisposition to Endocrine Tumors: Diagnosis, Surveillance and Challenges in Care



Note: examples of (some) highlighted syndromes connected to ovarian cancer

abstract

  In this review, we describe the main endocrine tumor manifestations found in familial cancer syndromes in an organ-based approach

Abbreviations:
ACC (Adrenocortical carcinoma), BWS (Beckwith-Wiedemann syndrome), CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium), CMV (Cribiform morullar variant of thyroid cancer), DTC (Differentiated thyroid cancer), ELST (Endolymphatic Sac Tumor), FAP (Familial Adenomatous Polyposis), FMTC (Familial Medullary Thyroid Cancer), GIST (Gastrointestinal Stromal Tumor), HPGL (Hereditary Paraganglioma Syndrome), HLRCC (Hereditary Leiomyomatosis and Renal Cell Cancer), LFS (Li-Fraumeni Syndrome), MEN1 (Multiple Endocrine Neoplasia type 1), MEN2 (Multiple Endocrine Neoplasia type 2), MNG (Multinodular Goiter), MNST (Malignant Nervesheath Tumor), MTC (Medullary Thyroid Carcinoma), NET (Neuroendocrine Tumor), NF1 (Neurofibromatosis type 1), NGS (Next Generation Sequencing), PCC (Pheochromocytoma), PGL (Paraganglioma), pHPT (Primary Hyperparathyroidism), PHTS (PTEN Hamartoma Tumor Syndrome), PPB (Pleuropulmonary Blastoma), RCC (Renal Cell Cancer), SDHx (Succinate Dehydrogenase Subunit (A,B,C,D,AF2)), SLCT (Sertoli Leydig Cell Tumor), VHL (von Hippel-Lindau Disease)

The Application of CA 125 in the Diagnosis and Follow up of Ovarian Cancer (Sudan)



open access

 DEFINITION OF STUDY AND STUDY AREA
Retrospective and hospital case study to assess the role
of CA125 levels in the diagnosis and follow up of ovarian
cancer, this study was done in the National cancer
institute (NCI), Wad Medani, Gezira state - Sudan. The
NCI is references hospital in central Sudan, established
in 1999 as the second cancer center in Sudan. It is the
only cancer center outside the capital of Sudan,
Khartoum. All discovered patients who attended NCI
clinic during the study period from Jan 2013 to June
2015, and was diagnosed histologically with ovarian
cancer and agreed to participate.

Risk-reducing surgery in BRCA 1/2 mutation carries: a point of view



open access
 Published online 2015 Nov 18
 
  Three separate questions can be raised to address the variety of approach: firstly, the choice of both risk-reducing surgies in patients with BRCA 1 / 2 mutation, secondly the optimal timing in performing surgical strategies and lastly the cost-effectiveness of prophylactic surgery.
 In conclusion, the management in BRCA 1 / 2 mutation carriers should be considered paramount and prevention strategies will be a dynamic area of research programs. The decision about prophylactic interventions remains highly personal, driven by women priorities. However the weight of the evidence suggests that the performance of both risk reduction surgeries could be a valid option to discuss with full knowledge of the facts.

Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review



abstract
 http://www.americanjournalofsurgery.com/pb/assets/raw/Health%20Advance/journals/ajs/logo.jpg

Background

Mutations in BRCA1 or BRCA2 genes results in an elevated risk for developing both breast and ovarian cancers over the lifetime of affected carriers. General surgeons may be faced with questions about surgical risk reduction and survival benefit of prophylactic surgery.

Methods

A systematic literature review was performed using the electronic databases PubMed, OVID MEDLINE, and Scopus comparing prophylactic surgery vs observation with respect to breast and ovarian cancer risk reduction and mortality in BRCA mutation carriers.

Results

Bilateral risk-reducing mastectomy provides a 90% to 95% risk reduction in BRCA mutation carriers, although the data do not demonstrate improved mortality. The reduction in ovarian and breast cancer risks using risk-reducing bilateral salpingo-oophorectomy has translated to improvement in survival.

Conclusions

Clinical management of patients at increased risk for breast cancer requires consideration of risk, patient preference, and quality of life.

The Role of Completion Surgery in Ovarian Cancer (J Obstet Gynecol India)



abstract
 

Introduction

Patients referred with inadequately staged ovarian malignancies present a clinical dilemma. We report our experience with completion surgery in ovarian cancer.

Aims and Objectives

To determine the benefits and risks of completion surgery in women with ovarian cancer who presented after having had inadequate primary surgery.

Methods

A retrospective case series of 30 women with ovarian cancer and one with fallopian tube cancer who had inadequate primary surgery underwent completion surgery at gynaecologic oncology unit in a tertiary level hospital in Tamil Nadu, India. Electronic medical records of patients with ovarian cancer who underwent completion surgery between January 2011 and September 2014 for ovarian were reviewed. Forty-five patients with initial inadequate surgery were identified of whom 31 underwent completion surgery; the remaining 14 did not return to our hospital.

Results

Thirty-one women with a mean age of 37 years (17–53) and median parity of 2 (0–4) with inadequately staged ovarian malignancy underwent completion surgery. Complex ovarian mass was the most common indication for initial surgery (94 %). The tumours were epithelial in 27 (87 %), germ cell in 3 (10 %) and sex cord stromal in 1 (3 %). In view of extensive disease at presentation, 19 % (6/31) were referred for neoadjuvant chemotherapy and underwent interval debulking. With regard to surgical complexity, 52 % (16/31), 38 % (12/31) and 10 % (3/31) underwent simple, intermediate and complex surgeries, respectively. Optimal cytoreduction (R0 and R1) was performed in 25 patients (81 %). Twelve (39 %) had upstaging of disease. Six patients required no further adjuvant treatment following surgical restaging. Complications included bladder injury (1), iliac vessel injury (1) and surgical site infections (2). During the study period of 45 months, 7 patients (23 %) presented with disease recurrence. There were 2 recorded deaths.

