Palliative resection of the primary tumour in stage IV rectal cancer.

AIM: The aim of this study was to investigate the use of resection in a cohort of palliatively treated patients with stage IV rectal cancer. To avoid selection bias, particular attention was paid to correction for comorbidity and extent of disease. METHOD: Patients with stage IV rectal cancer in two hospitals in Groningen were consecutively included over a 5-year period. Comorbidity was defined as major (dementia, cardiac failure or left ventricle ejection fraction <30%, or severe chronic obstructive pulmonary disease), minor (diabetes, hypertension, mild renal disease or mild pulmonary disease) or none. The effect of patient and disease characteristics on survival was assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Of 88 patients, 11 (13%) underwent elective surgical resection without chemotherapy, 15 (17%) received both elective resection and chemotherapy, 21 (24%) underwent palliative chemotherapy only and 41 (47%) had supportive care only. The extent of disease (P<0.01), hospital (P=0.02) and comorbidity (P=0.04) were correlated with worse survival. Patients treated surgically survived for longer than patients treated nonsurgically, when the data were corrected for age, comorbidity, extent of disease and hospital [hazard ratio (HR)=0.4 (95% CI=0.2-0.7)]. Perioperative morbidity was seen in 38% of the patients, and 30-day mortality was 0%. CONCLUSION: In this retrospective cohort, resection was associated with longer survival independently of the extent of distant metastases, age and comorbidity.

Intraoperative assessment of microperfusion with visible light spectroscopy for prediction of anastomotic leakage in colorectal anastomoses.

PURPOSE: Anastomotic leakage is associated with increased morbidity and mortality. However, there is no accurate tool to predict its occurrence. We evaluated the predictive value of visible light spectroscopy (VLS), a novel method to measure tissue oxygenation [saturated O(2) (StO(2) )], for anastomotic leakage of the colon and the rectum. METHOD: Oxygen saturation in the bowel was measured in 77 colorectal resections. The anastomosis was between 2 and 30 cm (mean 13 cm) from the anal verge. The oxygen saturation was measured in the colon and rectum before and after anastomosis construction. This was compared with a reference measurement in the caecum. Data on postoperative complications were prospectively collected. RESULTS: Anastomotic leakage occurred in 14 (18%) patients. When compared with a leaking anastomosis, normal anastomoses showed rising O(2) values during the operation (mean StO(2) 72.1 ± 9.0-76.7 ± 8.0 vs 73.9 ± 7.9-73.1 ± 7.4) (P ≤ 0.05). There were also higher StO(2) values in the caecum compared with those which ultimately leaked (73.6 ± 5.7 normal anastomoses, 69.6 ± 5.6 anastomotic leaks) (P ≤ 0.05). Both StO(2) values were predictive of anastomotic leakage. CONCLUSION: Tissue oxygenation O(2) appears to be a potentially useful means of predicting anastomotic leakage after colorectal anastomosis.

Surgeons lack predictive accuracy for anastomotic leakage in gastrointestinal surgery.

BACKGROUND: The dramatic clinical consequences of anastomotic leakage in gastrointestinal surgery can be reduced by a diverting stoma or drainage of the peri-anastomotic area. Currently, the surgeons' clinical judgement is of major importance in decision making, but reliable data of the diagnostic accuracy are lacking. In this prospective clinical study, the surgeons' predictive accuracy for anastomotic leakage was evaluated. MATERIALS AND METHODS: In 191 patients undergoing colorectal resection with anastomosis, the risk for anastomotic leakage was determined by the surgeon on the basis of a visual analogue scale (VAS). This risk assessment was compared to the actual occurrence of anastomotic leakage post-operatively. RESULTS: A total of 26 (13.6%) patients showed anastomotic leakage. The surgeons' median predicted leakage rate was 7.1% in anastomoses >15 cm from the anal verge and 9.5%

Intraoperative assessment of microperfusion with visible light spectroscopy in esophageal and colorectal anastomoses.

