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ABSTRACT: BACKGROUND: Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment of acute uncomplicated diverticulitis is feasible and safe, and which patients could benefit from outpatient care. MATERIALS AND METHODS: A retrospective cohort study was carried out in two teaching hospitals using hospital registry codes for diverticulitis. All patients diagnosed with acute uncomplicated diverticulitis between January 2004 and January 2012, confirmed by imaging or colonoscopy, were included. Exclusion criteria were patients with recurrent diverticulitis, complicated diverticulitis (Hinchey stages 2, 3, and 4), and right-sided diverticulitis. Inpatient care was compared with outpatient care. Primary outcome was admission for outpatient care and the complication rate in both groups. Multivariate analysis was carried out to identify potential factors for inpatient care. RESULTS: Of 627 patients with diverticulitis, a total of 312 consecutive patients were identified with primary uncomplicated diverticulitis of the sigmoid colon; 194 patients had been treated as inpatients and 118 patients primarily as outpatients. In this last group, 91.5% had been treated successfully without diverticulitis-related complications or the need for hospital admission during a mean follow-up period of 48 months. CONCLUSION: Despite inherent patient selection in a retrospective cohort, ambulatory treatment of patients presenting with uncomplicated acute diverticulitis seems feasible and safe. In mildly ill and younger patients, hospital admission can be avoided.
European journal of gastroenterology & hepatology 04/2013; · 1.66 Impact Factor
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ABSTRACT: BACKGROUND: In the setting of difficult dissection of Calot's triangle during laparoscopic cholecystectomy, conversion is commonly advocated. An alternative approach aimed at preventing bile duct injury is laparoscopic partial cholecystectomy (LPC). The safety and efficacy of this procedure are unclear. METHODS: A systematic review of the literature was performed independently by three researchers. The outcomes were conversion rate, hospital length of stay (LOS), bile duct injury, bile leak, symptomatic gallstones in the remnant gallbladder, need for reoperation, postoperative endoscopic retrograde cholangiopancreaticography (ERCP), percutaneous intervention, and mortality. RESULTS: The review included 15 publications, which reported on 625 patients. Four different operative techniques could be distinguished. Conversion to open (partial) cholecystectomy was performed in 10.4 % of the cases. The median LOS was 4.5 days (range, 0-48 days). The most common complication was postoperative bile leak, which occurred in 66 patients (10.6 %). One case of bile duct injury occurred. During the follow-up period, 2.2 % of the patients experienced recurrent symptoms of gallstones. Eight patients (2.7 %) underwent reoperation. Postoperative ERCP was performed for 26 (7.5 %) of 349 patients. A percutaneous intervention was performed for 5 (1.4 %) of 353 patients. Three deaths were described in the reviewed series (1 of pulmonary sepsis and 2 of myocardial infarctions). A rough comparison showed that fewer bile leaks, less need for ERCP, and less recurrent symptoms of gallstones seemed to occur when the cystic duct and gallbladder remnant were closed. CONCLUSIONS: Literature concerning LPC is scarce. Four different LPC techniques can be distinguished. When a difficult gallbladder is encountered during LC, LPC seems to be a safe and feasible alternative to conversion. Closing of the cystic duct, gallbladder remnant, or both seems to be preferable.
Surgical Endoscopy 07/2012; · 4.01 Impact Factor
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ABSTRACT: One of today's controversies remains the prevention of recurrent diverticulitis. Current guidelines advise a conservative approach, based on studies showing low recurrence rates and a high operative morbidity and mortality. Conservative measures in prevention recurrence are dietary advises and medical therapies, including probiotics and 5-aminosalicylic acid.
The aim of this systematic review is to assess whether medical or dietary therapies can prevent recurrent diverticulitis after a primary episode of acute diverticulitis. METHOD AND SEARCH STRATEGY: We searched different databases for papers published between January 1966 and January 2011.
Clinical studies were eligible for inclusion if they assessed the prevention of recurrent diverticulitis with a medical or dietary therapy. Exclusion criteria were studies without a control group.
