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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.

In a 41-year-old man who suffered from an increasing abdominal diameter and weight loss, CT revealed signs of pseudomyxoma peritonei, which was confirmed by pathological investigation after surgical debulking.

Background: Resection of liver metastases of non-colorectal primary malignancies has been reported to prolong survival. We studied the results in our hospital and compared the survival data with that described in the literature., Patients and Methods: Since 1991, a prospective database has been kept at The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital of patients undergoing hepatic surgery (n=180). Between 1991 and 1999, 32 patients underwent laparotomy for hepatic metastases of non-colorectal primaries. This study evaluates the operative technical aspects and determines morbidity, mortality, disease-free and overall survival., Results: There were 11 males and 21 females with a median age of 52 (25-69) years. Histology of the primary tumour were various carcinomas (n=22), melanomas (n=4) and sarcomas (n=6). Resection was performed in 28 patients; four patients appeared to be irresectable. There was no perioperative mortality. Morbidity was 23%. One re-operation was necessary because of haemorrhage. The median disease-free survival for the 28 patients was 12 months with an actuarial 5-year disease-free survival of 20% (Kaplan-Meier). The 5-year overall survival was 35% with a median survival of 21 months., Conclusion: Liver metastasectomy for selected types of non-colorectal primary tumours is relatively safe and shows in selected patients long-term survival comparable to that of metastasectomies for colorectal origin., (Copyright 2001 Harcourt Publishers Limited.)

Background: The aim of this study was to determine the feasibility, accuracy, and outcome of thoracoscopic resection of peripherally located pulmonary metastases., Methods: The 28 patients had three or fewer solitary metastases, located in the periphery of the lung, with a diameter 3 cm or less on computed tomography scan. A thoracoscopic resection was performed to remove all identified lesions evaluated by confirmatory thoracotomy., Results: A thoracoscopic resection was technically impossible in 10 patients. In 1 patient a confirmatory thoracotomy was not performed because the lesion was diagnosed as carcinoid. Among the 17 patients who underwent confirmatory thoracotomy, 12 patients had a complete thoracoscopic resection and 5 patients had residual disease. The success rate appeared to be higher (p = 0.01) in patients with one lesion (11 of 12 patients), than in patients with more than one lesion (1 of 5 patients) found by preoperative computed tomography scan., Conclusions: Thoracoscopic resection can be considered a viable treatment option for patients who present with a solitary pulmonary metastasis with a diameter of 3 cm or less, when the lesion is located in the periphery of the lung.

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.

There is little data in literature on survival of patients with lung cancer as a second primary (SP) malignancy. This retrospective study was undertaken to investigate whether a previous malignancy has prognostic significance in operable non-small cell lung cancer (NSCLC). Sixty-six patients with SP NSCLC were compared with 75 'first primary' (FP) NSCLC patients without a previous malignancy. All the 141 patients had been surgically treated with curative intent at The Netherlands Cancer Institute (NKI) between 1977 and 1996. Patients who had undergone resections for lung metastases were excluded. Clinical and pathological characteristics were collected and a multivariate analysis on all the 141 patients was carried out. All the previous malignancies were invasive cancers associated with metastatic potential and predominantly located in the aerodigestive tract. Female-male ratio was higher in the SP group (29 vs. 15%, P = 0.06). Tumour diameter was smaller in the SP group (3.0 vs. 4.7 cm, P < 0.0001). Pneumonectomy was performed less frequently in the SP group. Five-year survival rate was higher in the SP group (61 vs. 34%, P = 0.04). Univariate favourable prognostic factors were; small tumour diameter, female gender, favourable pTNM-stage, favourable pT-stage, favourable cTNM-stage, no post-operative radiotherapy and a history of previous malignancy. Multivariate analysis showed tumour diameter, female gender and pTNM-stage to be the major potential confounders. When adjustments were made for these three variables, the prognostic advantage of the SP group disappeared. It was concluded that SP NSCLC has a similar prognosis when compared with FP NSCLC. NSCLC diagnosed during the follow-up of a previous malignancy, and deemed operable, therefore, warrants the same diagnostic and therapeutic approach as NSCLC as first malignancy.

