Mainstreaming genetic counseling for BRCA testing into oncology clinics – Indian perspective

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%–65% cumulative lifetime risk of developing breast cancer and an 11%–39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years. In India, the prevalence of BRCA1/2 mutation varies from 2.9% to 38% among families with genetic predisposition toward hereditary cancers. With HBOC being linked to early-onset breast cancer and increased susceptibility to other cancers, early screening for BRCA mutations has become a pressing need. Though genetic counseling (GC) for BRCA mutation testing is common in most of the developed countries, India still faces several challenges in mainstreaming the same. Many barriers to effective GC for BRCA testing are unique to India. There is a dearth of trained geneticists which puts the pressure on oncologists to give GC for which they neither have the time or training. Presence of multiethnic/linguistic population acts as a major hindrance along the way toward development of robust predictive and effective GC models for BRCA testing. The current review discusses the need and benefits of GC in breast cancer prevention, through BRCA testing, from an Indian perspective. The functional framework of GC and the role of genetic counselors are discussed in detail. In addition, importance of GC training and role of a multidisciplinary team approach for mainstreaming pre- and post-BRCA test GC is highlighted.

Encysted hydrocele of the cord presenting as a groin swelling in an adult: a case report.

The hydrocele of the cord presents as a translucent swelling in the inguinal canal or scrotum, separately above the testis. It is more commonly seen in childhood and is rare in adults. It comprises of two varieties based on their communication with the peritoneal cavity. The encysted hydrocele of the cord does not communicate with the peritoneal cavity above or the tunica vaginalis below. The other variety known as the funicular hydrocele communicates with the peritoneal cavity above but does not communicate with the tunica vaginalis below. This case report presents the case of a 22 year old young male with an inguinal swelling. Clinical differential diagnoses were of inguinal lymphadenitis, encysted hydrocele of the cord and irreducible hernia. The aim of this report is to highlight the role of ultrasonogram in early diagnosis and surgical excision as mainstay of treatment.

Comparison of usefulness of topical capsicum ointment with diclofenac gel in the treatment of mastalgia

Objective: to compare the usefulness of topical capsicum ointment with diclofenac sodium gel in the treatment of mastalgia

Study design: comparative study

Place and Duration of study: ward-3 Surgical Unit I, Jinnah Postgraduate Medical Center Karachi, from September 2011 to March 2012

Methodology: women with mastalgia were assigned into two groups. Group A received topical diclofenac sodium gel while group B received capsicum ointment. Severity of pain was assessed on visual analogue scale [VAS] of 0-10. Chi-square test was applied to compare the outcome of two groups and p-value <0.05 was considered statistically significant

Results: a total of 72 women were enrolled. Each group had 31 participants. The mean age of the patients was 27.47 +/- 8.08 year [95% CI: 25.57 to 29.37]. Duration of disease was 38.66 + 9.34 months and 39.20 +/- 11.12 months in group A and B respectively. Of total study participants, 41[57%] improved with treatment. In diclofenac group more patients reported pain relief than capsicum group [69.4% vessus 44.4%-p-value:<0.001]

Conclusion: Topical diclofenac sodium and capsicum ointment both were found effective but diclofenac sodium was more effective in relieving mastalgia

Relationship between PTEN and gestational diabetes in Asian Indians womens

Gestational diabetes mellitus [GDM] is defined as glucose intolerance of variable severity with onset of first recognition during pregnancy. GDM occurs in at least 30% of women with a family history of T2DM/GDM, suggesting that some women are genetically predisposed to develop GDM. Phosphatase and tensin homolog [PTEN] on chromosome 10 is a tumor-suppressor gene. Studies have demonstrated that PTEN dysfunction affects the function of insulin. However, the relationship between GDM and PTEN has not been studied. The aim of the present study was to investigate the relationship between PTEN and GDM in Asian Indian women. The case-control study used PCR-RFLP analysis to assess the PTEN?9C/G polymorphism in 150 GDM cases and 150 controls [non-GDM]. No alleles or genotypes were detected at statistically significant frequencies. All subjects were normal, and no variants were detected in any of the pregnant women. In conclusion, PTEN has no role in GDM, consistent with previous studies

Accuracy of risk of malignancy index in preoperative evaluation of adnexal masses