Three randomized controlled trials (RCT), all with a Jadad quality score of 2 out of 5, were included in this systematic review. Mesalazine results in significantly less disease recurrence and fewer symptoms after an acute episode. The use of probiotics decreases symptoms but does not reduce recurrence. No difference in effect is seen when Balsalazide is added to probiotics compared to probiotics only. No relevant studies on dietary therapy/advices or antibiotics for prevention of recurrent diverticulitis were found.
The evidence that supports medical therapy to prevent recurrent diverticulitis is of poor quality. Treatment with 5-aminosalicylic acid seems promising. Based on current data, no recommendation of any non-operative relapse prevention therapy for diverticular disease can be made.
International Journal of Colorectal Disease 05/2012; 27(9):1131-6. · 2.38 Impact Factor
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ABSTRACT: Restorative proctocolectomy with an ileal pouch-anal anastomosis is thought to abolish the risk of colorectal adenoma development
in patients suffering from familial adenomatous polyposis. Both after mucosectomy with a handsewn anastomosis and after a
double-stapled anastomosis, rectal mucosa is left behind at the anastomotic site. This carries the potential for the development
of polyps and a subsequent malignancy. In our clinic, two patients recently developed an adenocarcinoma at the anastomotic
site, despite a yearly follow-up endoscopy. A 40-year-old female under-went an ileal pouch-anal anastomosis with a double-stapled
anastomosis in 1991. She refrained from follow-up for several years, but returned eight years postoperatively with a fistula
at the anastomotic site. Biopsies revealed an adenocarcinoma infiltrating in the fistula tract T2N0M0. The patient was treated
with preoperative radiotherapy (60 Gy), abdominoperineal resection, and a permanent ileostomy. A 27-year-old male underwent
an ileal pouch-anal anastomosis with a double-stapled anastomosis in 1990. Because of his profession, endoscopy was performed
only once every two years. Endoscopic biopsies ten years postoperatively revealed adenocarcinoma T4N0M0. The patient underwent
an abdominoperineal resection with partial resection of the prostate, and a permanent ileostomy was constructed.
Diseases of the Colon & Rectum 04/2012; 47(4):530-534. · 3.13 Impact Factor
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ABSTRACT: The exact pathogenesis of diverticular disease of the sigmoid colon is not well established. However, the hypothesis that a low-fibre diet may result in diverticulosis and a high-fibre diet will prevent symptoms or complications of diverticular disease is widely accepted. The aim of this review is to assess whether a high-fibre diet can improve symptoms and/or prevent complications of diverticular disease of the sigmoid colon and/or prevent recurrent diverticulitis after a primary episode.
Clinical studies were eligible for inclusion if they assessed the treatment of diverticular disease or the prevention of recurrent diverticulitis with a high-fibre diet. The following exclusion criteria were used for study selection: studies without comparison of the patient group with a control group.
No studies concerning prevention of recurrent diverticulitis with a high-fibre diet met our inclusion criteria. Three randomised controlled trials (RCT) and one case-control study were included in this systematic review. One RCT of moderate quality showed no difference in the primary endpoints. A second RCT of moderate quality and the case-control study found a significant difference in favour of a high-fibre diet in the treatment of symptomatic diverticular disease. The third RCT of moderate quality found a significant difference in favour of methylcellulose (fibre supplement). This study also showed a placebo effect.
High-quality evidence for a high-fibre diet in the treatment of diverticular disease is lacking, and most recommendations are based on inconsistent level 2 and mostly level 3 evidence. Nevertheless, high-fibre diet is still recommended in several guidelines.
International Journal of Colorectal Disease 09/2011; 27(4):419-27. · 2.38 Impact Factor
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ABSTRACT: Evidence-based medicine is the conscientious, explicit, and judicious use of best available evidence in making decisions for individual patient care. The present review gives an evidence-based review of esophageal cancer surgery. The literature search was restricted to the highest level of evidence on the surgical treatment of esophageal cancer.
