Critical Analysis of Advanced High-Grade Serous Epithelial Ovarian Cancer in Women: An Experience of 100 Cases from a Regional Cancer Center in Northeast India.

Debabrata BarmonOvarian cancer is the sixth most common cancer in women worldwide. Patients with ovarian carcinoma mostly present at an advanced stage with serous type of epithelial ovarian cancers, which is the most lethal of all pelvic malignancies. This study aims to critically analyze high-grade serous epithelial ovarian carcinomas in women from the Northeastern region of India and compare our data with Western literature to modify treatment strategies and improve survival outcomes. This hospital-based retrospective analysis involved data from the records of 100 women with high-grade epithelial ovarian cancer treated primarily with neoadjuvant chemotherapy followed by interval debulking surgery in the department of gynecologic oncology at a tertiary level regional cancer institute from January 2018 to December 2019. The demographic, clinical and pathological profile, and survival outcome were evaluated using descriptive statistics. The overall survival of the study population was calculated using Kaplan-Meier curves using SPSS software (version 24). The majority of women belonged to 41 to 55 years age group. At first presentation to the hospital, 89 and11% patients were in stage III and stage IV of disease, respectively. Clinically, 95% of women had ascites, and 18% had metastasis to lymph nodes. Distant metastasis to lungs and liver was present in 10 and 3% of cases, respectively. A substantial percentage (98%) of women had raised serum Ca125 > 1000 at baseline, ranging from 1,745 to 10,987 IU/mL. Almost two-thirds of the cases had partial-to-complete response to neoadjuvant chemotherapy (78%). In most of the women (72%), there was no residual disease at interval debulking surgery (R0), though 28% women had R1& R2 resection. The median overall survival time was 36 months. High-grade serous ovarian cancer is commonly seen in older age group, but its occurrence in younger population has also been observed. Early diagnosis is crucial in decreasing morbidity and mortality among these patients. Therefore, efforts should be made to identify risk factors for malignancy. Assessing each parameter of statistical information reflecting its own profile may be important for calculating the risk for the development of ovarian cancer, which can help in implementing preventive measures in the future.

The Interrelation Among Triad of Depth of Invasion, Perineural Invasion and Tumor Size in Squamous Cell Carcinoma of Tongue and Floor of the Mouth: An Analytical Appraisal.

Background: Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of the head and neck region. Squamous cell carcinoma of tongue has a peculiar behavior of occult and skips metastasis to regional lymph nodes. It occasionally occurs along with floor of the mouth. The purpose of this study is to evaluate the significance of correlation between, depth of invasion of the primary tumor, its proximity with the neurovascular bundle and subsequent perineural invasion and cervical lymph node metastasis in squamous cell carcinoma tongue and floor of the mouth and the sites involving both. Materials and Methods: A total of 108 patients with carcinoma tongue (59), floor of the mouth (20) and involving both together (29) who underwent treatment during January 2015 to June 2017 that were followed up until December 2019 were assessed. Out of 108 patients that were included in the study, 71 patients underwent primary surgery and 37 patients were inoperable (tongue-17, floor of the mouth-9 and involving both together-11). Results: Perineural invasion was seen in 15 cases of pT1-2 where depth of invasion was less than 1 cm and in 28 cases of pT3-4 where depth of invasion was more than 1cm (p-0.075). Skip metastasis was accounted for 61.9% overall. Conclusion: The triad of perineural invasion, depth of invasion and tumor size is interrelated and was responsible for cervical lymph node metastasis and prognosis of the disease. Obtaining clear deep margins of the tumor from the mucosal margin and removal of lympho-fatty tissue at the floor of the mouth is an important aspect which gives the indication about prognostic factors like depth of invasion, tumor size, cervical nodal metastasis and recurrence of the disease. High-grade tumors (T3-4), depth of invasion of tumor at 1 cm or > 1 cm, increase the propensity of perineural invasion highly.

An Overview of Vulvar Cancer: A Single-Center Study from Northeast India.

