Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

An expert consensus definition of failure of a treatment to provide adequate relief (F-PAR) for chronic constipation - an international Delphi survey.

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better. AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation. METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms. RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed). CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

Prevalence, symptom patterns and management of episodic diarrhoea in the community: a population-based survey in 11 countries.

BACKGROUND: The extent of episodic diarrhoea in the community is relatively unknown. AIM: To ascertain the prevalence, symptoms and management behaviours associated with self-reported diarrhoea across 11 countries. METHODS: Community screening surveys were conducted using quota sampling of respondents to identify a nationally representative sample of individuals suffering from 'episodic' diarrhoea (occurring once a month or more often). Second-phase in-depth surveys provided data on epidemiology, symptoms, attributed causes and management of episodic diarrhoea. RESULTS: A total of 11 508 phase 1 and 6613 phase 2 surveys were completed. The prevalence of self-reported episodic diarrhoea ranged from 16% to 23% across the 11 countries. The majority of episodic diarrhoea sufferers were female (57%) and were not diagnosed with pre-existing irritable bowel syndrome (IBS); IBS diagnosis ranged from 9% in Mexico to 44% in Italy. Diarrhoea was frequently attributed to anxiety/stress, food-related causes, gastrointestinal 'sensitivity' and menstruation. Accompanying symptoms included 'stomach pain/cramping' (35-62%), 'stomach grumbling' (29-68%) and 'wind' (18-74%). The proportion of episodic sufferers who reported treating their symptoms with remedies or medications ranged between 46% in Belgium and Canada and 90% in Mexico. CONCLUSIONS: A substantial proportion of the population in middle- to high-income countries report episodic diarrhoea in the absence of a pre-existing diagnosis. These symptoms are likely to be associated with substantial social and economic costs, and have implications on how best to configure and guide self-led, pharmacist-led and primary care management.

Infantile gastroenteritis in the community: a cost-of-illness study.

Rotavirus infections are the main cause of gastroenteritis in infants and children and it is expected that by the age of 5 years, nearly every child will have experienced at least one episode of rotavirus gastroenteritis. While severe cases are hospitalized, milder disease is either treated at home or by the GP, and as such the true prevalence of rotavirus infection in the community, and the burden of disease, is unknown. This paper reports the results of a cost-of-illness study which was conducted alongside a structured community surveillance study. Forty-eight percent of our sample was found to have rotavirus acute gastroenteritis; and the average total cost of a child presenting with rotavirus gastroenteritis ranged between pound sterling 59 and pound sterling 143 per episode, depending on the perspective. Given the prevalence and severity of the disease, the estimated burden of rotavirus gastroenteritis to society is pound sterling 11.5 million per year.

Structured surveillance of infantile gastroenteritis in East Anglia, UK: incidence of infection with common viral gastroenteric pathogens.

The aim of this study was to investigate the burden of disease associated with gastroenteric viruses (rotavirus, norovirus, sapovirus, astrovirus and enteric adenovirus) using structured surveillance of children aged <6 years in the community. Faecal samples were collected between 2000 and 2003 from 685 children with symptoms of gastroenteritis. The children comprised three groups; 223 in the structured surveillance cohort, 203 in a community cohort and 259 in a cohort of hospitalized children. All samples were tested for the presence of viral pathogens using molecular methods. Questionnaires were sent to the parents/carers of the children recruited to the structured surveillance cohort in order to collect data that would allow an estimation of the severity of illness by means of the Vesikari score, and of the cost associated with gastrointestinal disease in this age group. A viral aetiological agent was detected in 53.5% of samples tested. Rotavirus was the most common pathogen found in all three cohorts followed by norovirus and enteric adenoviruses. Multiple viruses were found in 8% of the samples, and commonly involved rotavirus and any other virus. G1P[8] was the most commonly detected rotavirus strain and there was no significant difference in the distribution of rotavirus genotypes among the three cohorts. Analysis of the questionnaires indicated that rotavirus infections were likely to be more severe than any other virus infection, and children from whom a viral pathogen was identified were more likely to require rehydration therapy.

Chemoradiation for primary invasive squamous carcinoma of the vagina.

