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Background: The incidence of pelvic fractures and associated risk factors was determined in women treated with curative-intent radiotherapy for cervical cancer., Methods: The records of 516 women treated with curative-intent radiotherapy for cervical cancer between 2001 and 2006 at the University of Texas M. D. Anderson Cancer Center were reviewed. Among these, 300 patients had at least 1 post-treatment computed tomography scan or magnetic resonance imaging study available for review, and they comprised our study population. All imaging studies were re-reviewed by a single radiologist to evaluate for fractures., Results: Pelvic fractures were noted in 29 of 300 patients (9.7%). Fracture sites included sacrum (n = 24; 83%), sacrum and pubis (n = 3; 10%), iliac crest (n = 1; 3%), and sacrum and acetabulum (n = 1; 3%). Thirteen patients (45%) were symptomatic, with pain being the most common presenting symptom. The median time from the completion of radiotherapy to the detection of fractures on imaging studies was 14.1 months (range, 2.1-63.1 months), with 38% of patients diagnosed within 1 year and 83% diagnosed within 2 years of completing therapy. The median age of the patients at diagnosis was higher in the women who developed a fracture compared with the women who did not (56.5 years vs 46.7 years; P = .04). A higher number of women with a fracture were postmenopausal (62% vs 37%; P = .03). The median body mass index was lower in the women who had a fracture (26.0 kg/m2 vs 28.0 kg/m2; P = .03)., Conclusions: Pelvic fractures were detected in a substantial proportion of women after radiotherapy for cervical cancer. Bone mineral density screening and pharmacologic intervention should be considered in these women., Competing Interests: DISCLOSURES The authors made no disclosures., (Copyright 2009 American Cancer Society.)

Endometrial carcinoma is the most common female pelvic malignancy and the seventh most common neoplasm worldwide, with the highest incidence in North America and Europe. Endometrial cancer is staged according to the International Federation of Gynecology and Obstetrics surgical system. Clinical estimation of stage, however, can be inaccurate in more than 20%, and therefore, preoperative imaging of the disease may assist in planning the optimal course of treatment. For example, cross-sectional imaging, especially magnetic resonance imaging (MRI), may detect gross myometrial extension or extension of tumor to the cervical stroma, which can alter management and therefore help in preoperative surgical planning. This issue is increasingly relevant as less invasive surgical techniques, such as laparoscopic surgeries, are becoming more commonplace for lower stage cancers. Several imaging techniques such as MRI, computed tomography, and transvaginal ultrasound have been used as tools for preoperative staging of endometrial cancer. Currently, MRI is the most widely used modality for preoperative planning. This article discusses the use of MRI in diagnosis, staging, and detection of endometrial cancer and treatment of recurrent disease.

Objective: To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-gamma1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer., Methods: In this phase II study, patients with recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer were treated with subcutaneous GM-CSF and rIFN-gamma1b before and after intravenous carboplatin until disease progression or unacceptable toxicity. All patients had measurable disease and a chemotherapy-free interval >6 months. Response was determined using RECIST criteria and CA 125 levels., Results: Between 2003 and 2007, 59 patients received a median of 6 cycles of therapy (range, 1 to 13 cycles). Median age at enrollment was 61 years (range, 35 to 79 years). Median time to progression prior to enrollment was 11 months (range, 6 to 58 months). Of 54 patients evaluable for response, 9 (17%) had a complete response, 21 (39%) had a partial response, and 24 (44%) had progressive disease. The overall response rate was 56% (95% CI: 41% to 69%). With a median follow-up of 6.4 months, median time to progression was 6 months. Myeloid derived cells and platelets increased on day 9 of each chemotherapy cycle. The most common adverse effects were bone marrow suppression, carboplatin hypersensitivity, and fatigue. Responders reported improved quality of life., Conclusion: This pre and post-carboplatin cytokine regimen resulted in a reasonable response and a hematologic profile that could invite further evaluation of its components in the treatment of patients with ovarian cancer.

Background: : The objective of this study was to determine the efficacy of mifepristone (RU-486) in women with advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma (LGESS)., Methods: : Mifepristone (RU-486; 200 mg orally) was given daily to patients with progesterone receptor-positive advanced or recurrent endometrioid adenocarcinoma or LGESS. Patients were evaluated every 4 weeks for toxicity and response. Quality-of-life data were obtained using the Memorial Symptom Assessment Scale and Functional Assessment for Cancer Therapy., Results: : Twelve of 13 enrolled patients were evaluable in the first phase of accrual. Stable disease was noted in 3 of 12 patients (at 8 weeks, 12 weeks, and > or =77 weeks, respectively), and the median time to disease progression was 48 days. Among the patients who had stable disease, 2 women had endometrioid endometrial cancer, and 1 woman had LGESS. No partial or complete responses were observed. The most frequent grade 1 and 2 toxicities were anorexia, fatigue, and mood alterations observed in 50%, 50%, and 58% of patients, respectively. The most common grade 3 toxicities were fatigue and dyspnea observed in 25% and 17% of patients, respectively. One patient experienced grade 4 dyspnea. Thirty-three percent of patients had asymptomatic elevations of corticotropin. No serious treatment-related adverse events occurred. There were no significant changes in quality of life., Conclusions: : Single-agent mifepristone used in the treatment of recurrent endometrioid adenocarcinoma or LGESS resulted in a stable disease rate of 25%. One patient who had a biopsy-positive disease recurrence remained stable at 77 weeks. Although mifepristone was tolerated well, as a single agent, it provided limited response as a single agent in women with progesterone receptor-positive uterine tumors. Recently, was been recognized that biologic agents used as single agents may result only in stable disease unless they are combined with cytotoxic agents. The authors concluded that further research into the best mode of application for mifepristone in the treatment of endometrial cancer is needed. Cancer 2009. (c) 2009 American Cancer Society.