We report a case of port site recurrence after thoracoscopic resection of pulmonary metastasis from an adenocarcinoma of the rectum. This case stresses the importance of careful manipulation and concealed removal of malignant pulmonary lesions if the minimal invasive technique is applied., (Copyright Harcourt Publishers Limited.)

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Background: Pseudomyxoma peritonei remains a fatal disease. However, extensive surgical cytoreduction combined with intraoperative heated intraperitoneal chemotherapy (HIPEC) has recently emerged as a new treatment modality, which might improve survival., Methods: Patients underwent treatment if the tumour appeared to be technically resectable on preoperative abdominal computed tomography and there were no distant metastases. After aggressive surgical cytoreduction, HIPEC with the administration of mitomycin C was performed for 90 min. Depending on histological grading, patients received adjuvant 5-fluorouracil and leucovorin therapy., Results: Forty-six patients were treated. Optimal surgical cytoreduction was obtained in 40 patients. Postoperative surgical complications occurred in 18 patients. Four patients died as a direct result of the treatment. Bone marrow suppression due to mitomycin C toxicity occurred in 22 patients. There was no other major toxicity related to the HIPEC procedure. After a median follow-up of 12 months, 40 patients are alive, eight of whom have proven recurrence. The actuarial survival rate (Kaplan-Meier) at 3 years was 81 per cent., Conclusion: These results confirm that extensive surgery combined with HIPEC is feasible in patients with pseudomyxoma peritonei and that improved long-term survival might be achieved.

Aims: Chylous ascites can be a problem after oncological abdominal surgery. The aim of this study was to report the incidence and the management of the problem., Methods: A retrospective study over a 2-year period of all oncological patients undergoing abdominal surgical procedures was carried out. Patients with resections in the upper abdomen and retroperitoneum were studied in more detail., Results: Twelve (7.4%) of 163 patients with complex surgical procedures developed a chyloperitoneum. Chylous ascites stopped in time with conservative management in nine patients. Three patients had a peritoneovenous shunt inserted with success. No relaparotomies to ligate leaking intestinal lymph vessels were necessary., (Copyright Harcourt Publishers Limited.)

Background/aims: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21)., Patients and Methods: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day., Results: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure., Conclusions: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Background: Malignant degeneration is a rare complication of pilonidal disease and is associated with a high recurrence rate and poor prognosis compared with regular nonmelanoma skin cancer. Treatment in our departments and in the international literature was evaluated., Methods: We analyzed the data from three patients with malignant degeneration who were treated in our departments and an additional 56 patients who were found after an extensive literature search., Results: A total of 47 males and 12 females, with a mean age of 52 years, were most frequently primarily treated with surgery. After a mean follow-up time of 28 months, 20% of all patients died with evidence of disease and an additional 10% died of unrelated causes. The overall recurrence rate was 39%, with a median time to recurrence of only 9 months. The local recurrence rate was lower when radiotherapy was added to surgical treatment alone (30% vs. 44%). Re-excision of local recurrence resulted in some long-term survivals., Conclusions: Early diagnosis and treatment may lead to improvement of the relative poor prognosis. Surgical treatment should be tailored according to the locoregional extent. The high recurrence rate after surgical treatment can be reduced by the addition of radiotherapy. Although repeat surgery for recurrent disease may involve extensive resection and morbidity, this may result in prolonged survival.