OBJECTIVE: To report outcomes for patients with primary, invasive, squamous carcinoma of the vagina treated with chemoradiation. METHODS: Between 1986 and 1996, 14 patients were treated with primary therapy consisting of synchronous radiation and chemotherapy. Patients were judged not to be surgical candidates based on tumor size, location, and concerns related to urinary, bowel, or sexual function. Three patients were FIGO stage I, ten patients stage II, and one patient stage III. Radiation consisted of teletherapy alone (six patients) or in combination with intravaginal brachytherapy (eight patients). Total radiation dose ranged from 5700 to 7080 cGy (median 6300 cGy). Chemotherapy consisted of 5-fluorouracil alone (seven patients), or with cisplatin (six patients) or mitomycin-C (one patient). RESULTS: One patient failed locally at 7 months and died of disease at 11 months. Four patients died of intercurrent illness (46, 92, 104, 109 months) and nine are alive and cancer-free 74-168 months after treatment (median 100 months). There were no vesicovaginal or enterovaginal fistulae. CONCLUSIONS: Radiation with synchronous chemotherapy is an effective treatment for squamous carcinoma of the vagina. Cancer control outcomes compare favorably with previously published results employing higher dose radiation as monotherapy.

Endometriosis-related malignancies.

The purpose of this study is to describe the clinical findings, treatment, and outcome of patients with endometriosis-related cancers. Patients meeting Sampson and Scott's criteria for cancer associated with endometriosis in the Sacramento region were identified by chart review and pathology reports. Twenty-seven patients were identified with endometriosis-related malignancies (mean age 51.4 years). The site of origin was ovary in 17 (63.0%) and extra-ovarian in 10 (37%) including vagina, fallopian tube or mesosalpinx, pelvic sidewall, colon, and parametrium. The pattern of spread was local in five (18.5%), regional in 20 (74.1%) and distant in two (7.4%). Six patients had taken unopposed estrogen replacement (mean duration 23.4 years) and all six had extragonadal disease. Surgical procedures included hysterectomy, salpingo-oophorectomy, radical local excision, partial colectomy, and surgical staging. Eighteen patients received postoperative chemotherapy since the majority of patients had ovarian involvement. Fifteen patients received regional radiation therapy. Nineteen patients are without evidence of recurrence (70.4%, mean follow-up of 31 months). Endometriosis-related malignancies have a favorable prognosis. Extragonadal disease was commonly associated with unopposed estrogen replacement therapy. The predominance of local and regional disease strongly influence the application of treatment modalities.

Outcomes following unilateral uterine artery embolisation.

Uterine artery embolisation has been described as successful only when both arteries are embolised. However, results in patients with one congenitally absent or previously ligated artery are unknown. Women suffering from symptomatic uterine myomata were treated at a university teaching hospital, a community hospital and an outpatient surgery centre. Retrospective review of patient response to embolisation was assessed by chart review and questionnaire. Uterine and dominant fibroid size response was assessed by comparing pre- and post-embolisation ultrasound examinations. This study analysed three patient groups within the general population: those who underwent unilateral embolisation because of technical failure, those who ultimately underwent bilateral embolisation after initial technical failure and those who underwent unilateral embolisation because of an absent uterine artery. 12 patients underwent unilateral embolisation, 4 of whom underwent this procedure because of an absent uterine artery. Three of these four patients had a congenitally absent uterine artery arising from the internal iliac artery and all three experienced successful outcomes. The fourth patient had a previously ligated internal iliac artery and her symptoms worsened after the procedure. Eight patients had unilateral embolisation due to technical failure. Five of these patients underwent a subsequent procedure during which the contralateral uterine artery was embolised. Four of these five patients had successful outcomes and one was lost to follow-up. Another of the eight patients suffered an arterial injury leading to technical failure, and was lost to follow-up. Of the two remaining patients with unilateral technical failure, only one had a successful outcome. This study concluded that patients who undergo unilateral embolisation for technical reasons should be offered a second embolisation procedure shortly after the initial procedure. Patients with a congenitally absent uterine artery may respond with similar success to those who underwent bilateral embolisation. In contrast, the patient with a previously ligated internal iliac artery failed. The numbers in this study are too small for statistical analysis and subsequent studies should be performed to confirm these findings.

Obstetrical deliveries associated with maternal malignancy in California, 1992 through 1997.

