Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma.

BACKGROUND: Infertility is a common late effect of chemotherapy and radiotherapy, and has a substantial effect on the quality of life for young survivors of cancer. For men, semen cryopreservation is a simple way of preserving reproductive potential but for women, storage of mature eggs rarely proves successful, and the alternative-immediate in vitro fertilisation with cryopreservation of embryos-is not always appropriate. Reimplantation of cryopreserved ovarian tissue has been shown to restore natural fertility in animals. We applied this technique in a woman who had received sterilising chemotherapy for lymphoma. METHODS: A 36-year-old woman underwent a right oophorectomy with cryopreservation of ovarian cortical strips before receiving high-dose CBV chemotherapy for a third recurrence of Hodgkin's lymphoma. 19 months later, when serum sex steroid analysis confimed a postmenopausal state, two ovarian cortical strips were thawed and reimplanted-one onto the left ovary and another at the site of the right ovary. FINDINGS: 7 months after reimplantation of ovarian cortical strips, the patient reported resolution of hot flashes and, for the first time, oestradiol was detected in the serum. This finding was associated with a decrease in the concentrations of follicle-stimulating hormone and luteinising hormone, and ultrasonography revealed a 10 mm thick endometrium, a poorly visualised left ovary, and a 2 cm diameter follicular structure to the right of the midline. The patient had one menstrual period, but by 9 months after the implantation, her sex steroid concentrations had returned to those seen with ovarian failure. INTERPRETATION: Orthotopic reimplantation of frozen/thawed ovarian cortical strips is a well tolerated technique for restoring ovarian function in women treated with sterilising chemotherapy for cancer.

Safety of bedside percutaneous dilatational tracheostomy in obese patients in the ICU.

STUDY OBJECTIVE: To examine the safety of bedside percutaneous dilatational tracheostomy in obese patients. DESIGN: Case series of consecutive obese patients (body mass index > or = 27 kg/m(2)) with acute respiratory failure in a medical, cardiac, or surgical ICU unit who required tracheostomy for failure to wean and continued mechanical ventilatory support. RESULTS: Thirteen obese patients were identified and consented to the procedure. Bedside percutaneous dilatational tracheostomy was successfully performed in the ICU for all 13 patients. Procedural complications were limited to paratracheal tracheostomy tube placement in one patient, with immediate identification and appropriate correction. Postprocedural complications were limited to a cuff leak in one patient. CONCLUSION: Bedside percutaneous tracheostomy can be safely performed in obese patients.

Ileoanal pouch operation: long-term outcome with or without diverting ileostomy.

HYPOTHESIS: Avoiding a diverting ileostomy does not influence the long-term overall morbidity and functional outcome of patients after ileoanal pouch operation (IAP). DESIGN: All patients undergoing IAP were prospectively entered into a database, and those undergoing operation from October 1, 1989, through January 31, 1996, were contacted by mail questionnaire. SETTING: Tertiary referral center. PATIENTS: One hundred thirty unselected sequential patients. INTERVENTIONS: The IAP was completed by a stapled method without diverting ileostomy, provided the patient agreed, and there were no other complicating factors. MAIN OUTCOME MEASURES: Need for reoperation, fecal leakage, pouch frequency, ability to defer evacuation, pouchitis, and overall quality of life. RESULTS: Of 102 patients (78.5%) who initially underwent IAP without diverting ileostomy, 10 (9.8%) developed an anastomotic leak and required a diverting ileostomy. Additional surgery was required in 12 (9.2%) of the 130 patients for bowel obstruction and in 3 (2.3%) for pouch excision. Two patients died of unrelated causes, leaving 125 functioning pouches (96.2%). Questionnaires were completed in 111 (88.8%) of the 125; 75 patients (67.6%) reported perfect continence for gas and stool, 10 patients (9.0%), regular nighttime leakage, and 24 patients (21.6%), occasional fecal leakage. Pouch evacuation frequency (+/-SD) per 24 hours was 7.8+/-2.4 (range, 4-12), and 95.5% of patients could defer pouch evacuation. Of the 111 patients, 42.3% reported pouchitis, with 7.2% receiving long-term antibiotic therapy. Of the patients, 74.8% reported total satisfaction, and 84.7% regarded themselves as being in perfect health. CONCLUSION: Long-term outcome after IAP remains favorable with or without diverting ileostomy.

Is 24-hour observation necessary after elective laparoscopic cholecystectomy?