The Annals of thoracic surgery 04/2010; 89(4):1319-26. · 3.74 Impact Factor
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Cağdaş Unlü,
Niels de Korte,
Lidewine Daniels,
Esther C J Consten,
Miguel A Cuesta,
Michael F Gerhards,
Anna A W van Geloven,
Edwin S van der Zaag,
Joost A B van der Hoeven,
Rutger Klicks, [......],
Rudi M H Roumen,
Quirijn A J Eijsbouts,
Johan F Lange,
Paul Fockens,
Corianne A J M de Borgie,
Wilem A Bemelman,
Johannes B Reitsma,
Hein B A C Stockmann, Bart C Vrouenraets,
Marja A Boermeester
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ABSTRACT: Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects.
A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included.
A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach.
Trial registration number: NCT01111253.
BMC Surgery 01/2010; 10:23. · 1.33 Impact Factor
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ABSTRACT: Isolated limb perfusion with high-dose chemotherapy is an accepted treatment modality to achieve locoregional control in advanced melanoma of the extremities. The drug of choice is melphalan. Tumor necrosis factor-alpha is frequently added to melphalan in bulky disease, and this combination may be an option for repeat perfusion for recurrent melanoma after a first perfusion. Results of perfusions performed with tissue temperatures between 37 degrees C and 38 degrees C seem to be equivalent to those of the perfusions performed under mild hyperthermic conditions. Perfusion cannot be recommended as an adjunct to wide local excision in patients who have primary melanoma. Adjuvant perfusion in repeatedly recurrent limb melanoma, however, may be of value because it lengthens the limb recurrence-free interval and decreases the number of lesions per recurrence significantly. Regional toxicity of perfusion should be mild when risk factors are taken into account.
Surgical Oncology Clinics of North America 11/2008; 17(4):785-94, viii-ix. · 1.12 Impact Factor
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ABSTRACT: The early-stage lymphatic dissemination in esophageal cancer poses challenges for adequate surgical treatment. The role of extensive lymph node dissections remains a matter of debate. Results of the only available large randomized controlled trial suggest that fit patients who have esophageal cancer are treated best by a transthoracic esophagectomy with extended en bloc (two-field) lymphadenectomy. For less fit patients or patients who have junctional or cardiac tumors, transhiatal esophageal resection could suffice. In patients who have truly "early" adenocarcinoma (ie, with high-grade dysplasia or intramucosal carcinoma) endoscopic resectional or ablative treatments may be suitable. When the tumor invades the submucosal layer, the high risk for lymph node involvement and tumor recurrence probably necessitates more extensive treatment schedules for definitive cure.
Surgical Oncology Clinics of North America 11/2006; 15(4):781-91. · 1.12 Impact Factor
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ABSTRACT: Adjuvant perfusion to excision of a primary melanoma cannot be recommended because of its limited effect. In patients who have frequently recur-ring resectable locoregional melanoma, perfusion may provide valuable loco-regional disease control by decreasing the number of recurrences and lesions per recurrence. Randomized studies are needed to further establish the role of perfusion as an adjuvant treatment for resectable recurrences of melanoma. Unresectable limb melanoma is the primary indication for perfusion. Better response rates tend to be seen when TNF-a is used in patients who have a high tumor load. Repeat perfusion is feasible, resulting in response rates similar to those of a first perfusion for locoregional melanoma. Older age itself is not a contraindication for perfusion. The long-term health-related quality of life of survivors of melanoma who underwent treatment with perfusion is comparable to that of their healthy peers in the general Dutch population.
Surgical Oncology Clinics of North America 05/2006; 15(2):373-84. · 1.12 Impact Factor
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ABSTRACT: In patients with truly unresectable melanoma of the extremities, results after isolated limb perfusion (ILP) are absent in the literature. Complete response rates are probably lower than the reported 54% for locoregional recurrent melanoma. In these patients, ILP with melphalan and tumor necrosis factor alpha (TNF-alpha) could be superior to ILP with melphalan alone.
Retrospective analysis with a median follow-up period of 21 months (interquartile range, 9-40 months).
Two tertiary care cancer centers in the Netherlands.
