Habitat influences skeletal morphology and density in the snailfishes (family Liparidae).

We tested the hypothesis that deep-sea fishes have poorly mineralized bone relative to shallower-dwelling species using data from a single family that spans a large depth range. The family Liparidae (snailfishes, Cottiformes) has representatives across the entire habitable depth range for bony fishes (0 m-> 8000 m), making them an ideal model for studying depth-related trends in a confined phylogeny. We used micro-computed tomography (micro-CT) scanning to test three aspects of skeletal reduction in snailfishes (50 species) across a full range of habitat depths: 1) reduction of structural dimensions, 2) loss of skeletal elements, and 3) reduction in bone density. Using depth data from the literature, we found that with increasing depth, the length of the dentary, neurocranium, and suborbital bones decreases. The ventral suction disk decreases width with increasing maximum habitat depth and is lost entirely in some deeper-living taxa, though not all. Although visual declines in bone density in deeper-living taxa were evident across full skeletons, individual densities of the lower jaw, vertebra, suction disk, hypural plate, and otoliths did not significantly decline with any depth metric. However, pelagic and polar taxa tended to show lower density bones compared to other species in the family. We propose that skeletal reductions allow snailfishes to maintain neutral buoyancy at great depths in the water column, while supporting efficient feeding and locomotion strategies. These findings suggest that changes in skeletal structure are non-linear and are driven not only by hydrostatic pressure, but by other environmental factors and by evolutionary ancestry, calling the existing paradigm into question.

Overview of a chemoresponse assay in ovarian cancer.

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.

The evolutionary origins of Syngnathidae: pipefishes and seahorses.

Despite their importance as evolutionary and ecological model systems, the phylogenetic relationships among gasterosteiforms remain poorly understood, complicating efforts to understand the evolutionary origins of the exceptional morphological and behavioural diversity of this group. The present review summarizes current knowledge on the origin and evolution of syngnathids, a gasterosteiform family with a highly developed form of male parental care, combining inferences based on morphological and molecular data with paleontological evidence documenting the evolutionary history of the group. Molecular methods have provided new tools for the study of syngnathid relationships and have played an important role in recent conservation efforts. Despite recent insights into syngnathid evolution, however, a survey of the literature reveals a strong taxonomic bias towards studies on the species-rich genera Hippocampus and Syngnathus, with a lack of data for many morphologically unique members of the family. The study of the evolutionary pressures responsible for generating the high diversity of syngnathids would benefit from a wider perspective, providing a comparative framework in which to investigate the evolution of the genetic, morphological and behavioural traits of the group as a whole.

Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

The benefits of a gynecologic oncologist: a pattern of care study for endometrial cancer treatment.

OBJECTIVES: Compare important aspects of initial endometrial cancer treatment in women with or without primary management by a gynecologic oncologist (GYO). METHODS: A retrospective pattern of care study was conducted using tumor registry data from a community-based health care system. Surgically treated endometrial cancer cases were reviewed with respect to histology, training of surgeon(s), procedures, TNM staging, and prescription of adjuvant radiation. RESULTS: Two hundred and seven consecutive cases completed between January 1998 and December 2000 were analyzed. Overall surgical stage was 78.4% stage I, 6.9% stage II, and 14.7% stage III-IV. Gynecologic oncologists (GYOs) provided care in 101 (48.8%) and gynecologists (GYNs) in 104 cases (50.2%). General surgeons (GSs) assisted gynecologists in 36.5% of cases. GYOs (94.0%) completed TNM staging two times more frequently (P < 0.05) than GYNs (45.2%). The incidence of lymph node assessment by GYOs was 83.0% (average number of nodes, 19.5) and GYNs 26.0% (average number of nodes, 7.7). Advanced disease (stage III-IV) was more frequently (P < 0.05) managed by GYOs (23.0%) than GYNs (6.7%). Radiation (RT) was prescribed to 36 (17.4%) patients. When evaluating TI and TII tumors at risk for extrauterine spread (G2-G3 or myometrial invasion), GYOs completed surgical staging more frequently than GYNs (95.7% vs. 18.8%, P < 0.05). GYO patients received radiation (six patients: 8.6%) less frequently than GYN patients (8.6% vs. 21.7%). No patient managed by GYOs with T1 N0 disease received RT. Eighteen percent of patients managed by GYNs with T1 N0 or T1 NX received RT. CONCLUSIONS: Gynecologic oncologists are more likely to evaluate and manage those with advanced endometrial cancer. Women with endometrial cancer managed by GYOs are more likely to receive comprehensive TNM surgical staging. The employment of complete TNM staging by GYOs reduced the use of RT in those with T1 N0 or Nx disease by 100%. These results suggest that primary management by gynecologic oncologists results in an efficient use of health care resources and minimized the potential morbidity associated with adjuvant radiation.

