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Abstract Objective To evaluate cost-utility of infliximab and adalimumab for the treatment of moderate-to-severe ulcerative colitis (UC) refractory to conventional therapies in Canada. Methods A Markov model was constructed to evaluate incremental cost-utility ratios (ICUR) of 5 mg/kg and 10 mg/kg infliximab and adalimumab therapies compared to 'usual care' in treating a hypothetical cohort of patients (aged 40 years and weighing 80 kg) over a five-year time horizon from the perspective of a publicly-funded health care system. Clinical parameters were derived from the Active Ulcerative Colitis Trials 1 and 2. Costs were obtained through provincial drug benefit plans. ICUR was the main outcome measure and both deterministic and probabilistic sensitivity analyses were conducted. Results Compared to the strategy A ('usual care') in the base case analysis, the ICURs were CA$358,088/QALY for the strategy B ('5 mg/kg infliximab + adalimumab') and CA$575,540/QALY for the strategy C ('5 mg/kg and 10 mg/kg infliximab + adalimumab'). The results were sensitive to: the remission rates maintained in responders to 'usual care' and to 5 mg/kg infliximab, the rate of remission induced by adalimumab in non-responders to 5 mg/kg infliximab, early surgery rate, and utility values. When the willingness to pay (WTP) was less than CA$150,000/QALY, the probability of 'usual care' being the optimal strategy was 1.0. The probability of strategy B being optimal was 0.5 when the WTP approximated CA$400,000/QALY. Conclusions The ICURs of anti-TNF-α drugs were not satisfactory in treating patients with moderate-to-severe refractory UC. Future research could be aimed at the long-term clinical benefits of these drugs, especially adalimumab for patients intolerant or unresponsive to infliximab treatment.

Background: In Ontario, bariatric surgery is publicly funded and is performed only in accredited tertiary care hospitals. The purpose of our study was to report on the safety and outcomes of performing bariatric surgery at an ambulatory site of a tertiary care hospital in southern Ontario., Methods: We conducted a retrospective cohort study of all adult (age ≥ 18 yr) patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) at the ambulatory site of our tertiary care hospital between September 2016 and August 2018. The 2 sites are 1.4 km apart. Patient demographic characteristics, duration of surgery, intraoperative and 90-day postoperative complications, number of transfers and readmission to the tertiary care hospital, and emergency department visits were collected., Results: A total of 314 patients (285 women [90.8%] and 29 men [9.2%] with a mean age of 41.8 yr [standard deviation (SD) 8.9 yr]) underwent surgery: LRYGB in 295 cases (93.9%) and LSG in 19 (6.0%). The mean body mass index was 45.3 (SD 5.1), the median American Society of Anesthesiologists score was 3 (range 2-4), and the median Edmonton Obesity Staging System score was 2 (range 0-4). The mean operative time was 119.8 (SD 23.1) minutes for LRYGB and 96.2 (SD 22.0) minutes for LSG, and the mean length of stay was 2.1 (SD 0.6) days and 2.1 (SD 0.2) days, respectively. Thirteen patients (4.1%) required transfer to the tertiary care hospital for a postoperative complication. Of 312 patients, 29 (9.3%) presented to emergency department within 90 days after surgery, and 8 (2.6%) required readmission to hospital; no deaths were reported., Conclusion: The findings suggest that LRYGB and LSG can be performed safely at an ambulatory site of a tertiary care hospital. However, caution should be exercised in performing these procedures at an ambulatory site without a tertiary care hospital affiliation, as patients may require urgent transfer for a serious postoperative complication., Competing Interests: Competing interests: Boris Zevin reports fellowship support from Ethicon and a research grant from Medtronic. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: Informed consent is of paramount importance in surgery. Digital media can be used to enhance patient's comprehension of the proposed operation. The objective of this study was to examine the effects of adding a digital educational platform (DEP) to a standard verbal consent (SVC) for a laparoscopic Roux-en-Y gastric bypass (LRYGB) on patient's knowledge of the procedure, satisfaction with the clinical encounter and duration of the consent appointment., Methods: This prospective non-blinded randomized controlled trial allocated 51 patients, who were candidates for a LRYGB, into DEP+SVC (intervention, n = 26) or SVC (control, n = 25) groups. Data were collected at one Bariatric Centre of Excellence (Ontario, Canada) between December 2018 and December 2019. DEP consisted of a 29-slide video-supplemented module detailing the risks, benefits, expectations and outcomes for the LRYGB. Primary outcome was knowledge about the LRYGB operation following the consent discussion. Secondary outcomes were knowledge retention, patient satisfaction, and duration of time required to obtain an informed consent., Results: Baseline demographic data were equivalent between groups except for a greater proportion of male patients in the DEP+SVC group (7/19 vs 0/25; p < 0.01). Baseline procedure-specific knowledge was equivalent between the groups (72.3 ± 11.3% vs 74.7 ± 9.6%; p = 0.41). Post-consent knowledge was significantly higher in the DEP + SVC vs SVC group (85.0 ± 8.8% vs 78.7 ± 8.7%; p = 0.01; ES = 0.72). The duration of time to obtain informed consent was significantly shorter for the DEP + SVC vs SVC group (358 ± 198 sec vs 751 ± 212 sec; p < 0.01; ES = 1.92). There was no difference in knowledge retention at 4-6 weeks (84.4 ± 10.2% vs 82.9 ± 6.8%; p = 0.55) and in patient satisfaction (31.5 ± 1.1 vs 31 ± 2.7; p = 0.10)., Conclusion: The addition of a DEP online module to a standard verbal consent for LRYGB resulted in improved patient's understanding of the procedure-specific risks and benefits, high patient satisfaction, and over 50% time savings for the bariatric surgeon conducting the consent discussion., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0&#95;{-1.7}^{+2.4}  fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.