Background: Despite the unquestionable importance of clinically oriented research designed to test the safety and efficacy of new therapies in patients with malignant disease, there is limited information regarding strategies to evaluate the quality of such efforts at academic institutions., Methods: To address this issue, a committee of senior faculty at the University of Texas M.D. Anderson Cancer Center established specific criteria by which investigators from all departments engaged in clinical research could be formally evaluated. Scoring criteria were established and revised based on the results of a pilot study. Beginning in January 2004, the committee evaluated all faculty involved in clinical research within 35 departments. Scores for individual faculty members were assigned on a scale of 1 (outstanding) to 5; a score of 3 was set as the standard for the institution. Each department also received a score. The results of the evaluation were shared with departmental chairs and the Chief Academic Officer., Results: 392 faculty were evaluated. The median score was 3. Full professors more frequently received a score of 1, but all faculty ranks received scores of 4 and 5. As a group, tenure/tenure track faculty achieved superior scores compared to nontenure track faculty., Conclusions: Based on our experience, we believe it is possible to conduct a rigorous consensus-based evaluation of the quality of clinical cancer research being conducted at an academic medical center. It is reasonable to suggest such evaluations can be used as a management tool and may lead to higher-quality clinical research., (Copyright 2009 S. Karger AG, Basel.)

Purpose: To evaluate the magnitude of cervix regression and motion during external beam chemoradiation for cervical cancer., Methods and Materials: Sixteen patients with cervical cancer underwent computed tomography scanning before, weekly during, and after conventional chemoradiation. Cervix volumes were calculated to determine the extent of cervix regression. Changes in the center of mass and perimeter of the cervix between scans were used to determine the magnitude of cervix motion. Maximum cervix position changes were calculated for each patient, and mean maximum changes were calculated for the group., Results: Mean cervical volumes before and after 45 Gy of external beam irradiation were 97.0 and 31.9 cc, respectively; mean volume reduction was 62.3%. Mean maximum changes in the center of mass of the cervix were 2.1, 1.6, and 0.82 cm in the superior-inferior, anterior-posterior, and right-left lateral dimensions, respectively. Mean maximum changes in the perimeter of the cervix were 2.3 and 1.3 cm in the superior and inferior, 1.7 and 1.8 cm in the anterior and posterior, and 0.76 and 0.94 cm in the right and left lateral directions, respectively., Conclusions: Cervix regression and internal organ motion contribute to marked interfraction variations in the intrapelvic position of the cervical target in patients receiving chemoradiation for cervical cancer. Failure to take these variations into account during the application of highly conformal external beam radiation techniques poses a theoretical risk of underdosing the target or overdosing adjacent critical structures.

Objective: The purpose of this retrospective study was to determine the sensitivity and specificity of combined PET/CT in differentiating benign from malignant adrenal nodules measuring at least 1 cm in diameter in patients with cancer., Materials and Methods: We reviewed the radiology reports and images of patients with known malignant disease who had undergone PET/CT for cancer staging or surveillance and who had adrenal nodules at least 1 cm in diameter. We identified 112 adrenal nodules in 96 patients. Two-dimensional PET had been performed 1 hour after administration of (18)F-FDG. Unenhanced CT was performed for attenuation correction, to determine lesion size, and for coregistration with PET data. Adrenal nodules were considered to have a positive PET result if the average standardized uptake value was greater than that of the liver. Follow-up data and biopsy reports were used to determine the pathologic status of the adrenal nodules., Results: Thirty adrenal lesions were malignant. Twenty-five of the 30 malignant nodules had positive PET results. Twelve of 82 benign nodules were PET positive with a sensitivity of 83.3% and specificity of 85.4%. Patients with four of five malignant nodules with negative PET results had received previous therapy. The positive predictive value for detection of malignant lesions was 67%, and the negative predictive value was 93%., Conclusion: Adrenal masses that are not FDG avid are likely to be benign with a high negative predictive value. Especially in patients undergoing therapy, however, there is a small but statistically significant false-negative rate. A considerable proportion of benign nodules have increased FDG activity.

Colorectal cancer is a common malignancy that afflicts many in the western world. Imaging studies are frequently used to evaluate patients in the screening, staging and surveillance of colorectal cancer. Cross sectional imaging studies such as ultrasound, computed tomography and magnetic resonance imaging provide anatomic and morphologic information about tumor and patterns of spread. Positron emission tomography (PET) differs in that it provides information about tumor metabolism.[(18)F]Fluorodeoxyglucose PET has been clinically used for the evaluation of patients with a wide variety of cancers since most malignancies, including colorectal cancer, typically show increased glucose metabolism. This review present the positron emission tomography/computed tomography imaging findings that may be encountered in the diagnosis, staging and follow-up of patients with colorectal cancer.