We assessed all 130 consecutive patients who underwent ILP for unresectable melanoma of the extremities, performed between 1978 and 2001. Of these patients, 38% had stage IIIA melanoma and 45% had stage IIIAB melanoma according to criteria of the MD Anderson Cancer Center. Lesions were considered unresectable on the basis of their size, number, or localization.
Forty ILPs were performed with melphalan, and 90 were done with TNF-alpha and melphalan.
Response rate, disease-free survival, limb salvage rate, and overall survival.
In 45% of the patients, a complete response was attained after ILP with melphalan (95% confidence interval, 29%-61%) compared with 59% after ILP with TNF-alpha and melphalan (95% confidence interval, 49%-69%; P = .14). The time to complete response was 3 months (interquartile range, 2-6 months) vs 2 months (interquartile range, 1-3 months; P = .01), respectively. The recurrence rate and median limb recurrence-free survival were not significantly different for both ILP types. The overall limb salvage rate was 96%. Overall 5-year survival was 29% (95% confidence interval, 20%-38%). The ILP type was not an independent prognostic factor for complete response, nor was limb recurrence-free survival, whereas stage IIIA was a favorable prognostic factor (P = .01 and P = .02, respectively). Favorable prognostic factors for improved survival were complete response (P<.001) and a tumor size of 3 cm or less (P = .01).
In more than half of the patients with truly unresectable melanoma of the extremities, a complete response was obtained after ILP with melphalan with or without TNF-alpha. The ILP type was not an independent prognostic factor for complete response, limb recurrence-free survival, or overall survival.
Archives of Surgery 11/2004; 139(11):1237-42. · 4.24 Impact Factor
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ABSTRACT: This study was conducted to assess the best available evidence for the use of isolated limb perfusion.
Following the principles of Evidence-Based Medicine, we reviewed the best available evidence for isolated limb perfusion (ILP) for melanoma and soft tissue sarcoma (STS) of the limb.
Adjuvant ILP with melphalan (M-ILP) to wide local excision cannot be recommended for patients with primary melanoma with a limited regional benefit and no increase in overall survival (level 1b evidence). Prophylactic M-ILP next to the excision of recurrent melanoma has resulted in a nonsignificant decrease in recurrence rate (33% to 50%), with a significantly longer recurrence-free interval (10 to 17 months), but no survival benefit (level 2b evidence). Therapeutic M-ILP, with or without tumor-necrosis factor alpha and interferon gamma (T(I)M-ILP), seems indicated in unresectable melanoma (level 3 to 4 evidence). In unresectable STS of the limbs, limb salvage can be obtained in 57% to 86% of patients with neoadjuvant T(I)M-ILP (level 3 evidence). A comparison of level 3 to 4 studies on ILP and other neoadjuvant treatment modalities for unresectable STS shows that ILP results in the highest limb salvage rate with the lowest complication rate.
Based on level 3 to 4 evidence, ILP is indicated in unresectable locoregional (recurrent) melanoma and unresectable STS of the limbs. Level 1 and 2b evidence does show an effect of prophylactic ILP on micrometastatic disease in locoregional (recurrent) melanoma of the limb. ILP seems the most effective limb sparing, neoadjuvant treatment modality when compared with other neoadjuvant treatment options for unresectable STS of the limb (level 3 to 4 evidence), although randomized studies are lacking.