Aims: The feasibility, morbidity and toxicity of an intensified surgical treatment strategy consisting of aggressive cytoreductive surgery, intra-operative intraperitoneal perfusion of cisplatin and hyperthermia were evaluated in women with recurrent ovarian cancer., Methods: Five heavily pre-treated patients with extensive abdominal tumour bulk entered this pilot study. In all cases aggressive cytoreduction leaving tumour remnants <5 mm in diameter could be performed. This was followed intra-operatively by perfusion of the abdominal cavity with hyperthermic cisplatin 50-70 mg/m(2)for 90 min. During perfusion the intra-abdominal temperature was maintained at 40 degrees C. The median duration of surgery was 10 hours (range 9-11 hours)., Results: No major intra- or post-operative complications emerged. Median post-operative ileus (resuming of soft diet) was 11 days (9-13 days). The mean period of hospitalization was 25 days (range 17-42). Toxicity due to i.p. cisplatin was mainly metabolic and of grade 1-2, while no nephrotoxicity was observed. The pharmacokinetics of cisplatin indicated that the maximum concentration of cisplatin measured in the perfusate was 15 times higher than in plasma., Conclusions: We conclude that aggressive cytoreduction combined with hyperthermic intra-operative intraperitoneal cisplatin was feasible in a small group of heavily pre-treated ovarian cancer patients with extensive tumour bulk with acceptable morbidity and toxicity. Further studies are required in larger groups of patients to further establish the feasibility of this intensified treatment strategy. We stress that OVHIPEC is not a treatment modality on its own for advanced ovarian cancer. The effectiveness of OVHIPEC is likely to be dependent on the effectiveness of post-operative adjuvant chemotherapeutic regimens., (Copyright 2000 Harcourt Publishers Ltd.)

Colorectal cancer is one of the most common human cancers, for which 5-fluorouracil (5FU) is usually part of the treatment. Thymidylate synthase (TS), the target enzyme for 5FU, can be predictive for the outcome of 5FU-based therapy. TS levels in tumor samples can be determined with radiochemical enzyme assays, RT-PCR, and immunohistochemical staining. We validated TS immunohistochemistry with a polyclonal rabbit anti-human TS antibody using the avidin-biotin method. This antibody can be used on paraffin-embedded, formalin-fixed material using an antigen retrieval method with citrate buffer and microwave treatment. The antibody shows a granular cytosolic staining pattern. The reproducibility in cross-sections from colorectal tumors from 50 patients was 90% and the interobserver variability was acceptable with a kappa of 0.45. On Western blotting it detects purified TS at 36 kD, while in 5FU-treated cells the ternary complex between FdUMP, TS, and 5, 10-methylene-tetrahydrofolate is clearly visible at 38 kD, with no other interfering bands. In a separate set of tumors, immunostaining was compared with enzyme levels; Western blots correlated with enzyme levels. Because both this polyclonal antibody and the monoclonal antibody TS-106 are being used for large-scale studies, we also determined whether they could be used interchangeably. No differences were observed. This polyclonal antibody is specific and gives reproducible results. A study on a larger scale is ongoing to determine the role of TS as a predictive parameter in patients with colorectal cancer treated either with postoperative adjuvant 5FU/levamisole or with surgery only.

In five patients who were treated for malignant pleural mesothelioma (MPM) with pleuropneumonectomy and intraoperative photodynamic therapy (IPDT), impending myocardial damage was monitored using ECG, the classical biochemical markers (creatine kinase [CK], total activity; CKMB, mass; and myoglobin), and the new cardiac markers troponin I (cTnI) and troponin T (cTnT). In the peroperative and postoperative period all classical markers were elevated, in contrast to cTnI and cTnT, because of the concomitant skeletal muscle damage. Sequential electrocardiogram monitoring showed no signs of myocardial damage. From this study in patients with MPM treated with pleuropneumonectomy and IPDT it can be concluded that measurement of cTnI and cTnT for the detection of myocardial damage is more suitable than measurement of the classical markers.

