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Anal cancer is a relatively rare neoplasm, accounting for roughly 4,500 cases per year. The evolution of the definitive treatment of anal cancer from a surgical to a nonsurgical approach, however, has been viewed as a model disease site in a larger paradigm shift in medicine. Organ preservation, in this case a functional anal sphincter, and durable cure are obtainable goals. To this end, anal cancer is a disease best treated primarily with chemoradiation. Although appropriate treatment can produce acceptable results, further investigation and improvement in therapy are still needed. [ABSTRACT FROM AUTHOR]

Background: Older patients in hemodialysis have high prevalence of malnutrition that is often associated with rapid weight loss till cachexia., Objectives: We aimed to investigate whether in older patients undergoing hemodialysis the association between poor nutritional status and mortality may be independent of comorbidities and other risk factors., Design: Retrospective longitudinal study., Setting: Unit of Nephrology, Dialysis and Kidney Transplantation of the Policlinic Hospital of Milan, Milan, Italy., Participants: A total of 107 prevalent patients undergoing hemodialysis for at least three months., Measurements: Sociodemographic, clinical, and biological data were recorded. Unintentional weight loss (UWL) was defined as loss of body weight > 5% in 3 months or > 10% in 6 months. We computed a 21-item Frailty Index that included clinical conditions associated with malnutrition and mortality in this population. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of UWL, albumin and transferrin levels with death. Survival analyses based on Kaplan-Meier estimates were performed., Results: Patients' age was 79 (±7.7) years; 38 (35%) were women. Thirty-one patients (29%) died during follow-up. Eighteen (16.8%) patients experienced UWL during the follow-up period. UWL was positively associated with death in the unadjusted model and even after the progressive inclusion of potential confounders. Low albumin levels were positively associated with death only in the unadjusted and partially adjusted models while low transferrin levels were not associated with death in none of the models. Mortality was significantly higher in those patients experiencing both UWL and albumin levels below 3.5 mg/dL., Conclusions: In older patients undergoing chronic hemodialysis UWL is associated with mortality independently of comorbidities and other risk factors. Patients presenting both UWL and low albumin levels were those experiencing the worst outcomes in terms of mortality., Competing Interests: The authors declare no conflict of interest.