Annals of Surgical Oncology 10/2004; 11(9):837-45. · 4.17 Impact Factor
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ABSTRACT: Large series with long-term follow-up of thrombolytic therapy in the treatment of lower limb arterial occlusion from a single, general, non-university hospital are absent. We studied retrospectively the results of 129 consecutive patients who underwent thrombolysis with intraarterial urokinase as initial treatment for lower limb native artery or bypass graft occlusions. The mean age of patients was 71 years; 55% of the patients were male, and preexisting peripheral arterial disease was present in 47%. Presenting symptoms were disabling claudication (31%) and limb-threatening ischemia (69%). Forty-two percent of the patients presented with acute symptoms (<1 week duration). The mean follow-up of patients still alive at the time of analysis was 36 months (range 1-120 months). Thrombolytic treatment was successful in 93 patients (72%). In 53% of the patients acute surgical intervention could be avoided: 28 patients (22%) did not need any additional procedure and 40 (31%) underwent a concomitant angioplasty. When thrombolysis failed, 6 patients (5%) underwent successful surgical revascularization and 11 patients (8%) eventually underwent major amputation during their hospital stay. Amputation-free survival at 6 months and at last follow-up was 88% and 83%, respectively. The mortality rates were 4% at 30 days, 5% at 6 months, and 30% at last follow-up. Thrombolysis was significantly less successful when patients had diabetes (62% vs. 81%, p = 0.019) or preexisting peripheral arterial disease (61% vs. 80%, p= 0.018). Successful radiological treatment (thrombolysis+/-angioplasty) could less often be performed in patients with preexisting peripheral arterial disease (41% vs. 59%, p = 0.011) and in patients with occluded bypass grafts (33% vs. 62%, p= 0.002). Duration of symptoms and Fontaine stage at presentation did not predict thrombolysis outcomes. Thrombolytic-related complications occurred in 17 patients (13%), with significant bleeding from the puncture site in 3 patients (2%). Thrombolysis can safely and effectively be performed in a general community hospital with results comparable to those reported from specialized university centers and large randomized trials.
Annals of Vascular Surgery 05/2004; 18(3):314-20. · 1.03 Impact Factor
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ABSTRACT: Restorative proctocolectomy with an ileal pouch-anal anastomosis is thought to abolish the risk of colorectal adenoma development in patients suffering from familial adenomatous polyposis. Both after mucosectomy with a handsewn anastomosis and after a double-stapled anastomosis, rectal mucosa is left behind at the anastomotic site. This carries the potential for the development of polyps and a subsequent malignancy. In our clinic, two patients recently developed an adenocarcinoma at the anastomotic site, despite a yearly follow-up endoscopy.A 40-year-old female underwent an ileal pouch-anal anastomosis with a double-stapled anastomosis in 1991. She refrained from follow-up for several years, but returned eight years postoperatively with a fistula at the anastomotic site. Biopsies revealed an adenocarcinoma infiltrating in the fistula tract T2N0M0. The patient was treated with preoperative radiotherapy (60 Gy), abdominoperineal resection, and a permanent ileostomy.A 27-year-old male underwent an ileal pouch-anal anastomosis with a double-stapled anastomosis in 1990. Because of his profession, endoscopy was performed only once every two years. Endoscopic biopsies ten years postoperatively revealed adenocarcinoma T4N0M0. The patient underwent an abdominoperineal resection with partial resection of the prostate, and a permanent ileostomy was constructed.
Diseases of the Colon & Rectum 05/2004; 47(4):530-4. · 3.13 Impact Factor
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ABSTRACT: The influence of isolated limb perfusion (ILP) on the limb recurrence-free interval (LRFI) and the number of lesions per recurrence was studied for patients with frequently recurring regional in-transit metastases previously managed by excisional surgery.
All 43 patients who had their first ILP for a third or further limb recurrence were selected from our computer database of 451 patients who underwent therapeutic ILP for recurrent extremity melanoma in our centers. Eighteen patients had resectable and 25 had locally unresectable lesions at the time of ILP. The patients had a total of 269 intervals between treatment of their primary melanoma and last recurrence or last follow-up. Median follow-up was 35 months (interquartile range, 14-64 months).
The median LRFI decreases over time from primary melanoma to the third or further recurrence for which ILP was performed (P < 0.001). The median LRFI is 4.7 times longer (95% confidence interval [CI], 2.8-7.9; P < 0.001) after ILP in comparison with the last interval before ILP. Patients with resectable lesions have a median LRFI that is 5.9 times longer (95% CI, 2.7-13; P < 0.001). In all patients, the number of lesions increases by 22% per recurrence number (95% CI, 10%-35%; P = 0.02). At the same recurrence number, patients before ILP have a 2.6-fold higher (95% CI, 1.6-4.5) mean number of lesions than do patients after ILP (P < 0.001).