Objective: To apply (HIPEC) using mitomycin in patients with peritoneal carcinomatosis., Design: Descriptive., Method: The HIPEC treatment includes cytoreductive surgery and subsequent peritoneal lavage with exposure of the superficial tumour residues to a high concentration of a cytostatic drug at an intra-abdominal temperature of 40-42 degrees C. The HIPEC treatment was given to 24 patients with pseudomyxoma peritonei and to 29 patients with peritoneal carcinomatosis of colorectal origin. The adequate dose of mitomycin was determined in the Netherlands Cancer Institute in 26 patients: doses of 15 mg/m2 (n = 8), 25 mg/m2 (n = 3), 35 mg/m2 (n = 7) and 40 mg/m2 (n = 8) were administered., Results: The maximal tolerable dose of mitomycin appeared to be 35 mg/m2, while unacceptable toxicity was recorded at a dose of 40 mg/m2. Therefore 35 mg/m2 was used in subsequent cases. Among the patients with pseudomyxoma peritonei 8 developed severe complications, two of which were fatal. After a median follow-up of 12 months, 21 patients were alive of whom 18 were free of disease. Among the patients with peritoneal carcinomatosis of colorectal origin one patient died from a treatment-related complication. After a median follow-up of 18 months, 18 patients were alive of whom 11 were free of disease. The actuarial 2 year survival was 59%., Conclusion: In the Netherlands Cancer Institute HIPEC treatment is considered the treatment of choice for pseudomyxoma peritonei. The results in cases of peritoneal carcinomatosis of colorectal origin are promising, but the results of a randomized trial are awaited.

Three cases of metastasizing pleomorphic adenoma are described. All three had a history of incomplete surgery of the primary tumour and several surgical procedures for local recurrences before systemic metastases became apparent. The histology of the primary tumour, recurrences and metastases were typical of pleomorphic adenoma. In view of the lack of information in the literature, it is concluded that inadequate surgical procedures, such as incomplete surgery or enucleation, leading to multiple recurrences, appear to be a prerequisite for the development of systemic disease.

The purpose of this study was to investigate the influence of hyperthermia on cisplatin pharmacokinetics and DNA adduct formation. The latter was investigated both in tumour cell lines in vitro and in tumour cells and buccal cells from cancer patients. The patients had advanced ovarian carcinoma and were entered into a phase I study for cytoreductive surgery followed by hyperthermia in combination with intraperitoneal cisplatin administration. The cisplatin-DNA modifications in vivo and in vitro were studied by an immunocytochemical method with the polyclonal antiserum NKI-A59. The patient samples for pharmacokinetic determinations were analysed by flameless atomic absorption spectrometry. In vitro, the combination of hyperthermia and cisplatin enhanced cell killing compared with either treatment alone, such that the cisplatin-resistant ovarian cell line A2780/DDP became almost as sensitive as the parent A2780 cell line (resistance factor reduced from 30 to 2 at the IC50). In addition, increased cisplatin-DNA adducts were observed in the resistant cell line after the combined treatment compared with cisplatin alone. A good correlation was found between nuclear staining density and surviving fraction for all groups, indicating that the DNA adducts generated are an important determinant of toxicity and that the mechanism by which hyperthermia enhances kill is by increasing adduct levels. In the patients, the ratio of drug concentration in the peritoneal perfusate compared with that in plasma was found to be approximately 15, indicating a favourable pharmacokinetic ratio. Cisplatin-DNA adduct formation in tumour cells from patients was higher than in buccal cells, reflecting this higher drug exposure, i.e. local plus systemic versus systemic only. In addition, the tumour cells but not buccal cells were exposed to hyperthermia. The higher number of tumour adducts also suggests that a favourable therapeutic ratio could be achieved. Platinum-DNA adduct formation was found to decrease with distance from the surface of the tumour nodules. However, at a distance of 3-5 mm, the nuclear staining density levels were still measurable and higher than in buccal cells. In conclusion, the combined pharmacokinetic and adduct data in patients support the advantages of the intraperitoneal route for drug administration, and the addition of heat.