OBJECTIVE: This study aims to characterize the rate of occurrence and nature of outcomes associated with obstetrical deliveries in women with malignant neoplasms among 3,168,911 women who delivered in California in 1992 through 1997. DESIGN: The study is a population-based retrospective review of infant birth and death certificates and maternal and neonatal discharge records. Cases of malignant neoplasms associated with obstetrical delivery were attributed to 1 of 3 categories, depending on the earliest documented hospital discharge diagnosis, as follows: "prenatal" if the diagnosis was first documented by hospitalization within 9 months preceding delivery, "at delivery" if the diagnosis was established from the delivery hospitalization, or "postpartum" if the diagnosis was first documented by hospitalization within 12 months after delivery. METHODS: Computer-linked infant birth and death certificates and maternal and neonatal discharge records were used to identify cases and outcomes. Cases of malignant neoplasms were identified by using International Classification of Diseases, Ninth Revision codes (140-208). Noninvasive neoplasms and carcinoma in situ neoplasms were excluded. In analysis of outcomes, the Mantel-Haenszel estimate for adjusted odds ratios was used. RESULTS: Among 3,168,911 obstetrical deliveries over the 6-year span, a total of 2247 cases of primary malignancy were identified. The observed rate of occurrence for primary malignant neoplasms was 0.71 per 1000 live singleton births. Most cases (53.3%) were first documented in the postpartum period as follows: prenatal, 587 cases (0.18 per 1000); at delivery, 462 cases (0.15 per 1000); and postpartum, 1198 cases (0.38 per 1000). The most frequently documented primary malignant neoplasms associated with obstetrical delivery were breast cancer (423 cases, 0.13 per 1000), thyroid cancer (389 cases, 0.12 per 1000), cervical cancer (266 cases, 0.08 per 1000), Hodgkin's disease (172 cases, 0.05 per 1000), and ovarian cancer (123 cases, 0.04 per 1000). Odds ratios for a variety of demographic factors identified maternal age as the most significant risk factor for development of malignant neoplasms (age greater than 40 vs 20-25, odds ratio 5.7, CI 4.6-6.9). Age-adjusted odds ratios for maternal cancer of any type suggested significantly elevated risks for cesarean delivery (odds ratio 1.4, CI 1.3-1.6), blood transfusion (odds ratio 6.2, CI 4.5-8.5), hysterectomy (odds ratio 27.4, CI 20.8-36.1), and maternal postpartum hospital stay greater than 5 days (odds ratio 30.6, CI 27.9-33.6), but not for postpartum maternal death (odds ratio 0.8, CI 0.6-1.0). Odds ratios also suggested significantly elevated risks for premature newborn (odds ratio 2.0, CI 1.8-2.2), very low birth weight (odds ratio 2.9, CI 2.2-3.8), and newborn hospital stay longer than 5 days (odds ratio 2.6, CI 2.4-3.0), but not for neonatal death (odds ratio 1.6, CI 0.8-3.1) or infant death (odds ratio 1.2, CI 0.5-3.3). However, several types of malignant neoplasms did confer significant elevations in risk for neonatal death. Hospital charges for both maternal and neonatal care were significantly elevated in the maternal malignant neoplasm group. CONCLUSION: A lower than expected occurrence rate of obstetrical delivery associated with maternal malignancy was seen when compared with previously published hospital-based reports. Malignant neoplasms associated with obstetrical delivery were most frequently first documented in the postpartum period. Maternal and neonatal morbidity were significantly increased, yet the risk of in-hospital maternal death was not significantly elevated. A significant increase in risk of neonatal death for infants of mothers with cervical cancer was found.

Cross sectional study of reporting of epileptic seizures to general practitioners.

OBJECTIVE: Comparison of reporting of recent epileptic seizures by patients to a doctor and anonymously. DESIGN: Cross sectional study of patients with epilepsy by comparison of paired questionnaires. SETTING: Rural and urban general practices in Norfolk. PARTICIPANTS: 122 patients aged over 16 years and able to self complete a questionnaire who were recruited by 31 general practitioners when attending for review of their epilepsy. MAIN OUTCOME MEASURE: The difference in reported occurrence of seizure to general practitioners and in a linked anonymous questionnaire. RESULTS: 18 patients failed to report a seizure in the past year to their general practitioner (uncontrolled epilepsy). 40% (24/60) of people with epilepsy who anonymously reported a seizure in the past year held a driving licence, but only six revealed this to their general practitioner. The unemployment rate was 34%, substantially higher than the 9% in the general population. Measures of anxiety, depression, and stigmatization were higher in patients with uncontrolled epilepsy. CONCLUSIONS: A significant proportion of patients with epilepsy under-report their seizures. Recognition of underreporting is important if patients are to benefit from adequate and appropriate treatment. General practitioners' ability to treat epilepsy is hampered by their role in regulating the rights of epileptic patients to hold a driving licence or access certain occupations.

Proliferating (LMP) mucinous tumors of the ovaries with microinvasion: morphologic assessment of 13 cases.

