Biomedical subjects

F A N Zoetmulder

Publications and source records attributed to F A N Zoetmulder.

At least 19 recordsLinked to original sources

PubMed2007

The influence of total mesorectal excision on local recurrence and survival in rectal cancer patients: a population-based study in Greater Amsterdam.

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.

Aged↗

PubMed2006

Pseudomyxoma peritonei.

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.

Combined Modality Therapy↗

PubMed2006

Harm and benefits of short-term pre-operative radiotherapy in patients with resectable rectal carcinomas.

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.

Carcinoma↗

PubMed2006

Pseudomyxoma peritonei and the urinary tract: involvement and treatment related complications.

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.

Adult↗

PubMed2006

Categorization of major and minor complications in the treatment of patients with resectable rectal cancer using short-term pre-operative radiotherapy and total mesorectal excision: a Delphi round.

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.

Belgium↗

PubMed2005

Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.

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.

Adenocarcinoma, Mucinous↗

PubMed2005

Preoperative computed tomography and selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

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.

Antineoplastic Agents↗

PubMed2005

Conventional surgery and systemic chemotherapy for peritoneal carcinomatosis of colorectal origin: a prospective study.

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.

Adult↗

PubMed2004

[New insights in the adjuvant treatment of gastric cancer].

The current standard treatment of patients with gastric cancer is partial or total stomach resection and dissection of the draining lymph nodes. This approach, however, results in a rather low survival rate, partly because the diagnosis is often established in an advanced stage. Various strategies, including adjuvant radiotherapy, chemotherapy or more extensive surgical procedures, have resulted mainly in increased morbidity without improving survival. In a recent randomised trial, concurrent postoperative radiotherapy and chemotherapy prolonged survival and reduced the chance of a local recurrence at an acceptable toxicity. Although several aspects of combined radiochemotherapy require further study, this new treatment concept appears to be a promising addition to the therapeutic arsenal for gastric cancer.

Antineoplastic Agents↗

PubMed2004

Predicting the survival of patients with peritoneal carcinomatosis of colorectal origin treated by aggressive cytoreduction and hyperthermic intraperitoneal chemotherapy.

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.

Adult↗

PubMed2004

Follow-up of patients treated by cytoreduction and chemotherapy for peritoneal carcinomatosis of colorectal origin.

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.

Adult↗

PubMed2004

Surgical treatment of locally recurrent rectal cancer.

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.

Adenocarcinoma↗

PubMed2003

Pseudomyxoma peritonei: a review of 62 cases.

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.

Adenocarcinoma, Mucinous↗

PubMed2003

Pharmacokinetics of doxorubicin and cisplatin used in intraoperative hyperthermic intrathoracic chemotherapy after cytoreductive surgery for malignant pleural mesothelioma and pleural thymoma.

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.

Adult↗

PubMed2003

Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy for stage I malignant pleural mesothelioma.

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.

Adult↗

PubMed2002

[Gastrointestinal toxicity caused by irinotecan in the case of preexistent passage problems].

Two female patients, aged 50 and 62 years respectively, who were treated with irinotecan, fluorouracil and folinic acid (Saltz scheme) due to metastasised colorectal carcinoma, developed progressive abdominal pain, fever and leucopenia. One patient also exhibited intestinal obstruction. The main problem was differentiating between an acute abdomen and irinotecan toxicity. Both patients recovered without the need for an operative intervention. One patient was treated by means of colonic stent placement. The combination of gastrointestinal irinotecan toxicity and pre-existing passage problems is dangerous. However, in such cases restraint should be exercised with respect to operative interventions.

Abdominal Pain↗

PubMed2002

Prognostic value of baseline and serial carcinoembryonic antigen and carbohydrate antigen 19.9 measurements in patients with pseudomyxoma peritonei treated with cytoreduction and hyperthermic intraperitoneal chemotherapy.

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.

Analysis of Variance↗

PubMed2002

Long term survival of thoracoscopic metastasectomy vs metastasectomy by thoracotomy in patients with a solitary pulmonary lesion.

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.

Adult↗