Gallbladder carcinoma: causes of misdiagnosis at CT.

Gallbladder carcinomas can present with varied imaging features on computed tomography. The three major imaging features include (1) focal or diffuse wall thickening with or without irregularity of the gallbladder; (2) polypoidal intraluminal mass; and (3) large mass obscuring and replacing the gallbladder, often extending to the liver. Patterns of wall thickening or polypoid growth are often confused with various benign gallbladder diseases due to overlap of imaging findings. Moreover, gallbladder carcinomas that coexist with benign gallbladder diseases make accurate preoperative diagnosis more difficult. Recently, high-resolution ultrasound (HRUS) has been regarded as a problem-solving tool for gallbladder diseases. In this article, we will illustrate various imaging presentations of gallbladder cancer, along with imaging pitfalls and recently updated HRUS findings.

Belching during gastroscopy and its association with gastroesophageal reflux disease.

Belching may result from transient lower esophageal sphincter relaxation; therefore, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). This study was conducted to investigate the frequency of belching during esophagogastroduodenoscopy (EGD) and its association with GERD. A retrospective review was performed on prospectively collected clinical and endoscopic data from 404 subjects who underwent EGD without sedation from December 2012 to May 2013 in a training hospital in Korea. All detectable belching events during endoscopy were counted. Frequency and severity of belching events were compared between the group with and without GERD using an ordinal logistic regression model. There were 145 GERD patients (26 erosive reflux disease and 119 nonerosive reflux disease [NERD]). In the multivariable analysis, GERD was significantly associated with a higher frequency of belching events (odds ratio = 6.59, P < 0.001). Central obesity, female, and younger age were also risk factors for frequent belching during EGD. Subgroup analyses were performed in subjects without erosive reflux disease (n = 378) and NERD (n = 293). NERD was also a predictive factor for frequent belching during EGD (odds ratio = 6.61, P < 0.001), and the frequency of belching was significantly correlated with GERD severity according to the Los Angeles classification (P < 0.05). Frequent belching during EGD was associated with GERD, including NERD. Future research should focus on its adjuvant role in the diagnosis of GERD/NERD and the necessity for applying differentiated endoscopy strategies for GERD patients, leading to less discomfort during EGD in patients at risk for intolerability.

Branch duct intraductal papillary mucinous neoplasms in a retrospective series of 190 patients.

BACKGROUND: A consensus conference has recommended close observation of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) smaller than 30 mm, without symptoms or mural nodules. This study investigated whether these recommendations could be validated in a single-centre experience of BD-IPMNs. METHODS: Some 190 patients with radiological imaging or histological findings consistent with BD-IPMN were enrolled between 1998 and 2005. Those with less than 6 months' follow-up and no histological confirmation were excluded. RESULTS: BD-IPMN was diagnosed by computed tomography and pancreatography in 105 patients and pathologically in 85. Eighteen patients had adenoma, 53 borderline malignancy, five carcinoma in situ and nine invasive carcinoma. Findings associated with malignancy were the presence of radiologically suspicious features (P < 0.001) and a cyst size of at least 30 mm (P = 0.001). Had consensus guidelines been applied, 54 patients would have undergone pancreatic resection, whereas only 28 of these patients actually had a resection; 12 of the latter patients had a malignancy compared with none of the 26 patients who were treated conservatively. CONCLUSION: A simple increase in cyst size is not a reliable predictor of malignancy. Observation is recommended for patients with a BD-IPMN smaller than 30 mm showing no suspicious features on imaging.

Relevance of abeta1-42 intrahippocampal injection as an animal model of inflamed Alzheimer's disease brain.

Injection of amyloid-beta peptide (Abeta1-42) into hippocampal and cortical regions of brain may have utility as an animal model of Alzheimer's disease (AD) emphasizing the inflammatory component of disease pathology. This review summarizes recent evidence supporting the relevance of the peptide injection model to describe inflammatory conditions in AD brain. A wide spectrum of responses are considered from effects of Abeta1-42 on animal behavior and cognitive performance to peptide actions at the cellular and molecular levels. In the latter case a particular focus is placed on inflammatory responses mediated by activated microglia. Specific pharmacological modulations of microglial signaling pathways and factors and how they shape patterns of inflammatory reactivity in peptide-injected brain are included. Overall, the considerations for the validity and limitations of Abeta1-42 injection as an animal model for AD pathology are also discussed.