Defects in biotin metabolism are mainly associated with either the enzyme Biotinidase or Holocarboxylase synthetase. Defects in either enzymes depletes biotin utilization by the cells. Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. This condition is inherited in an autosomal recessive pattern. We present a case of a 9 year old girl with atypical symptomology as a case holocarboxylase synthetase deficiency, who demonstrated an increased excretion of propionic and methyl malonic acids, with her biotinidase activity being normal. She demonstrated remarkable improvement on biotin supplementation.

Background: Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined., Methods: We recruited 2600 asymptomatic study participants, 50 years of age or older, at 15 study centers. CT colonographic images were acquired with the use of standard bowel preparation, stool and fluid tagging, mechanical insufflation, and multidetector-row CT scanners (with 16 or more rows). Radiologists trained in CT colonography reported all lesions measuring 5 mm or more in diameter. Optical colonoscopy and histologic review were performed according to established clinical protocols at each center and served as the reference standard. The primary end point was detection by CT colonography of histologically confirmed large adenomas and adenocarcinomas (10 mm in diameter or larger) that had been detected by colonoscopy; detection of smaller colorectal lesions (6 to 9 mm in diameter) was also evaluated., Results: Complete data were available for 2531 participants (97%). For large adenomas and cancers, the mean (+/-SE) per-patient estimates of the sensitivity, specificity, positive and negative predictive values, and area under the receiver-operating-characteristic curve for CT colonography were 0.90+/-0.03, 0.86+/-0.02, 0.23+/-0.02, 0.99+/-<0.01, and 0.89+/-0.02, respectively. The sensitivity of 0.90 (i.e., 90%) indicates that CT colonography failed to detect a lesion measuring 10 mm or more in diameter in 10% of patients. The per-polyp sensitivity for large adenomas or cancers was 0.84+/-0.04. The per-patient sensitivity for detecting adenomas that were 6 mm or more in diameter was 0.78., Conclusions: In this study of asymptomatic adults, CT colonographic screening identified 90% of subjects with adenomas or cancers measuring 10 mm or more in diameter. These findings augment published data on the role of CT colonography in screening patients with an average risk of colorectal cancer. (ClinicalTrials.gov number, NCT00084929; American College of Radiology Imaging Network [ACRIN] number, 6664.), (2008 Massachusetts Medical Society)

Purpose: To identify patterns of locoregional recurrence in patients treated with surgery and preoperative or postoperative radiotherapy or chemoradiation for rectal cancer., Methods and Materials: Between November 1989 and October 2001, 554 patients with rectal cancer were treated with surgery and preoperative (85%) or postoperative (15%) radiotherapy, with 95% receiving concurrent chemotherapy. Among these patients, 46 had locoregional recurrence as the first site of failure. Computed tomography images showing the site of recurrence and radiotherapy simulation films were available for 36 of the 46 patients. Computed tomography images were used to identify the sites of recurrence and correlate the sites to radiotherapy fields in these 36 patients., Results: The estimated 5-year locoregional control rate was 91%. The 36 patients in the study had locoregional recurrences at 43 sites. There were 28 (65%) in-field, 7 (16%) marginal, and 8 (19%) out-of-field recurrences. Among the in-field recurrences, 15 (56%) occurred in the low pelvis, 6 (22%) in the presacral region, 4 (15%) in the mid-pelvis, and 2 (7%) in the high pelvis. Clinical T stage, pathologic T stage, and pathologic N stage were significantly associated with the risk of in-field locoregional recurrence. The median survival after locoregional recurrence was 24.6 months., Conclusions: Patients treated with surgery and radiotherapy or chemoradiation for rectal cancer had a low risk of locoregional recurrence, with the majority of recurrences occurring within the radiation field. Because 78% of in-field recurrences occur in the low pelvic and presacral regions, consideration should be given to including the low pelvic and presacral regions in the radiotherapy boost field, especially in patients at high risk of recurrence.

This paper evaluates the imaging appearance of radiation injury in the liver on positron emission tomography (PET)/computed tomography (CT) in patients with distal esophageal cancer who underwent pre-operative chemoradiation therapy. Twenty-six patients with distal esophageal cancer who received chemoradiotherapy before esophagectomy were included. All patients had baseline and follow-up PET/CT. Fluorodeoxyglucose (FDG) uptake in both left and right lobes of the liver was evaluated. CT findings suggesting radiation damage were documented. Abnormal FDG uptake in the liver was observed in 5 (19%) patients after therapy. These abnormalities were in the left lobe (12%) and right lobe (12%) of the liver. In the irradiated left lobe, FDG uptake increased focally greater than 50% over baseline in two patients (54% and 133%); in one of these patients, biopsy confirmed radiation injury. In the non-irradiated right lobe, standard uptake values (SUV) increased diffusely in two different patients. In one patient, SUV decreased by at least 50% in both the right and left lobes. In the remaining patients, there were no significant changes in FDG uptake. Atrophy and attenuation changes of irradiated liver on CT were found in 15 (58%) patients. In patients receiving chemoradiotherapy, PET/CT may identify metabolic abnormalities in irradiated liver. Such abnormalities should be correlated with other imaging, clinical and laboratory findings to avoid confusion with hepatic metastases.

