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Volvulus of the transverse colon is very rare in children. Three cases that occurred in a short time span are described and the scarce literature is reviewed. All patients presented with colonic obstruction and in all three the condition was diagnosed at laparotomy, as CT-scanning is not an available option in either of the two institutions. The transverse colon had not become gangrenous but was resected after detorsion for redundancy. The postoperative course was complicated and relaparotomy had to be performed for reobstruction in all cases. Only if the 'reverse' bean sign is recognized on the preoperative plain abdominal radiograph this rare diagnosis can be suspected., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Selecting patients for cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (HIPEC) remains challenging. We compared the predictive power of three intra-operative assessment tools of peritoneal involvement of colorectal cancer., Methods: Ninety-two procedures (1999-2005) were prospectively scored using the Simplified Peritoneal Cancer Index (SPCI) and 7 Region Count. The Peritoneal Cancer Index (PCI) was retrospectively scored using the SPCI tool, operative notes and pathological reports. Endpoints were completeness of cytoreduction and overall survival. Logistic regression and Receiver Operating Characteristic (ROC) curves were applied to compare the predictive value of the three scoring systems on completeness of cytoreduction., Results: After a median follow-up of 31 months, the median overall survival was 25.6 months. It decreased to 7.3 months, when cytoreduction was incomplete (p=0.001). An increased PCI, SPCI or number of regions were all associated with a decrease in probability of complete cytoreduction (p<0.05). With complete cytoreduction as outcome, the ROC areas for the PCI, SPCI and 7 Region Count were 0.92, 0.94 and 0.90, respectively (p=0.14). Using a cut-off value of 16 in the PCI system (p=0.03), 13 in the SPCI system (p=0.04) and 6 regions in the 7 Region Count (p=0.0002) the probability of complete cytoreduction decreased significantly., Conclusion: The PCI, SPCI and 7 Region Count are useful and equally effective prognostic tools predicting completeness of cytoreduction and associated improved survival. The 7 Region Count may be preferred due to its practical simplicity.

Background: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1 per million per year, and is thought to originate usually from an appendiceal mucinous epithelial neoplasm. However it is not known exactly how often these neoplasms lead to PMP. The aim of this study is to investigate the incidence of both lesions and their relation., Methods: The nationwide pathology database of the Netherlands (PALGA) was searched for the incidence of all appendectomies, the incidence of primary epithelial appendiceal lesions and the incidence and pathology history of patients with PMP. All regarded the 10-year period of 1995-2005., Results: In the 10-year period 167,744 appendectomies were performed in the Netherlands. An appendiceal lesion was found in 1482 appendiceal specimens (0.9%). Nine percent of these patients developed PMP. Coincidentally, an additional epithelial colonic neoplasm was found in 13% of patients with an appendiceal epithelial lesion. A mucinous epithelial neoplasm was identified in 0.3% (73% benign, 27% malignant) of appendiceal specimens and 20% of these patients developed PMP. For mucocele and non-mucinous neoplasm the association with PMP was only 2% and 3%, respectively. From the nationwide database 267 patients (62 men and 205 women) with PMP were identified, which demonstrates an incidence of PMP in the Netherlands approaching 2 per million per year. The primary site was identified in 68% and dominated by the appendix (82%)., Conclusions: Primary epithelial lesions of the appendix are rare. One third of these lesions are mucinous epithelial neoplasms and especially these tumours may progress into PMP. The incidence of PMP seems to be higher than thought before. Furthermore there is a considerable risk of an additional colonic epithelial neoplasm in patients with an epithelial neoplasm at appendectomy.

Background: Cytoreductive surgery with intraperitoneal chemotherapy has emerged as a new standard approach for peritoneal surface disease. This study investigated the learning curve of this combined modality treatment at a single institute., Methods: Variables analysed over three consecutive treatment periods (1996-1998, 1999-2002 and 2003-2006) included number of abdominal regions affected, Simplified Peritoneal Cancer Index (SPCI) score, result of cytoreduction, morbidity, duration of hospital stay and survival., Results: A total of 323 procedures were performed between January 1996 and June 2006, 184 for peritoneal carcinomatosis of colorectal cancer origin and 139 for pseudomyxoma peritonei (PMP), including second procedures in 11 patients with PMP. The mean SPCI score decreased significantly over the study period (P < 0.001), but the number of regions affected did not. The rate of complete cytoreductions increased from 35.6 to 65.1 per cent (P = 0.012). The postoperative morbidity rate decreased from 71.2 to 34.1 per cent (P < 0.001). The median duration of hospital stay decreased from 24 to 17 days. The peak of the learning curve, graded by the percentage of complete cytoreductions, was reached after approximately 130 procedures., Conclusion: The learning curve of combined modality treatment for peritoneal surface disease is long, and reflects patient selection and treatment expertise., (Copyright (c) 2007 British Journal of Surgery Society Ltd.)

Background: Recently, pleural mesothelioma has been treated by cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy with doxorubicin and cisplatin. The well-established cardiotoxicity of doxorubicin and distressing data from an animal study raised concern about its impact on cardiac function. In the present study, early cardiotoxicity of this treatment modality was prospectively analyzed., Patients and Methods: In 13 pleural mesothelioma patients, cardiotoxicity was monitored by clinical examination, electrocardiography, Troponin levels, cardiac ultrasonography, and estimation of left ventricular ejection fraction (LVEF) by radionuclide ventriculography before and during the first 6 months after cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy with doxorubicin (25-54 mg/m(2)) and cisplatin (65-120 mg/m(2))., Results: No clinical cardiac failure or treatment-related death was observed. In two patients transient atrial fibrillation was noted; one associated with pulmonary emboli. Early posttreatment Troponin release was not of predictive value. Ultrasonography did not reveal significant alterations. LVEF decreased significantly (mean 0.07 or 11%, P = .001) during the first 3 months and remained stable thereafter. In univariate analysis, the degree of LVEF reduction was statistically related to maximal intrathoracic doxorubicin concentration (P = .031) and total cisplatin dose (P = .029). Direct exposure of the heart to the drugs as a result of partial pericardectomy was not associated with greater LVEF decrease. On the contrary, partial pericardectomy seemed to be associated with a smaller LVEF decline than when the pericardium remained intact (P = .045). In this small series, no statistically significant correlation between other treatment or pharmacokinetic parameters and LVEF decline was found. Notably, higher doxorubicin plasma concentrations and exposure were not associated with increased LVEF reduction., Conclusions: Early cardiotoxicity is limited after this treatment modality using substantial doses of doxorubicin and cisplatin. Hence, this study suggests that intrathoracic chemotherapy with doxorubicin and/or cisplatin may be used for primary and secondary pleural malignancies, even immediately after extensive thoracic surgery, without concern of severe early cardiotoxicity.