Primary clear cell adenocarcinoma of the rectovaginal septum treated with concurrent chemoradiation therapy: a case report.

Primary clear cell adenocarcinoma of the rectovaginal septum is rare and typically emerges in the setting of endometriosis. We report a case of a 52-year-old woman with clear cell adenocarcinoma of the rectovaginal septum presenting with vaginal hemorrhage. Management with concurrent chemoradiation with cisplatin and paclitaxel is discussed. Six years following the completion of treatment, the patient is without evidence of disease or significant long-term toxicity.

Can we predict spontaneous capsule passage after retention? A nationwide study to evaluate the incidence and clinical outcomes of capsule retention.

BACKGROUND AND STUDY AIMS: Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention. PATIENTS AND METHODS: Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention. RESULTS: Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage. CONCLUSIONS: Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.

Penile neurovascular structure revisited: immunohistochemical studies with three-dimensional reconstruction.

Penile erection is a neurovascular phenomenon that requires well coordinated and functional interaction between penile vascular and nervous systems. In order to provide a useful tool to examine pathologic changes in the erectile tissue, mainly focusing on penile neurovascular dysfunction, we established the technique to determine the differential distribution of endothelial cells, smooth muscle cells, pericytes, and nerve fibers in the mouse penis using immunohistochemical staining with three-dimensional reconstruction. Immunofluorescent staining of penile tissue was performed with antibodies against CD31 (an endothelial cell marker), smooth muscle α -actin (SMA, a smooth muscle cell marker), NG2 (a pericyte marker), or ßIII-tubulin (a neuronal marker). We reconstructed three-dimensional images of penile vascular or neurovascular system from stacks of two-dimensional images, which allows volume rendering and provides reliable anatomic information. CD31-positive endothelial cells, SMA-positive smooth muscle cells, and NG2-positive pericytes were evenly distributed and composed sinusoidal or venous wall. However, the endothelial layer of the cavernous artery or dorsal artery was mainly covered with smooth muscle cells and rarely associated with pericytes. The reconstructed three-dimensional images clearly visualized typical wavy appearance of nerve fibers that evenly innervate to cavernous sinusoids, cavernous artery, dorsal vein, and dorsal artery. We observed a significant decrease in CD31-positive endothelial cells, NG2-positive pericytes, and ßIII-tubulin-positive nerve fibers in the penis of diabetic mice compared with those in normal condition. Our protocol for immunofluorescent staining with three-dimensional reconstruction will allow a better understanding of the penile neurovascular anatomy and may constitute a standard technique to determine the efficacy of candidate therapeutics targeting therapeutic angiogenesis or neural regeneration.

Establishment of in vitro model of erectile dysfunction for the study of high-glucose-induced angiopathy and neuropathy.

Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes-induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high-glucose-induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal-glucose (5 mmoL) or high-glucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high-glucose condition. To study cellular interaction between MCECs and MCPs, co-culture systems including indirect contact, indirect non-contact, and direct mixed co-culture system, were established. We observed impaired tube formation and increased permeability in MCECs-MCPs co-culture exposed to high-glucose condition. To evaluate the effect of high-glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS-positive nerve fibers were significantly lower in MPG tissues exposed to the high-glucose condition than in the tissues exposed to the normal-glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for drug discovery and development of novel therapeutic modalities for erectile dysfunction.

Calorie restriction reverses age-related alteration of cavernous neurovascular structure in the rat.

Calorie restriction (CR) refers to a reduction of calorie intake without compromising essential nutrients to avoid malnutrition. CR has been established as a non-genetic method of altering longevity and attenuating biological changes associated with aging. Aging is also an important risk factor for erectile dysfunction. The aim of this study was to examine whether CR diet can reverse the age-related alterations of erectile tissue in the aged rat. Four groups of rats were used: young rats (7 months) + ad libitum, aged rats (22 months) + ad libitum, young rats + CR diet, and aged rats + CR diet. The ad libitum group had free access to both food and water, and CR groups were fed 60% of the food intake of their ad libitum littermates, starting from 6 weeks before sacrifice. The penis was harvested and stained with antibodies to von Willebrand factor, smooth muscle α-actin, platelet-derived growth factor receptor-ß, phospho-eNOS, nNOS, and neurofilament. We also performed Masson trichrome staining and TUNEL assay. The blood samples were collected for the measurement of serum total testosterone level. The contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells as well as serum testosterone levels were significantly lower in the penis of aged rats than in their young littermates. CR significantly restored cavernous endothelial cells, smooth muscle cells, pericytes, and neuronal cell contents and decreased cavernous endothelial cell apoptosis and fibrosis in both young and aged rats. CR also increased serum testosterone level in aged rats, but not in young rats. CR successfully improved age-related derangements in penile neurovascular structures and hormonal disturbance. Along with a variety of lifestyle modifications, our study gave us a scientific rationale for CR as a non-pharmaceutical strategy to reprogram damaged erectile tissue toward neurovascular repair in aged men.

Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington's disease.

The combination effects of minocycline (MC), a second-generation tetracycline compound and pyruvate (PY), a glycolysis end metabolite with antioxidant activity were investigated in the rat striatum following an excitotoxic insult. Striatal injection of quinolinic acid (QUIN) resulted in marked inflammation characterized by microgliosis, astrogliosis and enhanced expressions of pro-inflammatory enzymes inducible nitric oxide synthase and cyclooxygenase-2. Inflammatory responses were attenuated with administration of either MC or PY, however, the combination of both compounds was significantly more effective in reducing inflammation relative to MC or PY applied alone. Immunohistochemical analysis at 7 days post-intrastriatal QUIN injection showed extensive oxidative stress evident as lipid peroxidation, oxidative DNA damage and reactive oxygen species formation which was partially decreased by each agent applied separately but markedly inhibited with the combination of the two compounds. In addition, combination treatments significantly reduced neuronal loss in QUIN-injected striatum compared with the agents applied separately. Furthermore, long-term combination treatment decreased striatal lesions and inflammation after QUIN injection. These results demonstrate that MC and PY confer a considerably enhanced anti-inflammatory and neuroprotective efficacy when applied together and suggest this combinatorial procedure as a novel therapeutic strategy in neurodegenerative disorders such as Huntington's disease which exhibit excitotoxic insults.

Intracavernous delivery of clonal mesenchymal stem cells rescues erectile function in the streptozotocin-induced diabetic mouse.

The major hurdle for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. The aim of this study was to examine the effectiveness of mouse clonal bone marrow-derived stem cells (BMSCs) obtained from a single colony by using subfractionation culturing method for erectile function in diabetic animals. Twelve-week-old C57BL/6J mice were divided into four groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of PBS (20 µL) or clonal BMSCs (3 × 10(5) cells/20 µL). Clonal BMSCs were isolated from 5-week-old C3H mice. Two weeks after treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was stained with antibodies to PECAM-1, smooth muscle α-actin, neuronal nitric oxide synthase (nNOS), neurofilament, and phosphorylated endothelial NOS (phospho-eNOS). We also performed Western blot for phospho-eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of clonal BMSCs significantly restored cavernous endothelial and smooth muscle cell contents, and penile nNOS and neurofilament contents, and induced eNOS phosphorylation (Ser1177) in diabetic mice. Intracavernous injection of clonal BMSCs induced significant recovery of erectile function, which reached 80-90% of the control values. Clonal BMSCs successfully restored erectile function through dual angiogenic and neurotrophic effects in diabetic mice. The homogenous nature of clonal mesenchymal stem cells may allow their clinical applications and open a new avenue through which to treat diabetic erectile dysfunction.

Water-soluble lipopolymer as a gene carrier to corpus cavernosum.

Adenovirus or naked plasmid DNA (pDNA) has been used to deliver the therapeutic gene into corpus cavernosum. However, the potential risks of viral vector and inefficiency of naked pDNA have limited their clinical application. In this study, water-soluble lipopolymer (WSLP) was evaluated as a gene carrier to corpus cavernosum. The WSLP/pDNA complex was transfected to smooth muscle cells in vitro. WSLP had high transfection efficiency, which was comparable to poly(ethylenimine) (PEI). In addition, WSLP had much less cytotoxicity than PEI, suggesting that WSLP is a safer carrier than PEI. To evaluate the transfection efficiency to corpus cavernosum, the WSLP/pDNA complex was injected into the rat corpus cavernosum. As a result, the WSLP/pDNA complex showed higher transfection efficiency than naked pDNA. In addition, the gene expression was dependent upon the dose of the complex. The results suggest that WSLP may be useful for gene therapy of erectile dysfunction.