To evaluate the diagnostic accuracy of risk of malignancy index [RMI] in discriminating between benign and malignant adnexal masses taking histopathology as the gold standard. Validation study. The study was done at the department of Obstetrics and Gynaecology, Government Lady Aitchison Hospital, Lahore from January 2009 to July 2009. Total 60 patients were included in this study. Risk-of-malignancy Index level [RMI] <200 was taken as benign and RMI >200 was taken as malignant. Histopathology report was followed after surgery. Mean age of the patients was found to be 41.03 +/- 8.59 years. The results of RMI were compared with the histopathology with report at histopathology, 91.7% patients had benign masses and 8.3% patients had malignant masses. At RMI, 88.3% patients had benign masses and 11.7% patients had malignant masses. While RMI findings were confirmed with diagnosis made on histopathology the sensitivity, specificity and diagnostic accuracy were found to be 100%, 96.3%, 96.6%, respectively. Positive and negative predictive values of RMI were 71.4%, and 100%, respectively. RMI is an appropriate tool for diagnosing adnexal masses with high risk of malignancy and referring to specialist gynecological centers for suitable surgical operations

Knowledge of integrated management of neonatal and child illness [IMNCI] in final year medical students

To assess and compare the knowledge regarding Integrated Management of Neonatal and Child Illness [IMNCI] in final year medical students of two private and two public sector universities in Karachi, Pakistan. A cross-sectional Knowledge, Attitude and Practice [KAP] study was conducted in four different medical universities of Karachi using a self administered questionnaire, comprising of 20 questions. The sample size of 240 was selected, out of which 184 students responded positively. The mean age of students was M=22.9 [S.D= 0.88]. Basic knowledge was defined as students answering at least half of the questions correctly whereas partial knowledge was defined as students who could answer at least one option correctly. The Data was analyzed using SPSS 17. The study was commenced in July 2011 and completed by September 2012. Out of the respondents, 80.4% of the students had basic knowledge [being able to answer 50% or more of the questions correctly] of IMNCI. Of both the sectors, basic content knowledge was more in the public sector universities as compared to private sector universities. The hypothesis that more than 50 percent of the students will have basic knowledge of IMNCI was proven to be correct. It was shown that students of the public sector universities had relatively more knowledge; however more students have partial knowledge then complete knowledge. Although basic knowledge was found to be more in the students of public sector institutes, knowledge of IMNCI practice was correct in more students in the two private universities

Prevalence of depression in medical and pharmacy students in two private sector universities of Karachi, Pakistan

Depression is a debilitating psychological condition in young people which can affect their growth, health and performance laying profound effects on their quality of life. The objective of the study is to assess the degree of depression with feature specifications and diurnal variations in medical and Pharm. D students in two private sector universities of Karachi, Pakistan. Severity of symptoms was more frequently assessed as psychological anxiety [9.3%] than somatic anxiety [1.3%]. General feeling of wellbeing was distorted in 57.2% students with varying degrees of severity. The psychogenic condition implicated the quality of sleep [19.6%] and latency of sleep [34.3%]. Appetite was affected adversely in 23.3% students with mild symptoms, whereas 5% reported severity of symptoms. Severity of symptoms was majorly assessed in late insomnia. We concluded that the symptoms of depression in young individuals were fairly common with both psychogenic and somatic feature specifications

Gastrotomy in experimental natural orifice transluminal endoscopic surgery using technique of percutaneous endoscopic gastostomy / 中华消化内镜杂志

Objective To evaluate the feaibility and safety of gastrotomy in natural orifice transluminal endoscopic surgery(NOTES)using technique of percutaneous endoscopic gastostomy(PEG).Methods To retrospectively investigate and compare the success rate,complications and procedure time of gastrotomy in NOTES of dogs between PEG-like approach(PEG group,n =20)and needle knife incision(needle knife group,n =18).Results Gastrotomy was successfully performed in all animals.No mass bleeding or organ injury was observed in PEG group,while one dog in needle knife group encountered mass bleeding,and injuries to the adjacent organs were found in 3 others(0％ in PEG group vs.22％ in needle knife group,P ＜ 0.05).The procedure time of gastrotomy in PEG group was longer than that of needle knife group (15.0±3.7 min vs.6.0 ± 1.1 min,P ＜0.05).Conclusion Compared with the techniqued of needle knife incision,gastrotomy using PEG-like approach in NOTES is safe and feasible.