Positron emission tomography (PET)/computed tomography (CT) has important utility and limitations in the initial staging of esophageal cancer, evaluation of response to neoadjuvant therapy, and detection of recurrent malignancy. Esophageal cancer is often treated by using a combined modality approach (chemotherapy, radiation therapy, and esophagectomy); correct integration of PET/CT into the conventional work-up of esophageal cancer requires a multidisciplinary approach that combines the information from PET/CT with results of clinical assessment, diagnostic CT, endoscopic gastroduodenoscopy, and endoscopic ultrasonography. PET/CT has limited utility in T staging of esophageal cancer and relatively limited utility in detection of dissemination to locoregional lymph nodes. However, PET/CT allows detection of metastatic disease that may not be identifiable with other methods. PET/CT is not sufficiently reliable in the individual patient for determination of treatment response in the primary tumor. Interpretation of PET/CT results is optimized by understanding the diagnostic limitations and pitfalls that may be encountered, together with knowledge of the natural history of esophageal cancer and the staging and treatment options available., (RSNA, 2007)

Gynecologic cancers are a common cause of morbidity and mortality in women of all ages. While many gynecologic cancers are staged clinically using the International Federation of Gynecology and Obstetrics (FIGO) staging system, imaging can be a useful adjunct to clinical staging. Cross sectional imaging techniques such as ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) have been used to detect and follow patients with gynecologic cancer. These imaging modalities can show anatomic detail and morphologic changes in the female genitourinary tract to good advantage. Positron emission tomography (PET) differs in that it shows functional information that is not easily obtained by the other cross sectional imaging techniques. The fusion of PET with CT allows anatomic localization of functional abnormalities in the female genital tract and thereby allows the detection of gross disease in many malignant conditions both within and outside the confines of the female pelvis. The utility and limitations of imaging common gynecologic tumors such as cervical, ovarian and endometrial cancer are discussed with particular emphasis on PET/CT imaging.

Colorectal cancer is a leading cause of morbidity and mortality in the United States. It is also a disease that is preventable if precursor adenomatous polys are removed. Once a diagnosis of colorectal cancer is made, surgical resection is the only means of cure. The ability to resect colorectal cancer for cure is largely dependent upon the stage of tumor at presentation. Once a patient has been treated for colorectal cancer with surgery and in some cases neo-adjuvant or adjuvant therapy, they will present for follow-up. Surveillance is performed on these patients in order to detect local recurrence that if detected early can be surgically resected for cure. Surveillance also allows detection of distant metastatic disease that may in some cases also be cured with resection. Finally, surveillance of the remaining colon is important to detect the development of new or metachronous adenomatoid polyps that if left in place could develop into new colon cancers. Imaging can play a part in patient surveillance to detect recurrent disease at extracolonic sites as well as the development of new colonic lesions. CT colonography is a promising tool for surveillance in patients with a history of colorectal cancer.

Objective: The objective of this article is to describe the imaging appearances of radiation injury to normal tissues in the abdomen that may be seen during imaging surveillance of oncology patients., Conclusion: Therapeutic radiation is used to treat various malignant conditions in the abdomen. Radiation damages normal surrounding tissues as well as the intended tumor. Radiation changes vary based on the target organ and the time from completion of therapy. Familiarity with the spectrum of changes that may be seen on follow-up imaging studies should help in the differentiation of radiation injury from other causes such as recurrent malignancy.

The methyl-accepting chemotaxis protein, DcrH, from the anaerobic sulfate-reducing bacterium, Desulfovibrio vulgaris (Hildenborough), has a hemerythrin-like domain, DcrH-Hr, at its C terminus. DcrH-Hr was previously shown to contain a diiron site that binds O2, suggesting an O2-sensing function. X-ray crystal structures of diferric (met-), azido-diferric (azidomet-), and diferrous (deoxy-) DcrH-Hr reveal a "substrate tunnel" distinct from that in invertebrate hemerythrins. This tunnel is proposed to facilitate the rapid autoxidation of oxy-DcrH-Hr and suggests that sensing is triggered by O2 binding and subsequent oxidation of the diferrous active site. The N-terminal loop of DcrH-Hr is highly ordered in both met- and azidomet-DcrH-Hr but is disordered in deoxy-DcrH-Hr. These redox-dependent conformational differences presumably transduce the sensory signal of DcrH-Hr to the neighboring methylation domain in the full-length receptor. Given the putative cytoplasmic localization of its Hr-like O2-sensing domain, DcrH is proposed to serve a role in negative aerotaxis (anaerotaxis).

Objective: The purpose of this article is to show the appearance of atypical sites of metastasis in patients with recurrent ovarian cancer., Conclusion: Metastatic disease from ovarian cancer outside of the peritoneal cavity is generally rare at presentation but is increasingly seen in patients who have recurrent disease, despite multiple therapies. It is important for radiologists to recognize atypical sites of metastasis in patients with recurrent ovarian cancer to facilitate earlier diagnosis and treatment.

