Biomedical subjects
Publications and source records attributed to E de Bree.
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Paclitaxel and docetaxel are currently the two clinically available taxanes. The combination of a taxane and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer. Despite the high activity of these drugs in systemic chemotherapy, the majority of patients with advanced ovarian cancer will develop recurrent disease and ultimately decease of this disease. Therefore, more effective systemic chemotherapy regimens or alternative treatment modalities are warranted. Intraperitoneal chemotherapy is such an alternative treatment option. Pharmacokinetic studies on intraperitoneal administration of paclitaxel and docetaxel demonstrated very high locoregional drug concentrations and exposure. Their activity and response seem to be dose-dependent and hence higher efficacy with limited systemic toxicity is to be expected. Intraperitoneal chemotherapy may be combined intraoperatively with hyperthermia, which enhances tissue penetration and cytotoxic activity of many drugs. The data concerning thermal enhancement of taxanes are inconsistent, but at the high locoregional concentrations provided by intraperitoneal drug administration such a thermal enhancement seems to exist. Clinical studies have clearly demonstrated the feasibility and efficacy of intraperitoneal instillation chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of a phase III study demonstrated improved outcome with the addition of intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel has been performed in a single study, in which promising results were observed. Further clinical investigations with an adequate follow-up period are needed to confirm the promising initial results and to determine the exact efficacy of intraperitoneal chemotherapy with these drugs.
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.
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Malignant eccrine poroma is a rare disease with approximately 200 cases reported in the literature. Regional cutaneous and systemic metastases are rarely observed and their management has been generally unsuccessful. We report on a case in which topical 5-fluorouracil application and intra-arterial chemotherapy with docetaxel resulted in a histologically confirmed complete response of multiple regional skin metastases for more than 2 years. Despite intravenous administration of docetaxel, slow progression of systemic disease was observed.
PURPOSE: In the ongoing effort to improve patient treatment, a deeper understanding of the symptomatology, physical signs and management options of rare splenic, non-traumatic, benign diseases is extremely important. PATIENTS AND METHODS: The records of eight consecutive patients with benign splenic conditions, other than injury and abscess, were reviewed retrospectively in order to analyse the clinical presentation, diagnostic methodology and therapeutic procedures applied in these rare conditions. Of the eight patients, three were diagnosed with splenic hydatid cyst, two with pseudocysts, one with splenic epidermoid cyst, one with wandering spleen and one with infraction of an ectopic spleen with situs inversus of other intra-abdominal organs. RESULTS: Upper abdominal pain was the most common presenting symptom and a tender palpable mass in the left upper abdominal quadrant, the predominant clinical finding. Pre-operative CT scanning confirmed the diagnosis in six patients, but failed to reveal the splenic pathology in the remaining two cases. Seven patients underwent splenectomy while saving splenic parenchyma was feasible in only one patient (12,5%). CONCLUSIONS: Splenic, non-traumatic, benign diseases have vague clinical presentation and may create diagnostic difficulties. Although spleen saving intervention can be applied in selected cases, splenectomy would be required in most patients.
AIM: The purpose of the present study was to study the influence of external axillary compression dressing with immobilisation of the ipsilateral shoulder after axillary lymph node dissection (ALND) on postoperative axillary drainage. METHODS: One hundred consecutive women with breast cancer undergoing ALND were enrolled in this study. They were allowed free shoulder movement and were compared with a matched historical control group of 60 patients, in whom the ipsilateral arm was immobilised for four days. For all patients the amount of drainage was recorded each postoperative day until drain removal. Prognostic data on drainage amounts and duration were gathered from all patients. Complications were recorded. RESULTS: Hospital stay was the only statistically significant difference between the two groups, it was prolonged for patients with immobilisation of the arm. The parameters found to influence the drain production with a statistically significant difference were body mass index and the removal of more than 10 lymph nodes. Postoperative complications were similar in both groups. CONCLUSIONS: External compression dressing of the axillary cavity with immobilisation of the ipsilateral arm has no impact on the postoperative drainage volume and duration. It is associated with adverse effects, such as discomfort, prolonged hospital stay and shoulder stiffness.
BACKGROUND: Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age. METHODS: We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously. RESULTS: The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature. CONCLUSION: The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.