STUDY: Carcinoma vulva is a rare cancer of the female genital tract. It mostly presents in postmenopausal women. The treatment of vulvar cancer is surgery, chemoradiation, radiotherapy or a combination of all modalities. Here, we present a study of 33 cases of carcinoma vulva over a period of 2 years at a Northeast India regional cancer institute describing its demographic features and treatment outcomes. METHODOLOGY: A retrospective cohort study of vulvar cancer diagnosed at Northeast India regional cancer institute from January 2017 to December 2018. RESULTS: A total of 33 cases of biopsy proven carcinoma (Ca) vulva were studied. Maximum number of cases belonged to the age group: 60-69 years (39.4%). 66.67% cases had palpable inguinal lymph nodes at presentation, and 100% had squamous cell carcinoma on histopathology. Maximum number of cases belonged to stage III (44.8%), and least number of cases belonged to stage IV (10.3%) of FIGO 2009 staging of Ca vulva. 87.9% cases underwent treatment, and 12.1% were lost to follow-up. Out of the cases who underwent treatment, 55.2% cases were taken up for primary surgery and 44.8% cases for primary radiotherapy. 75% cases who underwent surgery received adjuvant radiotherapy. No complication was seen in patients post-radiation. But, 6.25% patients post-surgery developed lymphocyst and 18.75% patients developed wound necrosis (p > 0.05). CONCLUSION: Vulvar cancer is not a common malignancy of the female genital tract that presents in sixth and seventh decades of life and often with palpable inguinal lymph nodes. Though early stages of Ca vulva are treated by surgery, the incidence of immediate postoperative complications in our study was more as compared to post-radiotherapy. Also, maximum patients in the present study post-surgery received adjuvant radiotherapy. Thus, radiotherapy can be considered as the primary treatment modality for patients with early as well as advanced vulvar carcinoma.

Epidemiology of gynecological cancers in Kamrup Urban District cancer registry.

BACKGROUND: Cancers of the female reproductive system - namely cancer of the cervix, corpus uteri, ovarian, vulvar, vaginal, fallopian tube cancers and choriocarcinoma are an important cause of cancer morbidity and mortality among women worldwide. It is estimated to be the third most common group of malignancies in women. The comprehensive global cancer statistics from the International Agency for Research on Cancer indicate that gynaecological cancers accounted for 20% of the 14.1 million estimated new cancer cases and 8.2 million cancer deaths among women in the world in 2012. The estimation of cancer burden is necessary to set up priorities for disease control. Gynaecological cancers have increased in India and are estimated to be around 182,602 by the year 2020 constituting about 30% of the total cancers among women in India. Among these, cancer of the uterine cervix followed by ovary and corpus uteri are the major contributors. METHODS AND MATERIALS: Cancer is not notifiable in India, so method of collecting information on cancer was active with voluntary participation of different sources including major hospitals, diagnostic centers, state referral board and birth and death registration centers within registry area. RESULTS: A total of 3767 (44%) cases were registered in women out of the total number of 8561 cancer cases during the period from 2010-2014. In case of gynaecological cancers a total of 661 cases of cervical, ovarian and corpus uterine cancers were registered out of the total 3767 female cancer cases (17.5%) for the year 2010-2014.The annual average crude rate in women for all sites of cancer was 117.4 per 100000 population. The corresponding AARs was 166.6. CONCLUSIONS: Women's health issues have attained high concern in recent decades. Utmost efforts should be made to educate women in early cancer detection by creating awareness on risk factors and symptoms.

Effectiveness of ultrasonography and computed tomography in assessing thyroid cartilage invasion in laryngeal and hypopharyngeal cancers.

OBJECTIVE: To evaluate the adequacy of ultrasonography (US) and computed tomography (CT) in the assessment of thyroid cartilage invasion in patients with airway cancer. MATERIALS AND METHODS: Sixty-two consecutive patients referred to our institute underwent US and CT to stage laryngeal (n = 27) or hypopharyngeal (n = 35) cancer in this prospective study. Two radiologists, who were blinded to the patients' clinical histories and histopathology, evaluated thyroid cartilage invasion on US and CT separately and independently. Fifty-eight of the 64 patients (90%) underwent surgery. The histopathologic findings were used as the standard of reference for comparison and statistical analysis. RESULTS: For thyroid cartilage invasion, the detection rate on CT and US was 98%. CT achieved a sensitivity of 91% and a specificity of 75%, while US attained a sensitivity of 98% and a specificity of 75%. The difference between CT and US in terms of sensitivity was not statistically significant. CONCLUSION: US and CT have high diagnostic performance in evaluating thyroid cartilage invasion. US is more sensitive than CT in diagnosing invasion of the thyroid cartilage; however, the difference is not statistically significant. US can be used to solve the diagnostic dilemma of the presence or absence of cartilage invasion when CT is inconclusive, as CT is more widely used in staging laryngeal and hypopharyngeal cancers.