The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data.

We report on the results of the LISA Pathfinder (LPF) free-fall mode experiment, in which the control force needed to compensate the quasistatic differential force acting on two test masses is applied intermittently as a series of "impulse" forces lasting a few seconds and separated by roughly 350 s periods of true free fall. This represents an alternative to the normal LPF mode of operation in which this balancing force is applied continuously, with the advantage that the acceleration noise during free fall is measured in the absence of the actuation force, thus eliminating associated noise and force calibration errors. The differential acceleration noise measurement presented here with the free-fall mode agrees with noise measured with the continuous actuation scheme, representing an important and independent confirmation of the LPF result. An additional measurement with larger actuation forces also shows that the technique can be used to eliminate actuation noise when this is a dominant factor.

We describe an interferometric system that can measure the alignment and separation of a polished face of a optical component and an adjacent polished surface. Accuracies achieved are ∼ 1μrad for the relative angles in two orthogonal directions and ∼ 30μm in separation. We describe the use of this readout system to automate the process of hydroxide catalysis bonding of a fused-silica component to a fused-silica baseplate. The complete alignment and bonding sequence was typically achieved in a timescale of a few minutes, followed by an initial cure of 10 minutes. A series of bonds were performed using two fluids - a simple sodium hydroxide solution and a sodium hydroxide solution with some sodium silicate solution added. In each case we achieved final bonded component angular alignment within 10 μrad and position in the critical direction within 4 μm of the planned targets. The small movements of the component during the initial bonding and curing phases were monitored. The bonds made using the sodium silicate mixture achieved their final bonded alignment over a period of ∼ 15 hours. Bonds using the simple sodium hydroxide solution achieved their final alignment in a much shorter time of a few minutes. The automated system promises to speed the manufacture of precision-aligned assemblies using hydroxide catalysis bonding by more than an order of magnitude over the more manual approach used to build the optical interferometer at the heart of the recent ESA LISA Pathfinder technology demonstrator mission. This novel approach will be key to the time-efficient and low-risk manufacture of the complex optical systems needed for the forthcoming ESA spaceborne gravitational waves observatory mission, provisionally named LISA.

