Influence of tumor size on outcomes following pelvic exenteration.

OBJECTIVE: Pelvic exenteration (PE) is often the only curative option for locally advanced or recurrent pelvic malignancies. Despite radical surgery, recurrence risk and morbidity remain high. In this study, we sought to determine tumor size effect on perioperative outcomes and subsequent survival in patients undergoing PE. METHODS: Retrospective chart review was performed for female patients who underwent PE at two comprehensive cancer centers from 2000 to 2015. Demographics, complications and outcomes were recorded. Statistical analyses were performed using chi-square, student's t-test, logistic regression, non-parametric tests, log-rank test, and Cox proportional hazards. RESULTS: Of 151 women who underwent PE, 144 had available pathologic tumor size. Gynecologic oncology, surgical oncology, and urology performed 84, 29, and 31 exenterations, respectively. Tumor dimensions ranged from 0 to 25.5cm. Perioperative complications, 30-day mortality, reoperation, and readmission rates were not associated with tumor size. Obesity and prior radiation increased risk for major perioperative complication while anterior exenterations decreased risk. Larger tumors were more likely to undergo total pelvic exenteration (OR 1.14; 95%CI 1.03-1.27), have positive margins (OR 1.11; 95%CI 1.02-1.22), and recur (65%, 42% and 20% for tumors >4cm, ≤4cm and no residual tumor respectively, p=0.016). Tumor size >4cm and positive margins were associated with worse overall survival amongst gynecologic oncology patients. CONCLUSION: Tumor size was not associated with perioperative morbidity. Larger tumors were associated with positive margins, more extensive resection, and worse survival in gynecologic oncology patients. Larger studies are needed to further understand tumor size impact on PE outcomes within specific tumor types.

Omission of preoperative esophageal manometry does not alter operative approach or postoperative dysphagia following laparoscopic paraesophageal hernia repair.

Routine esophageal manometry for surgical planning before laparoscopic paraesophageal hernia (PEH) has been advocated in an effort to reduce the likelihood of postoperative dysphagia. The purpose of this study is to investigate whether omitting routine preoperative esophageal manometry is associated with a change in the type of fundoplication performed and with an increase in the incidence of postoperative dysphagia. A retrospective cohort study of consecutive patients with and without preoperative esophageal manometry undergoing PEH repair was performed between January 2011 and July 2014 at an academic medical center. Demographic and outcome data were collected in a prospective database. The primary outcome measures were the type of fundoplication performed and postoperative disease-specific quality-of-life (GERD-HRQL) dysphagia score. Secondary outcome measures were total GERD-HRQL score, proton pump inhibitor (PPI) use, and requirement for endoscopic dilation. One hundred twenty-five patients underwent laparoscopic PEH repair. Forty-seven (37%) patients had preoperative manometry and 79 (63%) did not. Patients who did not have manometry were older (67.9 ± 14.3 vs. 61.7 ± 13.5, P = 0.02), but the groups did not differ in terms of BMI, gender, PPI use, baseline GERD-HRQL dysphagia score, or baseline total GERD-HRQL score. Sixty-nine (87%) patients without manometry and 43 (93%) patients with manometry underwent a complete fundoplication (P = 0.55). At a median follow-up of 16 (4-44) months, the median GERD-HRQL dysphagia scores (0(0-1) vs. 0(0-1); P = 0.66) and total GERD-HRQL scores (3(1-8) vs. 4(0-8); P = 0.72) were equivalent between the groups. Equivalent proportion of patients without and with preoperative manometry used PPI (9% vs. 21%; P = 0.06) and required endoscopic dilation (6% vs. 6%; P = 0.99) in the postoperative period. Omission of routine preoperative manometry prior to laparoscopic PEH repair is not associated with a change in the type of fundoplication performed, an increased incidence of postoperative dysphagia, or an increased requirement for postoperative endoscopic dilation.

IWAVE-An adaptive filter approach to phase lock and the dynamic characterization of pseudo-harmonic waves.

We present a novel adaptive filtering approach to the dynamic characterization of waves of varying frequencies and amplitudes embedded in arbitrary noise backgrounds. This method, known as IWAVE (Iterative Wave Action angle Variable Estimator), possesses critical advantages over conventional techniques, making it a useful new tool in the dynamic characterization of a wide range of data containing embedded oscillating signals. After a review of existing techniques, we present the IWAVE algorithm, derive its key characteristics, and provide tests of its performance using simulated and real world data.