Background and Objectives: To determine retrospectively in a population-based setting, the influence of the introduction of total mesorectal excision (TME) on local recurrence and survival in patients with rectal carcinoma., Methods: All rectal carcinomas diagnosed during 1988-1991 (979 patients, conventional surgery with blunt dissection of the rectum) and 1998-2000 (890 patients, TME resection) were selected from the Amsterdam Cancer Registry. For all patients who underwent a macroscopically radical resection in the absence of distant dissemination, information on the occurrence of local recurrent disease and distant metastasis was collected., Results: The cumulative 5-year recurrence rate decreased significantly from 20% for patients diagnosed in 1988-1991 to 11% in 1998-2000. Stage (T-category, nodal status), period of diagnosis (conventional surgery vs. TME resection), radiotherapy, and chemotherapy were independent variables of local recurrence in multivariate analysis. There was a non-significant trend for improved 5-year relative survival for all rectal carcinoma cases from 52% (95% CI 48-55) for patients diagnosed in 1988-1991 to 59% (95% CI 55-63) in 1998-2000., Conclusions: A significant decrease in local recurrence and a trend for improved relative survival were observed. The broad introduction of TME and the shift towards preoperative radiotherapy are the most plausible explanations for these observations., (Copyright 2007 Wiley-Liss, Inc.)

Pseudomyxoma peritonei (PMP) is a rare condition, which is known for its high mortality when not treated properly. The first step to improve prognosis of these patients is to recognize this clinical syndrome preferably in an early stage. Knowledge of pathogenesis and common diagnostic tools is essential in this regard. Treatment strategy for PMP should pursue complete cytoreduction and prevention of recurrence or progression. Combined modality treatment, consisting of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, seems very efficient in this regard. This approach is currently carried out in many centers throughout the world with promising results and seems to win ground as the standard treatment approach.

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment strategy for pseudomyxoma peritonei (PMP) with curative intent. The aim of this study was to determine the patterns of failure in patients who underwent such a procedure and to evaluate management and outcome of progressive disease., Methods: After exclusion of patients with overt malignancy, progression was studied in 96 PMP patients treated primarily by CRS with HIPEC. Location, pathology, management and outcome were recorded., Results: Median follow-up was 51.5 months (0.1-99.5). Median progression free survival (PFS) was 28.2 months (95% CI 18.3->). Progressive disease was mainly located sub hepatic (38%) or in multiple regions (36%). Pathological dedifferentiation was observed in 8 patients (20%). The choice of treatment depended on pathology, extent of disease and PFS. Seventeen patients were treated for progression by second CRS with (n=8) or without HIPEC (n=10). The 3-years overall survival (OS) probability after this treatment was 100% and 53.3% (95% CI 28.2-100%), respectively. Fifteen patients with (slow) progression were observed. Three-years OS probability of these patients was 66.0% (95% CI 43.4-100%). All patients treated for progression by systemic chemotherapy only (n=6) had died of disease after a median follow up of 14.8 (9.8-33.6) months. A longer PFS after primary treatment was associated with longer OS after progression (P = 0.04)., Conclusions: Progressive PMP after primary CRS with HIPEC is probably the result of technical failure and/or tumor biology. Management of progressive PMP can be valuable for selected patients and should depend primarily on the PFS.

Background: Radiotherapy (RT) has become the primary treatment of choice for anal cancer in an effort to avoid colostomy. The current role of surgery appears generally to be underestimated, since diverting colostomy or abdominoperineal resection still often seems to be necessary for complications and local treatment failure after RT., Methods: The data of 83 patients primarily treated by RT with curative intent throughout a 20-year period in our institute were analyzed regarding the need for colostomy., Results: Totally, 28 patients (34%) required creation of a colostomy after primary RT for local failure or treatment-related complications during a mean follow-up period of 39 months. The 3-year actuarial colostomy-free rate was 59% (mean 85 +/- 9 months). Early stage disease, low T-score and absence of infiltration in adjacent organs were associated with a reduced need for colostomy in univariate analysis. In multivariate analysis only T-score was an independent variable in predicting prolonged colostomy-free interval. In this study, no statistically significant differences were noted for gender, age, nodal status, total radiation dose, radiation boost and concurrent chemotherapy., Conclusions: In approximately one-third of the patients treated by anal sphincter saving management with curative aimed primary RT, the creation of a colostomy appeared to be necessary for RT complications and local treatment failure. Therefore, patients should be well informed regarding the considerable risk of need for colostomy after RT for anal cancer.

Objective: To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors with prognostic value., Summary Background Data: PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology., Methods: A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival., Results: Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01)., Conclusion: Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.

Aim: To weigh the harms and benefits of short-term pre-operative radiotherapy in the treatment of resectable rectal cancer., Methods: The benefits (reduction of local recurrence) and harm (increase of short-term complications) of short-term pre-operative radiotherapy are balanced using a model which classifies patients in one of five outcome combinations; 1-benefit without additional harm, 2-benefit with additional harm, 3-no benefit, no additional harm, 4-no benefit but additional harm, 5-mortality due to combined treatment. The results of four randomised clinical trials (RCT) which study the addition of short-term pre-operative radiotherapy in rectal cancer were classified according to this model., Results: Five to thirteen percent of the patients have benefit without additional harm of pre-operative radiotherapy, while 0-2% have benefit with additional harm; 74-87% has neither benefit nor additional harm and 6-11% have no benefit but additional harm. A small percentage of patients (1-6%) dies post-operatively as a result of the addition of radiotherapy., Conclusion: This model provides a transparent appreciation of the harmful and beneficial effects of any treatment modality investigated by means of a randomised clinical trial. As for short-term pre-operative radiotherapy in resectable rectal cancer is shown, a small percentage of patients benefits from such treatment. Most patients have neither benefit nor additional harm, while a small percentage suffers from additional harm while not receiving any benefit.