Background: Incisional hernias are a well described complication of abdominal surgery. Previous studies identified malignancy and diverticular disease as risk factors. We compared incisional hernia rates between colon resection for colorectal cancer (CRC) and diverticular disease (DD)., Study Design: We performed a retrospective, population-based, matched cohort study. Provincial databases were linked through the Institute for Clinical Evaluative Sciences. These databases include all patients registered under the universal Ontario Health Insurance Plan. Patients aged 18-105 undergoing open colon resection, without ostomy formation between April 1, 2002 and March 31, 2009, were included. We excluded those with previous surgery, hernia, obstruction, and perforation. The primary outcomes were surgery for hernia repair, or diagnosis of hernia in clinic., Results: We identified 4660 cases of DD. These were matched 2:1 by age and gender to 8933 patients with CRC for a total of 13,593. At 5 years, incisional hernias occurred in 8.3% of patients in the CRC cohort, versus 13.1% of those undergoing surgery for DD. After adjusting for important confounders (comorbidity score, wound infection, age, diabetes, prednisone and chemotherapy), hernias were still more likely in patients with DD [HR 1.58, 95% Confidence Interval (CI) 1.43-1.76, P < 0.001]. The only significant covariate was wound infection (HR 1.63, 95% CI 1.43-1.87, P < 0.001)., Conclusion: Our study found that incisional hernias occur more commonly in patients with DD than CRC.

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency.

We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0  fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1  fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15}  g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3)  fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5  mHz we observe a low-frequency tail that stays below 12  fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

We describe the optical and mechanical design, construction philosophy, and testing of a pair of matched, spaceflight-qualified fiber couplers. The couplers were developed for the LISA Pathfinder mission but are relevant for other applications-both on ground and in space-where a robust fiber coupler with well-controlled beam parameters and stable beam pointing is required. This particular implementation of the design called for two couplers providing collimated beams with individual waist sizes and positions. The target values were a 522 μm waist 145 mm after the collimating lens for one coupler and a virtual 520 μm waist 194 mm before the collimating lens for the second coupler. Values of (542±4)  μm at (142±19) mm and (500±8)  μm at (-275±8)  mm were achieved, fully meeting the mission requirements. To control spurious noise effects in the interferometer, the optical system design also specified tight limits on relative beam curvature at an intended interference point. With nominal curvatures at this location of ∼2.35  m, the matching between the outputs of the two fiber couplers was measured to be λ/33 peak-valley over the central 1 mm of the beams. Results showing pointing stability of 3 μrad/°C over a 50°C range are presented. The vibration, shock, and thermal vacuum environmental testing conditions to which a pair of qualification fiber couplers were subjected-without change in performance-are listed.

We describe an instrument which, coupled with a suitable coordinate measuring machine, facilitates the absolute measurement within the machine frame of the propagation direction of a millimeter-scale laser beam to an accuracy of around ±4 μm in position and ±20 μrad in angle.

A method for constructing quasimonolithic, precision-aligned optical assemblies is presented. Hydroxide-catalysis bonding is used, adapted to allow optimization of component fine alignment prior to the bond setting. We demonstrate the technique by bonding a fused silica mirror substrate to a fused silica baseplate. In-plane component placement at the submicrometer level is achieved, resulting in angular control of a reflected laser beam at the sub-10-μrad level. Within the context of the LISA Pathfinder mission, the technique has been demonstrated as suitable for use in space-flight applications. It is expected that there will also be applications in a wide range of areas where accuracy, stability, and strength of optical assemblies are important., (© 2013 Optical Society of America)

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

A case of spontaneous internal carotid artery (ICA) dissection confined to the intrapetrous carotid canal that was confirmed by angiography and magnetic resonance imaging is presented. Isolated dissection involving the intrapetrous ICA is rare; however, whenever arterial dissection is a consideration, specific review of imaging in this region is warranted.