The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer.

The management of localized prostate cancer is based on stage, grade, PSA, and subjective assessment of comorbidity and life expectancy. Over the last 15 y, stage migration and the improved use of Gleason sum, PSA and TNM staging have led to many treatment options for patients with newly diagnosed localized prostate cancer. At the same time, advances in treatment techniques have helped decrease the long-term complications of surgery and radiotherapy. However, the importance of age and comorbidity, in survival outcomes and treatment decision-making has been largely overlooked. Currently, stage, grade, and PSA are the only quantifiable variables consistently used in research and treatment decision-making. Comorbidity and life expectancy have remained largely subjective variables. Increasing longevity and a rapidly aging population have made age and comorbidity increasingly important factors in clinical research and treatment decision-making. This article reviews the importance of age and comorbidity on treatment decisions and survival outcomes in prostate cancer, as well as their use as objectively quantifiable variables. Examples from the general oncology literature are given. The overview also examines validated comorbidity indices and advocates the use of the Charlson Comorbidity Index (CCI) in research outcomes and treatment decision-making in prostate cancer. Several clinical vignettes are provided to demonstrate the potential clinical utility of the CCI as applied to prostate cancer.

Effect of levitra on sustenance of erection (EROS): an open-label, prospective, multicenter, single-arm study to investigate erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction.

To investigate the change of erection duration measured by stopwatch with flexible dose vardenafil administered for 8 weeks in subjects with erectile dysfunction (ED). Effect of levitra on sustenance of erection was an open-label, prospective, multicenter and single-arm study designed to measure the duration of erection in men with ED receiving a flexible dose of vardenafil over an 8-week treatment period. Patients were instructed to take vardenafil 10 mg 60 min before attempting the intercourse. Vardenfil could be increased to 20 mg or decreased to 5 mg concerning patients' efficacy and safety. Following the initial screening, patients entered a 4-week treatment-free run-in phase and 8-week treatment period, during which they were instructed to attempt intercourse at least four times on four separate days. A total of 95 men were enrolled in 10 centers. After the 8 weeks treatment, the mean duration of erection leading to successful intercourse was statistically superior when patients were treated with vardenafil. After an 8-week treatment, the duration of erection leading to successful intercourse was 9.39 min. There were significant benefits with vardenafil in all domains of International Index of Erectile Function. Secondary efficacy end points included success rate of penetration, maintaining erection, ejaculation and satisfaction were superior when patients were treated with vardenafil. There was a significant correlation between duration of erection with other sexual factors. Also partner's sexual satisfaction was increased with vardenafil. Most adverse events were mild or moderate in severity. Vardenafil was safe and well tolerated. Vardenafil therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED with female partner.

Chemoradiotherapy for poor-risk stage III non-small cell lung cancer.

Cisplatin-based chemoradiotherapy is becoming a standard treatment for patients with stage III non-small cell lung cancer (NSCLC). However, a significant proportion of patients with lung cancer also present with co-morbid conditions that indicate a poor prognosis and poor tolerance of treatment. We have completed a phase I/II study to evaluate the tolerability and efficacy of carboplatin-based chemoradiotherapy for patients with poor-risk stage III NSCLC. Twenty-four patients with stage IIIA/B NSCLC and concurrent medical conditions rendering them ineligible for cisplatin-based chemoradiotherapy protocols were treated with thoracic irradiation, 1.8 to 2 Gy daily to the primary tumor and regional lymph nodes, for a total dose of 61 Gy. Concurrently, patients received carboplatin 200 mg/m2/d intravenously on days 1, 3, 29, and 31, and etoposide 50 mg/m2/d intravenously on days 1 through 4 and 29 through 32. Among 23 assessable patients, 96% completed the two planned courses of chemotherapy and 87% completed the planned chest irradiation. Grade 3/4 toxicities included neutropenia in nine patients (39%), thrombocytopenia in five (22%), esophagitis in seven (30%), and nausea in two (9%). Four patients (17%) achieved a complete response and 16 (70%) a partial response, yielding an overall response rate of 87%. The median survival was 12 months, and the 2- and 3-year survival rates were 30% and 20%, respectively. In conclusion, this treatment regimen was relatively well tolerated, with promising response and survival in patients with poor-risk stage III NSCLC. This pilot study provides a basis for further investigation of this treatment regimen.