Magnetic resonance imaging in pre-operative staging of endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is one of the most common gynecological cancers and the fourth most common cancer in the female. Although clinical evaluation with diagnostic imaging has not yet proved to be accurate enough in the evaluation of tumor extent to replace surgical staging, it may enable optimization of the surgical procedure and a better tailored therapeutic strategy. This study will review the characteristic magnetic resonance imaging (MRI) findings in endometrial carcinomas in the pre-operative staging of endometrial carcinomas and compare it with the newly revised Federation of Gynecology and Obstetrics (FIGO) staging scheme of 2009 based on post-operative surgical histopathology. MATERIALS AND METHODS: It is a retrospective analysis of 36 patients diagnosed and treated for endometrial carcinoma in our institute from January 2009 to December 2012. RESULTS: Majority of the patients (61%) were between the age group of 41-60 years. Most of the patients (72%) were postmenopausal at the time of presentation. Most common histopathology of endometrial carcinoma was endometroid adenocarcinoma (27 patients, 75%). FIGO staging of 12 patients (85.7%) showed concordance with MRI Staging for Stage Ia, with up-gradation of two patients to Stage Ib. CONCLUSION: The information provided by MRI can define prognosis, help planning the surgical approach and identify those patients requiring neoadjuvant chemotherapy or radiation therapy.

Synchronous primary cancers in the head and neck region and upper aero digestive tract: Role of triple endoscopy.

BACKGROUND: Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers. AIM: The aim of this study is to see the role of endoscopy in the pre-therapeutic works-up of patients with the cancers in the head and neck region. MATERIALS AND METHODS: Data of head and neck cancer patients from January 2010 to December 2011 were obtained from the hospital cancer registry for retrospective analysis of patients with synchronous cancers. All synchronous malignancies were analyzed for distribution of sites, association with smoking history and the average age of patients at presentation with synchronous cancers. The Chi-square test for association of upper aero digestive tract (UADT) and smoking and statistical formula of mode for average age have been employed for analyzing results. RESULTS: Incidence of synchronous primaries has been found to be 1.43% and mostly males were affected. The common index sites for synchronous primaries are oropharynx 22 (36.6%), oral cavity 14 (23.3%), hypopharyx 12 (20%) and larynx eight (13.3%) cases in decreasing order, 58.3% synchronous occurred at esophagus and 0.83% of all head and neck cancers developed synchronous primary at esophagus. Association of UADT synchronous cancers with smoking (odds ratio = 13.42, Chi-square 7.12 at 95% confidence interval, P = 0.0076) is highly significant and the average age is 62.6 years in males and 62 years in females. CONCLUSION: Endoscopy can be rationally used during the pre-therapeutic work-up of patients with a history of smoking and/or in patients over the age of 62 years. Instead of complete upper gastro intestinal endoscopy up to the second part of duodenum, only esophagoscopy is needed for the detection of synchronous primary of upper aero-digestive tract in cancers of the head and neck region.

Similar immunity profiles in patients with meningioma and glioma tumors despite differences in the apoptosis and necrosis of circulating lymphocyte and monocyte populations.