Background: To properly balance the benefit (reduction of local recurrence) of short-term pre-operative radiotherapy for resectable rectal cancer against its harm (complications), a consensus concerning the severity of complications is required. The aim of this study was to reach consensus regarding major and minor complications after short-term radiotherapy followed by total mesorectal excision in the treatment of rectal carcinoma, using the Delphi technique., Methods: A Delphi round was performed in cooperation with 21 colo-rectal surgeons from the Netherlands, United Kingdom and Sweden. The key-question was: 'Which of the predefined complications, caused or substantially aggravated by radiotherapy, are so important (major) that they might lead to the decision to abandon short-term pre-operative radiotherapy (5 x 5Gy) when treating patients with resectable rectal cancer (T1-3N0-2M0)?', Results: After three rounds, consensus was reached for 37 (68%) of 54 complications of which 13 were considered major and 24 considered minor. The following complications were considered to be major: mortality, anastomotic leakage managed by relaparotomy, anastomotic leakage resulting in persisting fistula, postoperative haemorrhage managed by relaparotomy, intra-abdominal abscess without healing tendency, sepsis, pulmonary embolism, myocardial infarction, compartment syndrome of the lower legs, long-term incontinence for solid stool, long-term problems with voiding, pelvic fracture with persisting pain, and neuropathy with persisting pain (legs). Three of 17 complications without consensus showed a tendency to be considered as major: perineal wound dehiscence managed by surgical treatment, small bowel obstruction leading to relaparotomy and long-term incontinence for liquid stool., Conclusion: The 13 major and three 'accepted as major' complications can be used to properly balance the benefit and harm of short-term pre-operative radiotherapy in resectable rectal cancer. This may eventually lead to improved treatment strategies for these patients.

Aims: To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors., Methods: A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality., Results: The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality., Conclusions: Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.

Aim: A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors could be identified on preoperative computed tomography (CT), in order to avoid unnecessary surgery., Patients and Methods: Films of abdominopelvic CT scans from 25 such patients treated by cytoreductive surgery and HIPEC were retrospectively analysed by two radiologists separately. A simplified peritoneal cancer index (SPCI) was used to determine the extent of peritoneal involvement. Correlation between the on preoperative CT based SPCI-scores as well as number of involved abdominopelvic areas (N) and survival was examined with the log-rank test. The relation between each affected region and survival was evaluated with Cox regression analysis., Results: The preoperative SPCI- and N-scores of one of the radiologists had no statistically significant prognostic value, while for the second radiologist SPCI > or = 7 and N > or = 4 were associated with particularly poor outcome. Additionally, the presence of ileocaecal region involvement and, depending on the radiologist, the occurrence of tumour deposits in the left subdiaphragmatic area on CT appeared to be unfavourable prognostic signs., Conclusions: The prognostic value of preoperative conventional CT appeared to be radiologist dependent and may, therefore, be of limited value in selecting colorectal cancer patients with peritoneal carcinomatosis who will not benefit from extensive cytoreductive surgery followed by HIPEC.

Background: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by intraperitoneal accumulation of mucus produced by neoplastic cells of mostly appendiceal origin. The aim of this study was to analyze primary and secondary involvement and treatment-related complications of the urinary tract in PMP., Methods: A retrospective study of 92 patients with PMP, treated by cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) at The Netherlands Cancer Institute between 1996 and 2004., Results: Seven patients presented with involvement of the urinary tract. Major urologic complications occurred in five patients, of which two had secondary involvement of the urinary tract. Major urologic complications consisted predominantly of surgical complications related to the bladder. All patients with secondary involvement and/or urologic complications had undergone previous pelvic surgery., Conclusions: The urinary tract is rarely involved in patients with PMP. Secondary involvement is mostly observed and may be a result of seeding of PMP of pelvic origin after prior pelvic surgery. There is a low urologic complication risk of treatment with cytoreduction and HIPEC. The combination of secondary involvement and previous pelvic surgery is an omen of treatment-related urologic complications, necessitating (surgical) re-interventions and further management in close collaboration with urologists., ((c) 2005 Wiley-Liss, Inc.)

Aims: To report the results of standard therapy for peritoneal carcinomatosis of colorectal origin, which consists of conventional surgery and systemic chemotherapy., Method: In a prospective study 50 patients with proven peritoneal carcinomatosis of colorectal origin were treated with conventional surgery combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by 5-fluorouracil within 12 months prior to entry. Survival and progression-free survival were studied and prognostic factors were analysed., Results: The median survival time was 12.6 months. The median time to progression was 7.6 months. Location of primary tumour and result of conventional surgery and systemic chemotherapy were prognostic factors related to survival., Conclusion: The survival time of patients with peritoneal carcinomatosis of colorectal origin seems to be increased in patients treated by conventional surgery and systemic chemotherapy when compared to minimal treatment.

Background: The prognosis for patients with liver metastases from colorectal carcinoma is limited because of the low number of patients who are eligible for curative hepatic resection. In this phase I study, 31 liver metastases in 24 patients with nonresectable metastases from colorectal carcinoma were treated with photodynamic therapy (PDT)., Methods: The photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) was intravenously administered in a dose of .6 mg/kg (n = 12) or .3 mg/kg (n = 12). After 120 hours (n = 18) or 48 hours (n = 6), tumors were illuminated for 300 to 600 seconds through percutaneously inserted optical fibers with a light dose of 60 J/cm of diffuser (740 nm)., Results: Tumor necrosis at 1 month after PDT was achieved in all treated lesions. Laser treatment was associated with mild pain (n = 8) and transient subclinical hepatotoxicity (n = 21). In one patient, PDT damage to the pancreas was inflicted, and in another patient, PDT damage of the skin occurred, but no serious clinical complications from PDT were reported. Administration of .6 mg/kg of mTHPBC led to transient phlebitis in 10 patients, and 3 patients experienced mild skin phototoxicity after excess light exposure., Conclusions: Colorectal liver metastases that are ineligible for resection can be safely and effectively treated with interstitial mTHPBC-based PDT.

