Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings: parallel pathways of tumorigenesis.

High-level microsatellite instability (MSI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting in the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might be discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of hMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta-catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than HNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta-catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all HNPCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.

Primary carcinoid tumour of the ileum associated with massive gastrointestinal haemorrhage.

A case of massive gastrointestinal haemorrhage due to a 3 mm primary carcinoid tumour of the ileum is described. Previously described instances of this problem have been due to larger tumours. The site of the haemorrhage was suggested by a technetium-labelled RBC isotope scan. The lesion was visualized by 'on-table' endoscopy via the colon and ileo-caecal valve. The patient did well after segmental resection of the lesion. This case highlights the diagnosis and current approach to massive lower gastrointestinal haemorrhage.

Visual field obstruction in single-puncture operative laparoscopy.

The use of the laser for translaparoscopic surgery has brought with it a renewed interest in single-puncture operative laparoscopy. Concern about the extent of visual obstruction created intraoperatively by the use of ancillary instruments through the accessory channel prompted this evaluation. Under normal operative conditions, a 5-mm instrument protruding 10 mm or more beyond the distal end of the laparoscope will obstruct 14.6% of the operator's visual field. Still greater curtailment of endoscopic visualization can be expected when large, modified laser probes are used. The double-puncture laparoscopic technique must be considered the method of choice for translaparoscopic conventional or laser surgical procedures.

Variations in gas flow of laparoscopic insufflators.

Maintenance of an adequate pneumoperitoneum is important in laparoscopy, yet little is known about the functioning of laparoscopic insufflators except for the manufacturer's description of the specifications. Frequent failure to maintain an established pneumoperitoneum with the insufflator switched to its automatic mode prompted evaluation of the volume of gas delivered per unit of time by machines in active use. Limited standardization was found between machines in regard to the gas flow mediated by the automatic flow control. In this mode, the insufflator did not adequately compensate for changes in resistance to flow. Disparity of response among flow control devices and interinstrument variations suggest the need to test and calibrate each unit separately for clinical use.

Amniotic fluid ferning in early gestation.

Ferning of amniotic fluid was studied in early pregnancy. Arborization was demonstrated during the interval of 6 1/2 to 16 weeks by flame-drying. Air-drying yielded a spectrum of crystallization from none prior to 8 weeks to full ferning by 16 weeks. Technical differences are stressed.

Ectopic pregnancy among early abortion patients: does prostaglandin reduce the incidence?

The availability and efficacy of prostaglandin (PG) F2 alpha and E series analogues has prompted their frequent use for pregnancy interruption. In the course of evaluating our experience with PGs for interrupting early first trimester gestations, we became increasingly impressed by the absence of any with extrauterine pregnancy. A review of 63 reports encompassing 2,965 patients whose pregnancies were less than 8 weeks' gestational age dating from the last menstrual period and who were similarly treated yielded only 2 cases of ectopic pregnancy. When compared with the generally accepted ectopic gestation rates of the order of 1 in 200 pregnancies, this frequency of 1 in 1,483 is unexpectedly low. Preselection does not appear to explain this impressive discrepancy. If the observation proves correct, it implies that PGs have some form of therapeutic effect in eradicating extrauterine pregnancy by nonoperative means. The implications are obvious in terms of its potential therapeutic benefits.

Early pregnancy interruption with a single PGF2 alpha 15-methyl-analogue vaginal suppository.

Pregnancy was interrupted successfully in 70% of 20 early pregnancies, 35-49 days in duration as dated from the first day of the last menstrual period, by administration of a single intravaginal suppository containing 3 mg of (15S)-15-methyl prostaglandin F2 alpha (PGF2 alpha). No correlation could be demonstrated with baseline beta-subunit human chorionic gonadotropin or serum levels of prostaglandin obtained within ten hours of treatment. Continued pregnancy was documented in 10%. The rate of failures and the frequency of gastrointestinal side effects were deemed too great to warrant adopting this agent for clinical usage.

Postconceptional induction of menses with double prostaglandin F2 alpha impact.

PIP: To evaluate whether a double prostaglandin impact enhances the effectiveness of the 15S-15-methyl prostaglandin (PG) F2 alpha methyl ester analogue in 1st and 2nd trimester abortion, 2 vaginal suppositories spaced 3 hours apart were administered to 10 patients. The patients' ranged from 19-39 years; length of gestation ranged from 44-56 weeks. Uterine contraceptions began from 40-190 minutes after suppository insertion, and bleeding was seen within 120-610 minutes. 3 of the 10 subjects expelled products of conception during the 10-hour observation period. All subjects reported persistent vaginal bleeding after the procedure, and in 8 subjects the bleeding continued for 14 or more days. 6 subjects reported repeated nausea and vomiting, and 7 experienced diarrhea. Both plasma progesterone values and human chorionic gonadotropin (hCG) beta-subunit levels declined during the 10-hour observation period. The significant drop in beta-subunit hCG levels noted at the follow-up visit indicated 8 of the pregnancies had been successfully interruped showed a drop in plasma progesterone levels, showing that this measure does not predict outcome. Overall, the results in this small series do not suggest any improvement in efficacy over that reported with a single vaginal suppository. The frequency and severity of gastrointestinal side effects appeared to be greater and vaginal bleeding was more porlonged. In addition, uterine contractions began earlier and were more intense, requiring greater use of analgesic medication. It is possible, however, that more applications of smaller dosages given at shorter intervals could improve efficacy and reduce the frequency and severity of side effects.^ieng