Assessing discards in an illegal small-scale fishery using fisher-led reporting.

About a third of all marine fish in the world are caught in Small-Scale Fisheries (SSF). SSF are increasingly recognised as essential for food security and livelihoods for vulnerable and economically fragile communities globally. Although individual SSF vessels are usually perceived as having little impact on the ecosystem, the cumulative impact of gear type and number of vessels may be substantial. Bottom trawling is a common fishing method that can greatly influence the marine ecosystem by damaging the seafloor and generating high levels of discards. However, appropriate sampling coverage using on-board observer programmes to collect these data from SSF are rare, as they are expensive and pose logistical constraints. A mobile App was used to assess whether self-reporting by fishers could provide reliable fine-scale information on fishing effort and discards over time in an illegal shrimp trawling fishery in northern Peru. Maps depicting the spatial distribution of trawling effort and the proportion of discards from observers and fishers were compared using the Similarity in Means (SIM) Index, which ranges from 0 when spatial patterns differ completely to 1 when spatial patterns are very similar. High levels of agreement between spatio-temporal patterns of effort (SIM Index = 0.81) and discards (0.96) were found between fisher and observer maps. Moreover, far greater spatial coverage was accomplished by fishers, suggesting that self-reporting via an App represents a useful approach to collect reliable fisheries data as an initial step for effective monitoring and management of these fisheries. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-022-09708-9.

Viruses in recreational water-borne disease outbreaks: a review.

Viruses are believed to be a significant cause of recreationally associated water-borne disease. However, they have been difficult to document because of the wide variety of illnesses that they cause and the limitations in previous detection methods. Noroviruses are believed to be the single largest cause of outbreaks, which have been documented in the published literature 45% (n = 25), followed by adenovirus (24%), echovirus (18%), hepatitis A virus (7%) and coxsackieviruses (5%). Just under half of the outbreaks occurred in swimming pools (49%), while the second largest outbreak occurred in lakes or ponds (40%). The number of reported outbreaks associated with noroviruses has increased significantly in recent years probably because of better methods for virus detection. Inadequate disinfection was related to 69% (n = 18) of swimming pool outbreaks. A lack of required reporting and nonuniform water quality and chlorination/disinfection standards continues to contribute to water-borne recreational disease outbreaks.

The effect of preoperative nutritional status on postoperative complications and overall survival in patients undergoing pelvic exenteration: A multi-disciplinary, multi-institutional cohort study.

INTRODUCTION: Optimization of preoperative nutritional status has been recommended and associated with improved outcomes for other oncologic procedures, but has not been studied in patients undergoing pelvic exenteration. METHODS: A retrospective chart review of 199 patients was conducted. Overall survival (OS) was calculated using the Kaplan-Meier method and multivariate analysis was performed with Cox proportional hazards. RESULTS: 199 patients underwent PE with 61 (31%), 78 (40%) and 58 (29%) patients having colorectal, gynecologic and urologic histological diagnoses, respectively. Median OS following PE was 25 months. Preoperative serum albumin <3.5 g/dL was associated with worsened OS (HR 1.661; 95% CI 1.052-2.624) as well as increased incidence of any postoperative complication (85.9% vs 72.3%, p = 0.034), but was not associated with 90-day mortality (11.3% vs 7.9%, p = 0.457). CONCLUSION: Poor preoperative nutritional status is associated with increased complications and decreased OS. Surgeons should maximize preoperative nutritional status to improve perioperative outcomes and long-term survival.

Correction to: Improving care at scale: process evaluation of a multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery (EPOCH trial).

Following the publication of this article [1], the authors reported a number of errors which are given below.

Improving care at scale: process evaluation of a multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery (EPOCH trial).