AIM: The present study aims to compare the host immune responses induced by benign (meningiomas) and malignant (gliomas) brain tumors. METHODS: Peripheral blood samples from 8 meningioma and 7 glioma patients collected pre- and post operatively were assessed for cell-mediated immunity, humoral immunity and IL-6, IL-8 and TNF-a expression. Apoptosis and necrosis of circulating lymphocytes and monocytes were evaluated by Annexin/PI, while DNA analysis was applied to trace circulating cells with an abnormal DNA content. RESULTS: Cell-mediated immunity was similar in the two groups either pre- or post- operatively. However, differences in the apoptosis and necrosis of circulating lymphocytes and monocytes were observed. Menigioma patients were characterized by increased percentage of apoptotic lymphocytes and necrotic monocytes pre-operatively and apoptotic monocytes postoperatively. In contrast glioma patients showed an increase in necrotic monocytes postoperatively. Humoral immunity and cytokine expression were at comparable levels both pre- and post-operatively. IL-6 expression was significant elevated after surgery in both groups. Circulating aneuploid cells were identified in three glioma patients pre-operatively, by DNA analysis. CONCLUSION: The presented data indicate that meningioma and glioma tumors trigger comparable systemic host immunity response mediated by impairments in cell-mediated immunity due to alternations in apoptosis and necrosis that also influence their shift towards the Th2 immunity profile. Moreover, the presented evidences on the circulation of aneuploid cells in glioma patients may substantiate further the immunosuppressive phenotype detected in these patients and offer a mechanism for the rare cases that extra- neural dissemination was observed without previous surgical intervention.

Synchronous primary cancers of the head and neck region and upper aero digestive tract: defining high-risk patients.

BACKGROUND: Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers. AIM: To see the epidemiology of synchronous cancers of the head and region and identification of high-risk factors for the development of synchronous primary in the head and neck cancers. MATERIALS AND METHODS: Data of head and neck cancer patients from January 2010 to December 2011 were obtained from the hospital cancer registry for retrospective analysis of patients with synchronous cancers. All synchronous malignancies were analyzed for distribution of sites, association with smoking history, stage of index head, and neck tumor and the average age of patients at presentation with synchronous cancers. The Chi-square test for association of upper aero digestive tract (UADT) and smoking and statistical formula of median for calculating the average age have been employed for analysis. RESULTS: Incidence of synchronous primaries has been found to be 1.33%, majority were seen at the oropharynx (39.2%) and 60.7% synchronous occurred at the esophagus, 0.81% of all head and neck cancers developed synchronous primary at the esophagus. Approximately, 65% of all synchronous primaries were in Stage III and Stage IV disease and 88.2% esophageal synchronous had Stage II disease. Association of UADT synchronous cancers with smoking is highly significant, relative risk = 1.95 95% confidence interval for relative risk 1.05-3.64 P = 0.00010981 (P < 0.05) and the average age is 62.4 years in males and 57.8 years in females. CONCLUSION: Patients who are at the high-risk for the development of synchronous primary tumors in the cancers of the head and neck region are patients with oropharyngeal carcinoma, smoking population, patients over the age of 62 years in males, and 57 years in females and in patients with higher staged index tumor.

Identification of germline BRCA1 and BRCA2 genetic alterations in Greek breast cancer moderate-risk and low-risk individuals--correlation with clinicopathological data.

The current study was designed to evaluate the prevalence of BRCA1 and BRCA2 germline mutations in Greek moderate- and low-risk individuals with respect to clinicopathological phenotype and clinical outcome of breast cancer. Ninety-four consecutive individuals were prospectively recruited from two University Breast Cancer Clinics (Hippokrateion Hospitan and Laikon Hospital) between 1989 and 1999 and were categorized as moderate-risk and low-risk individuals for carrying BRCA1/2 germline mutations. To identify the underlying mutations, protein-truncation test and single-strand conformation polymorphism methods were used, followed by direct sequencing. Three novel BRCA1 missense mutations, one novel BRCA1 intronic deletion, three novel (previously reported) BRCA2 truncating mutations, and one novel BRCA2 missense mutation were identified in the moderate-risk group of individuals studied. The BRCA1/2 missense mutations as well as the single intronic variant identified were designated as unclassified genetic variants. Two BRCA1 unclassified genetic variants (missense mutations) were detected in two of the three (66.7%) male breast cancer patients analyzed, while the third one was identified in a sporadic (low-risk) breast cancer patient. Clinicopathological characteristics of breast carcinomas originating from BRCA1/2 heterozygotes were consistent with those already reported and not different from those observed in BRCA1/2 mutation (-) breast cancer patients. Furthermore, BRCA1/2 mutation carriers presented an excellent 4.5-year overall survival (100%). Our results reveal the unique characteristics of BRCA1/2 mutation status, genotype-phenotype correlations, and prognosis, in moderate- and low-risk individuals of Greek ancestry. Breast cancer due to mutations in BRCA1 and BRCA2 genes appears to be a heterogeneous syndrome in the Greek population.