The aim of this study was to determine prognostic factors and outcome after liver resection for colorectal metastases in 102 patients over a period of 10 years. A stepwise procedure using proportional hazard regression analysis was used to identify prognostic factors. Estimated survival at 2 years was 71%, and at 5 years, 29% (Kaplan-Meier). Of 19 patients with isolated liver recurrence, 6 had a second metastasectomy; 4 of the 6 are still alive. We found that the number of hepatic lesions on computed tomography (P=0.012), the interval between resection of the primary colon tumor and the hepatic metastasectomy (P=0.012), and synchronicity of the primary and the hepatic metastasis (P=0.048) showed evidence of independent prognostic value regarding survival. Resection of hepatic colorectal metastases may result in long-term survival. Patients with recurrence after a first liver resection may benefit from a repeat metastasectomy. Our data suggest there is no strong predictor of survival. Survival seems to decrease with increasing number of metastases found on computed tomography.

Background: Peritoneal carcinomatosis of colorectal cancer is probably best treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). In The Netherlands Cancer Institute, this treatment has been performed since 1995. The long tradition of this treatment enabled us to study long-term survival in detail., Methods: Between 1995 and 2003, 117 patients were treated by cytoreduction and HIPEC. The aim of the cytoreduction was to remove all visible tumor. After the cytoreduction, the abdomen was perfused with mitomycin C (35 mg/m2) at 40 degrees C to 41 degrees C for 90 minutes. Survival was calculated by the Kaplan-Meier method. Survival was also analyzed for the following subgroups: no residual tumor, residual tumor < or = 2.5 mm, and more residual tumor. Hazard ratios for each of the seven abdominal regions were calculated to determine the influence on survival., Results: The median survival was 21.8 months. The 1-, 3-, and 5-year survival rates were 75%, 28%, and 19%, respectively. The Kaplan-Meier curve reached a plateau of 18% at 54 months. In 59 patients a complete cytoreduction was achieved, and in 41 patients there was minimal residual disease. The median survival of these patient groups was 42.9 and 17.4 months, respectively. When gross macroscopic tumor was left behind, as was the case in 17 patients, the median survival was 5 months. Involvement of the small bowel before cytoreduction was associated with poorer outcome., Conclusions: Cytoreduction followed by HIPEC showed a median survival of 21 months. From 3 years on, a consistent group of 18% of patients stayed alive.

Background: The aim of our study was to analyse data of patients treated by salvage surgery for locally recurrent rectal cancer, with emphasis on the question whether salvage surgery is still worthwhile when adjuvant radiotherapy is no longer a treatment option., Methods: Forty patients (19 males/21 females) treated by surgery with curative intent for locally recurrent rectal carcinoma were analysed. Local recurrence was defined as cancer recurrence within the lower pelvis. Salvage surgery included abdominoperineal resection, abdominosacral resection, exenteration (posterior or total) and local resection. Clinical and pathological factors were analysed to identify prognostic factors for survival., Results: The median overall survival was 25 months (95% CI: 13-37 months) and 5-year survival was 28% (95% CI: 12-45%). The absence of symptoms at the time of recurrence, central localisation and the absence of microscopic involvement of surgical margins, but not additional radiotherapy, were found to be significant independent prognostic factors for better survival after salvage surgery., Conclusion: Salvage surgery, alone or in combination with radiotherapy, can achieve radical resection of locally recurrent rectal cancer and can result in long-term survival.

Background: Peritoneal carcinomatosis in the absence of distant metastasis occurs in approximately 8 per cent of patients with colorectal cancer. Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment option. Patient selection is crucial to outcome., Methods: Cytoreduction followed by HIPEC was performed in 102 patients with peritoneal carcinomatosis. The following factors were studied for association with survival: perforation and obstruction of the primary lesion, location of the primary lesion, obstruction associated with carcinomatosis, presentation, tumour differentiation and histological type. Extent of disease and completeness of cytoreduction were also studied. Hazard ratios (HRs) were used to study these factors., Results: Location of the primary tumour in rectum (HR 3.14 (95 per cent confidence interval (c.i.) 1.11 to 8.91); P = 0.069), poor differentiation (HR 1.73 (95 per cent c.i. 1.04 to 2.88); P = 0.031) and signet cell histological type (HR 2.24 (95 per cent c.i. 1.21 to 4.16); P = 0.008) were associated with shorter survival. Important factors predicting survival were the number of affected regions (HR 1.38 (95 per cent c.i. 1.20 to 1.59); P < 0.001), the simplified peritoneal cancer score (HR 1.19 (95 per cent c.i. 1.12 to 1.26); P < 0.001) and completeness of cytoreduction (HR 8.54 (95 per cent c.i. 4.01 to 18.18); P < 0.001). No other factor correlated with survival., Conclusion: The survival of patients with peritoneal carcinomatosis of colorectal origin is dominated by the extent of disease and the amount of residual tumour after cytoreduction., (Copyright 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background and Objectives: In patients with colorectal cancer, it is important to diagnose peritoneal carcinomatosis as well as to detect location and size of peritoneal tumor dissemination in view of treatment planning. The aim of this study was to investigate the detection accuracy of computed tomography (CT)., Methods: Preoperative CT-scans from 25 consecutive patients with peritoneal carcinomatosis from colorectal or appendiceal origin were independently blindly reviewed by 2 radiologists. The presence and diameter of tumor deposits were noted in seven abdominopelvic areas. Intraoperative findings were regarded as the gold standard. Agreement was assessed using the Kappa index and the chi-square test., Results: The presence of peritoneal carcinomatosis was detected in 60 and 76% of those patients by each of the radiologist. Detection of individual peritoneal implants was poor (kappa = 0.11/0.23) and varied from 9.1%/24.3% for tumor size <1 cm to 59.3%/66.7% for tumor size >5 cm. Overall sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) for tumor involvement per area were 24.5%/37.3%, 94.5%/90.4%, 53.0%/60.0%, 86.2%/84.4%, and 47.3%/50.8%, respectively. Accuracy of tumor detection varied widely per anatomic site. Statistically significant interobserver differences were noted, specifically for tumor size of 1-5 cm (P = 0.007) and localization on mesentery and small bowel (kappa = 0.30, P = 0.04)., Conclusions: In colorectal cancer, CT detection of peritoneal carcinomatosis is moderate and of individual peritoneal tumor deposits poor. Interobserver differences are statistically significant. Therefore, preoperative CT seems not to be a reliable tool for detection of presence, size, and location of peritoneal tumor implants in view of treatment planning in patients with colorectal cancer., (Copyright 2004 Wiley-Liss, Inc.)