Background: The Italian Society of Echography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand the volumes of activity, modalities and stressors used during stress echocardiography (SE) in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved through an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories, and SE examinations were performed in 179 centers (80.6%): 87 centers (47.5%) were in the northern regions of Italy, 33 centers (18.4%) were in the central regions, and 61 (34.1%) in the southern regions. We annotated a total of 4057 SE. We divided the SE centers into three groups, according to the numbers of SE performed: <10 SE (low-volume activity, 40 centers), between 10 and 39 SE (moderate volume activity, 102 centers) and ≥40 SE (high volume activity, 37 centers). Dipyridamole was used in 139 centers (77.6%); exercise in 120 centers (67.0%); dobutamine in 153 centers (85.4%); pacing in 37 centers (21.1%); and adenosine in 7 centers (4.0%). We found a significant difference between the stressors used and volume of activity of the centers, with a progressive increase in the prevalence of number of stressors from low to high volume activity ( P = 0.033). The traditional evaluation of regional wall motion of the left ventricle was performed in all centers, with combined assessment of coronary flow velocity reserve (CFVR) in 90 centers (50.3%): there was a significant difference in the centers with different volume of SE activity: the incidence of analysis of CFVR was significantly higher in high volume centers compared to low - moderate - volume (32.5%, 41.0% and 73.0%, respectively, P < 0.001). The lung ultrasound (LUS) was assessed in 67 centers (37.4%). Furthermore for LUS, we found a significant difference in the centers with different volume of SE activity: significantly higher in high volume centers compared to low - moderate - volume (25.0%, 35.3% and 56.8%, respectively, P < 0.001)., Conclusions: This nationwide survey demonstrated that SE was significantly widespread and practiced throughout Italy. In addition to the traditional indication to coronary artery disease based on regional wall motion analysis, other indications are emerging with an increase in the use of LUS and CFVR, especially in high-volume centers., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Background: The Italian Society of Echocardiography and Cardiovascular Imaging (SIECVI) conducted a national survey to understand better how different echocardiographic modalities are used and accessed in Italy., Methods: We analyzed echocardiography laboratory activities over a month (November 2022). Data were retrieved via an electronic survey based on a structured questionnaire, uploaded on the SIECVI website., Results: Data were obtained from 228 echocardiographic laboratories: 112 centers (49%) in the northern, 43 centers (19%) in the central, and 73 (32%) in the southern regions. During the month of observation, we collected 101,050 transthoracic echocardiography (TTE) examinations performed in all centers. As concern other modalities there were performed 5497 transesophageal echocardiography (TEE) examinations in 161/228 centers (71%); 4057 stress echocardiography (SE) examinations in 179/228 centers (79%); and examinations with ultrasound contrast agents (UCAs) in 151/228 centers (66%). We did not find significant regional variations between the different modalities. The usage of picture archiving and communication system (PACS) was significantly higher in the northern (84%) versus central (49%) and southern (45%) centers ( P < 0.001). Lung ultrasound (LUS) was performed in 154 centers (66%), without difference between cardiology and noncardiology centers. The evaluation of left ventricular (LV) ejection fraction was evaluated mainly using the qualitative method in 223 centers (94%), occasionally with the Simpson method in 193 centers (85%), and with selective use of the three-dimensional (3D) method in only 23 centers (10%). 3D TTE was present in 137 centers (70%), and 3D TEE in all centers where TEE was done (71%). The assessment of LV diastolic function was done routinely in 80% of the centers. Right ventricular function was evaluated using tricuspid annular plane systolic excursion in all centers, using tricuspid valve annular systolic velocity by tissue Doppler imaging in 53% of the centers, and using fractional area change in 33% of the centers. When we divided into cardiology (179, 78%) and noncardiology (49, 22%) centers, we found significant differences in the SE (93% vs. 26%, P < 0.001), TEE (85% vs. 18%), UCA (67% vs. 43%, P < 0001), and STE (87% vs. 20%, P < 0.001). The incidence of LUS evaluation was similar between the cardiology and noncardiology centers (69% vs. 61%, P = NS)., Conclusions: This nationwide survey demonstrated that digital infrastructures and advanced echocardiography modalities, such as 3D and STE, are widely available in Italy with a notable diffuse uptake of LUS in the core TTE examination, a suboptimal diffusion of PACS recording, and conservative use of UCA, 3D, and strain. There are significant differences between northern and central-southern regions and echocardiographic laboratories that pertain to the cardiac unit. This inhomogeneous distribution of technology represents one of the main issues that must be solved to standardize the practice of echocardiography., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cardiovascular Echography.)

Older persons with chronic kidney disease (CKD) undergoing hemodialysis represent a growing portion of patients characterized by high vulnerability but still marginally studied. This study aimed at exploring the relationship between the number of prescriptions and fractures in older patients with CKD undergoing hemodialysis. A 24-item Frailty Index (FI) based on sociodemographic, clinical and biological data was computed. Unadjusted and adjusted logistic regression models were performed to test the association of prescribed medications with history of fractures. A total of 107 older patients undergoing hemodialysis (38 [35.5%] women, mean age 79.1 standard deviation, SD=7.7) were included in the study. Mean number of prescribed medications was 9.9 (SD=3.9) and was significantly associated with fractures (OR 1.18, 95% CI 1.06-1.32, p=0.003), even after adjustment for potential confounders (OR 1.16, 95% CI 1.03-1.30, p=0.016). If these results will be confirmed, interventions based on deprescribing will become essential in older persons undergoing hemodialysis., Competing Interests: The authors declare no conflict of interest.

Background: In older people, the prevalence frailty is inversely proportional to renal function, therefore it is supposed to be the highest in haemodialysis patients. However, frailty and its association with adverse outcomes have been scarcely investigated in this population. The aim of the present study was to characterize the frailty status and explore its association with hospitalization and mortality in a cohort of older patients undergoing chronic haemodialysis., Materials and Methods: This is a retrospective longitudinal study based on data from 105 older patients undergoing haemodialysis for at least 3 months. We computed a 24-item frailty index (FI) based on sociodemographic, clinical and biological data collected at baseline. During the follow-up, death and hospitalizations events were recorded. Unadjusted and adjusted Cox proportional hazard models were performed to test the association of frailty with hospitalization and death., Results: Mean age of the patients was 79.1 (SD 7.6) years, and their mean FI was 0.23 (SD 0.10). About 55% of patients were classified as frail (i.e., FI≥ 0.25). Patients were observed for 21 (interquartile range [IQR] 8-32) months. Overall, during the follow-up, 75% of patients required hospitalization and 28% died. Frail subjects where at higher risk of hospitalization (HR 1.60, 95% CI 1.00-2.57, p = 0.05) and of all-cause mortality (HR 2.52, 95% CI 1.10-5.80, p = 0.03) CONCLUSIONS: : Frailty is highly prevalent among older people undergoing haemodialysis. Frail individuals present a higher risk of hospitalizations and mortality. The FI is a reliable tool to study vulnerability in this population., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti- Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables' effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient's response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients.