This retrospective review evaluates the outcome benefit of a standard follow-up protocol for 435 patients treated for endometrial carcinoma between 1981 and 1986. Routine follow-ups consisting of physical examinations and vaginal cytologies were done every 3 months for the first year, 4 months for the second year, and 6 months thereafter. Chest X rays were done biannually. Demographic, histopathologic, therapeutic, and follow-up data were studied. Exclusions due to incomplete follow-up (70), persistent disease (40), or other primary malignancies (8) left 317 patients with a disease-free state assigned to follow-up. Recurrences developed in 53 patients being followed, 40 (75%) of whom were symptomatic. Family physicians primarily diagnosed recurrences in 34 patients while recurrences in only 11 of the 53 patients (21%) were detected on routine follow-up at the cancer center (5 by examination and 6 by chest X ray). Therefore, only one recurrence was detected for every 206 routine follow-up visits. Vaginal vault cytology was not diagnostic in any patient. Seventy percent of recurrences occurred within 3 years. There was no statistical difference in survival between the group detected on routine follow-up and those who were symptomatic (P = 0.55). Routine follow-up of patients treated for endometrial cancer did not improve detection of recurrences or survival.

An automatic alignment system, based on a differential phase-sensing technique described in a companion paper [Appl. Opt.33, 0000, (1994)], has been experimentally demonstrated on the 10-m prototype laser interferometric gravitational wave detector in Glasgow. The alignment system developed was used to control the orientations of two mirrors in a 10-m-long suspended Fabry-Perot cavity with respect to the direction defined by the input laser beam. The results of the test and a discussion of the performance of the system are given.

We present a description of a system for automatic alignment of optical interferometers. The technique relies on using differential phase modulation to permit the detection of the phase difference between two fundamental-mode Gaussian beams at the output of an interferometer. Measurements of the spatially varying phase difference between the two beams by use of one or more multielement photodiodes permits information to be derived about the mismatch in overlap between the phase fronts at the output of the interferometer.

We report a case of pelvic inflammatory disease complicated by a tubo-ovarian abscess containing Taenia spp. proglottids and ova which migrated through a fistula with the sigmoid colon.

From 1980 to 1991, 13 patients had pregnancy-associated invasive carcinoma of the cervix: four carcinomas were stage IA; eight were stage IB; and one was stage IVB. Gestational ages range from 8 weeks to 3 months postpartum. Two patients are dead of disease and a third is alive with metastases. Results of immunoenzyme studies for estrogen receptors (ER) were variably positive in all except one tumor, whereas results of studies for progesterone receptors (PR) were uniformly negative. Thus, these hormone receptor studies are unlikely to be of prognostic significance. Six tumors contained human papillomavirus (HPV) DNA by in situ or dot blot hybridization (three, HPV 16; two, HPV 18; one, HPV 31/33/35). Thus, neither ER nor PR expression appears to be related to the infecting HPV type. Using flow cytometry, three tumors were determined to be aneuploid and a fourth, tetraploid. To correlate HPV or DNA flow cytometry data with prognosis will require study of larger numbers of patients from multiple centres.

Between 1974 and 1985, 16 patients (7 men, 9 women) with a diagnosis of genital verrucous carcinoma were identified from the cancer registry of the Tom Baker Cancer Centre in Calgary. All the men had lesions on the penis. In the women, five lesions were on the vulva, four were on the cervix and two were on the vagina (two women each had two involved sites). The histologic slides from the surgically excised specimens were reviewed, and, by applying strict criteria, all cases could be reclassified as giant condyloma (five cases), intraepithelial neoplasia with or without condylomatous features (eight cases) or invasive squamous cell carcinoma (five cases). The authors believe that, in genital lesions associated with the human papillomavirus, a diagnosis of verrucous carcinoma is nonspecific and may lead to inappropriate clinical management.

A rare case of malakoplakia involving the omentum and endometrium is presented. This is the first documented case of malakoplakia in the Thai population.

In summary, we have presented proposed new diagnostic terminology and screening frequencies for cervical cytology with some of the surrounding debate. As Thailand develops its own cervical screening program for squamous cell carcinoma, an awareness of these new recommendations may help in the design of a local program in the most cost effective manner.