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma.

PURPOSE: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma. METHODS AND MATERIALS: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient's symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated. RESULTS: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression. CONCLUSIONS: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.

Endometrial cancer: is surgical staging necessary?

Surgical staging has become the standard of care for the treatment of women with endometrial cancer. Recent scientific publications have confirmed the relative safety of this procedure when performed by subspecialty trained surgeons and have provided compelling evidence that the routine use of postoperative teletherapy is not cost effective, nor does it offer improved survival. New questions as to the safety and effectiveness of a laparoscopic staging approach have been answered in the affirmative. Although the extent of staging has not yet been defined, growing evidence suggests that preoperative studies and intraoperative clinical opinion cannot be consistently counted on to be predictive of postoperative histologic status. Therefore, all patients should be considered at risk and should undergo an operation in a clinical situation that offers the immediate availability of retroperitoneal staging or cytoreductive surgery if necessary.

Subspecialty training: does it affect the outcome of women treated for a gynecologic malignancy?

A review of available direct and indirect scientific reports strongly suggests that subspecialty training increases the likelihood that the appropriate surgical procedure will be completed in women operated on for gynecologic cancer. It is likely that specialty care lessens the costs associated with diagnosis, treatment and surveillance, and frequently improves survival.

Ligand-induced conformational changes observed in single RNA molecules.

We present the first demonstration that fluorescence resonance energy transfer can be used to track the motion of a single molecule undergoing conformational changes. As a model system, the conformational changes of individual three-helix junction RNA molecules induced by the binding of ribosomal protein S15 or Mg(2+) ions were studied by changes in single-molecule fluorescence. The transition from an open to a folded configuration was monitored by the change of fluorescence resonance energy transfer between two different dye molecules attached to the ends of two helices in the RNA junction. Averaged behavior of RNA molecules closely resembles that of unlabeled molecules in solution determined by other bulk assays, proving that this approach is viable and suggesting new opportunities for studying protein-nucleic acids interactions. Surprisingly, we observed an anomalously broad distribution of RNA conformations at intermediate ion concentrations that may be attributed to foldability differences among RNA molecules. In addition, an experimental scheme was developed where the real-time response of single molecules can be followed under changing environments. As a demonstration, we repeatedly changed Mg(2+) concentration in the buffer while monitoring single RNA molecules and showed that individual RNA molecules can measure the instantaneous Mg(2+) concentration with 20-ms time resolution, making it the world's smallest Mg(2+) meter.

Cost-effective treatment of women with advanced ovarian cancer by cytoreductive surgery and chemotherapy directed by an in vitro assay for drug resistance.