Twice-weekly paclitaxel and radiation for stage III non-small cell lung cancer.

A phase I study was conducted to investigate the safety and efficacy of twice-weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and concurrent thoracic irradiation in patients with stage III non-small cell lung cancer. Radiation therapy beginning on day 1 was delivered in 1.8- to 2.0-Gy daily fractions, to a total dose of 61 Gy. Paclitaxel at a starting dose of 25 mg/m2/d was administered intravenously over 1 hour before daily radiation on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39, for a total of 12 doses over 6 weeks. The paclitaxel dose was escalated by 5 mg/m2/d in each cohort of patients to determine the maximum tolerated dose. The highest paclitaxel dose reached was 40 mg/m2/d, as defined by dose-limiting toxicities of esophagitis and desquamation within the radiation fields. For each dose group, the median total number of paclitaxel doses administered was 12 and the median total radiation dose was 61 Gy. Response rates ranging from 50% to 100% were observed (three of six patients at paclitaxel 25 mg/m2, four of six at 30 mg/m2, seven of seven at 35 mg/m2, six of six at 40 mg/m2), for an overall response rate of 80%. We conclude that the maximum tolerated dose of paclitaxel is 35 mg/m2 given twice weekly in a 1-hour infusion for 6 weeks concurrently with thoracic irradiation. This study provides the basis for an ongoing trial combining twice-weekly paclitaxel and carboplatin with concurrent thoracic irradiation for patients with stage III non-small cell lung cancer.

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk stage III non-small-cell lung carcinoma: a pilot study.

PURPOSE: A pilot study was conducted to assess the tolerance and efficacy of concurrent carboplatin, etoposide, and thoracic radiation in poor-risk patients with Stage III non-small-cell lung carcinoma (NSCLC). METHODS AND MATERIALS: Patients had Stages IIIA/IIIB NSCLC and were ineligible for available clinical trials employing cisplatin-based chemoradiation due to one or more protocol-defined poor-risk factors or concomitant medical conditions. Treatment consisted of thoracic radiation, 1.8 to 2 Gy daily, to the primary tumor and regional lymph nodes to a total dose of 61 Gy. Concurrently, patients received carboplatin 200 mg/m2/day intravenously on days 1, 3, 29, and 31, and etoposide 50 mg/m2/day intravenously on days 1-4 and 29-32. Response was assessed by chest computed tomography (CT) 4 weeks after treatment was completed. RESULTS: A total of 26 patients were enrolled and 23 of these patients, including 11 with Stage IIIA and 12 Stage IIIB NSCLC, were eligible and assessable. Ninety-six percent (96%) of the patients completed the two planned courses of chemotherapy, and 87% completed the planned chest radiation. Grade III/IV toxicities included neutropenia in nine patients (39%), thrombocytopenia in five (22%), esophagitis in seven (30%), and nausea in two (9%). One patient died of a pulmonary embolism during treatment, and another died of complications due to a tracheoesophageal fistula. Four patients (17%) achieved a complete response and 16 (70%) a partial response, yielding an overall response rate of 87%. The median survival was 12 months, and the 2-year actuarial survival was 40%. CONCLUSION: This treatment regimen was well tolerated, with promising response and survival in poor-risk patients with Stage III NSCLC. These results are being validated in a Phase II trial conducted by the Southwest Oncology Group.

Immobilization improves the reproducibility of patient positioning during six-field conformal radiation therapy for prostate carcinoma.