Low-dose prostaglandin E2 analogue for cervical dilatation prior to pregnancy termination.

The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins may reduce cervical rigidity but are accompanied by undesirable side effects. Our aims were to ascertain if a low-dose (10 mg) analogue (9-deoxo-16, 16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, we studied 39 women with gestational ages ranging from 7 to 19 weeks who were given a single vaginal suppository 1 to 4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortions, we determined progesterone, human chorionic gonadotropin and prostaglandin plasma levels. This low-dose prostaglandin E2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in one patient only). Mean cervical dilatation achieved was 7.8 +/- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or human chorionic gonadotropin levels. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage.

PIP: The trauma of mechanical cervical dilatation preceding abortion is directly related to the degree of cervical resistance. Prostaglandins (PGs) may reduce cervical regidity but are accompanied by undesirable side effects. The aims of this study were to ascertain if a low dose (10 mg) analogue (9-deoxo-16,16 dimethyl-9-methylene PGE2) is effective and well tolerated and, if so, to try to determine the possible mechanism by which it works. To this end, there were 39 women studied withgestational ages ranging from 7-19 weeks who were given a single vaginal suppository 1-4 hours before suction curettage. In addition to demographic data on age, gravidity, parity, and previous abortion, the authors determined progesterone, human chorionic gonadotropin (hCG) and PG plasma levels. This low dose PGE2 analogue was found to be effective in achieving cervical dilatation and softening with minimal side effects (mild nausea in only 1 patient). Mean cervical dilatation was achieved 7.8 +or- 2.3 mm. Softening was apparent and facilitated additional instrumental dilatation when required. No correlation was found between drug effectiveness and gravidity, gestational age, or duration of action. There was no detectable trend with regard to baseline progesterone or hCG. This suggested a specific sensitivity to the local effect by the drug, apparently unrelated to dosage.

Spontaneous prevesical (Retzius-space) abscess with extraperitoneal presacral dissemination. A case report.

The workup of a pelvic mass should not be limited to intraperitoneally located organs. Pathologic conditions of the abdominal wall, although rare, can mimic an intraabdominal process. One example of such conditions is the spontaneous (atraumatic) appearance of an abscess in the retrofascial-prevesical space of Retzius.

Equilibration between breast surface and ambient temperature by liquid crystal thermography.

Controversy surrounds the need for a waiting period (equilibration, or cooling period) before obtaining a breast thermogram. Temperature differences between an intrinsic lesion (carcinoma) and the overlying skin are said to be amplified by cooling of the skin. Some investigators have found no qualitative difference between thermographic evaluations done 3-15 minutes after the patient disrobes; others assert that tests done within this period are invalid. We evaluated nine ovulatory women thermographically twice during a menstrual cycle (proliferative and secretory phases) to ascertain the significance of such a waiting period and to investigate when thermal equilibrium is achieved with the environment. Breast thermograms were obtained with a cholesteric liquid crystal contact plate at 1-minute intervals for a 20-minute period following exposure of the breast to a room temperature of 72 F (22 C). A significant drop in breast skin temperature was found to occur during the first 15 minutes before equilibrium takes place; this finding suggests that a waiting period is necessary for accurate evaluation.

Continued pregnancy after failed first-trimester abortion.

By means of simple changes in the observation and recording process after induced first-trimester abortion, it has been possible to reduce the frequency of failed abortion to one third its former incidence. The operator is merely required to note whether the amniotic sac and fetal parts are actually seen on gross examination and flotation in fluid. This formal requirement appears to serve as an alert mechanism to ensure that women at risk will be effectively evaluated and managed.

Translaparoscopic hemostasis with microfibrillar collagen in lieu of laparotomy. A report of two cases.

Laparoscopy has become an integral part of the gynecologist's armamentarium in the diagnosis and treatment of abdominopelvic conditions. Although it was originally designed only for diagnostic purposes, experienced laparoscopists are performing an increasing amount of surgery translaparoscopically, thereby avoiding the need for major surgical procedures, such as laparotomy. Evaluation of a source of active bleeding is a common indication for diagnostic laparoscopy. A suspected uterine perforation during dilatation and curettage requires such an investigation in most instances when active bleeding is suspected. We report two instances in which laparoscopic visualization identified a source of continuous bleeding at the uterine serosal surface following perforation during curettage. Translaparoscopic application of a microcrystalline collagen hemostatic substance (Avitene) was used to control bleeding at the hemorrhagic site and thus avoid a major abdominal surgical procedure.