Conclusions

In inadequately staged ovarian malignancies, completion surgery should be considered based on the patients’ performance status and disease assessment. Considering the low specificity of imaging and Ca 125, completion surgery provides information to plan adjuvant therapy, besides allowing optimal cytoreduction but delays initiation of adjuvant therapy

Wednesday, September 21, 2016

Medical students revise their Hippocratic oath to reflect modern values



Medical news


Dell let its inaugural class select and revise their own oath earlier this month. The students decided to modify parts of a more humanistic oath written in 1964 by Dr. Louis Lasagna, a former dean at Tufts University School of Medicine.
“I will remember that I do not treat a fever chart, or a cancerous growth, but a sick human being,” the students vowed at their symbolic white coat ceremony. In these ceremonies, now common nationwide, students accept white coats, recite oaths, and commit to practice ethically as they begin their medical education.....
 
(wiki) Lasagna’s oath is the most popular one used by medical schools: 33 percent use it, according to a 2009 survey of 135 US and Canadian medical schools. Just 11 percent of the schools use the classical Hippocratic version, researchers found.
“I will remember that there is art to medicine as well as science, and that warmth, sympathy and understanding may outweigh the surgeon’s knife or the chemist’s drug,” Lasagna’s oath reads in part. Lasagna’s version also calls on doctors to admit when they don’t know the answer; prevent diseases; and to take responsibility not just for the patient’s health, but for the way an illness affects a person’s “family and economic stability.”

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions: A Systematic Review



open access

The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies.

Why Was This Study Done?

  • Research on medical treatments provides information on the efficacy of such treatments, and on side effects.
  • The balance between efficacy and side effects is important in assessing the overall benefit of a new treatment.
  • How much information on the side effects of medical treatments that is currently not published in journal articles is not known.

What Do These Findings Mean?

  • These findings suggest that researchers should search beyond journal publications for information on side effects of treatments.
  • These findings also support the need for the drug industry to release full data on side effects so that a complete picture can be given to health professionals, policy makers, and patients.

Getting Pharmacogenomics Into the Clinic



JAMA | JAMA Network

 Advocates of pharmacogenomics say the field is an emerging resource for improving patient safety. Since 2012, more than 1 million adverse drug events have been reported each year to the US Food and Drug Administration (FDA), “many of which might be preventable using PGx testing,” Geoffrey S. Ginsburg, MD, PhD, director of the Center for Applied Genomics and Precision Medicine at Duke University Medical Center, said in an email.

Ignite 

Patient Version

Clinicians

Helping Patients Make the Right Decisions - stats vs stories



The New York Times

 This is partly because while many doctors tend to think in stats, most people think in stories.

Titanic clash over CRISPR patents turns ugly



Nature News

 

Antioxidants and Cancer Prevention (what/who/when?)



National Cancer Institute

Index Sept 2016 Issue : International Journal of Gynecological Cancer



Current Issue

Clinical protocol: RCT - Lymphadenectomy in urothelial carcinoma in the renal pelvis and ureter



Clinical protocol
LYMPHADENECTOMY IN UROTHELIAL CARCINOMA IN THE RENAL PELVIS AND URETER- A RANDOMIZED INTERNATIONAL CLINICAL TRIAL ON LYMPHADENECTOMY IN UROTHELIAL CARCINOMA IN THE RENAL PELVIS AND URETER
August 2016

 Background:
Two out of three tumors in the upper urinary tract are located in the renal pelvis [1]. Muscle-invasive urothelial carcinoma is probably more common among tumors in the upper urinary tract compared to tumors in the urinary bladder. Thus, muscle-invasive tumors represent approximately 45 % of renal pelvic tumors [2,3] compared to 25 % of tumors within the urinary bladder. As in the bladder, lymph node metastases are rare in non-muscle invasive disease. Information regarding indications, extent and possible curative potential is currently lacking for lymphadenectomy in conjunction with nephroureterectomy for urothelial carcinoma in the upper urinary tract (UUTUC). There are, however, retrospective series with survival data for pa-tients with lymph node metastasis that report long term survival after surgery as monotherapy [4] with similar survival proportions as in bladder cancer with lymph node metastases after radical cystectomy. A retrospective study from Tokyo [5] was expanded to the only available prospective study, where 68 patients with UUTUC were submitted to template-based lymphad-enectomy [6]. Another retrospective study by the same Japanese group showed that 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups [7]. Tanaka N et al. reported recurrence rate after nephroureterectomy without lymphadenec-tomy at 1 and 3 years were 18.9 and 29.8 %, respectively [8].....

 Design: Prospectively randomized to template based lymphadenectomy or not, in patients with clinically muscle-invasive UUTUC in the renal pelvis or upper 2/3 of the ureter. One to one, controlled clinical trial. Patients will be randomly allocated into two groups, 183 patients in each group. Group A will be scheduled to receive routine standard open or robot assisted nephroureterectomy without lymphadenectomy except for clinically enlarged. Group B will be scheduled to receive mapped lymphadenectomy in conjugation with nephroureterectomy.