BACKGROUND: Improving the quality and safety of perioperative care is a global priority. The Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial was a stepped-wedge cluster randomised trial of a quality improvement (QI) programme to improve 90-day survival for patients undergoing emergency abdominal surgery in 93 hospitals in the UK National Health Service. METHODS: The aim of this process evaluation is to describe how the EPOCH intervention was planned, delivered and received, at both cluster and local hospital levels. The QI programme comprised of two interventions: a care pathway and a QI intervention to aid pathway implementation, focussed on stakeholder engagement, QI teamwork, data analysis and feedback and applying the model for improvement. Face-to-face training and online resources were provided to support senior clinicians in each hospital (QI leads) to lead improvement. For this evaluation, we collated programme activity data, administered an exit questionnaire to QI leads and collected ethnographic data in six hospitals. Qualitative data were analysed with thematic or comparative analysis; quantitative data were analysed using descriptive statistics. RESULTS: The EPOCH trial did not demonstrate any improvement in survival or length of hospital stay. Whilst the QI programme was delivered as planned at the cluster level, self-assessed intervention fidelity at the hospital level was variable. Seventy-seven of 93 hospitals responded to the exit questionnaire (60 from a single QI lead response on behalf of the team); 33 respondents described following the QI intervention closely (35%) and there were only 11 of 37 care pathway processes that > 50% of respondents reported attempting to improve. Analysis of qualitative data suggests QI leads were often attempting to deliver the intervention in challenging contexts: the social aspects of change such as engaging colleagues were identified as important but often difficult and clinicians frequently attempted to lead change with limited time or organisational resources. CONCLUSIONS: Significant organisational challenges faced by QI leads shaped their choice of pathway components to focus on and implementation approaches taken. Adaptation causing loss of intervention fidelity was therefore due to rational choices made by those implementing change within constrained contexts. Future large-scale QI programmes will need to focus on dedicating local time and resources to improvement as well as on training to develop QI capabilities. EPOCH TRIAL REGISTRATION: ISRCTN80682973 https://doi.org/10.1186/ISRCTN80682973 Registered 27 February 2014 and Lancet protocol 13PRT/7655.

The effects of proton pump inhibitors on autonomic tone in patients with erosive and non-erosive esophagitis.

BACKGROUND: Reduction in autonomic tone as measured by heart rate variability (HRV) has been associated with various inflammatory conditions including reflux disease. The nature of and permanence of this damage have not been fully assessed. METHODS: Fourteen individuals with non-erosive reflux disease (NERD) and 10 individuals with erosive reflux disease (ERD) as identified on endoscopy were assessed for HRV prior to starting a course of proton pump inhibitor (PPI) therapy and 8 weeks from the start of PPI therapy. KEY RESULTS: Reflux symptoms were significantly improved by PPI therapy (p = 0.001), with no significant difference in reflux symptoms between the NERD and ERD groups either before (p = 0.45) or following therapy (p = 0.17). The ERD group displayed reduced HRV prior to PPI therapy as compared with a non-symptomatic group. There was significant improvement of HRV resulting from PPI therapy in the ERD group as measured by inspiration/expiration ratio on forced breathing (p = 0.02), Valsalva ratio (p = 0.03), and extended metronome-guided breathing at 6 breaths per minute (p = 0.03). While a similar pattern was seen in the NERD group, the effects were not as strong and did not reach statistical significance. CONCLUSIONS & INFERENCES: The results are consistent with a growing body of evidence that cardiac autonomic neuropathy as measured by HRV is associated with gastro-esophageal reflux disease and also suggest that successful treatment of the inflammation can lead to reversal of the deterioration of autonomic tone associated with that inflammation.

Characterization of the ATP-promoted aspect of Na+-Ca2+ exchange present in squid retinal nerve axolemma.

Using an in vitro system which consists of an axolemma-rich vesicle fraction prepared from squid retinal nerve fibers, an Na+-Ca2+ exchange process has been characterized and appears identical with that reported in squid giant axon. This exchange is absolutely dependent on the establishment of an Na+ gradient, shows monovalent and divalent cation specificity and is highly sensitive to monensin, A23187 and valinomycin but not to ouabain, digitoxigenin, vanadate, pentylenetetrazole, tetrodotoxin or tetraethylammonium. Furthermore, it was found that the exchange process is enhanced by the addition of ATP. This ATP-promoted aspects of Na+-Ca2+ exchange shares many similar characteristics with Na+-Ca2+ ATP hydrolysis and may indicate a common mechanism for both activities via a protein phosphorylation-dephosphorylation event.

Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease.