Seven patients with a histologic diagnosis of lichen sclerosus et atrophicus of the vulva were treated by laser ablation of the affected area to a depth of 1.0 to 2.0 mm. The inpatient procedure was performed under general anesthesia with a carbon dioxide laser unit. Healing was complete 6 weeks postoperatively. All but one patient was free of recurrent symptoms at follow-up, which ranged from 12 to 37 months. Laser ablation is an acceptable treatment for patients who have symptoms due to lichen sclerosus of the vulva that are refractory to other measures.

From May 1986 to March 1988, there were 3,622 "new" female clients at the Calgary Sexually Transmitted Disease (STD) Clinic of whom 2,278 registered for the first time. A cervico-vaginal (Pap) smear was obtained from those who had not had one in the previous 6 to 12 months and any history of venereal warts (VW) was recorded. 621 smears were accessed of which 611 were suitable for inclusion in this study. 65 (10.6%) smears revealed human papillomavirus (HPV) and/or cervical intraepithelial neoplasia (CIN). Any history of VW increased the likelihood of an abnormal smear by 5.3 times. Those with currently visible VW were more likely (8.8 times) to have an abnormal smear than those with a past history (3.5 times). These data re-affirm the recommendation of the first "Walton Report" that Pap smears should be obtained in STD Clinics.

The charts and pathology specimens of 27 patients with ovarian tumors of low malignant potential were reviewed in an attempt to document the rationale for a second laparotomy in those patients with clinical stage 1 disease and who did not have a complete staging laparotomy at their initial surgery. Four of 13 patients with serous tumors, none of 12 patients with mucinous tumors, and one patient with a mixed tumor of LMP were upstaged at the staging laparotomy. The major morbidity rate associated with the procedure was 7.4%. The low yield of a staging laparotomy in patients with mucinous tumors (0%) does not warrant a second operation. The higher yield of a staging laparotomy in patients with serious tumors (30.8%) suggests that the likelihood of upstaging the disease exceeds the potential morbidity, and for this reason, the procedure may be warranted. However, the specific role of a staging laparotomy even in those with serous tumors awaits further study of the prognostic significance of invasive versus noninvasive implants.

We describe a unique case of Pneumocystis carinii organisms within a peritoneal effusion of a patient with acquired immunodeficiency syndrome (AIDS). The patient, a 28-yr-old homosexual male with profound immunosuppression, presented with splenomegaly and ascites. A peritoneal tap was performed for diagnostic purposes. Cytologic examination of the cytospin specimen showed reactive mesothelial cells along with aggregates of debris reminiscent of the foamy exudates seen in the alveoli of lungs infected with the Pneumocystis carinii organism. A modified methanamine silver stain was performed and revealed the presence of scattered Pneumocystis carinii in the specimen. Extrapulmonary Pneumocystis carinii infection is occasionally seen in AIDS, but we could find no other reports of its detection in peritoneal fluid.

Two cases in which tumours of contrasting malignant potential arose in mature cystic teratomas (dermoid cysts) of the ovary are presented: one patient had a spindle-cell sarcoma and the other a trabecular carcinoid. The first patient's clinical course was characterized by rapid recurrence of the tumour and death 3 months after surgery. The second patient is alive and well with no evidence of residual carcinoid, although the follow-up time is short. Since the surgical procedure of choice differs substantially if malignant transformation occurs in an ovarian dermoid cyst, the pathologist should be consulted intraoperatively in selected cases.

To determine the prevalence of human papillomavirus (HPV) infection in 401 patients attending colposcopy for the first time, scraped cervical cells were investigated using dot blot hybridization and biotinylated DNA probes to HPV 6 and 11 (low-risk types) and 16, 18, and 33 (high-risk types). The HPV DNA was isolated from 52% of patients (low-risk types = 4%, high-risk types = 48%). Seventy-five percent had a cervical intraepithelial neoplasia (CIN)-condyloma. Low-risk types were infrequent (7%) and high-risk types (41%) predominant in condyloma/CIN I lesions when converse rates were expected. As CIN I lesions harboring high-risk types are at some risk of progressing to a higher grade dysplasia, colposcopic examination and treatment of this subgroup would seem justified. As expected, high-risk types were statistically associated with increasing grades of dysplasia. This hybridization method identified typeable HPV DNA in 60% of patients with a CIN-condyloma, and highlighted a unique HPV profile for this patient cohort.