Background: Locoregional recurrence after initial treatment of breast carcinoma occurs in up to 35% of patients. In selected patients, chest wall resection (CWR) can be performed to regain local control. Extensive surgery is justifiable only if good palliation and possibly a better prognosis can be offered and the morbidity is limited., Methods: The authors conducted a retrospective review of the medical records of 44 females with locally recurrent breast carcinoma who underwent chest wall resection between 1979 and 1995 at the Netherlands Cancer Institute. Preoperative patient characteristics were recorded, and complications were scored. Analysis was made of disease free and overall survival after resection as well as the influence of presumed prognostic factors on survival. The median duration of follow-up was 3.2 years., Results: The mean patient age at diagnosis of breast carcinoma was 47.5 years. The median interval between first treatment and relapse was 3.9 years. Thirty patients (68%) underwent CWR with curative intent. Postoperative complications occurred in 18 patients, but no mortality occurred. The median disease free interval after curative CWR was 3.3 years; the projected 5-year disease free survival rate was 35%. A disease free interval of more than 2 years after primary treatment predisposed patients to significantly longer tumor free survival after CWR, compared with an interval shorter than 2 years (P = 0.0001). New local recurrence after curative CWR occurred in 6 patients (20%), and distant metastases occurred in 17. Median overall survival was 4.8 years; the projected 5-year survival rate was 45%. After curative resection, these figures were 8.9 years and 58%, respectively, whereas palliative resection resulted in a median survival of 2.3 years and a projected 5-year survival of 21% (P = 0.008). Age > or =35 years at the time of the first diagnosis of breast carcinoma predisposed patients to significantly better survival than age <35 years (P = 0.02)., Conclusions: CWR can provide local control, good palliation, and an acceptable prognosis for patients with recurrence of breast carcinoma. Outcome mainly depends on the completeness of the resection.

Purpose: Total anorectal reconstruction with a double dynamic graciloplasty was performed after abdominoperineal reconstruction (APR) for low rectal cancer. In four patients an additional pouch was constructed to improve neorectal motility and capacity. The aim of this study was to evaluate the results in the first 20 patients and to report on the preliminary results of patients with an additional pouch., Methods: Twenty patients with a mean age of 52 (range, 25-71) years and a rectal tumor at a mean of 3 (range, 0-5) cm from the anal verge were treated. In 14 patients the Miles resection, colon pull-through, and construction of a neosphincter were performed in one session. Six patients had the double graciloplasty at an average of 4.1 (range, 1.1-8.8) years after APR. In four patients a pouch was constructed with an isolated segment of distal ileum., Results: After a mean follow-up of 24 (range, 1-60) months after APR, none of the patients developed local recurrence, whereas four patients developed distant metastasis. Fifteen of 20 patients were available for evaluation, and 5 patients were still in training. Of these 15 patients, 8 patients were continent (53 percent), 2 patients were incontinent, and in 5 patients the perineal stoma was converted to an abdominal stoma. Failures were attributable to necrosis of the colon stump (n = 2) and incontinence (n = 3). At 26 weeks mean resting pressure was 44 (standard deviation (SD), 28) mmHg, and mean pressure during stimulation was 90 (SD, 46) mmHg at a mean of 3.5 (SD, 1.2) volts at 52 weeks. Mean defecation frequency was three times per day (range, 1-5). Of the eight patients who were continent, six used daily enemas. Mean time to postpone defecation was 11 (range, 0-30) minutes., Conclusion: In experienced hands, the double dynamic graciloplasty is an oncologically safe procedure that can have an acceptable functional outcome in a well-selected group of patients. However, to improve the outcome, further modifications will be necessary. So far, the addition of a pouch has not resulted in improved outcome.