ILP lengthens the LRFI and decreases the number of lesions per recurrence significantly in patients with repeatedly recurrent limb melanoma. Therefore, ILP could be a valuable adjunct to excisional surgery for in-transit metastases in these patients whose LRFIs tend to shorten over time.
Annals of Surgical Oncology 05/2004; 11(5):491-9. · 4.17 Impact Factor
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ABSTRACT: Since 1992, isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFalpha-ILP at their institution.
From 1992 to 2001, 49 patients (mean age, 51 years; range, 14-85 years) underwent ILP for unresectable soft tissue sarcomas of the extremities. All patients received melphalan and TNFalpha (four patients also received interferon-gamma). The median follow-up was 26 months (range, from 2 days to 103 months).
In 1 patient (2%) who died 2 days after undergoing ILP, response and acute limb toxicity could not be assessed. One patient (2%) attained a clinical complete response (2%), 23 patients (47%) attained a clinical partial response, 17 patients (35%) demonstrated no change, and 7 patients (14%) had tumor progression. Thirty-one patients (63%) underwent tumor resection. Histologic material also was available from eight amputations and three punctures/biopsies. Pathologic response was complete in 4 patients (8%), partial in 14 patients (29%), and no change was observed in 24 patients (49%). Final response, based on both clinical and pathologic assessment in which pathology was decisive, was complete in 4 patients (8%) and partial in 27 patients (55%), resulting in a final overall response rate of 63%. Local control with preservation of the limb was attained in 28 patients (57%). Four of 32 patients (13%) who had been rendered tumor free by ILP with or without undergoing resection and radiation therapy, developed a local recurrence. The 5-year disease specific survival rate was 48% for the 49 patients. Acute limb toxicity after ILP was a mild Grade 1-2 reaction in 35 patients (71%) patients, a Grade 3 reaction in 12 patients (25%), and a Grade 4 reaction in 1 patient (2%). Three major ILP-related complications were encountered, including arterial thrombosis in two patients and a fulminant Clostridial infection leading to death in one patient. There were no severe cardiovascular reactions after ILP.
In patients with unresectable soft tissue sarcomas of the limbs who underwent ILP with TNFalpha and melphalan followed by resection of the tumor remnant when possible, a 63% overall tumor response rate and a 57% local control rate with limb preservation was achieved.
Cancer 11/2003; 98(7):1483-90. · 4.77 Impact Factor
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ABSTRACT: BACKGROUND
Since 1992, isolated limb perfusion (ILP) with tumor necrosis factor-α (TNFα) and melphalan has been used for the treatment of patients with unresectable soft tissue sarcomas of the extremities. The authors retrospectively studied the results of limb salvage surgery using TNFα-ILP at their institution.METHODS
From 1992 to 2001, 49 patients (mean age, 51 years; range, 14–85 years) underwent ILP for unresectable soft tissue sarcomas of the extremities. All patients received melphalan and TNFα (four patients also received interferon-γ). The median follow-up was 26 months (range, from 2 days to 103 months).RESULTSIn 1 patient (2%) who died 2 days after undergoing ILP, response and acute limb toxicity could not be assessed. One patient (2%) attained a clinical complete response (2%), 23 patients (47%) attained a clinical partial response, 17 patients (35%) demonstrated no change, and 7 patients (14%) had tumor progression. Thirty-one patients (63%) underwent tumor resection. Histologic material also was available from eight amputations and three punctures/biopsies. Pathologic response was complete in 4 patients (8%), partial in 14 patients (29%), and no change was observed in 24 patients (49%). Final response, based on both clinical and pathologic assessment in which pathology was decisive, was complete in 4 patients (8%) and partial in 27 patients (55%), resulting in a final overall response rate of 63%. Local control with preservation of the limb was attained in 28 patients (57%). Four of 32 patients (13%) who had been rendered tumor free by ILP with or without undergoing resection and radiation therapy, developed a local recurrence. The 5-year disease specific survival rate was 48% for the 49 patients. Acute limb toxicity after ILP was a mild Grade 1–2 reaction in 35 patients (71%) patients, a Grade 3 reaction in 12 patients (25%), and a Grade 4 reaction in 1 patient (2%). Three major ILP-related complications were encountered, including arterial thrombosis in two patients and a fulminant Clostridial infection leading to death in one patient. There were no severe cardiovascular reactions after ILP.CONCLUSIONS