Fifty-five ovarian mucinous tumours, 22 benign, 16 borderline and 17 malignant, were examined for intestinal differentiation (ID). This was defined by the presence of one or more of endocrine, absorptive, goblet or Paneth cells, and identified by routine haematoxylin and eosin as well as histochemical and immunoperoxidase techniques. Twenty benign (91%), 14 borderline (88%) and all malignant tumours contained foci of ID. The frequency of ID was not significantly different between the mucinous tumour types (chi-squared test for independence). Follow-up was available on all patients with borderline tumours: 14 were stage Ia, including both cases without ID, and 2 were stage Ic at presentation. All are alive and free of disease at 9-39 months (median 15.5 months). We conclude that the presence of ID in borderline mucinous tumours is unlikely to be of prognostic significance, and that a subdivision of these tumours into müllerian and intestinal types is unnecessary.

A case of chordoid sarcoma which presented as a painful mass on the dorsum of the right hand in a 72-year-old man was studied by light and electron microscopy. The tumor was composed of lobules separated by thin connective-tissue bands. At the periphery of the lobules, the cells were epithelioid in appearacne and there were numerous nests of clear cells. From the periphery, stellate and spindle shaped cells were radially oriented and formed a loose cobweb arrangement in an abundant loose ground substance. Distinctive ultrastructural features included pseudoacinar formation, microvilli, long cytoplasmic filopodia (often with complex interdigitations), numerous desmosomes, partial basal lamina, scanty endoplasmic reticula, and numerous intracytoplasmic filaments 80--100 A in width. We believe these ultrastructural features indicate a synovial origin of this uncommon neoplasm.

The cytologic findings in percutaneous fine needle aspiration biopsy of two bronchial mucoepidermoid carcinomas are presented. The main features of this unusual tumor of the lung observed in the aspiration biopsy are sufficiently distinctive from those of other lung lesions to be diagnostic.

This is the first report of an ovarian carcinoma developing in a patient immunosuppressed by Cyclosporin A. Thirteen months before the diagnosis of malignancy, the patient received a living related donor kidney transplant whose rejection was controlled by Cyclosporin A and prednisone. The tumor was rapidly fatal five weeks from diagnosis. The literature on malignant transformation in the immunosuppressed patient is reviewed with emphasis on a gynecologic perspective.

Laser vaporization was used to treat 27 women diagnosed at the Tom Baker Cancer Centre, Calgary, Alberta, Canada, as having vaginal intraepithelial neoplasia. The diagnosis was established after review of vaginal cytologic examination and a histologic biopsy. Treatment was performed with a carbon dioxide laser unit attached to an operating microscope. All but three patients had general anesthesia for the purpose of treatment. Tissue destruction was accomplished to a depth of 2 to 3 mm. Patients were followed up for an average of 14.4 months with regular colposcopy, cytologic evaluation, and biopsy when persistent or recurrent disease was suspected. Failure of therapy was defined as evidence of intraepithelial neoplasia in any one of these three parameters. Four patients required a second treatment. After one or two treatments the success rate of therapy was 78%. In our institution, laser vaporization with the patient under general anesthesia on an outpatient basis is the treatment of choice for vaginal intraepithelial neoplasia.

Ultrastructural examination of six rare sarcomas--four monophasic spindle cell tumours, one epithelioid sarcoma, one chordoid sarcoma--has revealed marked similarities at the electron microscopic level despite widely divergent light microscopic appearances. These features consisted of: 1 the presence of two cell types, viz. a clear cell and a cell resembling the fibroblast; 2 pseudoglandular spaces with projecting microvilli or filopodia, and with related tight junctions; 3 an amorphous intercellular ground substance with focal condensation into recognizable basement membrane. The findings suggest a common maturation of these diverse tumours to synovial-like tissue, and support the proposal of Hajdu Shiu & Fortner (1977) that these be considered variants of synovial sarcoma. Published ultrastructural studies of synovial, epithelioid and chordoid sarcoma are reviewed in the light of these findings. The ultrastructural differentiation of synovial sarcoma from extraskeletal myxoid chondrosarcoma, chordoma and the spectrum of malignant spindle cell tumours is discussed.