The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions. These Criteria are reviewed every 2 years by a multidisciplinary expert panel. The development and review of these guidelines includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Local recurrence of rectal cancer can result in devastating symptoms for patients, including intractable pain and discharge. Prior treatment can limit subsequent treatment options. Preoperative 5-FU based chemoradiotherapy is the treatment of choice for patients with a local recurrence who did not receive adjuvant therapy after initial resection or who might have received chemotherapy alone. Chemoradiotherapy followed by evaluation for surgery is the preferred treatment for patients who have undergone previous radiotherapy after surgery. The inclusion of surgery has resulted in the best outcomes in a majority of studies. Palliative chemoradiotherapy is appropriate for patients who have received previous radiotherapy whose recurrent disease is considered inoperable. Radiotherapy can be delivered on a standard or hyperfractionated treatment schedule.Newer systemic treatments have improved response rates and given physicians more options for treating patients in this difficult situation. The use of induction chemotherapy prior to radiotherapy is an evolving treatment option. Specialized treatment modalities should be used at institutions with experience in these techniques and preferably in patients enrolled in clinical trials.

In 2009, an estimated 40,870 new cases of rectal cancer will be diagnosed in the USA. After decades of treating metastatic colorectal cancer (CRC) with 5-fluorouracil alone, newer agents have resulted in significant improvements in disease-free and overall survival rates. These improvements stem from combinations of newer cytotoxic agents and targeted therapies. Based on performance status and burden of disease, metastatic CRC patients are generally treated with either a curative or palliative intent. Curative paradigm patients often have low burden liver or lung metastases which are technically resectable. Patients with resectable colorectal liver metastases and no evidence of any extrahepatic metastases have impressive 5-year survival rates of 30%-70% following resection. Unfortunately, only 20%-30% of patients with colorectal liver metastases are candidates for resection at initial presentation. Patients with unresectable liver or lung metastasis are candidates for local therapies including radioablation, chemoembolization, radioembolization, and stereotactic radiation therapy. In select patients with metastatic CRC, neoadjuvant or adjuvant pelvic chemoradiation (CRT) is indicated to prevent local recurrence. Patients who have resectable metastatic disease with symptomatic, obstructive, Stage T3-4 and N1, or low-lying (

Low anterior resection or abdominoperineal resection is considered standard treatment for early rectal cancer. These procedures, however, carry a risk of morbidity and mortality that may not be warranted for early distal lesions, which may be treated with local excision. Emerging data has investigated the efficacy of local excision in patients with early stage rectal cancers. An expert panel designated by the American College of Radiology has reviewed supporting data, from a few prospective multi-institutional trials and a number of single-institution, retrospective reviews. The consensus recognizes the importance of accurate staging to identify patients who may be candidates for a local excision approach. Optimal candidates for local excision alone include small, low-lying T1 tumors, without adverse pathologic features. A number of procedures may be safely used including transanal, posterior trans-sphincteric, posterior proctotomy, transanal excision, or transanal microsurgery. It is important to note that none of these include lymph node evaluation, and depending on the risk of lymph node metastases, adjuvant radiation with or without chemotherapy may be warranted. Patients with positive margins or T3 lesions are at high risk of local recurrence and should be offered immediate APR or LAR. However, patients with high-risk T1 tumors, T2 tumors, or those who are not amenable to more radical surgery may benefit from adjuvant treatment. Data have also reported excellent local control rates for neoadjuvant radiation +/- chemotherapy followed by local excision in higher risk patients, but it is not yet clear if this approach reduces recurrence rates over surgery alone., (Copyright 2010 American College of Radiology. Published by Mosby, Inc. All rights reserved.)