Background: Monocyte/macrophages (MO/MA), a polymorphic population of innate immune cells, have the potential to mediate antitumor effects, and may also contribute to protumor effects. A priming and post-chemotherapy schedule of the myeloid cell mobilizing and immune stimulatory growth factor, granulocyte monocyte stimulating factor (GM-CSF, Leukine) and the MO/MA activating cytokine recombinant interferon gamma 1b (rIFN-gamma1b, Actimmune) has been developed. The pre- and post-chemotherapy design is based upon known in vivo kinetics and immune modulatory effects of these molecules. Carboplatin (Paraplatin) was selected as the cornerstone of treatment of epithelial ovarian cancer (EOC)., Methods: We studied hematopoietic and immunologic effects of GM-CSF and rIFN-gamma1b before and after carboplatin in patients with recurrent EOC. Potentially chemotherapy-sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF (starting at 400 mug/day) for 7 days plus subcutaneous rIFN-gamma1b (100 mug) on days 5 and 7, before and after intravenous carboplatin (area under the curve of 5). We performed standard hematologic assessment and monitored monocyte (MO), dendritic cell, major cell subset counts, and antibody-dependent cell-mediated cytotoxicity (ADCC) against a Her2neu+ tumor cell line, as well as selected plasma inflammatory cytokine, chemokine and growth factor levels., Results: Our analysis comprised only the first 3 months of treatment in the initial 25 patients. Relative to pretreatment baseline values, white blood cell, neutrophil, MO, and eosinophil counts increased (P

Proteins from thermophilic microorganisms are stabilized by various mechanisms to preserve their native folded states at higher temperatures. A thermostable glucose-6-phosphate dehydrogenase (tG6PDH) from the hyperthermophilic bacterium Aquifex aeolicus was expressed as a recombinant protein in Escherichia coli. The A. aeolicus G6PDH is a homodimer exhibiting remarkable thermostability (t1/2 = 24 hr at 90 degrees C). Based on homology modeling and upon comparison of its structure with human G6PDH, it was predicted that cysteine 184 of one subunit could form a disulfide bond with cysteine 352 of the other subunit resulting in reinforced intersubunit interactions that hold the dimer together. Site-directed mutagenesis was performed on tG6PDH to convert C184 and C352 to serines. The tG6PDH double mutant exhibited a dramatic decrease in the half-life from 24 hr to 3 hr at 90 degrees C. The same decrease in half-life was also found when either C184 or C352 was mutated to serine. The result indicates that C184 and C352 may play a crucial role in strengthening the dimer interface through disulfide bond formation, thereby contributing to the thermal stability of the enzyme.

Purpose: To evaluate retrospectively the utility of intensity-modulated radiotherapy (IMRT) in reducing the volume of normal tissues receiving radiation at varying dose levels when the female pelvis after hysterectomy is treated to doses of 50.4 Gy and 54 Gy., Methods and Materials: Computed tomography scans from 10 patients who had previously undergone conventional postoperative RT were selected. The clinical tumor volume (vaginal apex and iliac nodes) and organs at risk were contoured. Margins were added to generate the planning tumor volume. The Pinnacle and Corvus planning systems were used to develop conventional and IMRT plans, respectively. Conventional four-field plans were prescribed to deliver 45 Gy (4F(45 Gy)) or 50.4 Gy; eight-field IMRT plans were prescribed to deliver 50.4 Gy (IMRT(50.4 Gy)) or 54 Gy (IMRT(54 Gy)) to the planning tumor volume. All plans were normalized so that > or =97% of the planning tumor volume received the prescribed dose. Student's t test was used to compare the volumes of organs at risk receiving the same doses with different plans., Results: The mean volume of bowel receiving > or =45 Gy was lower with the IMRT(50.4 Gy) (33% lower) and IMRT(54 Gy) (18% lower) plans than with the 4F(45 Gy) plan. The mean volume of rectum receiving > or =45 Gy or > or =50 Gy was also significantly reduced with the IMRT plans despite an escalation of the prescribed dose from 45 Gy with the conventional plans to 54 Gy with IMRT. The mean volume of bladder treated to 45 Gy was the same or slightly lower with the IMRT(50.4 Gy) and IMRT(54 Gy) plans compared with the 4F(45 Gy) plan. Compared with the 4F(45 Gy) plan, the IMRT(50.4 Gy) plan resulted in a smaller volume of bowel receiving 35-45 Gy and a larger volume of bowel receiving 50-55 Gy. Compared with the 4F(45 Gy) plan, the IMRT(54 Gy) plan resulted in smaller volumes of bowel receiving 45-50 Gy; however, small volumes of bowel received 55-60 Gy with the IMRT plan., Conclusion: Intensity-modulated RT may permit an increase in the radiation dose that can safely be delivered to the central pelvis and pelvic lymph nodes after hysterectomy. However, dose-volume calculations using individual CT scans do not account for internal organ motion. Detailed data concerning the relationships among radiation dose, treatment volume, and treatment effects are lacking, and prospective studies of pelvic IMRT are needed to determine the safety and efficacy of this treatment.