This case study of a sclerosing stromal tumor of the ovary in a 29-year-old woman demonstrates that the tumor was a functioning lesion that secreted estradiol, progesterone, and testosterone. Clinically, there was anovulation with resultant infertility, which was resistant to therapy with clomiphene citrate. Removal of the tumor was followed by reversal of these abnormalities.

The clinical features are presented of three patients in whom lymphangiosarcoma developed after radical mastectomy followed by local irradiation. The median time between radical mastectomy and the diagnosis by biopsy of lymphangiosarcoma was 9.9 years. No form of therapy, including high-dose combination chemotherapy, appeared able to control the disease. All three patients died with residual lymphangiosarcoma and in two it was the direct cause of death. These results stress that prevention of postmastectomy lymphangiosarcoma is vital. This can be accomplished by avoiding radical mastectomy followed by local irradiation. Ultrastructural observations in one case suggest that the tumour has a primitive vasoformative origin.

Infection of the cervix with specific types of the human papillomavirus (HPV) results in condylomatous, dysplastic and/or neoplastic epithelial changes. To enable routine screening of premalignant cervical lesions for HPV DNA, we have developed a sensitive method of detecting HPV -6, -11, -16, -18 and -33 in cervical scrapes using a non-isotopic, dot-blot hybridization assay. Cloned, genomic HPV DNA is labelled with biotin-11-dUTP by nick translation, and used to screen for HPV types under high stringency conditions. DNA is extracted from cervical cells and spotted on nitrocellulose membranes. Cervical cells, from 20 patients attending colposcopy were screened for HPV types. All patients had a dysplasia or condyloma. HPV DNA was isolated from 80%. The method visualized an amount of target DNA as low as 1 pg without background. Compared with Southern blot hybridization utilizing radiolabelled probe, this assay is equally sensitive and specific. The technique is easy to do, and may significantly contribute to the management of cervical dysplasia.

Endometrial adenocarcinoma is frequently unsuspected in women under the age of 45 years by the gynecologist or the pathologist, but it does occur. Twenty-seven cases of endometrial adenocarcinoma in this age group, from 1980 to 1985, were reviewed clinically and pathologically. Five cases were excluded by histologic examination. Obesity and abnormal vaginal bleeding were shown to be risk factors. Endometrial screening is to be encouraged. This cancer may arise de novo rather than from a premalignant precursor. Implications of this neoplasm for the premenopausal woman are considered.

Extraspinal ependymomas have been described in the subcutaneous sacrococcygeal and presacral areas. Since 1984, eight pelvic ependymomas have been reported that have originated in the ovary, broad ligament, mesovarium, and omentum. This report documents an additional case arising from the right uterosacral ligament in a 48-year-old woman. The diagnosis of ependymoma was supported by a histologic pattern of true rosettes and pseudo-rosettes, glial fibrillary acidic protein (GFAP) positivity, and electron microscopic findings of cilia, blepharoplasts, and intermediate filaments. The tumor was positive for cytokeratin and vimentin. Ultrastructurally, neurosecretory granules were present within the cytoplasm. These features have not been described previously in pelvic ependymomas. These tumors, although easily confused with serous papillary carcinoma, should be distinguished from serous papillary carcinoma because of their apparently better prognosis and tendency for late recurrence.