A 58-year-old white man with prostate-specific antigen (PSA) level of 6 ng/mL, a Gleason score of 6 (3+3), and T2a adenocarcinoma of the prostate underwent prostatectomy. On review of the pathology, the specimen contained a Gleason score of 8 (3+5) with other high-risk features. The patient had a persistently elevated postoperative PSA level and was placed on total androgen blockade. The PSA continued to increase, and the patient developed bone-only metastatic disease. The patient was treated with palliative external-beam radiation and samarium. Six months later, he presented with bilateral hearing loss and was found to have pathologic and radiographic evidence of metastatic prostate cancer to the external auditory canals. This was an unusual late finding. The patient died shortly afterward before completing palliative treatment to the area.

Radiation therapy for prostate cancer can cause erectile dysfunction (ED). Intensity Modulated Radiation Therapy (IMRT) can reduce the amount of radiation to surrounding tissues associated with ED. We characterize the incidence of and factors associated with ED in prostate cancer patients after IMRT at the National Naval Medical Center (NNMC). Patients potent by definition of the Sexual Health Inventory for Men (SHIM) before treatment completed the specific erectile questions of the SHIM after IMRT. Statistical analyses were performed to examine the relationships between several factors and ED. Thirty-two of 45 patients with mean age of 68.2 years (50-86 years) completed the SHIM. The median follow-up was 36.8 months (16-63.6 months) as defined by the time from completion of therapy to reassessment with the SHIM. Eight of 32 patients (25%) had no post-treatment ED (SHIM score 22-25), three of 32 (9%) had mild post-treatment ED (SHIM score 17-21), five of 32 (16%) had mild to moderate ED (SHIM score 12-16), five of 32 (16%) had moderate ED (SHIM score 8-11) and 11 of 32 (34%) had severe post-treatment ED (SHIM score<8). Post-treatment potency was significantly associated with the pre-treatment SHIM score (P=0.001) and history of hypertension (P=0.03). The mean radiation dose to the penile bulb and volume of penile bulb treated were not associated with post-treatment potency (P=0.38, 0.76, respectively). IMRT maintains potency in the majority of patients. This analysis compares favorably in preserving erectile function to previously reported series using conventional external beam radiation therapy techniques. The dose of radiation received by the penile bulb and volume of penile bulb were not associated with post-treatment ED in this analysis.

Background: Lymphovascular invasion (LVI) is found in approximately 5% to 53% of specimens after radical prostatectomy (RP). Although LVI is associated with higher rates of recurrence after RP, its prognostic significance after postprostatectomy radiotherapy (P-XRT) is unclear., Methods: The medical records of men who received P-XRT from 1991 to 2001 at 2 institutions were reviewed for the presence of LVI in RP specimens. Multiple patient variables were evaluated for their association with LVI using Fisher exact tests and Wilcoxon rank-sum tests. The time to biochemical recurrence (BCR) and the time to distant metastases (DM) after RP were analyzed using Kaplan-Meier estimations, log-rank tests, and Cox regression analyses., Results: Eighteen of 160 patients (11%) who received P-XRT had LVI in their RP specimen. High Gleason score and seminal vesicle invasion were associated significantly with LVI. After a median follow-up of 8.3 years after RP, 16 patients with LVI had BCR after P-XRT, 9 of whom developed DM. The median time to BCR in patients with LVI was 2.6 years (95% confidence interval [95% CI], 1.8-5.4) compared with 7.8 years (95% CI, 6.8-10.3) in patients without LVI (P < .001). Multivariate analysis revealed an adjusted relative risk for LVI of 5.5 (P < .001). Other significant factors were Gleason score, undetectable post-RP serum prostate-specific antigen (PSA) levels, preradiotherapy serum PSA levels, and the interval from RP to P-XRT. LVI was the only significant factor associated with an increased risk of DM in univariate analysis (hazard ratio, 7.4; P < .001)., Conclusions: LVI was useful as a pathologic marker for reduced efficacy of P-XRT after RP in terms of increased risk of BCR and DM. Future studies will be needed to validate these findings., (Copyright 2006 American Cancer Society.)