BACKGROUND: Laparoscopic cholecystectomy is now the procedure of choice for symptomatic gallbladder disease. The procedure can be done safely and cost effectively on an outpatient basis, either as same-day surgery or with 24-hour observation. METHODS: This report represents a retrospective chart review of 60 patients having elective laparoscopic cholecystectomy. A comparison was made between same-day surgery and 24-hour observation. RESULTS: Of the 60 elective cases, 33 were done as a same-day procedure, and 27 were followed by 24-hour observation. There were no major complications and no return visits to the emergency room (ER) or hospital in either group. The average cost of same-day surgery was $4,940, and the average cost for 24-hour observation was $6,118. CONCLUSIONS: We found no advantage to routinely keeping patients for 24-hour observation. Elective laparoscopic cholecystectomy as same-day surgery is safe and cost effective.

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements.

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.

Trocar site closure: a simple, inexpensive technique.

Trocar site complications continue to plague laparoscopic surgeons. Described in this report is an inexpensive simple technique to close all layers of the trocar site defect.

A prospective evaluation of cryopreservation strategies in a two-embryo transfer programme.

A total of 364 consecutive patients requesting in-vitro fertilization (IVF) treatment were divided randomly into two groups. In the first group, two embryos in the original IVF cycle were allowed to divide prior to transfer, with any remaining embryos being cryopreserved at the pronucleate (PN) stage. In the second group, all the embryos were allowed to divide to the early cleavage (EC) stage, and the best two replaced; any suitable remaining embryos were frozen at the 2- to 4-cell stage. A total of 134 cycles (36.8%) fulfilled the study criteria for a fresh embryo replacement and supernumerary embryos cryopreserved. In the PN group, 72 out of 182 (39.6%) patients had a fresh embryo replacement accompanied by embryo cryopreservation, which was not significantly different from the EC group (62/182; 34.1%). The livebirth rate per fresh embryo transfer in the EC group (17/62; 27.4%) was significantly higher than that for the PN group (8/72; 11.1%; P < 0.05). Embryo survival following thawing was similar for the PN (96/129; 74.4%) and EC (79/102; 77.4%) stages. Although not significant, the livebirth rate following the transfer of thawed embryos was higher in the PN group (11/44; 25.0%) than in the EC group (4/38; 10.5%). Following one fresh and two freeze-thaw embryo replacements, the observed cumulative viable pregnancy rates were comparable for patients in both the PN (40.2%) and EC (41.1%) groups.

Open versus closed epididymal sperm retrieval in men with secondarily obstructed vasal systems--a preliminary report.

OBJECTIVE: To evaluate and compare sperm quality and suitability for intracytoplasmic sperm injection (ICSI) from open and percutaneous epididymal aspiration in men with obstructive azoospermia, and to determine the relevance of epididymal morphology. PATIENTS AND METHODS: A series of 20 men undergoing vasectomy reversal were evaluated by percutaneous (PESA) and open epididymal sperm aspiration (MESA) before undergoing surgery for reversal. Two samples were taken with PESA, one with the needle in situ (PESA1) and the second while withdrawing the needle (PESA2). Epididymal morphology was graded as normal, distended and grossly distended. Five men undergoing vasectomy served as a control, nonobstructed group for percutaneous aspiration. Analysis of the aspirates was performed immediately after operation with no knowledge of the treatment, and aspiration was considered successful if sperm suitable for ICSI were retrieved. RESULTS: In the obstructed group, 15 of 20 men had successful PESA and 13 of these also had successful MESA. PESA was successful bilaterally eight times compared with MESA on five occasions; two men with successful PESA had no success with MESA. PESA2 was five times more successful than PESA1. Only one PESA in the non-obstructed group was suitable for ICSI. PESA was successful in 21 of 25 distended or grossly distended epididymi compared with only three of 21 non-distended systems. CONCLUSION: PESA is a viable alternative to MESA in patients with obstructive azoospermia, particularly when associated with clinically distended epididymi.

Outcome of early surgical complications following ileoanal pouch operation without diverting ileostomy.

BACKGROUND: Many surgeons use a diverting ileostomy routinely following ileoanal pouch operation because they fear that complications may lead to permanent unsatisfactory pouch function or even death. We report the outcome of early surgical complications when ileoanal pouch operation is performed without a diverting ileostomy. We performed 74 consecutive ileoanal pouch operations since ileoanal pouch operations since October 1989 using a transition-zone-sparing stapled J pouch method. RESULTS: Of the 74 patients, 68 (92%) underwent the operation without a diverting ileostomy. Five of the 68 patients (7.4%) required reoperation within 30 days of operation. Pouch excision was necessary in 2 patients (3%) for reasons not resulting from omitting the diverting ileostomy, and they now have excellent pouch function. CONCLUSION: Patients who required early reoperation and placement of a temporary diverting ileostomy did not suffer long-term consequences. The fear that early surgical complications following ileoanal pouch operation without diverting ileostomy are permanently detrimental is unjustified.

Factors favoring continence, the avoidance of a diverting ileostomy and small intestinal conservation in the ileoanal pouch operation.