Breast-conserving therapy is widely accepted as an appropriate method of primary treatment of T1 and T2 breast cancers that measure up to 5 cm. For safe and cosmetically acceptable breast-conserving therapy in patients with larger breast cancers, the tumor volume has to be reduced preoperatively, and lost tissue volume should be replaced after wide local excision. In 1993, the authors' group reported encouraging short-term results of a combination of preoperative radiotherapy, breast-conserving surgery, and immediate tissue replacement by myocutaneous (myosubcutaneous) latissimus dorsi flap transplantation in patients with relatively large T2 and T3 breast cancers. To evaluate the long-term oncologic local control and cosmetic outcome of this treatment modality, the authors studied the results obtained in 20 patients after a minimum follow-up of 5 years. The local control rate was 0.95, as locoregional recurrence was observed in one patient who refused adjuvant chemotherapy. Both the observed 5-year survival (0.75) and the actuarial 10-year survival (0.60) in the authors' series equaled that of more radical surgical therapy. The cosmetic outcome compared with that obtained by conventional breast-conserving therapy modalities for small breast cancers. In general, patient assessment of cosmetic outcome (2.8 of 3) was higher than the assessment of a professional panel (6.3 of 10). Of six criteria providing a detailed description of the cosmesis of the reconstructed breast and donor area, the symmetry and shape of the reconstructed breast were felt to be most important by the patients and professionals alike. The authors conclude that breast-conserving therapy combining preoperative irradiation and immediate myocutaneous (myosubcutaneous) latissimus dorsi flap reconstruction is an oncologically safe and cosmetically rewarding but logistically straining modality of treatment of relatively large T2 and T3 breast cancers.

Background: After treatment of peritoneal carcinomatosis of colorectal cancer origin by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC), recurrences develop in approximately 80% of patients. This study evaluates the outcome of such recurrences after initial treatment by cytoreduction and HIPEC., Methods: Between November 1995 and May 2003, 106 patients underwent cytoreduction and HIPEC. The progression-free interval, the location of the recurrence, and its treatment were recorded. Factors potentially related to survival after recurrences were studied., Results: Sixty-nine patients had a recurrence within the study period. For patients who had undergone a gross incomplete initial cytoreduction, the median duration of survival after recurrence was 3.7 months (standard error of the mean [SE], .3). If a complete cytoreduction had been accomplished initially, the median duration of survival after the recurrence was 11.1 months (SE, .9). A shorter interval between HIPEC and recurrence was associated with shorter survival after treatment of recurrence (hazard ratio, .94; SE, .02). After effective initial treatment, a second surgical debulking for recurrent disease resulted in a median survival duration of 10.3 months (SE, 1.9), and after treatment with chemotherapy it was 8.5 months (SE, 1.6). The survival was 11.2 months (SE, .5) for patients who received radiotherapy for recurrent disease. Patients who did not receive further treatment survived 1.9 months (SE, .3)., Conclusions: Treatment of recurrence after cytoreduction and HIPEC is often feasible and seems worthwhile in selected patients. Selection should be based mainly on the completeness of initial cytoreduction and the interval between HIPEC and recurrence.

Aim: The aim of this study was to determine the value of medical history and physical examination, tumour marker testing, and CT-scanning in the follow-up of patients treated for peritoneal carcinomatosis of colorectal origin., Methods: Between November 1995 and June 2003, 107 patients were treated by cytoreduction and hyperthermic intra-peritoneal chemotherapy. The treatment was considered effective if residual tumour after cytoreduction was no thicker than 2.5 mm. The follow-up consisted of history, physical examination, serum CEA and CA 19.9 testing three-monthly, and CT-scanning of the abdomen six-monthly. Location of the recurrence was categorized into intra-abdominal, hepatic, thoracic, and both intra-abdominal and systemic. The investigation that led to the detection of a recurrence was ranked according to its invasiveness and costs. The simplest investigation that could have led to the detection was marked., Results: A recurrence developed in 63 patients of the 74 patients effective initial treatment during the study period. Physical examination revealed the recurrence in 38 patients, at least one of the markers was raised above normal value in 39 patients and in 37 patients the CT-scan showed the recurrence. History and physical examination could have triggered the finding of a recurrence in 38 patients, tumour markers in 21 patients and CT-scanning in only three of the 74 recurrences., Conclusion: Physical examination and tumour marker testing detect most recurrences. CT-scanning is not an effective tool in the follow-up, and should be reserved for on-demand use.

Background and Objectives: Cytoreduction with hyperthermic intra-peritoneal chemotherapy (HIPEC) is a treatment with a high morbidity. Optimal patients selection can possible reduce toxicity and complications., Patients and Methods: Complications and toxicity of 102 patients were studied. Toxicity was graded according National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A complication was defined as any post-operative event that needed re-intervention. Potential patients, tumor, and treatment factors were studied on their relation to complications., Results: Grade 3, 4, or 5 toxicity was observed in 66 patients (65%). Eight patients died of treatment-related causes. Surgical complications occurred in 36 patients (35%). Fistulae were frequently encountered (18 patients). The risk of a complicated recovery was higher in carcinomatosis with recurrent colorectal cancer (P = 0.009) and in the case of more than five regions affected (P = 0.044), who had a Simplified Peritoneal Cancer (SPC) score of 13 (P = 0.012) and with an incomplete initial cytoreduction (P = 0.035). Patients with blood loss exceeding 6 L (P = 0.028) and those with three or more anastomoses also had an increased post-operative complication rate (P = 0.018)., Conclusions: Toxicity of cytoreduction followed by HIPEC was 65% (Grade 3-5 NCI CTC), with a surgical complication rate of 35%. Patients with six or seven regions involved and those in whom complete cytoreduction cannot be reached are probably better off without this treatment., (Copyright 2004 Wiley-Liss, Inc.)