Context: Conventional colonoscopy is the best available method for detection of colorectal cancer; however, it is invasive and not without risk. Computed tomographic colonography (CTC), also known as virtual colonoscopy, has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers., Objective: To assess the accuracy of CTC in a large number of participants across multiple centers., Design, Setting, and Participants: A nonrandomized, evaluator-blinded, noninferiority study design of 615 participants aged 50 years or older who were referred for routine, clinically indicated colonoscopy in 9 major hospital centers between April 17, 2000, and October 3, 2001. The CTC was performed by using multislice scanners immediately before standard colonoscopy; findings at colonoscopy were reported before and after segmental unblinding to the CTC results., Main Outcome Measures: The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm. Secondary outcomes included detection of all lesions, detection of advanced lesions, possible technical confounders, participant preferences, and evidence for increasing accuracy with experience., Results: A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures; 104 participants had lesions sized at least 6 mm. The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0% (95% confidence interval [CI], 29.6%-48.4%) and for lesions sized at least 10 mm, it was 55.0% (95% CI, 39.9%-70.0%). These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99.0% (95% CI, 97.1%->99.9%) and 100%, respectively. A total of 496 participants were without any lesion sized at least 6 mm. The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5% (95% CI, 87.9%-93.1%) and 100%, respectively, and without lesions sized at least 10 mm, 96.0% (95% CI, 94.3%-97.6%) and 100%, respectively. Computed tomographic colonography missed 2 of 8 cancers. The accuracy of CTC varied considerably between centers and did not improve as the study progressed. Participants expressed no clear preference for either technique., Conclusions: Computed tomographic colonography by these methods is not yet ready for widespread clinical application. Techniques and training need to be improved.

Cervical cancer traditionally has been staged clinically. Advances in imaging could improve the staging of cervical cancer by facilitating the detection of lymph node metastases and micrometastases in distant organs. Such progress could lead to improvements in treatment selection and therefore increase overall survival rates. At the Second International Conference on Clinical Cancer (Houston, TX, April 11-14, 2002), a panel composed of gynecologic oncologists, radiation oncologists, and diagnostic radiologists reviewed relevant technologies. Advances in lymphangiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and lymphatic mapping were reviewed, along with the impact of these advances on the diagnosis, treatment, and survival of patients with cervical cancer. Few cancer centers still use lymphangiography, but the sensitivity of this method ranges from 28% to 83%, with specificity ranging from 47% to 100%. The roles of transabdominal and transvaginal ultrasonography in evaluating cervical cancer are expected to expand when new contrast agents increase the sensitivity of these techniques to parametrial invasion and lymph node metastases; meanwhile, ultrasonography's most significant contributions may involve the identification of uterine and cervical leiomyomas and the evaluation of urinary tract obstruction. Advances in CT have made it a rival technique to MRI, but limitations prevent CT from providing definitive information on certain parameters. MRI, which is valuable because of its superior soft tissue contrast resolution, multiplanar capabilities, and cost-effectiveness, is used to determine the size of the cervix and to detect certain types of invasion, characteristics of lymph nodes, and the presence of disease in the ureter, lung, and liver. PET with 2-[fluorine-18]fluoro-2-deoxy-D-glucose has been found to detect abnormal lymph node regions better than CT does but PET can also be used in conjunction with CT to measure tumor dimensions. PET also has become a method for identifying tumors that are unresponsive to chemoradiation. When used together with immunohistochemical and molecular techniques as well as conventional stains, sentinel lymph node mapping, an important development in the surgical management of solid tumors, is expected to improve gynecologic cancer management. Advances in imaging methods and in contrast agents, along with advances in the combined use of the two, are expected to make imaging technologies more valuable in cervical cancer assessment., (Copyright 2003 American Cancer Society.)

Our objective was to assess the value of lymphangiography in selecting patients for surgical staging of locally advanced cervical cancer. We reviewed our computerized database to identify patients with cervical cancer who had abnormal findings on lymphangiography and underwent retroperitoneal lymph node dissection between September 1991 and January 1996. The records of these patients were retrospectively reviewed, and the following data were retrieved: clinical tumor stage and findings on lymphangiography at surgery, and on pathologic examination of resected lymph nodes. The lymphangiograms were reviewed and reinterpreted in blinded fashion by two of the authors. The positive and negative predictive values of lymphangiography for the presence of lymph node metastases were calculated, with findings on pathologic examination of lymph nodes used as the gold standard. The positive and negative predictive values of surgeons' clinical assessments at surgery were also calculated. Fifty patients met the selection criteria and constituted the study population. Fourteen patients (28%) had histologically negative nodes, and 36 patients (72%) had lymph node metastases. Thirty-three patients had metastases to pelvic nodes, 1515 patients had metastases to common iliac nodes, and 1616 patients had metastases to para-aortic nodes. The positive predictive value of lymphangiography for lymph node metastases was 74% for pelvic nodes, 73% for common iliac nodes, and 88% for para-aortic nodes. The negative predictive value of lymphangiography for lymph node metastasis was 76% for common iliac nodes and 77% for para-aortic nodes. Overall, 46% of the patients selected for surgical exploration had histologic findings of either common iliac or para-aortic lymph node metastases; these findings led clinicians to extend radiation fields to cover the para-aortic lymph nodes. Lymphangiography is helpful in selecting patients with cervical cancer who have a high risk of common iliac or para-aortic lymph node metastasis. However, more accurate and more readily available noninvasive methods of evaluating cervical patients for the presence of regional disease continue to be needed.