PURPOSE: To determine the efficacy of mantle radiation therapy alone in selected patients with early-stage Hodgkin's disease. PATIENTS AND METHODS: Between October 1988 and June 2000, 87 selected patients with pathologic stage (PS) IA to IIA or clinical stage (CS) IA Hodgkin's disease were entered onto a single-arm prospective trial of treatment with mantle irradiation alone. Eighty-three of 87 patients had > or = 1 year of follow-up after completion of mantle irradiation and were included for analysis in this study. Thirty-seven patients had PS IA, 40 had PS IIA, and six had CS IA disease. Histologic distribution was as follows: nodular sclerosis (n = 64), lymphocyte predominant (n = 15), mixed cellularity (n = 3), and unclassified (n = 1). Median follow-up time was 61 months. RESULTS: The 5-year actuarial rates of freedom from treatment failure (FFTF) and overall survival were 86% and 100%, respectively. Eleven of 83 patients relapsed at a median time of 27 months. Nine of the 11 relapses contained at least a component below the diaphragm. All 11 patients who developed recurrent disease were alive without evidence of Hodgkin's disease at the time of last follow-up. The 5-year FFTF in the 43 stage I patients was 92% compared with 78% in the 40 stage II patients (P =.04). Significant differences in FFTF were not seen by histology (P =.26) or by European Organization for Research and Treatment of Cancer H-5F eligibility (P =.25). CONCLUSION: Mantle irradiation alone in selected patients with early-stage Hodgkin's disease is associated with disease control rates comparable to those seen with extended field irradiation. The FFTF is especially favorable among stage I patients.

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.

PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

Results of coronary surgery after failed elective coronary angioplasty in patients with prior coronary surgery.

The results of coronary artery bypass surgery after failed elective coronary angioplasty in patients who have undergone prior coronary surgery are unknown. Coronary angioplasty may be performed to relieve angina after surgery either to the native coronary vessels or to grafts. Failure of attempted coronary angioplasty may mandate repeat coronary surgery, often in the setting of acute ischemia. From 1980 to 1989, 1,263 patients with prior coronary bypass surgery underwent angioplasty; of these patients, 46 (3.6%) underwent reoperation for failed angioplasty during the same hospital stay. Of the 46 patients who underwent reoperation, 33 had and 13 did not have acute ischemia. In the group with ischemia, 3 patients (9.1%) died and 14 (42.4%) died or had a Q wave myocardial infarction in the hospital compared with no deaths (p = NS) and no deaths or Q wave myocardial infarction (p = 0.005) in the group without ischemia. At 3 years, the actuarial survival rate was 88 +/- 6% in the group with ischemia, whereas there were no deaths in the group without ischemia (p = NS), and freedom from death or myocardial infarction was 51 +/- 10% in the group with ischemia, versus no events in the group without ischemia (p = 0.006). In most patients with prior coronary bypass surgery, coronary angioplasty was performed without the need for repeat coronary bypass surgery. Should coronary angioplasty fail, reoperation in patients without acute ischemia can be performed with overall patient survival comparable to that of elective reoperative coronary bypass without coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in patients with prior coronary bypass surgery.

To improve symptomatic status and avoid reoperation, 122 initial and 7 repeat percutaneous transluminal coronary angioplasty procedures were performed in 116 patients with disabling angina pectoris at a mean of 26.8 months (range 2 to 132) after coronary bypass surgery. Marked angiographic improvement (greater than 30% reduction in diameter stenosis) was obtained in 107 (88%) of the 122 initial procedures and in all 7 repetitions. Mean stenosis was reduced from 78 +/- 13% (mean +/- standard deviation) to 25 +/- 13% (p less than 0.0001) and mean pressure gradient from 49 +/- 15 to 11 +/- 8 mm Hg (p less than 0.0001). Complications were: emergency surgery (three patients), Q wave infarction (one patient), myocardial infarction by enzyme criteria only (four patients) and non-occluding coronary dissection (one patient). There were no neurologic or peripheral vascular complications and no early deaths. One late death occurred 14 months after an unsuccessful but uncomplicated angioplasty procedure. At a mean follow-up of 8.3 months, 88 patients (76%) were free of angina or in improved condition. In patients followed up for at least 6 months, evidence of restenosis occurred in 9 (53%) of 17 saphenous veins, 1 (50%) of 2 proximal graft anastomoses, 4 (18%) of 22 distal graft anastomoses and 5 (14%) of 37 native coronary arteries. When coronary anatomy is suitable, percutaneous transluminal angioplasty is an attractive alternative to reoperation in symptomatic patients with prior coronary bypass surgery.

Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease.

OBJECTIVES: This study sought to compare the outcome of percutaneous transluminal coronary angioplasty (PTCA) (n = 834) and coronary artery bypass graft surgery (CABG) (n = 1805) in diabetic patients with multivessel coronary disease from an observational database. BACKGROUND: There is concern about selection of revascularization in diabetic patients with multivessel coronary artery disease. METHODS: Data were collected prospectively and entered into a computerized database. Follow-up was by letter or telephone or additional events resulting in readmission. RESULTS: After CABG there were more in-hospital deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q wave myocardial infarctions than after PTCA. Five- and 10-year survival rates were 78% and 45% after PTCA and 76% and 48% after CABG, respectively (p = 0.47). At 5 and 10 years, insulin-requiring patients had lower survival rates of 72% and 31% after PTCA and 70% and 48% after CABG, respectively (p = 0.54). Multivariate correlates of long-term mortality were older age, low left ventricular ejection fraction, heart failure and hypertension. In the total group, insulin requirement was a correlate of long-term mortality. For the total group, choice of therapy had a multivariate hazard ratio close to 1. In the insulin-requiring subgroup, the multivariate hazard ratio was 1.35 (95% confidence interval 1.01 to 1.79) for PTCA versus CABG. Corrected for baseline differences, 5- and 10-year survival rates were 68% and 36% after PTCA and 75% and 47% after CABG, respectively, in the insulin-requiring subgroup. Nonfatal events were more common after PTCA, especially additional revascularization. CONCLUSIONS: This study reveals a high incidence of events in diabetic patients and raises further questions about angioplasty in insulin-requiring diabetic patients with multivessel disease.

In vitro tumoricidal activity of resting and glucan-activated Kupffer cells.

Kupffer cells compose 80-90% of fixed tissue macrophages and have been suggested to play an important role in hepatic antitumor resistance. In the present study, the ability of resting and activated Kupffer cells to lyse syngeneic mammary adenocarcinoma BW10232 cells was evaluated. Activated Kupffer cells were isolated from C57Bl/6J mice following single of multiple intravenous (IV) injections of glucan (0.45 mg/mouse), a potent macrophage-activating agent. Mice receiving 5% (w/v) dextrose served as control. Resting Kupffer cells induced significant (P less than .05) 4% and 12% specific lysis of adenocarcinoma cells at target:effector ratios of 1:10 and 1:50, respectively. Kupffer-cell-mediated tumoricidal activity was depressed on day 1 following a single IV injection of glucan. By day 3 postglucan, the antitumor activity of Kupffer cells returned to control levels and was enhanced on days 5 and 10. Following multiple IV injections of glucan on days -5, -3, and -1, Kupffer-cell-mediated cytotoxicity was elevated on days 1 and 4. These observations demonstrate that resting Kupffer cells are significantly cytotoxic to adenocarcinoma cells at T:E ratios of 1:10 and 1:50 and following a transient inhibition of Kupffer-cell-mediated tumoricidal activity, glucan was effective in significantly enhancing the antitumor activity of Kupffer cells.

Chemical, physical, and sensory properties of dairy products enriched with conjugated linoleic acid.

Recent studies have illustrated the effects of cis-9,trans-11 conjugated linoleic acid (CLA) on human health. Ruminant-derived meat, milk and dairy products are the predominant sources of cis-9,trans-11 CLA in the human diet. This study evaluated the processing properties, texture, storage characteristics, and organoleptic properties of UHT milk, Caerphilly cheese, and butter produced from a milk enriched to a level of cis-9,trans-11 CLA that has been shown to have biological effects in humans. Forty-nine early-lactation Holstein-British Friesian cows were fed total mixed rations containing 0 (control) or 45 g/kg (on dry matter basis) of a mixture (1:2 wt/wt) of fish oil and sunflower oil during two consecutive 7-d periods to produce a control and CLA-enhanced milk, respectively. Milk produced from cows fed the control and fish and sunflower oil diets contained 0.54 and 4.68 g of total CLA/100 g of fatty acids, respectively. Enrichment of CLA in raw milk from the fish and sunflower oil diet was also accompanied by substantial increases in trans C18:1 levels, lowered C18:0, cis-C18:1, and total saturated fatty acid concentrations, and small increases in n-3 polyunsaturated fatty acid content. The CLA-enriched milk was used for the manufacture of UHT milk, butter, and cheese. Both the CLA-enhanced butter and cheese were less firm than control products. Although the sensory profiles of the CLA-enriched milk, butter, and cheese differed from those of the control products with respect to some attributes, the overall impression and flavor did not differ. In conclusion, it is feasible to produce CLA-enriched dairy products with acceptable storage and sensory characteristics.