Background: During recent years, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin has been used for various malignancies., Objective: To characterise the population pharmacokinetics and pharmacodynamics of mitomycin during HIPEC., Methods: Forty-seven patients received mitomycin 35 mg/m2 intraperitoneally as a perfusion over 90 minutes. Mitomycin concentrations were determined in both the peritoneal perfusate and plasma. The observed concentration-time profiles were used to develop a population pharmacokinetic model using nonlinear mixed-effect modelling (NONMEM). The area under the plasma concentration-time curve (AUC) was related to the haematological toxicity., Results: Concentration-time profiles of mitomycin in perfusate and plasma were adequately described with one- and two-compartment models, respectively. The average volume of distribution of the perfusate compartment (V1) and rate constant from the perfusate to the systemic circulation (k12) were 4.5 +/- 1.1L and 0.014 +/- 0.003 min(-1), respectively (mean +/- SD, n = 47). The average volume of distribution of the central plasma compartment (V2), clearance from the central compartment (CL) and volume of distribution of the peripheral plasma compartment (V3) were 28 +/- 16L, 0.55 +/- 0.18 L/min and 36 +/- 8L, respectively. The relationship between the AUC in plasma and degree of leucopenia was described with a sigmoidal maximum-effect (Emax) model., Conclusions: The pharmacokinetics of mitomycin during HIPEC could be fitted successfully to a multicompartment model. Relationships between plasma exposure and haematological toxicity were quantified. The developed pharmacokinetic-pharmacodynamic model can be used to simulate different dosage schemes in order to optimise mitomycin administration during HIPEC.

Background: The incidence of plantar fibromatosis (PF) is unknown. Sometimes PF tends to recur repetitively after surgical treatment. In our institute we have used postoperative radiotherapy in an attempt to diminish the change on recurrence., Methods: The Dutch Network and National Database for Pathology (PALGA) was consulted to establish the incidence of plantar fibromatosis (PF). Data from 9 patients (11 feet) with PF referred to our institute for recurrent disease were analyzed and the role of postoperative radiotherapy in prevention of recurrence was studied., Results: An average of 1.2 operations for PF was performed per 100,000 citizens yearly in the Netherlands. Twenty-six operations were performed and postoperative radiotherapy was used in 6 cases. Plantar fasciectomy was associated with the lowest recurrence rate. After microscopically incomplete excision or excision of early recurrence (< or =6 months) alone all tumors recurred, while recurrence was rarely observed after adjuvant radiotherapy. However, radiotherapy was associated with significantly impaired functional outcome in 3 cases., Conclusions: Plantar fibromatosis is relatively rare. Plantar fasciectomy seems to be the operation of choice. Although effective in decreasing the recurrence rate, adjuvant radiotherapy should be used very selectively because of its serious side effects.

Purpose: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin., Patients and Methods: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival., Results: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001)., Conclusion: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.

Aim: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the abundance of mucus in the abdomen without extra-peritoneal growth., Methods: Our patients with PMP have been treated with cytoreduction and hyperthermic intraperitoneal chemotherapy since 1996. The clinical and histopathological features of PMP and the relation of these features with disease-free interval and survival were assessed., Results: Sixty-two patients with PMP (24 M/38 F) were studied. Adenomatous mucosal changes were present in 31 patients. In females, the ovaries were normal in 5 patients and pseudomyxoma ovarii was present in 20 patients. Patients with minimal atypia and with 1% focal proliferation or less (n=38) had a better survival (p=0.0008) than those with more focal proliferation (n=14)., Conclusion: In most patients with PMP the appendix is affected; in females the ovaries are usually also involved. Focal proliferation appears to be a prognostic factor.

The favorable pharmacokinetics of MMC, used during intraperitoneal chemotherapy, has been reported in several studies [11-19]. A major safety issue in studies using intraperitoneal chemotherapy perfusion is the resulting systemic drug exposure. The AUCplasma is determined by the dose, the clearance, and the fraction absorbed from the peritoneal cavity. The reported mean plasma peak concentrations are about one-third of the systemic exposure following a therapeutic dose of MMC given by intravenous administration [30]. The best method to quantify the exposure to MMC are the time concentration profiles (AUC). Because MMC can still be found in plasma the day after intraperitoneal administration, the AUC0-90 is an underestimate of the real AUC; extrapolation to infinity gives the most reliable AUCplasma value. In our series the AUCplasma is about half the AUCplasma when given a therapeutic dose MMC intravenously [30]. What is the best dose in intraperitoneal chemotherapy perfusion? The ideal amount of MMC should include a high AUCperfusate, a high AUCplasma and an acceptable systemic toxicity. In our series grade III/IV leucopenia was observed in 28% patients. We find this rather high percentage acceptable as the problem has proved to be transient, and we have experienced no toxic deaths in recent years. In a phase I study it was estimated that a dose of 25 mg/m2 would result in approximately 10% of grade III/IV leucopenia [20]. Our data indicate that dosing based on body surface area is rational and reliable. The variation between individuals is low. Dosing based on a fixed concentration per liter perfusion fluid is probably more liable to have unforeseen variations, given the fact that we deal with linear pharmacokinetics of MMC [20]. As represented in Fig. 3, the dose of MMC can best be administered in three divided doses, resulting in the more equal exposure of peritoneal structures to MMC during the perfusion. It must be emphasized that our findings only hold true for the perfusion system as used in The Netherlands Cancer Institute. This involves a semi-open abdomen, basic perfusate volume of 3 L, perfusion rate of 1 L/min, abdominal temperature of 40 degrees C, 90 minutes of perfusion, and three drug additions (50% at t = 0, 25% at t = 30 and t = 60 minutes). The differences in perfusion techniques make comparisons of published pharmacokinetics data difficult. Cautions comparison suggest that most groups are dosing far below the maximal tolerated dose. We assume that there is a dose-effect relation for MMC. This means that obtaining a maximal safe dose is important to get maximal results. It seems that better dosing of intraperitoneal MMC can still improve results. The pharmacokinetics of intraperitoneal MMC can, however, be influenced by many details. Open or closed perfusion for instance may make some essential differences. It is therefore important that each treatment group performs its own pharmacokinetics studies on intraperitoneal MMC to achieve the optimal dose method for their chemotherapy perfusion setting. In conclusion, the major advantage of intraperitoneal chemotherapy is the regional dose intensity provided. Following intraperitoneal MMC administration, the affected peritoneal surface is exposed to high concentrations while the systemic toxicity is limited. Comparative analyses on MMC pharmacokinetics are difficult to perform because the diversity of treatment techniques. We recommend administration of MMC, divided in three drug additions, based on BSA.