Purpose: We assessed the efficacy of salvage radiotherapy (SRT) and analyzed predictors of biochemical progression-free survival (bPFS) and distant metastasis-free survival in patients with clinically localized disease recurrence after radical prostatectomy., Materials and Methods: The records of 114 patients treated with SRT at 2 institutions between 1991 and 2001 were retrospectively reviewed. Time to biochemical recurrence and to distant metastases was analyzed using the Kaplan-Meier estimation. Candidate predictors of bPFS and distant metastasis-free survival were analyzed using the log rank test and Cox regression. Acute and late complications were scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria., Results: At a median followup of 6.3 years (range 1.9 to 13.3) for SRT 4 and 6-year bPFS was 50% (95% CI 42% to 61%) and 33% (95% CI 24% to 43%), respectively. The 6-year actuarial probability of distant metastases after SRT was 14%. Multivariate analysis demonstrated an independent association of increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT with decreased 5-year bDFS. These factors were associated with significantly less 5-year distant metastasis-free survival. Pre-RT prostate specific antigen greater than 2.0 ng/ml was associated with significantly decreased 5-year bDFS and distant metastasis-free survival, although it was not maintained on multivariate analysis., Conclusions: SRT results in durable prostate specific antigen control in select patients. It is well tolerated with few severe late effects. Increasing Gleason score, lymphovascular invasion and lack of a complete response to SRT are significant risks for disease progression requiring additional management.

Purpose: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival., Methods and Materials: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models., Results: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival., Conclusions: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.

Background: Between 1979-1987, the National Cancer Institute conducted a randomized, prospective study of mastectomy (MT) versus breast conservation therapy (BCT) in the treatment of patients with early-stage breast carcinoma. After a median potential follow-up of 18.4 years, the authors present the updated results., Methods: After informed consent was obtained from each patient, 237 evaluable women with clinical AJCC Stage I and Stage II breast carcinoma were enrolled on an institutionally reviewed protocol and randomly assigned to undergo modified radical MT (116 patients) or BCT (121 patients), which was comprised of lumpectomy, axillary lymph node dissection, and radiation therapy. Negative surgical margins in the lumpectomy arm were not required. The 237 randomized patients were followed for a median potential follow-up of 18.4 years. The primary endpoints were overall survival and disease-free survival., Results: At a median follow-up of 18.4 years, there was no detectable difference with regard to overall survival between patients treated with MT and those treated with BCT (58% vs. 54%; P = 0.67 overall). Twenty-seven women in the BCT arm (22%) experienced an in-breast event. After censoring in-breast events in the BCT arm that were salvaged successfully by MT, disease-free survival also was found to be statistically similar (67% in the MT arm vs. 63% in the BCT arm; P = 0.64 overall). There was no statistically significant difference with regard to contralateral breast carcinoma between the two treatment arms (P = 0.70)., Conclusions: After nearly 20 years of follow-up, there was no detectable difference in overall survival or disease-free survival in patients with early-stage breast carcinoma who were treated with MT compared with those treated with BCT. For BCT patients, long-term in-breast failures continued to occur throughout the duration of follow-up. There was no statistically significant difference in the incidence of contralateral breast carcinoma between the two treatment groups.

Purpose: Marker seed location was analyzed to test the hypothesis that there is no intraseed migration within the prostate, a premise fundamental to the technique of marker seed localization of this organ. Despite increasing interest in the use of implanted seeds as fiducial markers for gland location, there are few data available with which to evaluate the validity of this technique, particularly over the entire course of external beam radiation therapy., Methods and Materials: Between May 2001 and December 2001, after obtaining fully informed written consent, 9 patients with early stage prostate cancer were enrolled on an institutionally reviewed protocol. Patients had four to five marker seeds implanted into the prostate under transrectal ultrasound guidance before definitive radiotherapy. The porous gold seeds were each 1.2 x 2.0 mm in dimension. Seed locations from orthogonal radiographs based on the initial simulation and weekly orthogonal films were digitized using a CMS Focus planning system, thereby facilitating the determination of intraseed spacing. The digitization of the isocenter from each orthogonal pair of radiographs was used to determine digitizing error for seed localization. Pubic symphysis, bilateral femoral heads, and isocenter were also digitized and will be analyzed at a later date., Results: Overall, the average migration of all the seeds in the patients was 1.2 +/- 0.2 (SD) mm. The greatest average movement of any seed in any patient was 1.9 mm over the entire 7-week course of radiotherapy. The smallest average movement was 0.6 mm. The greatest change in intraseed spacing in any of the patients during the full course of therapy was 6.6 mm. One seed in 1 patient was lost at the start of the third week of therapy and censored from analysis. Digitizing error in seed localization was calculated to be 0.20 +/- 0.03 (SD) mm., Conclusions: As an aggregate, there is negligible seed migration within the prostate over the entire course of definitive radiotherapy. However, there are small, detectable movements in individual seed locations, perhaps resulting from topographic changes in the gland secondary to seed placement, anatomic changes in bladder and rectum, or treatment itself. With respect to seed migration, prostate marker seeds represent an accurate and reliable surrogate of gland location during a full course of radiotherapy.