The gsdA gene of the extreme thermophilic bacterium Aquifex aeolicus, encoding glucose-6-phosphate dehydrogenase (G6PDH), was cloned into a high-expression vector and overexpressed as a fusion protein in Escherichia coli. Here we report the characterization of this recombinant thermostable G6PDH. G6PDH was purified to homogeneity by heat precipitation followed by immobilized metal affinity chromatography on a nickel-chelate column. The data obtained indicate that the enzyme is a homodimer with a subunit molecular weight of 55 kDa. G6PDH followed Michaelis-Menten kinetics with a K(M) of 63 micro M for glucose-6-phosphate at 70 degrees C with NADP as the cofactor. The enzyme exhibited dual coenzyme specificity, although it showed a preference in terms of k(cat)/ K(M) of 20.4-fold for NADP over NAD at 40 degrees C and 5.7-fold at 70 degrees C. The enzyme showed optimum catalytic activity at 90 degrees C. Modeling of the dimer interface suggested the presence of cysteine residues that may form disulfide bonds between the two subunits, thereby preserving the oligomeric integrity of the enzyme. Interestingly, addition of dithiothreitol or mercaptoethanol did not affect the activity of the enzyme. With a half-life of 24 h at 90 degrees C and 12 h at 100 degrees C, this is the most thermostable G6PDH described.

Objective: Our goal was to define the lesion enhancement characteristics of renal cell carcinoma metastases to the pancreas using three-phase helical CT., Materials and Methods: Thin-section three-phase contrast-enhanced CT scans of nine patients with renal cell carcinoma metastases to the pancreas were evaluated. The helical CT protocol included 3-mm collimation and a 2:1 pitch. Scans through the pancreas were obtained in three series beginning 25, 60, and 120 sec after the start of administration of i.v. contrast material delivered at 3 ml/sec. The Hounsfield densities of the pancreatic lesions and normal pancreatic parenchyma during each of the enhancement phases were recorded and compared., Results: The enhancement patterns of the metastatic deposits and the normal pancreas differed. Thirty-four lesions ranging in size from 6 to 110 mm were identified. All metastases showed rapid enhancement during the early (arterial and portal) phases, resulting in differential attenuations (compared with normal pancreatic parenchyma) of approximately 50-100 H. The differential attenuations were approximately 5-45 H on delayed-phase scans, resulting in poorer conspicuity of the lesions. Multifocal metastases were clearly identified on the early-phase scans in seven patients., Conclusion: Renal cell carcinoma metastases to the pancreas enhance most conspicuously during the early phases of helical CT. Such metastases may fail to be appreciated in the delayed phase. In patients with suspected renal cell carcinoma metastases to the pancreas, early-phase scanning after i.v. contrast administration should be performed.

Aim: To determine, in an in vitro animal model, the feasibility of subtracting residual faecal material, during virtual colonoscopy, by uniform mixing of the colonic contents with barium., Materials and Methods: Segments of animal colon containing simulated soft-tissue polyps, measuring 3-10 mm, were filled with a faecal substitute consisting of a barium and peanut butter mix that had an attenuation value greater than 200 Hounsfield units. The colonic segments were then examined by CT using 3-10 mm beam collimations, and at pitch factors of 1 and 2. Using subtraction cut-off levels varying from 100-250 Hounsfield units, the barium and peanut butter mix was then subtracted to reveal the underlying polyps., Results: Our optimal technical parameters required 3-mm beam collimation, a helical pitch factor of 2, reconstruction intervals of 3 mm, and a subtraction cut-off level of 150 Hounsfield units. The subtraction technique, in this animal model, had a sensitivity of 94% and a specificity of 80% for polyps measuring greater than 3 mm., Conclusion: In this limited animal model, the subtraction technique utilized was technically feasible and had an acceptable sensitivity.

Five healthy volunteers underwent ultrasonography (US) to determine the feasibility of visualizing the brachial plexus. The roots, trunks, and cords could be identified in the supraclavicular and infraclavicular regions. The roots within the neural foramina and the epidural space could not be evaluated. US may play a complementary role in the evaluation of patients with brachial plexopathy.

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph nodes. The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions.