Background: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is compared with computer tomography (CT) scanning for its diagnostic accuracy in assessing mediastinal lymph nodes during preoperative workup., Methods: Computer tomography scans of the chest and CM were performed in 43 patients with proven unilateral MPM. The CT scans were reviewed by one radiologist and two chest physicians. At CM the lymph node samples were taken from stations Naruke 2, 3, 4, and 7. Computer tomography and CM results were compared with final histopathologic findings obtained at thoracotomy or, if this was not performed, at CM., Results: Computer tomography scanning revealed pathologic enlarged lymph nodes with a shortest diameter of at least 10 mm in 17 of 43 patients (39%). There was histopathologic evidence of lymph node metastases at CM in 11 of these patients (26%). This resulted in a sensitivity of 60% and 80%, a specificity of 71% and 100%, and a diagnostic accuracy of 67% and 93% for CT and CM, respectively., Conclusions: Cervical mediastinoscopy is a valuable diagnostic procedure for patients with MPM who are considered candidates for surgical-based therapy. Results of CM are more reliable than those obtained by CT scanning. Our data confirm results of previous studies reporting that mediastinal lymph node involvement is a frequent event in MPM.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C has been applied following cytoreductive surgery for various peritoneal surface malignancies. The aim of this study was to evaluate heat penetration in the abdomen during 10 HIPEC procedures., Materials and Methods: Temperature measurements were taken at 5 levels through the abdominal wall. Core temperature and room temperature were also measured. The relationships between the temperature gradient and room or core temperature were studied., Results: At the start of perfusion, the temperature was estimated on average to be 40.6 degrees C at the first level, then it decreased by 1.7 degrees C (SD 1.0 degree C, p = 0.0001) in the first mm. In outward direction, it decreases by a further 1.5 degrees C per cm (SD 0.3 degree C/cm, p < 0.0001). The core temperature influenced the temperature gradient; the room temperature was not found to be a significant factor. At the end of perfusion, the temperature is estimated on average to be 40.1 degrees C at the first level, then it decreased by 0.8 degree C (SD 0.7 degree C, p = 0.011) in the first mm. In an outward direction, it decreased by a further 1.7 degrees C per cm (SD 0.4 degree C/cm, p = 0.0001). No evidence of an association between the temperature gradient and the room temperature or the core temperature was observed., Conclusion: Hyperthermia used during HIPEC procedures has a limited penetration depth. The slope in temperature seems to be related to the core temperature.

Background: Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the thoracic cavity while having limited systemic side effects., Methods: From August 1998 to August 2001, 22 patients with stage I MPM were included in this study. Two patients were irresectable at operation because of extrathoracic tumor growth. Twenty procedures were performed. After cytoreduction, a perfusion was performed with cisplatin and doxorubicin at 40 degrees C to 41 degrees C for 90 minutes. Adjuvant radiotherapy was given to surgical scars and drainage tracts., Results: There was no perioperative mortality, but significant morbidity was seen in 13 patients (65%), including bronchopleural fistula, diaphragm rupture, wound dehiscence, persistent air leakage, and chylous effusion. No hair loss or leucopenia was noticed. The median follow-up was 14 months. The median survival (Kaplan-Meier) was 11 months, with a 1-year survival of 42%. A favorable pharmacokinetic ratio was observed for both cisplatin and doxorubicin., Conclusions: Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for stage I MPM is feasible. However, this treatment is accompanied by considerable morbidity. Survival data were less encouraging.

Despite many years of clinical research, there is still no effective therapy for malignant pleural mesothelioma (MPM). Untreated, the prognosis is poor, with a median survival of < 1 year. Single-agent or combination chemotherapy as well as radiotherapy have not shown persistent improvements in response or survival. In general, MPM is a disease confined to the pleural cavity for a long time before metastasizing. Therefore, focus on local treatment seems rational. Surgical resection has been considered the mainstay of treatment by some. However, surgery alone results in high recurrence rates, and the survival benefit remains questionable. In recent years, the emphasis has been on surgery combined with adjuvant therapies. In this article, the present state of surgical management of MPM will be reviewed.

Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) is studied in a phase I study in the treatment of malignant pleural mesothelioma and pleural thymoma. We studied the pharmacokinetics of doxorubicin and cisplatin used during the HITHOC procedure. Furthermore, the penetration characteristics of doxorubicin were examined. Between 1998 and 2001, 24 perfusions were performed with a solution containing doxorubicin and cisplatin for 90 min at 40-41 degrees C. The dose was first based on square meters body surface, whereas in later studies a fixed concentration of the perfusion fluid was used. Samples of blood and perfusion fluid were collected for doxorubicin and cisplatin measurements. The penetration characteristics of doxorubicin in tissue were determined by fluorescence microscopy. The mean AUC(perfusate):AUC(plasma) ratios for doxorubicin and cisplatin (ultrafiltration for plasma) were 99 and 59, respectively. During perfusion the concentration in the perfusate declined essentially according to first-order elimination kinetics for both doxorubicin and cisplatin with half-lives of 74 and 138 min, respectively. At the end of the perfusion, about 35 and 52% of the dose of doxorubicin and cisplatin, respectively, was recovered in the perfusion fluid. One patient developed a nephrotoxicity grade II. No leukopenia or hair loss was seen. Doxorubicin penetrated into the intercostal muscle specimen, albeit that there was considerable variation in distribution throughout the specimen. We conclude that HITHOC with doxorubicin and cisplatin is relatively a safe procedure with the advantage of high intrathoracic cytostatic drug concentrations, while having limited systemic side effects., (Copyright 2003 Lippincott Williams & Wilkins)

Aims: The aim of this study was to compare long term survival after resection of solitary pulmonary metastasis on CT scan performed by either thoracoscopy or through a standard thoracotomy., Methods: Patients with a solitary, CT scan confirmed, peripherally located lesion suspected for metastasis, less than 3cm in diameter were included. End points were: postoperative complication rate, disease free and overall survival and location of recurrence in the lung., Results: Thirty-five patients who underwent a thoracoscopic metastasectomy with (n=19) or without (n=16) confirmatory thoracotomy were included in this study. Patients experienced more complications following a thoracotomy (n=5) compared to those who had a thoracoscopy (n=0) (P=0.049). Two patients appeared to have further disease at thoracotomy besides the CT scan identified lesion, and some at thoracoscopy. At definitive histology, seven lesions were benign and eight appeared to be a second primary. Analysis of 20 patients with histological confirmed metastasis demonstrated a 2-year disease free and overall survival rate of 50% and 67% respectively following thoracoscopic metastasectomy (n=8) compared to 42% and 70% respectively following confirmatory thoracotomy (n=12). Recurrence occurred in three of the patients after thoracoscopic metastasectomy and in five patients after thoracotomy., Conclusion: Our results suggest that thoracoscopic resection of solitary peripherally located metastasis is a safe and potentially curative procedure with a long term outcome that is comparable with that after resection by thoracotomy.