Purpose: To determine the maximal tolerated dose and dose-limiting toxicities (DLTs) of weekly gemcitabine with concurrent radiotherapy (RT) in patients with unresectable adenocarcinoma of the pancreas., Methods and Materials: Patients who had locally advanced or recurrent unresectable pancreatic cancer were eligible. Gemcitabine was administered as a 30-min infusion once weekly for a total of five cycles during the course of RT. The starting dose of gemcitabine was 350 mg/m(2)/wk. Doses were escalated by increments of 25% in successive cohorts of 3-6 patients. RT was delivered at 180 cGy/d to a total dose of 5400-5580 cGy to the gross tumor volume., Results: Nineteen patients were entered in this study through three dose levels (350-550 mg/m(2)/wk). The maximal tolerated dose was determined to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of gemcitabine. Other non-DLTs included 16 Grade III toxicities, which consisted of thrombosis, infection, nausea, vomiting, hypotension, constipation, diarrhea, and fatigue. One patient at each gemcitabine dose level experienced Grade IV vomiting, and the patient at the 550 mg/m(2) dose developed Grade IV anorexia., Conclusion: The maximal tolerated dose of gemcitabine when administered as a 30-min infusion once weekly during RT for unresectable pancreatic cancer was found to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of chemotherapy. Concurrent gemcitabine and RT is reasonably well tolerated and deserves additional evaluation against the current standard of care.

Background: Although the gastrointestinal tract is the most common site of extranodal non-Hodgkin's lymphoma (NHL), primary small intestine lymphomas remain relatively rare, especially localized low-grade follicular B-cell lymphomas. When lymphomas do occur at this site, most are high grade and require aggressive therapy. We report three cases of small intestinal follicular lymphoma diagnosed on endoscopic biopsy and review the clinical history, pathologic features, and treatment outcome., Study: A review of the medical records and pathology from three cases of small intestine follicular NHL was performed. The pathology specimens were formalin-fixed, paraffin-embedded tissues processed for routine microscopic examination, immunohistochemical staining, and molecular analysis., Results: Histologic and immunophenotypical studies were diagnostic of grade 1 follicular lymphoma (Revised European-American Lymphoma classification/World Health Organization classification). All cases expressed bcl-2 protein, and polymerase chain reaction analysis supported the diagnosis in two cases with adequate DNA. With 23.3 months' median follow-up, one untreated and one treated patient were alive without symptoms; a third untreated patient died of a nonlymphoma cause., Conclusion: Isolated indolent lymphomas of the small intestine are rare. Accurate pathologic staging and histologic classification are paramount in delineating treatment options.

Although positron emission tomography (PET) is an established diagnostic method in brain and lung cancer, its use is often confined to research. The authors report a case of a minimally symptomatic intramedullary spinal cord metastasis, an uncommon and often diagnostically challenging lesion, that was confirmed by PET. A 37-year-old man with a history of metastatic renal cell carcinoma treated with systemic agents, an autologous stem cell transplant, and local palliative radiotherapy with a 2-month history of vague right foot numbness and right leg dysesthesias was found to have an intramedullary lesion at the level of T12. Although the findings of magnetic resonance imaging suggested central necrosis, a PET scan revealed a metabolically active lesion and confirmed the diagnosis of intramedullary metastasis. PET can be used to detect and confirm intramedullary spinal cord metastatic carcinoma. PET imaging may have a vital role in clinical diagnosis by helping to distinguish diagnostically troublesome lesions based on metabolic activity.

U.S. Navy general medical officers (GMOs) are physicians serving as general practitioners. Although exceptions exist, most GMOs are not board-certified in a specialty. They are post-graduate year 1 (PGY-1)-trained, state-licensed physicians analogous to civilian general practitioners. We conducted a retrospective study using data generated from patient visits with active duty males and females from June 1 to 30, 1998, to describe diagnoses, demographics, and utilization of care patterns encountered by three PGY-1-trained GMOs at an ambulatory clinic. A total of 781 patient encounters with 123 diagnoses from a patient population of 3,178 were recorded. This is an average of 260 patient encounters per GMO, at a rate of 2.52 patients seen per patient-care hour. Fifty-seven consultations/referrals were requested (7.3% of encounters, 1.8% of the patient population). Personnel assigned to the clinic accounted for 4.2% of visits (2% of the patient population). Patient satisfaction was rated as "excellent" to "satisfactory," and no significant morbidity was observed at 1.5-year follow-up. With PGY-1 training, GMOs provide primary care to a substantial volume of prescreened patients and treat patients with a majority of diagnoses without referral or unacceptable complications. The role of GMOs, and perhaps other physicians without specialty training (i.e., general practitioners), in selected settings seems valid and may have advantageous medicoeconomic implications for military and civilian managed care systems.