PURPOSE: Epithelial ovarian cancer is the fourth leading cause of cancer-related death in women. Five-year survival is about 25%, and new approaches to the treatment of this disease are dearly warranted. This study was designed to determine the feasibility of using an in vitro assay for drug resistance to guide treatment after cytoreductive surgery. We present preliminary results of this study after a median follow-up of 24 months. MATERIALS AND METHODS: We treated 66 patients with advanced ovarian cancer by use of a combination of cytoreductive surgery and chemotherapy. Patient inclusion criteria included histologic confirmation of epithelial ovarian cancer, International Federation of Gynecology and Obstectrics (FIGO) stage III, no prior chemotherapy or radiation therapy, no coexisting neoplasm, and optimal residual disease (< 2 cm). Malignant tissue from the involved ovary of each patient was tested in vitro for drug resistance, and chemotherapy was directed individually by assay results. On the basis of the assay we treated 19 patients with platinum/paclitaxel (TP) and 47 with platinum/cyclophosphamide (CP). RESULTS: Three-year survival (Kaplan-Meier estimate) was 69%; the 95% confidence interval was 58% to 80%. There was no difference in 3-year survival between the 19 patients treated with TP (66%) and the 47 patients treated with CP (74%). The cost-effectiveness of each treatment option was determined. It cost $4615 to achieve 3-year survival for patients receiving CP and $17,988 to obtain a similar survival with TP. The cost-effectiveness of assay-directed therapy was $9768. DISCUSSION: Because of the high recurrence rate and the poor long-term survival of women with advanced ovarian cancer, improved therapies for this disease are needed. After surgical debulking, we used results of an in vitro assay for drug resistance to individually select chemotherapy for the patients in this study. Although the 3-year survival of 69% obtained in the present study appears good compared with previously published studies of optimally debulked patients, the results must be viewed with caution. Patients were not randomized, and differences in prognostic factors, such as tumor grade, patient age, and performance status, could account in part for the higher survival found in the current study compared with previously published studies. Treatment with either CP or TP resulted in equivalent 3-year survival. The cost to achieve 3-year survival with this protocol, including the cost of the drug resistance assay, was $9768. We believe that consideration of costs avoided by the elimination of ineffective treatments, needless toxicity, and loss of quality of life would likely increase the cost-effectiveness of assay-directed therapy compared with conventional therapy. This study demonstrates that it is feasible to use an in vitro assay in routine clinical practice to eliminate ineffective chemotherapeutic agents.

Mandibular metastasis in a patient with endometrial cancer.

Gynecologic cancers metastatic to bone are a rare entity, and a metastasis to the mandible at initial presentation is even more infrequently seen. We present a case of a 71-year-old woman with stage IV endometrial cancer with a metastasis to the mandible, with no other sites of distal spread apparent. The endometrial tumor was a FIGO grade III adenocarcinoma. The pathologic evaluation of the mandibular lesion revealed poorly differentiated adenocarcinoma with focal squamous differentiation. She was treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy, radiation therapy to the mandible, and chemotherapy consisting of Taxol and carboplatin for six cycles. She had a complete response, but 10 months after the original diagnosis developed spinal cord compression and progressive disease in the pelvis. Patients in good clinical condition with a single bone metastasis should be treated aggressively, as survival can be extended.

Cervical cancer.

Despite the development of cervical cytology, cancer of the cervix continues to be a major health problem for women. The cause, diagnostic, and therapeutic management of women with preinvasive and invasive disease is discussed.

Protein and Mg(2+)-induced conformational changes in the S15 binding site of 16 S ribosomal RNA.

The Bacillus stearothermophilus ribosomal protein S15 binds to the central domain of the 16 S rRNA inducing a conformational change in a three-way helical junction. To understand the nature of this conformational change, extended-helical junctions were prepared to examine the effects of S15 or Mg2+ binding on the relative helical orientation using native gel electrophoretic mobility and transient electric birefringence. The free junction is planar with approximately 120 degrees interhelical angles, whereas S15 and Mg2+ yield a junction conformation that remains planar in which two helices, 21 and 22, become colinear and the third, helix 20, forms a 60 degrees angle with respect to helix 22. This conformational change is thought to be important for directing the assembly of the central domain of the 30 S ribosomal subunit.

Stage I corpus cancer: is teletherapy necessary?

OBJECTIVE: Our aim was to evaluate the perioperative morbidity after hysterectomy and lymphadenectomy as primary treatment of endometrial cancer and to analyze the recurrence and survival of patients classified as having surgical stage I disease who did not receive adjunctive teletherapy. STUDY DESIGN: Over a 10-year interval 444 patients underwent extensive surgical staging for corpus cancer. Perioperative events were recorded prospectively. Outcome events were updated after the last year of study. RESULTS: After patients with high-risk histologic types of cancer were excluded, 396 patients were evaluable. The risk of extrauterine disease, detected in 21.8% of patients, increased with increasing lack of tumor differentiation. The associated surgical morbidity, including blood loss (mean 336 ml), surgical site infection (3.5%), thromboembolic events (1.5%), and urinary injury (0.6%), and deaths (0.6%) did not differ from those in reports of women undergoing lesser operative procedures. Late complications, including lymphocyst (1.2%), leg edema (1.8%), and hernia (2.9%), were infrequent. Recurrence and survival analysis indicated a calculated 5-year survival of 97% of all patients with surgical stage I disease. There was a significant survival difference related to grade and stage for women in whom disease was confined to the uterus. Overall survival in patients with stage IA (100%) was significantly different (p < 0.0001) from that of patients with stage IB (97%) and stage IC (93%). All recurrences included a distal component. CONCLUSION: Extensive surgical staging including lymphadenectomy can be performed safely. Our results suggest that the risk of pelvic recurrence is not increased and the risk of survival is not compromised in those women not receiving adjunctive teletherapy.