Five patients with a pleural malignancy (four malignant mesotheliomas and one localized low grade carcinoid) were treated with maximal surgical resection of the tumour followed by intraoperative adjuvant photodynamic therapy (PDT). The additional photodynamic treatment was performed with light of 652 nm from a high power diode laser, and meta-tetrahydroxy phenylchlorin as the photosensitizer. The light delivery to the thoracic cavity was monitored by in situ isotropic light detectors. The position of the light delivery fibre was adjusted to achieve optimal light distribution, taking account of reflected and scattered light in this hollow cavity. There was no 30-day post-operative mortality and only one patient suffered from a major complication (diaphragmatic rupture and haematopericardium). The operation time was increased by a maximum of 1 h to illuminate the total hemithoracic surface with 10 J cm(-2) (incident and scattered light). The effect of the adjuvant PDT was monitored by examination of biopsies taken 24 h after surgery under thoracoscopic guidance. Significant damage, including necrosis, was observed in the marker lesions with remaining malignancy compared with normal tissue samples, which showed only an infiltration with PMN cells and oedema of the striated muscles cells. Of the five patients treated, four are alive with no signs of recurrent tumour with a follow-up of 9-11 months. One patient was diagnosed as having a tumour dissemination in the skin around the thoracoscopy scar and died of abdominal tumour spread. Light delivery to large surfaces for adjuvant PDT is feasible in a relatively short period of time (< 1 h). In situ dosimetry ensures optimal light distribution and allows total doses (incident plus scattered light) to be monitored at different positions within the cavity. This combination of light delivery and dosimetry is well suited for adjuvant treatment with PDT in malignant pleural tumours.

Pseudomyxoma peritonei is a rare disease caused by a perforated adenoma of the appendix. It results in extensive accumulation of mucinous tumour at specific locations within the abdomen and pelvis. The study was undertaken to examine patterns of recurrence in patients with grade I disease treated by cytoreductive surgery and early postoperative intraperitoneal chemotherapy. After a median follow-up of 1.9 years (range 0.5-7.4 years) 42 out of 118 patients had recurred. In 32 patients, detailed information regarding the anatomical location of recurrent tumour from CT-scan and second-look laparotomy were available and these form the basis of this study. The volume of recurrent tumour was recorded at eight abdominal sites, the laparotomy scar and at suture lines. Patient, tumour and treatment factors were analysed for possible relationship with the pattern of recurrence. With recurrence, true metastatic disease was observed in 3 patients and a distinctly higher grade of intraperitoneal tumour in another patient. Pleural spread of pseudomyxoma was found in 6 patients, always related to entering the pleural cavity during cytoreduction (P = 0.000031). Two abdominal sites consistently had an increase in tumour deposits at re-operation as compared to the initial cytoreduction. Small bowel had large deposits at re-operation in 17% versus 3% at initial cytoreduction and retroperitoneal surfaces 10% versus 0%. Recurrences were most frequent in the left subhepatic/lesser omentum area (28%), while the right subdiaphragmatic area (3%) was least involved. Pseudomyxoma peritonei recurrence in the laparotomy scar was found in 15/29 patients (52%), significantly more frequent if tumour had been present at former laparotomy scars during cytoreduction (P = 0.042). In 15/25 (60%) of patients, recurrences were found at suture lines. Differences in the completeness of cytoreduction, inadequate distribution of intraperitoneal chemotherapy to upper abdominal and small bowel surfaces, and entrapment of tumour within suture lines were thought to be causal factors consistent with this pattern of recurrence. Consequences for future treatment strategies are discussed.

Background: Literature shows no data about a complete cohort of head and neck cancer patients who developed pulmonary metastases. In this study, we investigate factors related to survival, with emphasis on the role of a pulmonary metastasectomy., Methods: A retrospective review of 138 patients who developed pulmonary metastases (5.5% of all head and neck cancer patients) in the period 1978 to 1994 is presented. In a stepwise regression analysis (Cox), factors were identified related to survival. Also investigated was whether the prognostic value of potential prognosticators differed between the group that underwent metastasectomy and the group that did not., Results: One hundred thirty-eight patients had metastases originating from head and neck cancer. The 5-year survival rate for all these patients was 13%. Younger patients (P = .011), patients with a longer disease-free interval (DFI) (P = .011), patients with a longer disease-free interval (DFI) (P = .016), and patients with a nonsquamous cell carcinoma (P = .038) did better. No evidence of a relationship between survival and sex or survival and number of metastases was found. Twenty-one patients underwent surgical resection of their pulmonary metastases. In 18 patients the resection was complete. The 5-year survival rate for patients who underwent a metastasectomy was 59%, compared with 4% in the nonmetastasectomy group (P = .0033)., Conclusion: Isolated pulmonary metastases from head and neck cancer are potentially curable by surgical resection. Preconditions for this approach are locoregional control of the primary lesion and technical resectability of the pulmonary metastases. Patients with a long interval between primary treatment and the diagnosis of pulmonary metastases may benefit more from resection therapy.