Treatment of psoriasis with oral mycophenolic acid.

Mycophenolic acid (MPA), an inhibitor of purine synthesis, was evaluated for its therapeutic and adverse effects in 29 patients with psoriasis. MPA was administered orally for at least 12 weeks, during which time the daily dose was increased from 1600 to 4800 mg depending on occurrence of adverse reactions. Complete clearing occurred in 1 of the patients, almost complete clearing in 14, definite improvement in 13, slight or doubtful improvement in 1. The full effect of MPA required a median time of 8 weeks (range 5-14). After discontinuing MPA, relapses began at a median time of 4 weeks (range 3-8). The severity of psoriasis was scored on a 0 to 108 scale using a newly devised system. The mean severity and range before treatment was 47 (21-88); after 12 weeks, 15 (0-50). Adjustment of dose on the basis of side effects resulted in a median daily dose of 3600 mg (range 2400-4800 mg; 30-96 mg/kg ideal weight). Characteristic dose-limiting side effects were soft or frequent bowel movements, diarrhea, nausea, and anorexia. One instance of reversible, dose-related leukopenia was identified.

The treatment of high-grade soft tissue sarcomas with preoperative thermoradiotherapy.

PURPOSE: To explore the use of a novel program of preoperative radiation and hyperthermia in the management of high-grade soft tissue sarcomas (STS). METHODS AND MATERIALS: Eligible patients were adults over 18 with Grade 2 or 3 STS, surgically resectable without a local excision prior to referral to Duke University Medical Center and without distant metastases. Patients were staged generally with CT and/or MR imaging. The diagnosis was established with fine needle aspiration or incisional biopsy. Patients were then treated with 5000 to 5040 cGy, 180-200 cGy per fraction. Chemotherapy was usually not employed. Generally two hyperthermia treatments per week were given with a planned thermal dose of 10-100 CEM 43 degrees T90. Invasive thermometry and thermal mapping were done in all patients. Surgical resection was planned 4-6 weeks after the completion of radiation and hyperthermia. RESULTS: Ninety-seven patients were treated on study between 1984 and 1996. Follow-up ranged from 12 to 155 months (median 32). All tumors were high-grade in nature, 44 greater than 10 cm in size (maximum tumor diameter), 43 5-10 cm in size, 10 less than 5 cm. Seventy-eight of the 97 tumors were located in an extremity. Of the 97 patients, 48 remain alive and continually free of disease following initial therapy. Of the remaining 49 patients, 44 have relapsed (34 dead, 10 living with disease), 3 have died secondary to complications of therapy, and 2 have died of unrelated causes. Ten-year actuarial overall survival, cause-specific survival, and relapse-free survival are 50, 47, and 47% respectively. The predominant pattern of failure has been distant metastases with only 2 patients developing local failure alone. Ten-year actuarial local control for extremity tumors is 94%, 63% for the 19 patients with tumors at sites other than the extremity. Of the 78 patients with extremity lesions, 63 have had limb preservation and remain locally controlled. Overall 38 patients experienced 57 major complications. There were 3 deaths, one due to adriamycin cardiomyopathy and two secondary to wound infections. Four patients required amputation secondary to postoperative wound healing problems. Complications directly attributable to hyperthermia occurred in 15 patients with 11 instances of second- or third-degree burns and two instances of subcutaneous fat necrosis. The hyperthermia complications were generally not severe and either healed readily or were excised at the time of surgical resection of the primary tumor. CONCLUSIONS: For these aggressive high-grade soft tissue sarcomas, this treatment program of preoperative thermoradiotherapy provided excellent local regional control for extremity lesions (95%) and satisfactory local regional control (63%) of nonextremity sarcomas, but did not appear to influence the rate of distant metastases or survival. Complications were frequent but apart from the direct thermal burns, not too different from those reported for preoperative radiotherapy alone. More effective adjuvant systemic therapy is necessary to impact favorably on survival.