An improved immunohistochemical determination of the cytokeratin profiles of epithelia and their neoplasms is possible using monoclonal antibodies that will either identify all 19 cytokeratins (AE1/3) or delineate specific subsets (35 beta H11, 34 beta E12, 34 beta B4 and Cam 5.2). Ovarian common "epithelial" tumors (CET) contain cytokeratin filaments. To determine the nature and differences in the cytokeratin profiles of ovarian CET, eight benign Brenner tumors, four serous cystadenofibromas, 28 mucinous tumors, 27 serous tumors and six endometrioid, five clear cell and five undifferentiated carcinomas, as well as nine normal ovaries were immunostained with the above five antibodies. AE1/3 staining was predominant, while Cam 5.2 and 35 beta H11 displayed the most frequent staining thereafter. Statistically significant staining differences were found between a number of tumor groups using the antibodies 35 beta H11, 34 beta E12 and Cam 5.2. In this study, all ovarian CET, except the benign Brenner tumors, displayed a predominantly low molecular weight cytokeratin profile. The same profile in the normal surface epithelium lends credence to the belief that these tumors are derived from this epithelium. A significant staining difference between some of the tumor types using some of the antibodies suggests a possible ancillary, diagnostic role of cytokeratin profiling in situations where exact tumor typing is difficult.

Infection with types 6, 11, 16, and 18 of the human papillomavirus (HPV) is associated with condylomatous, dysplastic, or carcinomatous changes in the genital tract. Emerging evidence suggests that a similar series of lesions develops in the anal canal after exposure to the same HPV types. In situ hybridization was performed with the use of biotinylated DNA probes to HPV 6, 11, 16, and 18, so as to determine the frequency of HPV DNA in 45 perianal and/or anal condylomata, 6 anal intraepithelial neoplasias, and 13 anal squamous cell carcinomas. Of the 33 perianal and/or anal condylomata in which HPV DNA was detected, 13 contained HPV 6 and 11, 12 HPV 6, 7 HPV 11, and 1 HPV 6, 11, and 18. Two of four severe anal dysplasias contained HPV 16, whereas one case each of mild and moderate anal dysplasia contained HPV 6. No HPV DNA was detected in the anal squamous cell carcinomas. The study demonstrated the presence of HPV DNA in 73% of condylomata and 67% of anal dysplasias. The observations suggest that the cloacogenically derived anal epithelium is susceptible to infection by the same HPV types as infect the similarly derived epithelium of the lower female genital tract and that these HPV types result in some similar lesions, i.e., condylomata and dysplasias in both sites. A role in the genesis of anal cancer was not found in this study.

Forty-five patients with invasive cervical squamous cell carcinoma were registered in the Tom Baker Cancer Centre from 1980 to 1985. The natural history of 22 patients (48.9%) who developed persistent or recurrent disease including 11 Stage IB, 8 Stage IIB, and 3 Stage IIIB is reported. Only one patient who had the uncommon papillary variant is alive without evidence of residual disease. The remainder are either dead (16) or alive with residual disease (5). Four patients never achieved a disease-free status and in the remainder recurrences developed on average in 8.7 months. Central or regional disease was not controlled in 20 of 22 patients. Neither radical surgery nor radiotherapy was evidently more effective in preventing persistent or recurrent disease. A reliable predictive marker for persistent or recurrent disease is required: lymph-vascular invasion in the radical hysterectomy specimens was present in 5 of 6 cases but it is subject to interpretive error. Since the disease is frequently systemic at the time of diagnosis, early adjuvant therapy and improved staging techniques are required to improve the survival.

Inguinal intranodal blue nevus is a rare lesion, but awareness of the condition will avoid a mistaken diagnosis of metastatic melanoma. The authors describe the case of a 40-year-old woman in whom an inguinal node blue nevus was discovered incidentally during radical vulvectomy for squamous cell carcinoma. They describe the characteristic light and electron microscopic features. With increased awareness of this lesion the authors believe it will be found in lymph-node chains other than the inguinal and axillary ones previously reported.

In a randomised double blind study to determine whether an increase in the polyunsaturated fat linoleic acid might influence leucocyte membrane sodium transport 22 normotensive volunteers received an oral supplement of linoleic acid or placebo daily for four weeks. Mean total sodium efflux rose significantly during supplementation with linoleic acid compared with placebo. In addition, all components of lying and standing blood pressure fell, though only the fall in supine systolic pressure was significant. Dietary supplementation with linoleic acid may alter ion fluxes across the cell membrane, presumably through changes in its physicochemical structure. In addition, the change in fat intake may lower blood pressure, though to only a very modest extent.