AIMS: In view of the increasing application of breast-conserving therapy (BCT) for early breast cancer during the last decades, the number of BCT-associated angiosarcomas is likely to increase. Their aetiology is not completely clear. The aim of this study was to examine the potential role of genetic predisposition for development of this rare tumour. METHODS: The authors report on a case of consecutive bilateral development of angiosarcoma of the breast 6 and 12 years after BCT for bilateral invasive breast carcinoma. The literature was reviewed and the potential role of genetic predisposition was examined. RESULTS: Such a case of bilateral BCT-induced breast angiosarcoma has not been previously reported in the international literature. The change on development of such a tumour bilaterally is 0.25-2.6 per million women who underwent bilaterally BCT with radiotherapy for invasive carcinoma. The case history and the literature review suggest that gene mutations are likely to play a role in development of post-radiation angiosarcoma of the breast. CONCLUSIONS: It is assumed that genetic predisposition may play a role in the development of angiosarcoma after BCT. When such a predisposition is known, one might decide to avoid BCT in favour of mastectomy.
BACKGROUND: Primary psoas abscesses are a rare clinical entity with subtle and non specific symptoms, most commonly seen in patients predisposed to infections. Early diagnosis and appropriate management are therefore challenging aspects for physicians. PATIENTS AND METHODS: We present three patients with primary pyogenic psoas abscess, treated at the Heraklion University Hospital, during a 5-year period. The two male and one female patient, aged 36-51 years were admitted with fever, abdominal pain and a palpable tender mass. RESULTS: The classical sign of limping was absent in all cases. Positive psoas symptoms were detected in only two patients. CT scan accurately confirmed the diagnosis in all cases. The patients were successfully treated with antibiotics and prolonged surgical drainage. Staphylococcus aureus was the causative microorganism in the first two and Bacteroides fragilis in the third patient. This is the first reported case resulting from this specific bacteria. None of our patients had any predisposing risk factor. CONCLUSIONS: A high index of suspicion is mandatory to enable early recognition of this rare clinical disease. CT scan is the standard diagnostic tool to confirm diagnosis. Prolonged drainage and appropriate antibiotics are essential for the successful treatment of primary psoas abscesses.
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.
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.
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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.
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Pseudomyxoma peritonei is a rare neoplastic condition in that gelatinous intraperitoneal fluid collections and mucinous implants on the peritoneal surfaces and omentum are found. The pathological origin is usually an adenoma or well-differentiated adenocarcinoma of the appendix. A smaller number of cases arises from ovarian tumors. We report two unusual cases of pseudomyxoma peritonei. As a child, the first patient underwent several surgical procedures of the large bowel to relieve the consequences of Hirschsprung disease that were complicated by recurrent enteric fistulae. Colonic epithelial cells, with neoplastic changes due to chronic inflammation in the presence of enteric fistulae, were probably dislocated during these episodes, causing pseudomyxoma peritonei. In the second patient, pseudomyxoma was caused by intraperitoneal seeding of a mucinous urachal adenocarcinoma. We hypothesize that seeding of mucus producing epithelial cells into the abdominal cavity may result in this rare entity called pseudomyxoma peritonei, regardless of the source.
Malignant mesothelioma of the peritoneum is a rare tumour for which the therapeutic approach has not yet been standardized. The efficacy of the current regimes is limited. Effective locoregional therapy is crucial, since this tumour is most often confined to the peritoneal cavity at the time of the initial diagnosis and remains there for much of its clinical course. If and when haematogenous metastases occur, they rarely contribute to the death of the patient, which is often caused by the overgrowth of the primary tumour and its local complications. A case of diffuse malignant peritoneal mesothelioma treated by cytoreductive surgery and continuous hyperthermic peritoneal perfusion with cisplatin is reported. The patient received systemic combination chemotherapy postoperatively. She is in good condition and free of disease 28 months after her treatment. Continuous hyperthermic peritoneal perfusion chemotherapy has recently been used in patients with secondary peritoneal carcinomatosis from digestive and gynecological malignancies with promising results. It is also possible that the same treatment alone or in combination with systemic chemotherapy may be effective in the treatment of primary peritoneal malignancies, as in the case of diffuse peritoneal mesothelioma.
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