Ileoanal pouch operation was performed upon 38 consecutive patients with ulcerative colitis (36 patients) or familial polyposis (two patients). Mucosectomy was avoided by rectal mobilization to the dentate line and eversion and stapling of the exteriorized anorectal junction with the dentate line in view. An 8 centimeter J pouch was stapled to the anorectal junction. A diverting ileostomy was not used in 34 of the 38 patients. Physicians independent of the operation evaluated patients postoperatively. Eighty-four percent of the patients did not experience any problems with incontinence or nocturnal spotting at one month postoperatively. No incontinence or nocturnal spotting was seen in any patient by one year postoperatively, with the exception of one patient with chronic pouchitis who had occasional nocturnal spotting that continues to improve. The average number of bowel movements per 24 hours was five at 12 months postoperatively, despite the small pouch. The mean distance from the dentate line to the ileoanal anastomosis was 0.9 +/- 0.5 centimeter (range of zero to 2 centimeters).

Comparison of two transfusion strategies after elective operations for myocardial revascularization.

We performed a prospective, randomized trial of two different strategies for postoperative packed red blood cell replacement in 39 autologous blood donors undergoing elective myocardial revascularization. The "liberal" group received blood to achieve a hematocrit value of 32%, and the "conservative" group received transfusions for a hematocrit value less than 25%. Although the groups had significantly different mean hematocrit values from the fourth postoperative hour (28.7% versus 31.2%) through the fifth postoperative day (28.4% versus 31.3%), there were no significant differences in fluid requirement, hemodynamic parameters, or hospital complications. Significantly fewer units of packed cells were required in the conservatively transfused group (20 units/20 patients) compared with the liberally transfused group (37 units/18 patients) (p = 0.012). Exercise tests were performed on the fifth and sixth postoperative days, with a transfusion being given to the conservative group between tests. Although a significant improvement in exercise endurance occurred in the conservative group receiving a transfusion (p = 0.008), no significant difference in duration or degree of exercise was demonstrated between the two groups on either day. In comparing these two groups of profoundly anemic patients, we identified no adverse consequence associated with the greater degree of hemodilution and could identify no correlation between hematocrit value and exercise capacity. We conclude that although the limits of hemodilution are still poorly defined, postoperative blood transfusion in revascularized patients should be guided by clinical indications and not by specific hematocrit values.

The use of cryopreserved aged human oocytes in a test of the fertilizing capacity of human spermatozoa.

The use of cryopreserved aged human oocytes in a diagnostic test of sperm fertilizing ability was evaluated. Oocytes arising from assisted conception cycles and showing no signs of fertilization 48 h post-insemination were cryopreserved by one of two methods. An ultrarapid method using dimethyl sulphoxide gave poor post-thaw results, with only 5/69 (7.2%) oocytes surviving. Oocytes frozen by a slow method using propanediol as the cryoprotectant gave better survival rates (359/594; 60%). Fertilization by donor spermatozoa of these thawed oocytes was poor (15/63; 24%) when the zona pellucida was left intact. To improve this, the zona was enzymatically removed using pronase. These zona-free oocytes were then inseminated with spermatozoa from a fertile donor or from men previously exhibiting fertilization failure in an in-vitro fertilization treatment cycle. The fertilization rate in the patient group (41/91; 45%) was significantly lower than in the donor group (16/18; 89%) (P less than 0.02). There was also a significant (P less than 0.03) reduction in the median number of pronuclei per oocyte (2.9 versus 4.5). These results show that aged oocytes can be effectively cryopreserved to establish a bank for use in a test to identify men with impaired sperm fertilizing capacity.

A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.

PURPOSE: The study was designed to determine the duration of complete response (CR) for patients with unresectable or metastatic breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) while responding to conventional-dose therapy. METHODS: Eligibility criteria included histologically documented metastatic or unresectable breast cancer, at least a partial response (PR) to conventional-dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m3, and physiologic age between 18 and 55 years. Patients with inadequate renal, hepatic, pulmonary, and/or cardiac function or tumor involvement of marrow or CNS were excluded. Cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 were given by continuous infusion over 4 days. After recovery, sites of prior bulk disease were to be radiated or resected if feasible. RESULTS: Of 29 registered patients, one died of toxicity (3%; hemorrhage). CRs and PRs continued a median of 16 and 5 months after transplant, respectively (26 and 9 months from initiation of chemotherapy for metastatic disease). Of 10 patients transplanted in CR, four have not progressed at 17 to 31 months after transplantation (25 to 43 months after beginning standard-dose therapy). One of four patients with uptake on bone scan as their only sites of residual disease before transplant and one of three who converted from PR to CR with transplant have not progressed at 27 and 29 months, respectively, after transplant. CONCLUSIONS: CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer. Although the duration of PR is short as expected, CRs appear to be durable.

A phase I study of high-dose ifosfamide and escalating doses of carboplatin with autologous bone marrow support.