Temporal variations of temperature of the breast by cholesteric liquid crystal contact plate thermography.

Thermography of the breast is considered by some to be a risk marker for the presence of abnormalities of the breast. Circadian variations in the temperature of the skin of normal and cancerous breasts have been documented. A temporal study was undertaken to verify whether or not thermograms obtained at different hours of the day are sufficiently similar to be clinically useful. Eleven healthy women underwent four serial thermographic evaluations each at three to four hour intervals. Significant differences were observed between the early morning results and subsequent evaluations. Reproducible thermograms were obtained for all studies done from 12 noon onward. This is a possible indication that the timing of thermographic examinations has to be standardized to ensure that reliable comparisons are being made.

Recurrent anaphylactic reaction to intraperitoneal dextran 75 used for prevention of postsurgical adhesions.

The use of intraperitoneal dextran at the conclusion of a gynecologic surgical procedure to prevent postoperative adhesions has increased recently. Although anaphylactic reaction to dextran administered intravenously is well documented, the authors report such a reaction after intraperitoneal administration. The delayed appearance and the continuation of the undesirable reaction until the intraperitoneal reservoir of dextran was removed by means of a culdocentesis are noteworthy. Physicians should be alerted to this potential complication.

Placement of umbilical artery catheters: high vs. low.

Placement of umbilical artery catheters was retrospectively reviewed in 181 newborns to evaluate random placement of catheter tip in the "high" position between T7 and T9 in the thoracic aorta of 127 infants and in the "low" position below L3 in the abdominal aorta of 54 infants. Group differences in gestational age, asphyxia, hypotension, respiratory disease, duration of catheterization, or infusate type were not significant. Cyanosis or blanching in the low extremities occurred in 67% of the "low" group and 21% of the "high" group (P less than .001). Hematuria occurred in 39% of the "low" group and 21% of the "high" group (P less than .05). High placement appears to have fewer complications. Prompt intervention by neonatal nurse practitioners can help reverse complications that occur during umbilical artery catheterizations.

The temporal relationship between the luteinizing hormone surge and human oocyte maturation.

The temporal relationship of oocyte maturation to endogenous luteinizing hormone (LH) in vivo throughout the preovulatory period has not been previously reported. In order to study in vivo oocyte maturation follicular aspiration was carried out from 4 to 38 hours after the onset of the LH surge. Oocytes were obtained in 72% of cases. If oocytes were harvested more than 18 hours after the onset of the LH surge, resumption of meiosis had occurred. Twenty-eight to thirty-eight hours after the onset of the LH surge preovulatory oocytes in metaphase II were obtained. A corpus luteum was found 38 hours after the onset of the LH surge.

Evaluation of a balloon dilator before second-trimester abortion by vacuum curettage.

We evaluated the cervical dilator device (CDD), an expanding balloon, as a substitute for laminaria tents before abortion at 13 to 16 1/2 weeks by extraction and vacuum curettage. The CDD was found to be an effective dilator, although it did not appear to have any advantage over laminaria tents when placed overnight and was associated with significant pain upon insertion and an apparent increased risk of endometritis. The present CDD or a subsequent modification may offer advantages over laminaria tents for short-term placement.

PIP: A volunteer study was conducted to evaluate the cervical dilator device (CDD) as a substitute for laminaria tents before induced abortion at 13-16 1/2 weeks by extraction and vacuum curettage. 58 2nd-trimester abortion patients were offered the CDD instead of laminaria. Amounts of dilatation resulting from the CDD were compared to results with laminaria; the results are presented in tabular form. The mean dilatation resulting from the CDD compared favorably with use of 1 medium laminaria tent. Parity had no consistent relation to dilatation. The CDD was found to be an effective dilator, but it had no advantage over laminaria tents placed overnight. The CDD caused significant pain on insertion and increased the risk of endometritis, as measured by fever and uterine tenderness. Further modification and refinement of the CDD are necessary to render insertion easier and less painful.

Duration of colposcopic changes associated with trichomonas vaginitis.

The possibility that an abnormal Papanicolaou smear of the uterine cervix may be associated with vaginitis due to trichomonas vaginalis has been known for some time. Since colposcopy is being used with increased frequency to evaluate patients with cytologic abnormalities noted on the cervical smear and the colposcopic changes produced by trichomonal vaginitis are quite typical, a study was designed to evaluate the duration of these changes after effective eradication of the parasite. Among 12 patients in whom the infection was successfully treated, none showed evidence of colposcopically detected abnormalities due to the trichomonal vaginitis at 2 weeks and again at 4 weeks after initiation of therapy.