From a consecutive series of 124 proliferating (low malignant potential) mucinous ovarian tumors, 13 FIGO stage Ia tumors exhibited 1 or more microfoci of stromal invasion. The proliferating mucinous tumors with microinvasion were of intestinal (7/88), endocervical-like (4/26), or mixed epithelial differentiation (2/10) and were more likely to show high-grade (10/42) than low-grade (3/82) epithelial proliferative changes. Morphologically, foci of microinvasion were characterized by single or small groups of epithelial cells in the tumor stroma. These cells were accompanied by a sparse lymphocytic infiltrate and stromal desmoplasia in their immediate vicinity and by a greater degree of nuclear anaplasia in the invading cells and in the lining cells of the nearby glands or cysts than was present elsewhere in the tumors. Focal inflammatory and degenerative changes, commonly seen in ovarian mucinous tumors, were discriminated from microinvasive carcinoma by the nature of the inflammatory response, the presence of stromal mucin deposits, and the absence of nuclear anaplasia. Follow-up was available in 10 of 13 cases (mean 7.5 years) and did not identify any adverse clinical consequences for the patients.

Why do patients default from follow-up at a genitourinary clinic?: a multivariate analysis.

OBJECTIVE: Firstly to compare the proportion of patients defaulting from follow up at a genitourinary medicine clinic with those attending other hospital based clinics. Secondly to determine which factors are associated with non attendance at a city centre genitourinary medicine clinic. METHODOLOGY: The proportion of patients who defaulted at a genitourinary medicine clinic, a general medical clinic, a general surgical clinic and a dermatology clinic during March 1995 were compared. A multivariate logistic regression analysis was performed comparing attenders and non attenders at the genitourinary medicine clinic with respect to time of appointment, diagnosis, previous contacts with clinic staff, potential domestic commitments and patient demographics in a prospective case control study. RESULTS: The default rate at the genitourinary medicine clinic was 15% compared with 13%, 15% and 14% for medical, surgical and dermatology clinics respectively. Patients who defaulted from the genitourinary medicine clinic (167) were compared with 172 attenders and significant differences found for timing of appointments, area of residence, frequency of counselling by the health advisor and age of the patient. Other factors such as the diagnosis, whether a woman had children, sexual orientation, whether negative results had been given over the phone, source of referral, sex of patient, employment status and the weather were not found to be significantly associated with defaulting from an appointment. CONCLUSIONS: The time of the appointment and being seen by a health advisor were the only variables identified over which the clinic has control and therefore could potentially reduce non attendance rates.

Squamous endometrial neoplasia-are Fluhmann's postulates still relevant?

A review of squamous neoplasia of the endometrium (in situ and/or invasive) with or without coexistent similar disease of the cervix, revealed four anatomical variants in 22 patients. The patterns were: Group (i), endometrial squamous neoplasia only; Group (ii), discontiguous endometrial and cervical squamous neoplasia; Group (iii), possibly discontiguous endometrial and squamous neoplasia; and Group (iv), contiguous endometrial and squamous disease. The details of the histology, management and outcome are discussed, the latter being much poorer for the fourth group. The criteria for diagnosing squamous neoplasia involving the endometrium are re-examined and a recommendation for these criteria is suggested.

Clinical results from intracytoplasmic sperm injection at monash IVF.

The impact of a modification of the intracytoplasmic sperm injection (ICSI) technique on fertilization and pregnancy rates was examined in a retrospective analysis of 171 consecutive ICSI treatment cycles (156 patients). Patients were selected for ICSI on the basis of severe oligoasthenozoospermia (65 patients) or following conventional in vitro fertilization (IVF) with failed or poor fertilization (70 patients). Seven patients in which epididymal or testicular sperm was used, 10 patients with sperm antibodies and 4 patients with retrograde ejaculation or who required electro-ejaculation were also treated with ICSI. In the first 105 cycles (102 patients), single sperm, rendered immotile, were injected into the ooplasm of 979 metaphase II (M II) oocytes using an established technique (Method 1). In the following 66 cycles (513 M II oocytes injected), the ICSI procedure was modified by increased aspiration of the oolemma to ensure the intracytoplasmic deposition of sperm (Method 2). The patient groups did not differ between the two injection procedures. The normal (two pronuclear) fertilization rate increased significantly (P < 0.001) from 34.3% with Method 1 to 73.1% with Method 2, with no difference in the oocyte degeneration rate (4.3% v. 4.5% respectively). The incidence of failed fertilization was significantly (P < 0.01) reduced from 17.1% (18 cycles) to 1.6% (1 cycle) with the change in technique. As a consequence of the increased fertilization rates with Method 2, more embryos were available for assessment and transfer, and a pregnancy rate per oocyte retrieval of 21.2% was obtained for Method 2. Fertilization, embryo transfer and pregnancies were obtained in all patient groups treated with ICSI.(ABSTRACT TRUNCATED AT 250 WORDS)

An electronic approach to the detection of pre-cancer and cancer of the uterine cervix: a preliminary evaluation of Polarprobe.