P53 and C-FOS overexpression in patients with thyroid cancer: an immunohistochemical study.

A sequence of genetic events characterized by deletion and expression of several oncogenes may lead progressively to tumorgenesis. The expression of certain oncogenes is believed to be related with thyroid carcinogenesis and tumor progression. We investigated immunohistochemically p53 tumor suppressor gene and c-fos oncogene expression in forty patients with thyroid cancer. Thyroid biopsies from twenty patients with benign thyroid diseases were also examined. The forty patients with thyroid cancer varied histologically; 24 with papillary carcinoma (60%), 12 with follicular carcinoma (30%), 3 with anaplastic carcinoma (7.5%) and one with medullary carcinoma (2.5%). The patients with benign thyroid diseases consisted of 10 with adenomatous goiter (50%), 7 with goiter (35%) and three with Hashimoto thyroiditis (15%). Individual p53 and c-fos expression was more prevalent in thyroid carcinomas compared to benign tumors (p=0.001 and p=0.04, respectively). A marked increase of p53 and c-fos coexpression was found (p=0.02) in patients with thyroid cancer and metastasis to the regional lymph nodes. Furthermore c-fos was overexpressed in only female thyroid cancer patients. In conclusion, p53 and c-fos are significantly overexpressed in thyroid cancer patients, indicating their role in the genetic mechanisms leading to thyroid tumorigenesis. This hypothesis is further supported by the observation that p53/c-fos coexpression was related with more advanced disease status.

Common pathways for primary hypertrophic and dilated cardiomyopathy.

Testing the hypothesis that hypertrophic and dilated cardiomyopathy as well as viral myocarditis share a common mitogenic growth response pathway with mitotically competent cell types are the aims of this study. The expression of the c-fos, H-ras and c-myc genes was immunohistochemically determined in biopsies from 12 patients with dilated cardiomyopathy, 24 patients with hypertrophic cardiomyopathy, and 4 patients with myocarditis. Normal myocardium from 9 subjects was used as the control group. Staining results were correlated with patient's demographic data. C-fos, H-ras and c-myc protein overexpression was seen in 15 patients (62.5%) with primary hypertrophic and 4 patients (33.3%) with dilated cardiomyopathy. The majority of hypertrophic and dilated cardiomyopathy patients expressed at least one of the genes studied compared with the control group (p = 0.006). Primary cardiomyopathy patients also showed a statistically significant difference in the gene co-expression compared with the control group (p = 0.042). C-fos, H-ras, and C-myc protein expression did not differ substantially between patients with hypertrophic and dilated cardiomyopathy. Patients with myocarditis expressed only the C-fos protein (n = 2, 50%). C-fos, h-ras and c-myc genes are overexpressed in patients with cardiac hypertrophy and cardiac dilation. Cardiac myocytes respond to biomechanical stress by initiating several different processes. One of them is oncogene expression. This results in a hypertrophy of the myocytes proportional in length and width (hypertrophic cardiomyopathy or with a relatively greater increase in length than in the width (dilated cardiomyopathy).

Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in patients with malignant melanoma.

AIM: Use of molecular markers indicative of the tumour oncogenic potential and host response may enhance our prognostic information for more effective treatment of melanoma patients. The roles of HSP-70 protein, c-myc oncogene and HLA-DR antigen expression were examined in melanoma patients and related to prognostic factors, recurrence rate and long-term survival. METHODS: Forty patients with tumours thicker than 1 mm were included in this study. All had elective node dissection and were followed for at least 7 years. Twenty-two had microscopic nodal metastases. Both primary melanoma tumour and lymph nodes were examined for the immunohistochemical expression of HSP-70 protein, c-myc oncogene and HLA-DR antigen. RESULTS: Eighteen patients had a recurrence (45%) and 23 patients survived overall (57.50%). Positive HSP-70 expression was observed in 52.50% of the primary melanomas and was associated with improved overall survival, especially in the patient group with tumours > or = 1.5 mm (70%vs 26.70%, P=0.0159). C-myc oncogene was overexpressed in 47.50% and HLA-DR antigen in 42.50% of the primary melanomas, but no correlation with survival was observed. The expression profile of these molecular markers in the primary tumour did not predict the status of regional nodes. HLA-DR expression in lymph nodes was observed exclusively in the nodal tissue surrounding the metastatic melanoma tumour in five patients. CONCLUSIONS: The immunohistochemical expression profile of HSP-70 but not of c-myc oncogene or HLA-DR antigen in the primary melanoma tumour could be of certain value in the identification of patients with graver prognosis who may benefit from more aggressive therapeutic strategies.