In patients with unresectable soft tissue sarcomas of the limbs who underwent ILP with TNFα and melphalan followed by resection of the tumor remnant when possible, a 63% overall tumor response rate and a 57% local control rate with limb preservation was achieved. Cancer 2003;98:1483–90. © 2003 American Cancer Society.DOI 10.1002/cncr.11648
Cancer 09/2003; 98(7):1483 - 1490. · 4.77 Impact Factor
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ABSTRACT: The aim of this study was to assess the results of an isolated limb perfusion (ILP) schedule with high dose hyperthermia (42-43 degrees C) and melphalan, applied sequentially in patients with advanced melanoma of the limbs. Seventeen patients with extensive recurrent or bulky melanoma of a limb were treated with hyperthermic femoral ILP (42-43 degrees C) without drugs followed by normothermic (37-38 degrees C) ILP with melphalan. Eleven patients (65%) had a complete response. Three patients (27%) had limb recurrences after 5, 6 and 18 months, respectively. The 5 year limb recurrence-free interval for patients with a complete response was 63%. Limb toxicity was mild; pressure-related blistering and transient sensory disturbances occurred after the hyperthermic ILP, and 88% of the patients had a grade II reaction (mild erythema and oedema) after the second ILP. This sequential ILP schedule resulted in a high complete response rate and a low limb-recurrence rate in patients with extensive, recurrent melanoma of the limbs at the cost of only mild toxicity. This regimen could be an alternative to ILP with tumour necrosis factor-alpha and melphalan.
Melanoma Research 09/2003; 13(4):395-9. · 2.19 Impact Factor
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Journal of Surgical Oncology 05/2002; 79(4):252-5. · 2.10 Impact Factor
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ABSTRACT: Background: Severe systemic toxicity and hemodynamic changes after isolated limb perfusion (ILP) with tumor necrosis factor- (TNF-) and melphalan, with or without interferon-, have been reported in several series. We studied whether these side effects could be precluded by preventing leakage from the isolated circuit into the systemic circulation.Methods: Clinical and pharmacokinetic data for 20 consecutive patients with recurrent melanoma of the limbs who were treated by ILP with TNF- (3–4mg) and melphalan, with or without interferon-, were studied. Leakage rates and TNF- levels were determined during and after ILP and were correlated with systemic toxicity and hemodynamic changes.Results: Only two patients experienced leaks (2% and 13%) during ILP. For 18 patients without leakage, the mean peak systemic TNF- level was 2.8 ng/ml at 10minutes after ILP. After leakage, the peak systemic TNF- levels were 31.9 and 88.3ng/ml at 5minutes. Toxicity was mild and consisted mainly of fever (n = 17) and nausea/vomiting (n = 19) during the first day after ILP. Some patients developed tachycardia (n = 6), hypotension (n = 3; responding immediately to fluid challenge), a decrease in the WBC count (n = 3; grade I) or thrombocyte count (n = 11; grade I/II, no hemorrhage or therapeutic intervention), or hepatotoxicity [cytolysis (n = 15; 14 grade I/II and 1 grade IV) or hyperbilirubinemia (n = 7; grade I/II, all resolving spontaneously)]. Patients with tachycardia or hepatotoxicity exhibited significantly higher TNF- levels after ILP, compared with other patients.Conclusions: Systemic toxicity after ILP with TNF- is minimal and does not differ from that after ILP with melphalan alone when leakage is adequately controlled.
Annals of Surgical Oncology 01/1999; 6(4):405-412. · 4.17 Impact Factor