We report on the testing of a prototype of an electronic device for the detection of cervix cancer and its precursors, known as the Polarprobe. The device monitors three aspects of the cervix tissue; two relate to optical properties and the other to dielectric characteristics. The response to tissue stimulation takes the form of an energy pattern which, in conjunction with spectroscopic discriminants, can be digitized to prepare an algorithm. The pattern algorithms are sufficiently characteristic to be afforded names which correspond to tissue states recognizable as normal or abnormal by the clinician. On a tissue observation basis the previously established recognition algorithms derived from 106 volunteers produced assessments which related strongly to colposcopy/histology diagnoses obtained on 77 additional volunteers. This concordance between colposcopy/histology and Polarprobe diagnoses on this primary analysis subgroup ranged from 85% on low-grade intraepithelial abnormalities, and 90% on high-grade cervical intraepithelial squamous neoplasia, to 99% on invasive cancer. An extrapolation of these results suggests false-positive/false-negative rates in the order of 10% are achievable with the current Polarprobe device.

Serological relationships among viruses in the Hantavirus genus, family Bunyaviridae.

We examined the serological relationships among 32 hantavirus isolates collected from numerous geographic regions and hosts. We prepared rat immune sera to each virus and used these sera in hemagglutination inhibition (HAI) tests, enzyme-linked immunosorbent assays (ELISA), and plaque-reduction neutralization tests to establish the antigenic relationships among the isolates. Our studies included viruses that had been partially characterized previously, as well as isolates for which little or no serological data were available. Our results indicate that, in addition to the four established serological groups of hantaviruses, represented by Hantaan, Seoul, Puumala, and Prospect Hill viruses, there exist at least two other distinct groups of hantaviruses. These groups are represented by Thailand 749 virus, an isolate from Bandicota in Thailand, and by Thottapalayam virus, an isolate from Suncus in India. To compare more closely the antigenic relationships of the isolates to prototype Hantaan virus, we examined the reactivities of Hantaan G1- or G2-specific monoclonal antibodies with the envelope proteins of a number of the isolates. We found that several epitopes defined by monoclonal antibodies to the G2 protein were highly conserved as detected by HAI tests and ELISA. Almost all of the isolates could be neutralized by at least one G2-specific monoclonal antibody. In contrast, epitopes defined by G1 monoclonal antibodies were conserved only among Hantaan-like viruses.

Localization of Hantaan viral envelope glycoproteins by monoclonal antibodies in renal tissues from patients with Korean hemorrhagic fever H.

The role of viruses in several renal diseases is not documented clearly. The authors attempted to localize envelope glycoproteins of Hantaan virus in biopsy specimens from patients with Korean hemorrhagic fever (KHF) as evidence of direct viral invasion of renal tissues. The authors studied sequential sections of kidney biopsy specimens from 23 of 35 patients with serologically confirmed KHF diagnosed between June 1985 and December 1989. The sections were stained with the avidin-biotin-peroxidase complex method with monoclonal antibodies to G1 and G2 envelope glycoproteins. Control antibodies of the same isotype were used to rule out nonspecific staining, and hyperimmune rabbit sera or convalescent sera of patients with KHF were used for blocking tests. Normal renal tissues and kidney biopsy tissues from minimal-change nephrotic syndrome were used as negative control sections. The kidney biopsies were performed between the fifth and thirtieth days after onset of fever. The authors detected viral glycoproteins in renal tissues from 22 of the 23 patients. The viral glycoproteins were localized in the cytoplasm of the tubular epithelial cells, and the distribution of viral glycoproteins in the tubules was focal. Glycoproteins also were localized in the cytoplasm of the sloughed renal tubular epithelial cells, where tubular degenerative changes were prominent. These findings suggest the direct invasion of renal tubules by the virus and may partly explain the pathogenesis of acute renal failure in KHF.

Primary endometrial squamous cell carcinoma with long-term survival.

Primary endometrial squamous cell carcinoma is a rare variant of uterine epithelial malignancy. A review of records over a 10-year period at a major referral centre for gynaecological malignancy identified 4 patients with this disease. They were treated primarily by surgery, with adjuvant radiotherapy or chemotherapy in 3 cases. In comparison to previously reported cases the length of survival for these patients was long.