BACKGROUND: We evaluated the technical feasibility and stability of measurements using visible light spectroscopy to measure microvascular oxygen saturation (StO(2)) in gastrointestinal anastomoses. METHODS: In consecutive esophageal (n = 14) or colorectal (n = 30) resections, during which an uncomplicated anastomosis was performed, measurements of serosal StO(2) were performed during the procedure. RESULTS: In esophageal resections, median (+/- standard error) StO(2) was stable before and after anastomosis in the proximal esophagus (before: 66.0 +/- 4.6, after: 68.3 +/- 6.0%) and the gastric conduit (before: 70.6 +/- 8.6, after: 69.8 +/- 8.0%). Mean colorectal StO(2) before and after anastomosis increased in the proximal part (71.3 +/- 8.4 to 76.6 +/- 8.2%; p < 0.005). Mean StO(2) in the distal part remained stable (72.4 +/- 6.6 to 74.8 +/- 6.7%). CONCLUSIONS: Visible light spectroscopy is a feasible and fast method for intraoperative assessment of microperfusion of the serosa in esophageal and colorectal anastomosis. Future clinical studies will define its role in the prediction of anastomotic leakage.

Effect of modified Davidson's fixative on examined number of lymph nodes and TNM-stage in colon carcinoma.

AIMS: We evaluated the effect of modified Davidson's fixative (mDF) on the number of lymph nodes examined and staging in patients with colon carcinoma. METHODS: The results of two different fixation methods used in the pathological preparation of the resection specimens were analyzed. A traditional formalin preparation with manual dissection of all nodes was performed in 117 colon specimens between January 2003 and July 2004. After July 2004, the resected specimens of 125 patients was fixated in mDF. Differences in the retrieval and number of nodes and size of suspected nodal metastases were measured. All lymph nodes were stained with conventional H&E methods. RESULTS: The median number of examined nodes increased from 5 (0-17) to 13 (0-35) nodes after the introduction of mDF (p<0.001). The type of resection and the T-stage influenced the number of retrieved nodes significantly. The percentage of node-positive cases increased from 30% to 41% (p=0.077) with mDF, the median size of the retrieved lymph nodes decreased from 9 mm before to 6 mm after mDF (p<0.001) and more micrometastases were found (6% vs. 16%, p=0.03). CONCLUSIONS: With mDF technique more lymph nodes were retrieved in the resected colon specimens. Smaller nodes and more micrometastases were found, leading to more node positive patients.

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ.

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696-13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126-28.926; HR=2.778, 95% CI 0.982-6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272-5.776 for time period 1992-1995 and HR=1.976, 95% CI 0.526-7.421 for time period 1996-1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.

Ductal carcinoma in situ presenting as microcalcifications: the effect of stereotactic large-core needle biopsy on surgical therapy.

The aim of this investigation was to study the efficacy of surgical therapy in patients with non-palpable ductal carcinoma in situ (DCIS) presenting as microcalcifications diagnosed by means of stereotactic large-core needle biopsy (SCNB). This is a retrospective study with a historical control group within a 12-year period. Two groups of consecutive patients diagnosed with DCIS (1991-2002) by means of needle-localised open breast biopsy (NLBB, n=49) and SCNB (n=51) were studied. Both groups were comparable for clinical, radiological and pathological characteristics. The therapeutic interval (time from presentation to definitive of therapy) was 62-days in the SCNB group versus 32-days in the NLBB group (p<0.001). In the SCNB group fewer surgical procedures were required for completion of surgical therapy (p=0.006) and after local excision the surgical margins were more often tumour free (p=0.002). It is postulated that the need for fewer surgical procedures and the greater frequency of tumour-free margins after local excision may be attributable to SCNB.

Hyperthermic Isolated Limb Perfusion with TNF alpha and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs.