In patients with a very low rectal carcinoma, an abdominoperineal resection with the creation of a permanent colostomy is the surgical treatment of choice. Creation of a colostomy can be avoided without compromise to oncological safety. The distal colon is pulled through to the perineum and both gracilis muscles are used to create a new sphincter and pelvic floor. These muscles are electrically stimulated by an implanted neurostimulator. Contraction is then no longer dependent upon volition and, due to fibre transformation, the muscle will become fatigue-resistant. The outcome in 11 patients was assessed. After a mean follow-up of 1.3 years, continence was achieved in 7 patients, and 2 patients are awaiting completion of the therapy. In 2 patients, necrosis of the distal colon led to failure of the technique. There was no local recurrence, but 2 patients had distant metastasis. Double dynamic graciloplasty after abdominoperineal resection proves to be an oncologically safe procedure with a reasonable chance of continence and a life without a stoma in the majority of patients.

Study Objective: To develop selection criteria for pulmonary metastasectomy in patients with metastases of colorectal cancer confined to the lungs., Design: A retrospective study., Setting: Medical records of all patients operated on for this condition in the Netherlands in the period 1982 to 1992 (n = 38)., Intervention: Evaluation by means of Cox's proportional hazards regression analysis of factors, which might relate to postthoracotomy disease-free survival and/or postthoracotomy survival., Measurements and Results: The 5-year disease-free survival was 31%, and the overall 5-year survival was 43% (Kaplan-Meyer). Multivariately, a number of three or fewer metastases (p = 0.012) and a short delay between detection of pulmonary metastases and resection (p = 0.05) related to a longer postthoracotomy disease-free interval. A longer interval between resection of the primary tumor and detection of lung metastases related to a longer postthoracotomy survival (p = 0.021)., Conclusions: Patients with three or less pulmonary metastases of colorectal origin may benefit from resection; once metastases have been detected, resection should not be postponed.

Purpose: A new operation was developed to treat patients with local recurrence of cancer at the anal margin after radiotherapy. This operation aims at resection of the tumor with oncologically safe margins, preservation of fecal continence, and reliable wound healing., Methods: After intensive radiotherapy, three patients with local recurrences of squamous-cell carcinoma of the anus refused to undergo abdominoperineal resection. These patients were treated by wide local excision and primary reconstruction. Wide local excision included perianal skin with subcutis and the anal canal including the internal sphincter up to the dentate line. To reconstruct the anus, the rectum was mobilized and brought down to the level of the perineum through the external sphincter and anastomosed to bilateral biceps femoris myocutaneous flaps., Results: In the first three patients no tumor recurrences have occurred, and fecal continence has been good., Conclusion: The first results with this continence-preserving operation in patients with recurrent anal margin cancers after radiotherapy have been encouraging.

Background: Soft tissue malignancies of the retroperitoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities., Methods: From 1973 to 1990, 34 patients were initially treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands Cancer Institute. In a retrospective study, the prognostic effect of extent of primary surgery and postoperative radiation therapy was examined., Results: Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most commonly found. Grade of malignancy was defined as medium to high (II/III) in 44% and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was achieved in 29 patients. After complete resection, the 5-year survival rate and the local recurrence rate were 35% and 63%, respectively. Extended surgery (performed in eight patients) showed a local recurrence rate of 50%. Thirteen patients received high-dose postoperative radiation therapy, which was found to have a significant favorable effect on the recurrence-free interval (P < 0.01)., Conclusions: We conclude that complete (extended) resection followed by high-dose postoperative radiation therapy improves the prognostic outcome of patients with retroperitoneal soft tissue sarcomas.