Biliary passage dilator assisted percutaneous endoscopic gastostomy in natural orifice translumenal endoscopic surgery / 中华消化内镜杂志

Objective To explore the feasibility and safety of the biliary passage dilator assisted percutaneous endoscopic gastostomy(PEG)in natural orifice translumenal endoscopic surgery(NOTES).Methods Eleven hybrid dogs were recruited to the study.One dog was used for pilot study of biliary passage dilator assisted PEG.The rest ten were divied into 2 groups randomly(5 per group), receiving conventional PEG and biliary passage dilator assisted PEG, respectively.The efficacy and safety of these 2 methods in NOTES were compared.Two weeks later, routine gastroscopy was performed to detect the healing of luminal incision and all animals were sacrificed to explore the possible complications in the abdominal cavity.Results With the assistance of the biliary passage dilator, successful transgastric access to the peritoneal cavity was achieved in the pilot study.Biliary passage dilator assisted PEG was completed in all the 5 dogs of the experimetal group, while tradional PEG succeded in only 4.The average transgastric puncture time in the biliary passage dilator assisted PEG(7.0 ± 1.7 min)was significantly shorter than that of conventional PEG (11.0 ± 3.2 min, P ＜ 0.05).Nine dogs survived for 2 weeks postoperatively without loss of weight or peritonitis.Endoscopy showed transgastric puncture healed well.Autopsy revealed no gross adhering zone,bleeding, injury of adjacent organs or abcasses.Conclusion Compared with the conventional PEG, the biliary passage dilator assisted PEG shows the advantages of reduced difficulty and shoter time of puncture without any apparent complications.There is a good prospect of its application in NOTES.

Polymorphic [CAG]n repeats in the androgen' receptor gene: a risk marker for endometriosis and uterine leiomyomas

Endometriosis and uterine leiomyomas are leading hormone responsive, benign uterine disordders responsible for high morbidity in women of reproductive age group. A polymorphic [CAG]n repeat length located in exon 1 of the androgen receptor [AR] gene has been proposed as a risk marker for both endometriosis and leiomyomas in some ethnic groups. The present study was carried out to assess the frequency of AR [CAG]n repeat polymorphism as a risk marker for endometriosis and uterine leiomyomas in Asian Indian women. DNA was isolated from peripheral blood samples of 331 subjects, which include 90 endometriosis cases, 140 cases of leiomyomas and 101 healthy age- and sex-matched controls. PCR was carried out to amplify exon 1 of the AR gene. All the PCR amplicons were analysed initially on 2% agarose gel electrophoresis, folllowed by bidirectional sequencing to calculate the number CAG repeats in individuals. The CAG repeat ranges detected in endometriosis cases were 4-33 [Mode-19] and in leiomyomas cases 5-34 [Mode-20], whereas in controls it was 5-34 [Mode-22]. A distinct variation was observed in the three groups at 14, 18, 19, 20 and 22 [CAG]n repeats, which were statistically analyzed using chi-square and odds ratio tests. 19 CAG repeats were found to be higher in endometriosis cases [19.09%] when compared with conttrols [9.04%], while 20 CAG repeats were higher in leiomyomas cases [14.02%] compared to controls [6.14%]. A statistically significant [P < 0.05] association was observed in 19 and 20 CAG repeats in endometriosis and leiomyomas, respectively. This is the first report from an Asian Indian population proposing that 19 and 20 CAG repeats of the AR gene are associated with endometriosis and leiomyoma and can be regarded as high-risk markers