Background: Tumor markers are useful for diagnosis and follow-up. We studied the prognostic value of baseline and serial carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) measurements in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: Sixty-three patients with pseudomyxoma peritonei were treated with cytoreductive surgery and HIPEC. The tumor markers CEA and CA19.9 were collected before therapy and at 3-month intervals during follow-up., Results: Preoperative CEA and CA19.9 levels were increased in, respectively, 75% and 58% of the patients. Baseline tumor marker values were related to the extent of tumor. Immediately after HIPEC, both tumor markers decreased markedly (P <.0001). CA19.9 was shown to be a more useful tumor marker than CEA for follow-up. During follow-up, a high absolute CA19.9 level (P =.0005) was predictive for imminent recurrence. Patients who never attained a normal CA19.9 level showed a higher recurrence rate at 1 year (53%; SE, 15%), in comparison to patients who did so (6%; SE 4%). The median lead time of increased CA19.9 to recurrence was 9 months., Conclusions: The measurement of the tumor marker CA19.9 is useful in evaluating therapy in patients with pseudomyxoma peritonei treated with cytoreductive surgery and HIPEC. CA19.9 is a prognostic factor for predicting recurrent disease.

Peritoneal benign cystic mesothelioma is a rare tumour of unknown aetiology. It usually presents with mild abdominal pain and a solid tumour on physical examination. The differential diagnosis with solid abdominal tumours is difficult. Computed tomography, magnetic resonance imaging as well as aspiration cytology are useful in suggesting the pre-operative diagnosis. We present one case report and discuss this entity., (Copyright Harcourt Publishers Limited.)

Study Objectives: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the feasibility and safety of this multimodality treatment in the thoracic cavity., Design: Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded., Setting: The Netherlands Cancer Institute., Patients: Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated., Interventions: Cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were performed. The mesothelioma patients received adjuvant radiotherapy on the thoracotomy wound and drainage tracts., Measurements and Results: Morbidity and mortality rates were 47% and 0%, respectively. Reoperation was necessary in four cases. Severe chemotherapy-related complications were not observed. A solitary mediastinal and a contralateral pleural thymoma recurrence were successfully treated by radiotherapy and a contralateral HITHOC procedure. All thymoma patients were alive and free of disease after a mean follow-up period of 18 months. After a mean follow-up period of 7.4 months, nine mesothelioma patients are alive. Two mesothelioma patients died of contralateral pleural and peritoneal recurrent disease, while one patient is alive with locoregional recurrence., Conclusions: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is feasible in patients with pleural thymoma metastases and early-stage MPM, and is associated with acceptable morbidity rates. Early data on locoregional disease control are encouraging, and a phase II study will be conducted.

The peritoneal surface remains an important failure site for patients with colorectal cancer. Peritoneal metastases of colorectal cancer are at present considered equal to distant metastatic disease. Consequently, peritoneal carcinomatosis is treated with systemic chemotherapy and surgery only to palliate complications such as obstruction. Despite the development of new chemotherapeutic agents and combinations, the results remain disappointing with a limited impact on survival. Colorectal carcinoma cells are relatively resistant to chemotherapy. Intraperitoneal chemotherapy seems to be an attractive approach in the treatment of high-risk colorectal cancer and peritoneal carcinomatosis from colorectal origin providing high local drug concentration with limited systemic side effects. Adjuvant early postoperative intraperitoneal chemotherapy is worthwhile for consideration as treatment option after resection of high-risk colorectal cancer. In the treatment of peritoneal carcinomatosis postoperative intraperitoneal chemotherapy leads to inadequate exposure of the peritoneal surface. Only an intraoperative intraperitoneal chemotherapy performed with direct cytotoxic drugs such as MMC and cisplatin overcome this problem. The limited drug penetration in tissue implies the need for extensive cytoreductive surgery. The results of phase II studies suggest that an increased median survival can be achieved with this approach. The natural history of this disease and the heterogeneity of the patients are such that only a randomized trial design will adequately answer the question whether regional treatment of patients with peritoneal dissemination of colorectal cancer actually prolongs survival. The results of such a study are to be expected in approximately 2 years time., (Copyright 2002 Wiley-Liss, Inc.)

Background: In recent years surgical cytoreduction followed by intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced as treatment modality in patients with peritoneal surface malignancy. In the current review the rational for this approach, the prerequisites and the different techniques used are discussed., Methods: A literature search through PubMed was performed., Results: Pharmacokinetic studies have shown an important dose advantage for intraperitoneal versus intravenous application. Hyperthermia enhances the penetration of cytostatic drugs into tumour tissue and also shows synergism with various cytostatic drugs. The penetration depth of drugs into tissue is limited, therefore HIPEC can only be effective in patients with minimal residual disease after (aggressive) surgery. HIPEC can be conducted in various ways, without clear proven advantage of one method over the others. Local complications after this combined treatment approach are mainly surgery related. Intraperitoneal chemotherapy may cause systemic toxicity, dependent on the drug used. In randomised studies cytoreductive surgery followed by HIPEC has proven its value in the prevention of peritoneal dissemination in gastric cancer. Phase II data on HIPEC in peritoneal carcinomatosis of colorectal origin and pseudomyxoma peritonei are promising, but randomised studies are still not available., Conclusion: Aggressive surgical cytoreduction and HIPEC in patients with peritoneal surface malignancy has a clear rational and seems to have clinical value., (Copyright 2002, Elsevier Science Ltd. All rights reserved.)

Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (< 4 weeks) did not affect results. Compliance to 5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.