In a retrospective study, 58 patients with bowel obstruction due to advanced ovarian cancer were analysed. In a forward stepwise proportional hazard regression analysis, we looked for factors influencing bowel obstruction-free survival. Patients who presented with bowel obstruction as the first sign of ovarian cancer and those with a longer interval between last cancer treatment and bowel obstruction did better. Patients with ascites did worse. No other independent factors were found. Based on these data, we classified patients into a favourable prognosis group (no previous treatment or interval since last treatment exceeding 6 months; no ascites) and a poor prognosis group (interval since last treatment shorter than 6 months; ascites). Patients from the favourable prognosis group had a median bowel obstruction-free survival of 8 months, compared to 1 month for the poor prognosis group (P < 0.001). Surgery had a marginally significant positive effect on bowel obstruction-free survival when compared to medical treatment in the favourable prognosis group (P = 0.052). Surgery had no effect at all in the poor prognosis patients.

We studied the records of 46 patients who had been operated on between 1974 and 1990 in The Netherlands Cancer Institute because of complications due to late radiation damage of the small bowel. Data were collected on preoperative history, surgical intervention, postoperative complications and survival. By means of Cox's proportional hazards regression analysis we sought to identify factors that contribute to complication-risk and survival. The following factors led to an increase in complication-risk: hypoalbuminemia, more than one laparotomy prior to irradiation and a short interval (< 12 months) between irradiation and surgical intervention. The following factors related to a poorer survival: incomplete resection of the primary tumor and a short interval (< 12 months) between irradiation and surgical intervention. The type of surgical intervention did not have cumulative prognostic value in relation to complication-risk or survival. As patients undergoing resections differed considerably from patients undergoing bypass-procedures, no conclusions could be drawn about the superiority of one technique over the other. We think that both types of intervention have their own field of indication.

We investigated the feasibility of breast conserving treatment (BCT) in patients with large (T2, T3) breast cancers, by combining preoperative radiotherapy and tissue replacement after wide excision by a myosubcutaneous flap transposition. The treatment consisted of 50 Gy whole breast irradiation followed by a 15-25 Gy iridium implant to the primary tumour with 2 cm margins. Four weeks after completion of the radiotherapy, wide excision of the original tumour area with a 1 cm margin and an axillary dissection was performed. In the same session the breast was reconstructed with an ipsilateral latissimus dorsi transposition flap. The treatment results in the first 6 patients are encouraging with respect to treatment toxicity and cosmetic outcome. The clinical tumour response after radiotherapy was difficult to evaluate. However, microscopic evaluation showed residual tumour in all specimens with (focal) involvement of the surgical margins in two. With a minimum follow-up of over 2.5 years no tumour recurrences in the breast have occurred.

To study the possible role of ras oncogene activation in the dissemination of colon cancer, we determined point mutations in codons 12, 13 and 61 in K- and N-ras in 3 groups of tumors: (A) primary tumors of patients who had undergone surgery for Dukes' B (early-stage) colon cancer, (B) primary tumors and metastases from patients undergoing resection of isolated lung metastases and (C) primary tumors and metastases from patients undergoing resection of isolated liver metastases. In 129 samples from 93 patients, 54 (42%) were positive for point mutations in either K- or N-ras. Most mutations (89%) were found in the K-ras gene. In group A (n = 50) ras point mutations were detected in 16 cases (32%) (15 in K-ras and 1 in N-ras). Thirteen out of 23 cases in group B (57%) were positive for a ras point mutation: 10 in K-ras and 3 in N-ras. In group C (n = 20), point mutations in codon 12 of K-ras, but none in H- or N-ras, were found in 10 cases (50%). In 31 cases the primary tumors from the metastases in groups B and C were available for analysis and 15 contained a ras point mutation (48%). Not all mutations were present in both the primary tumor and the metastasis. In 3 instances, a mutation was detected in the metastasis but not in the primary tumor, whereas in 1 case a mutation was found in the primary tumor.