A glycocalyx layer composed of glycosaminoglycans (GAGs) and other molecules lines the transitional epithelium of the urinary bladder. This layer forms a barrier between the transitional cells and urinary bladder environment and is believed to help prevent the adherence of bacteria, minerals and carcinogens. Investigators postulate that quantitative and/or qualitative defects in the GAG component may be responsible for a spectrum of acute and chronic disease processes ranging from urinary tract infections to cancer. While the presence of epithelium GAGs has been confirmed biochemically and histochemically, few rigorous characterizations have been performed. This study establishes the methodology and feasibility of using routine cold-cup biopsies from cadaveric human bladders for GAG analysis and establishes baseline contents of the sulfated and non-sulfated GAGs in the urinary bladder glycocalyx. Using detergent extraction, the GAGs from cold-cup biopsies (n = 34) from four cadaveric bladders were isolated. The isolates were subjected to two colorimetric assays to quantify both sulfated and non-sulfated GAGs. The nonsulfated GAG content of the bladder epithelium ranged from 2.15 x 10(-4) to 5.50 x 10(-4) mmol/kg of dry, defatted bladder. The sulfated GAG content ranged from 2.00 x 10(-1) to 7.40 x 10(-1) mmol/kg of dry, defatted bladder. These values are consistent with reports found in the literature using electrophoresis on full-thickness human bladder specimens. The GAG content of human bladder epithelium can be readily and accurately characterized from cold-cup biopsy samples. Our future plans involve using this routinely used technique to analyze samples from live control and disease-state bladders thereby demonstrating any quantitative and/or qualitative differences in GAG constituents.

Radiotherapy has a well-defined role in prophylaxis of recurrent heterotopic ossification of the hip, but has been described infrequently in other situations. This article reports the use of excision and low-dose external beam radiotherapy in three patients with heterotopic ossification of the elbow treated between February 1995 and September 1996. Radiotherapy was delivered in a single fraction of 7-8 Gy within 48 hours postoperatively using opposed anteroposterior portals. After a median follow-up of 10.5 months, all three patients demonstrated a significant increase in range of motion without any evidence of recurrence. These results indicate adjuvant postexcision radiotherapy may be used for prophylaxis of recurrent heterotopic ossification of the elbow.

Since the concept of a fabricated skin replacement was first proposed, it has been recognized that a permanent skin replacement must contain a functional complex structure consisting of epidermis integrated with dermis. Although a practical solution for the replacement of missing epidermis exists through the culture expansion of the autologous epidermis, a practical solution for permanently replacing missing dermis has not been achieved. While it is generally recognized that the insoluble matrix components--largely collagen and elastin--are essential, the role of other matrix components such as glycosaminoglycans (GAGs) and proteoglycans remains undefined. This article describes both the qualitative and quantitative GAG composition of fresh and cryopreserved human dermis. Through the use of 2 different colorimetric assays and cellulose acetate electrophoresis, we found the following: 1) the principal dermal GAGs are those of the heparin family; 2) dermatan sulfate is the second most predominant GAG component; 3) chondroitin-6-sulfate is found at concentrations of 2 orders of magnitude less than the heparins; and 4) hyaluronan and keratan sulfate were both found as only minor constituents. When the GAG composition of fresh skin was compared with that of cryopreserved skin, no significant differences were observed. This study also examined the time course of GAG leaching during the preparation of deconstructed human dermis, which is human dermis reduced to the native insoluble matrix components by exhaustive saline soaking. We found that GAG leaching was readily detectable even within the first day. Sixty percent of total GAG leaching occurred by day 7. These investigations establish a benchmark for the reproduction of GAGs in synthetic dermal constructs. Further, the results of the leaching study generate important considerations for short-term skin storage and long-term skin banking. Because GAG leaching commences immediately, appropriate precautions must be taken to minimize the potential functional compromise of cryopreserved human dermis.