Early experience of sentinel lymph node biopsy in breast cancer

To assess the results of sentinel lymph node biopsy in breast cancer. Case Series. Surgical Ward 3, Jinnah Postgraduate Medical Centre Karachi, from April 2007 to March 2009. In this study patients with biopsy proven carcinoma breast and clinically negative lymph nodes in the axilla were included. Patients with history of previous breast surgery, clinically palpable lymph nodes, Stage IV disease, bleeding disorders, chronic liver disease or history of allergic reaction to the dye were excluded. The study patients underwent sentinel lymph node mapping and dissection. One ml of gentian violet or methylene blue dye injected into the peritumoral area followed by one minute massage. Simple mastectomy or wide excision with axillary clearance was done after 30 minutes of injection. This study was conducted on 35 patients with the age range from 28 years to 68 years. In all the patients diagnosis was infiltrating ductal carcinoma. Wide local excision with axillary clearance was possible in only two patients with clinically stage 1 disease. In rest of the patients simple mastectomy with axillary clearance was done. According to the tumor size; T1 was observed in 15 patients, 72 in nine, T3 in six and T4 in five patients. In all patients [n 15] with T1 tumor, stained lymph node was positive in eight patients while tumor metastasis in the remaining lymph nodes removed by axillary clearance showed involvement in six patients. In patients with T2 masses, tumor involvement was seen in both groups of lymph nodes in six patients. In three patients with T4 tumor, sentinel lymph nodes were negative for tumor metastasis however in rest of the lymph nodes tumor involvement was seen in four patients. In patients with T3 masses, three showed involvement of the entire axillary lymph node group and sentinel lymmph node as well. If sentinel lymphnode is involved by the tumor, axillary clearance should be done irrespective of the tumor size. Sentinal node biopsy should be avoided in patients with T4 lesions

Endoscopic assessment of effacement of balloon waist during pneumatic dilatation of primary achalasia cardia under topical anesthesia

Balloon dilatation of Primary Achalasia Cardia [PAC] is usually performed under antegrade endoscopic guidance, with conscious sedation. The main goats of this prospective study were to assess the safety and efficacy of pneumatic dilatation without conscious sedation and to determine the endoscopic signs of effacement of the balloon "waist". Pneumatic dilatation was successfully performed as outdoor procedure without conscious sedation in patients [n= 25; mean age 42.56 years] with endoscopic and radiologic diagnosis of PAC. Immediate relief of symptoms was observed in 23 [92%] cases. Effacement of the balloon "waist" under endoscopic vision was appreciated in all cases in the present study. Common complications of pneumatic dilatation were chest pain in all [100%] subjects and mild local bleeding in 17 [68%] patients. There was no cancellation of procedure. Re-dilatation was required in 2 [8%] cases. The duration of follow-up was from 6 weeks to 23 months. Pneumatic dilatation of PAC can be safely performed as same day procedure, without conscious sedation. Obliteration of the balloon "waist" can be readily determined by antegrade "endoscopic assessment of stretch on the lower oesophageal sphincter [EASL]"

cadaveric study of ossification of spinal ligaments

A Cadaveric study of ossification of spinal ligaments. A descriptive study. Place and duration of study' University College of Medicine and Dentistry, Fatima Jinnah Medical College Lahore, FMH College of Medicine and Dentistry, Lahore. The study lasted from January 2002 till March 2004. A cadaveric study was done on vertebral columns of 50 skeletons Skeletons were studied in anatomy departments of different medical colleges. Each vertebral column was observed for any ligamentous ossification, and frequency of ossification of spinal ligaments was noted. Result: It was seen that in 2% of cadaveric skeletons spinal ligaments were ossified. This ossification was observed in thoracic and lumbar regions. Although ossification of spinal ligaments is a rare occurrence: by correlating this cadaveric study with some of the clinical studies the possibility of ossified spinal ligaments should he considered in evaluation of back pain, dysasthesia, urinary hesitancy, myelopathy, dysphagia and dyspnoea

(CTG)n expansion at DMPK locus seen only in muscle tissue: a novel case.

Triplet repeat expansion in 3 untranslated region of myotonic dystrophy protein kinase (DMPK) gene has been implicated as causative in myotonic dystrophy (DM). In cases of DM, high levels of somatic instability have been reported, in which inter-tissue repeat length differences as large as 3000 repeats have been observed. This study highlights the inter-tissue (CTG)n expansion variability at the DMPK locus. Molecular analysis of DMPK gene, encompassing the triplet repeat expansion, was carried out in 31 individuals (11 clinically identified DM patients, 20 controls). All controls showed a 2.1kb band (upto 35 CTG repeats), while four cases exhibited an expansion (>50 repeats). A novel observation was made in one case, wherein the DNA from lymphocytes showed a normal 2.1kb band while the muscle tissue DNA from the same patient was heterozygous for normal and 4.3 kb band (>700 repeats). Our results suggested that because inter-tissue variability existed in the (CTG)n repeat number at DMPK locus, an attempt should be made to evaluate affected tissue along with blood wherever possible prior to making a final diagnosis. This is important not only for diagnosis and prenatal analysis, but also while providing genetic counseling to families.