The dose-limiting toxicity in two separate phase I trials of the high-dose single agents ifosfamide and carboplatin was renal insufficiency at 18 g/m2 and hepatic and ototoxicity at 2,400 mg/m2, respectively. In this phase I study, 16 adults were treated with ifosfamide at 75% of the single-agent maximum-tolerated dose (MTD) (12 g/m2) and escalating doses of carboplatin (400 to 1,600 mg/m2) to determine the nonhematologic dose-limiting toxicity and the maximum-tolerated dose of the combination. Both drugs as well as mesna for uroprotection were given by continuous infusion over 4 days with an additional day of mesna (total dose per course, 15 g/m2). Autologous bone marrow support was stipulated for subsequent dose levels once granulocytes remained less than 500/microL for more than 14 days in two of three to five patients entered at a given dose level. Autologous bone marrow support was used at doses above the 400 mg/m2 carboplatin dose level. At the maximum-tolerated dose level of 1,600 mg/m2 of carboplatin, renal toxicity precluded further dose escalation. Of the five patients entered at this dose level, reversible creatinine elevation greater than 2 mg/dL (median peak, 2.6 mg/dL) was observed in three patients, and irreversible renal failure occurred in an additional patient (peak creatinine, 6.9 mg/dL. Transient gross hematuria appeared more common with the combination than with ifosfamide alone. Two patients developed severe somnolence and confusion associated with a rising creatinine. There were two complete (CRs) and four partial responses (PRs) in 14 heavily pretreated assessable patients (including four partial or complete responses in eight assessable patients with advanced refractory sarcoma, and one CR in two patients with germ cell carcinoma). Carboplatin and ifosfamide appear to have overlapping renal toxicity. Nevertheless, carboplatin and ifosfamide can be combined at 80% and 75% of the single-agent maximum-tolerated doses, respectively, with acceptable nonhematologic toxicity. Ifosfamide and carboplatin are an attractive core combination for further studies in the treatment of sarcoma, germ cell, ovarian, and lung carcinomas.

Escalating doses of carboplatin with high-dose ifosfamide using autologous bone marrow as support: a phase I study.

In this phase I study, 16 adult cancer patients were treated with concurrent 4-day continuous infusions of ifosfamide at 12 g/m2 and escalating doses of carboplatin (400-1600 mg/m2) to determine the major non-haematological dose-limiting toxicity of the combination. Mesna was given by continuous infusion over 5 days for uroprotection (total dose per course = 15 g/m2). Autologous bone marrow support, which was mandated for subsequent dose levels once granulocytes remained below 500/microliters for more than 14 days in at least 2 patients entered at a given dose level, was used at dose levels above 400 mg/m2 carboplatin. Renal toxicity became dose-limiting at the maximum tolerated dose level of 1600 mg/m2 carboplatin. Temporary creatinine elevations above 2 mg/dl (median peak 2.6 mg/dl) were observed in 3 and irreversible renal toxicity occurred in 1 (peak creatinine 6.9 mg/dl, chronic creatinine 5-6 mg/dl) of the 5 patients entered at this dose level. Severe confusion and lethargy associated with rising creatinine developed in 2 patients. Two complete and four partial responses were documented in 14 heavily pretreated evaluable patients. The complete responses continue at 14+ and 20+ months in a patient with germ cell carcinoma and Ewing's sarcoma, respectively. Carboplatin appears to contribute to the renal toxicity of ifosfamide. Nevertheless, the combination of carboplatin and ifosfamide at 80% and 75% of the single-agent maximal tolerated doses respectively produced acceptable non-haematological toxicity. Further studies in the treatment of sarcoma, germ cell, ovarian and lung carcinomas with this combination are warranted.

Cryopreservation of human embryos at the pronucleate, early cleavage, or expanded blastocyst stages.

Supernumerary embryos following treatment by IVF or GIFT were cryopreserved at the pronucleate, early cleavage or expanded blastocyst stages. The success of embryo cryopreservation at these stages was evaluated in terms of (i) the proportion of embryos surviving the freeze/thaw procedure; (ii) the proportion of patients reaching embryo replacement; and (iii) the incidence of pregnancy per replacement. Significantly more embryos survived when frozen/thawed at the pronucleate (44/61; 72%) or early cleavage stages (48/80; 60%), than at the expanded blastocyst stage (13/34; 38%). A significantly higher proportion of patients had embryo replacements when embryos were frozen/thawed at the pronucleate (17/19; 89%) or early cleavage stages (21/24; 88%), than at the expanded blastocyst stage (9/17; 53%). Following replacement of frozen/thawed pronucleate and early cleavage stage embryos, clinical pregnancy rates of 8/17 (47%) and 3/21 (14%) clinical pregnancies were achieved, respectively. No pregnancies were achieved following replacement of frozen/thawed expanded blastocysts.