PURPOSE: To determine the magnitude of patient positioning errors associated with six field conformal therapy for carcinoma of the prostate, and to assess the impact of alpha-cradle immobilization on these errors. METHODS AND MATERIALS: The records of 22 patients, treated at two of the treatment facilities within our department, using computed tomography-planned conformal six field therapy for carcinoma of the prostate, were reviewed. At one facility (UCD), patients were routinely treated with immobilization, while at the other (UCSF) no rigid immobilization was used. Portal films of patients treated at both facilities were subsequently reviewed, and the deviation of each portal from the simulation film was determined (simulation-to-treatment variability). In addition, for each patient, the average deviation of each portal film from the average portal film (treatment-to-treatment variability) was determined. RESULTS: The mean and median simulation-to-treatment variability was 0.4 cm for those patients treated with immobilization, versus 0.6 cm for those treated without immobilization. The 90th percentile of simulation-to-treatment variability was 0.7 cm for those patients treated with immobilization, versus 1.1 cm for those not immobilized. There was a significant reduction in the number of portals observed with errors of > or = 0.50 cm (132/201 vs. 37/87, 66% vs. 43%; p < 0.001), 0.75 cm (184/201 vs. 59/87, 92% vs. 68%; p < 0.001), and 1.0 cm (196/201 vs. 74/87, 98% vs. 85%; p < 0.001) for patients treated with immobilization. There was also a significant reduction in the number of patients with treatment-to-treatment variability > or = 0.5 cm (1/10 vs. 8/12; p = 0.01) for patients treated with immobilization. CONCLUSION: The use of immobilization devices significantly reduces errors in patient positioning, potentially permitting the use of smaller treatment volumes. Immobilization should be a component of conformal radiation therapy programs for prostate carcinoma.

Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma.

PURPOSE: To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. METHODS AND MATERIALS: Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was < 1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0-2.24 Gy in 62, and > or = 2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3-436 months). RESULTS: Five-year local control was 85% for T1 and 70% for T2 glottic carcinomas (p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor (p = 0.02), and anterior commissure (AC) involvement was of borderline significance (p = 0.056). Five-year local control was 77% for patients treated between 1956-1970, 89% for between 1971-1980, and 91% for between 1981-1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time (p = 0.003), fraction size (p = 0.003), total dose (p = 0.01), impaired vocal cord mobility (p = 0.02), and subglottic extension (p = 0.04). Five-year local control was 100% for T2 lesions treated with overall time < or = 43 days vs. 84% for overall time > 43 days; 100% for fraction size > or = 2.25 Gy vs. 44% for fraction size < 1.8 Gy; 78% for total dose > 65 Gy vs. 60% for total dose < or = 65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. CONCLUSIONS: Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation.

PURPOSE: To evaluate the soft tissue and bone tolerance of radiation therapy (RT) in patients undergoing radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. METHODS AND MATERIALS: From 1990 to 1994, 47 patients with primary or recurrent oral cavity or oropharyngeal carcinomas were treated with radical composite resection and mandibular reconstruction using a bridging titanium plate with myocutaneous flap closure. Eleven patients received no RT (no RT), 10 patients received RT greater than 10 months from the time of surgery (remote RT), and 26 patients received RT within 12 weeks of surgery (perioperative RT). The radiation dose to the reconstructed mandible ranged from 45 to 75 Gy (median 63 Gy). The effect of the titanium plate on the radiation dose was measured using film dosimetry and soft tissue and bone-equivalent materials. The median follow-up was 17 months (range: 3-50 months). RESULTS: Late complications included four patients with osteomyelitis or necrosis, two plate exposures requiring flap revision, one chronic infection, two cases of chronic pain, two fistulae, and one case of trismus and malocclusion. The crude incidence of late complications by treatment was: (a) no RT: 3 of 11 patients (27%); (b) remote RT: 2 of 10 patients (20%); and (c) perioperative RT: 9 of 26 patients (35%). One patient in the no-RT group lost the plate due to chronic pain. Five patients in the perioperative RT group also had plate loss, four due to osteomyelitis and/or necrosis, and one due to pain related to a recurrent tumor. No patients in the remote RT group had plate loss. The actuarial prosthesis preservation rate at 2 years was 88% for the no RT, 100% for the remote RT, and 57% for the perioperative RT groups (p = 0.05). Phantom dose measurements showed that for parallel opposed 6 MV photon beams, there was no significant increase in the dose proximal or distal to the plate in either a soft tissue- or bone-equivalent phantom. CONCLUSIONS: The impact of radiation therapy on plate preservation after mandibular reconstructive surgery using a titanium plate may be dependent on the timing of RT relative to surgery. Significantly more mandibular reconstruction plates were lost when the involved mandible received RT in the perioperative period than when RT was delivered beyond 10 months from surgery or when no RT was given. The use of alloplastic implants such as titanium plates in conjunction with myocutaneous flap coverage for mandibular reconstruction is attractive because it allows immediate reconstruction of the defect and promotes a good functional and cosmetic result; however, administration of perioperative RT may result in a higher plate failure rate.