Reflections on the European Conference "Molecular Screening of Individuals at High Risk for Developing Cancer: Medical, Ethical, Legal, and Social Issues".

The fascinating progress of molecular biology in the last decades has made possible the early identification of persons at risk of developing malignant neoplasms, such as thyroid, colon, and breast cancer. This has changed conventional medical practice and has raised a number of ethical questions. Despite the fact that there has been substantial development throughout the Western countries in legislation dealing with medical information, there is an acute need for further exploration and assessment of the moral and social dimensions of medical practices to achieve more precise and uniform regulations. These topics were discussed in a multidisciplinary European Conference entitled "Molecular Screening of Individuals at High Risk of Developing Cancer: Medical, Ethical, Legal, and Social Issues," which took place in March, 1999, in Athens, Greece.

Influence of SDZ-PSC833 on daunorubicin intracellular accumulation in bone marrow specimens from patients with acute myeloid leukaemia.

The multidrug resistance (MDR) modulating activity of SDZ-PSC833 (PSC), a non-immunosuppressive cyclosporine analogue, was investigated and compared with cyclosporin A (CSA) in bone marrow clinical specimens from 45 patients with acute myeloid leukaemia (AML) taken at diagnosis, using double-labelling flow cytometry with simultaneous determination of P-glycoprotein (PGP) expression and intracellular daunorubicin fluorescence (IDF). On the basis of pre-clinical results in multidrug-resistant K562 leukaemic cells, concentrations leading to iso-effective complete restoration of IDF were used: 5 and 10 micromol/l, respectively for PSC and CSA. In the clinical specimens, PGP expression was correlated with a significant decrease in IDE PSC was found to be significantly more potent than CSA since it was found to induce a significant increase in IDF in a higher number of cases and to a higher extent than CSA. PGP-unrelated activity of PSC was also observed in specimens expressing no PGP but exhibiting low IDF, thus probably expressing alternative resistance mechanisms. The results confirm the potency of PSC as MDR-modulating agent in clinical AML specimens whose resistance pattern differed from that of highly resistant cell models and suggest that the activity of PSC is not limited to P-glycoprotein inhibition.

French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

Since there is no consensus on the techniques for multidrug resistance (MDR) phenotype evaluation, many discrepancies concerning the importance and frequency of mdr1 gene expression in leukemias and solid tumors are observed in the literature. In order to establish an inter-laboratory consensus in France, a multicenter study was carried out to propose further guidelines for MDR phenotype evaluation. The techniques used by the 38 laboratories participating in the trial were: immunodetection (immunohisto and/or cytochemistry, flow cytometry), functional tests, reverse transcription-polymerase chain reaction (RT-PCR) or Northern blot. We present the results obtained by 19 laboratories concerning the measurement of mdr1 gene expression assessed by RT-PCR or Northern blot in: (1)19 samples of tumor cells obtained from leukemic patients; (2) six solid tumor samples obtained at surgery; (3) eight cell lines exhibiting variable levels of resistance, and; (4)10 preparations of RNA and of cDNA obtained from solid tumors. Standardization of the RT-PCR technique and preliminary results comparing RT-PCR with immunohistochemistry in solid tumors are also reported.

Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes.

One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1-2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8.

Twinning in Greece.

Mean MZ and DZ twinning rates in seven big Greek cities were 3.2 and 4.75 per 1,000 maternities, respectively, during the 1980-1985 period. The seasonal variations in twinning frequencies are not significant. The total twinning rate in Greece shows a decreasing trend from 1956 to 1985.