Surgical staging endometrial cancer.

Nothing improves the subsequent care of a woman with endometrial cancer more than the accurate determination of the extent of her disease. A significant number of women whose malignancy is apparently confined to the uterus will have extrauterine disease after careful, complete surgical staging. The failure to detect and effectively treat unrecognized metastatic disease can have fatal consequences; the decision to prescribe potentially harmful therapy to women who do not have metastatic disease also has deleterious effects. Although the optimal surgical management of any patient must be individualized, careful and complete surgical staging at the time of hysterectomy offers the most complete data for future management.

Radical hysterectomy: does the type of incision matter?

OBJECTIVE: Our purpose was to evaluate and compare aspects of operative accessibility and perioperative outcome after radical hysterectomy and pelvic lymphadenectomy performed through a vertical, Pfannenstiel, or Maylard abdominal incision. STUDY DESIGN: During an 8-year interval, 236 patients underwent radical hysterectomy and pelvic lymphadenectomy as primary treatment for cervical cancer at the Watson Clinic. Patients were admitted under a standard perioperative protocol, and all procedures were performed by a gynecologic oncologist. All clinical data was recorded prospectively and updated regularly. RESULTS: Radical hysterectomy and pelvic lymphadenectomy was completed through a vertical (n = 113), Pfannenstiel (n = 78), or Maylard (n = 45) incision. Although lesion size and depth of stromal invasion was not different between incision types, patients with a Pfannenstiel incision were younger (p < 0.001) and weighed less than those with a vertical (p = 0.001) or Maylard (p < 0.025) incision. The Pfannenstiel was associated with a shorter operative time (Pfannenstiel vs Maylard, p < 0.05; Pfannenstiel vs vertical, p < 0.001), less blood loss (Pfannenstiel vs Maylard, p < 0.025; Pfannenstiel vs vertical, p < 0.001), a lower risk of transfusion, and a shorter hospital stay (Pfannenstiel vs Maylard, p < 0.025; Pfannenstiel vs vertical, p < 0.001). These differences persisted when controlled for patient weight and surgical experience. There was no significant difference in the total number of nodes evaluated. No patient had a positive vaginal margin. CONCLUSION: Radical hysterectomy and pelvic lymphadenectomy can be safely performed through a vertical, Maylard, or Pfannenstiel incision. In a selected population a Pfannenstiel incision offers the potential benefit of less abdominal wall trauma without compromising surgical exposure or increasing the risk of surgical complications.

Incisional bowel herniations after operative laparoscopy: a series of nineteen cases and review of the literature.

OBJECTIVES: The objectives of this report were (1) to identify all cases of incisional bowel herniations noted after operative laparoscopy in 11 participating institutions and (2) to report the clinical details of such patients. STUDY DESIGN: A retrospective case review was performed. RESULTS: Nineteen cases of incisional bowel herniation were identified. The average age of the patients was 50.5 years. Initial laparoscopic procedures varied and included laparoscopically assisted vaginal hysterectomy (six patients), laparoscopically assisted vaginal hysterectomy with lymphadenectomy (five patients), oophorectomy (two patients), adhesiolysis (two patients), myomectomy (two patients), lymphadenectomy alone (one patient), and ovarian cystectomy (one patient). The average time to reoperation was 8.5 days. CONCLUSIONS: Incisional bowel herniation is a serious complication of operative laparoscopy. Herniations occur through ports > or = mm in size at both umbilical and extraumbilical sites. New techniques are needed to avoid this serious complication.