The purpose of the present study was to determine whether peripheral blood lymphocytes (PBL) from primary open angle glaucoma (POAG) patients have reduced 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity as was previously found in POAG-derived cultured trabecular meshwork cells. The availability of PBL from both POAG and control patients makes this a useful system for studying the association of decreased 3 alpha-HSD activity with POAG. PBL were isolated from the venous blood of 17 POAG patients and 22 non-glaucoma controls and assayed for 3 alpha-HSD activity with tritiated 5 beta-dihydrocortisol as a substrate. The mean 3 alpha-HSD activity +/- S.E.M., expressed in comparable units of specific activity, of the POAG derived PBL was 13.8 +/- 1.3 U as compared to 32.8 +/- 2.0 U for control cells. This reduction (> 50%) was statistically significant (P < 0.001). Quantitative immunoblot analysis of PBL indicated that the POAG and control cells, despite their difference in 3 alpha-HSD activity, had nearly identical amounts of 3 alpha-HSD protein. The molecular weight of PBL 3 alpha-HSD from both groups of patients was 38,000, the same as previously reported for human liver. The results of this study show an association of decreased PBL 3 alpha-HSD activity and POAG which was not related to antiglaucoma therapy. The reduced levels of 3 alpha-HSD activity in the readily obtainable PBL may serve as a marker for POAG or those at risk for developing the disease.

The anatomy of the posterior intercostal lymphatics and lymph nodes is reviewed. These lymph nodes are occasionally visualized by bipedal conventional lymphography. Opacified and/or enlarged posterior intercostal lymph nodes may also be identified with computed tomography of the chest. Familiarity with the lymphatic drainage patterns of the intercostal spaces and recognition of abnormal intercostal lymph nodes may provide additional information regarding disease status in patients with inflammatory or malignant disease of the thorax.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500-fold from human liver cytosol. The purification was monitored using 5 beta-[3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous enzyme was obtained using a procedure that involved ammonium sulfate precipitation and three successive column chromatography steps: DEAE-cellulose, hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column, and the denatured subunit molecular weight was determined to be 38,500, by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated 4,5 double bond was required for substrate activity. The conformation at the 5 position, however, did not influence substrate activity since 5 alpha- and 5 beta-DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18 microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing 10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in a large loss of activity during early stages of the purification. This is the first report of the purification to homogeneity of 3 alpha-HSD from human tissue.

3 alpha-Hydroxysteroid dehydrogenase is a cytosolic, monomeric, NADPH-dependent oxidoreductase which reduces 3-keto-5-dihydrosteroids to their tetrahydro products. We present here the first partial amino acid sequence data for the human liver enzyme and show these sequences to be identical to the deduced amino acid sequence for human hepatic chlordecone reductase. In addition, these two enzymes exhibit similar substrate and cofactor specificities and immunological reactivity. The results suggest that the natural substrates for chlordecone reductase are 3-keto-5-dihydrosteroids and that these two proteins may be identical.

The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.

Plasma and lipoprotein distribution of cholesterol and triglycerides were measured in experimentally induced hypercholesterolemia associated with moderate hypothyroidism and after Anna Pavala Sindhooram (APSm) therapy in rat models. Feeding atherogenic diet increased all the three lipoprotein classes (HDL, LDL and VLDL). When APSm was administered for 90 days at a dose of 30 mg/rat/day, orally with and without atherogenic diet, it brought down the already raised levels of cholesterol and triglycerides in LDL and VLDL. Histological studies on the aorta revealed that APSm therapy produces regression of the atherosclerotic lesions.

Inhibitor-1 following phosphorylation by protein kinase A inhibits phosphoprotein phosphatase-1. We have found that in the rat heart inhibitor-1 is present only in the cytosolic fraction and that its phosphorylation in ventricular slices was increased by isoproterenol but not by isoproterenol and propranolol together. Cardiac microsomal phosphoprotein phosphatase activity, with added phosphorylase a as the substrate, was inhibited 33% by phosphorylated inhibitor-1. Phosphorylated inhibitor-1 decreased the dephosphorylation by exogenous phosphoprotein phosphatase-1 of phospholamban present in the sarcoplasmic reticulum membranes. These results suggest an interaction of cytoplasmic inhibitor-1 with either cytoplasmic or membrane-bound phosphoprotein phosphatase-1 with a subsequent effect on the level of phosphorylated phospholamban and the probable involvement of this interaction in the cardiac response to beta-adrenergic hormones.

Adrenocorticotropin (ACTH) acts via protein kinase A and the putative phosphorylation of a regulatory protein(s). We have examined a role in this process for inhibitor-1 which, following phosphorylation by protein kinase A, inhibits a phosphoprotein phosphatase activity. In the tissues we have examined inhibitor-1 was found primarily in the cytosol (90%) with the rest in the mitochondrial pellet. The highest concentration was in the adrenal cortex. Using adrenal cortex slices, the stimulation of steroidogenesis by ACTH and dibutyryl cAMP is paralleled by a corresponding increase in the phosphorylation of inhibitor-1 and this is not affected by inhibitors of protein synthesis which inhibit the steroidogenic response. The increase in the phosphorylation of inhibitor-1 occurs in the cytosol, while that in the mitochondrial pellet is not affected. Exogenous phosphorylated inhibitor-1, however, was found to inhibit phosphoprotein phosphatase activity in the mitochondrial pellet. The results suggest that the ACTH-induced increase in phosphorylated inhibitor-1 in the cytosol can affect susceptible phosphoprotein phosphatase activity both in the cytosol and the mitochondrial pellet and, hence, the level of phosphorylation of regulatory protein(s) involved in steroidogenesis.