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNFalpha ) and cisplatin for the management of osteosarcoma was studied in the canine model.Methods. During seven perfusions in six healthy mongrel dogs (weight 32+/-2 kg) technical aspects of HILP under mild hyperthermia (39- 40) were studied. In five experiments HILP was performed with TNFalpha alone (0.5 mg/l extremity volume), and in two experiments TNFalpha was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFalpha and total cisplatin concentrations were determined.Results. Perfusion conditions (pH, PCO(2) , PO(2), flow and pressure) remained within physiological ranges.Three dogs died within 24 h despite a sublethal systemic concentration of TNFalpha that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb.Conclusions. This feasibility study in healthy dogs demonstrated that HILP with TNFalpha and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFalpha and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma.

Significance of aneuploidy in melanoma of the extremity.

Tumor nuclear DNA content was determined by flow cytometry in routinely prepared paraffin blocks from 25 primary malignant melanomas of the extremities. Twelve of the tumors were aneuploid, and 13 were euploid. In this series the presence of aneuploidy appeared to have no prognostic value.

Groin dissection in the treatment of lower-extremity melanoma. Short-term and long-term morbidity.

Groin dissection was performed in 151 consecutive patients from 1970 to 1984. Groin dissections were therapeutic in 138 cases (91%) and elective in 13 (9%). One hundred forty-three patients (95%) underwent an ilioinguinal node dissection, while eight (5%) were treated with an inguinal node dissection. In 88 patients, the groin dissection was combined with isolated regional perfusion. Primary wound closure was performed in 140 patients (93%). There was no 30-day postoperative mortality. Complications included temporary seroma (26 [17%] of 151 patients), wound infection (14 patients [9%]), wound necrosis (five patients [3%]), and edema (30 patients [20%]). Residual inguinal node metastases after groin dissection did not occur. Morbidity of groin dissection did not increase when the groin dissection was combined with isolated regional perfusion. Quantification of the degree of edema in 66 patients revealed functional limitation due to edema in three patients (4.5%). This technique of groin dissection gives good results with minimal functional morbidity of the affected leg.

Isolated regional perfusion in the treatment of subungual melanoma.

Subungual melanoma is rare and represents only 1% to 3% of all diagnosed melanomas in Western countries. The tumor is frequently mistaken for a benign lesion and the delay in diagnosis and final treatment may be responsible for the high local recurrence rate and the low disease-free survival rate. From 1965 to 1982 the combined-modality therapy of amputation and adjuvant isolated regional perfusion with melphalan with or without dactinomycin was used in the treatment of 22 patients with subungual melanoma. Disease was staged according to the M. D. Anderson classification, as follows: stage I (primary melanoma), 11 patients; stage IIIA (in-transit metastases and/or satellitosis), three patients; stage IIIB (regional lymph nodes), seven patients; and stage IIIAB (in-transit metastases and/or satellitosis and regional lymph nodes), one patient. There were no cardiovascular complications and no treatment mortality. During a follow-up of at least 4.5 years, 12 patients (55%) developed distant metastases, including four patients with stage I disease (36%) and eight patients with stage III disease (73%). There were no locoregional recurrences. The median survival was three years (range, 0.5 to 12.5 years) and the overall five-year survival was 40%, with 56% of patients having stage I disease and 27% having stage III disease. The prognosis of subungual melanoma is determined by the stage of the disease. Isolated regional perfusion may prolong disease-free survival in patients with subungual melanoma compared with previously published data.

Hyperthermic isolated regional perfusion in the treatment of extremity melanoma in children and adolescents.

From 1973 to 1982 six children and eight adolescents with extremity melanomas were treated by local excision and adjuvant hyperthermic isolated regional perfusion with Melphalan (L-phenylalanine mustard, manufactured by Burroughs Wellcome Company, Research Triangle Park, NC). The median Breslow thickness of the melanomas was 2.7 mm (range, 1 to 15 mm). According to the M.D. Anderson classification, nine patients were in Stage IA and five were in Stage IIIB. The median follow-up period was approximately 10 years. Distant metastases developed in three patients (21%) (one patient was in Stage IA [11%] and two patients were in Stage IIIB [40%]). In two cases the development of distant metastases was preceded by local recurrence (14%). The 5-year survival rate was 93%. The 10-year survival rate was 81%. The high survival rate, even for patients with unfavorably thick melanomas, seems to be attributable to isolated regional perfusion.