To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients ...with peritoneal carcinomatosis of colorectal cancer origin.
Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival.
After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001).
Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.
To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors ...with prognostic value.
PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology.
A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival.
Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval CI, 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01).
Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.
Peritoneal carcinomatosis of colorectal cancer is probably best treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). In The Netherlands Cancer Institute, this treatment has ...been performed since 1995. The long tradition of this treatment enabled us to study long-term survival in detail.
Between 1995 and 2003, 117 patients were treated by cytoreduction and HIPEC. The aim of the cytoreduction was to remove all visible tumor. After the cytoreduction, the abdomen was perfused with mitomycin C (35 mg/m2) at 40 degrees C to 41 degrees C for 90 minutes. Survival was calculated by the Kaplan-Meier method. Survival was also analyzed for the following subgroups: no residual tumor, residual tumor < or = 2.5 mm, and more residual tumor. Hazard ratios for each of the seven abdominal regions were calculated to determine the influence on survival.
The median survival was 21.8 months. The 1-, 3-, and 5-year survival rates were 75%, 28%, and 19%, respectively. The Kaplan-Meier curve reached a plateau of 18% at 54 months. In 59 patients a complete cytoreduction was achieved, and in 41 patients there was minimal residual disease. The median survival of these patient groups was 42.9 and 17.4 months, respectively. When gross macroscopic tumor was left behind, as was the case in 17 patients, the median survival was 5 months. Involvement of the small bowel before cytoreduction was associated with poorer outcome.
Cytoreduction followed by HIPEC showed a median survival of 21 months. From 3 years on, a consistent group of 18% of patients stayed alive.
After treatment of peritoneal carcinomatosis of colorectal cancer origin by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC), recurrences develop in approximately 80% of patients. ...This study evaluates the outcome of such recurrences after initial treatment by cytoreduction and HIPEC.
Between November 1995 and May 2003, 106 patients underwent cytoreduction and HIPEC. The progression-free interval, the location of the recurrence, and its treatment were recorded. Factors potentially related to survival after recurrences were studied.
Sixty-nine patients had a recurrence within the study period. For patients who had undergone a gross incomplete initial cytoreduction, the median duration of survival after recurrence was 3.7 months (standard error of the mean SE, .3). If a complete cytoreduction had been accomplished initially, the median duration of survival after the recurrence was 11.1 months (SE, .9). A shorter interval between HIPEC and recurrence was associated with shorter survival after treatment of recurrence (hazard ratio, .94; SE, .02). After effective initial treatment, a second surgical debulking for recurrent disease resulted in a median survival duration of 10.3 months (SE, 1.9), and after treatment with chemotherapy it was 8.5 months (SE, 1.6). The survival was 11.2 months (SE, .5) for patients who received radiotherapy for recurrent disease. Patients who did not receive further treatment survived 1.9 months (SE, .3).
Treatment of recurrence after cytoreduction and HIPEC is often feasible and seems worthwhile in selected patients. Selection should be based mainly on the completeness of initial cytoreduction and the interval between HIPEC and recurrence.
Despite many years of clinical research, there is still no effective therapy for malignant pleural mesothelioma (MPM). Untreated, the prognosis is poor, with a median survival of < 1 year. ...Single-agent or combination chemotherapy as well as radiotherapy have not shown persistent improvements in response or survival. In general, MPM is a disease confined to the pleural cavity for a long time before metastasizing. Therefore, focus on local treatment seems rational. Surgical resection has been considered the mainstay of treatment by some. However, surgery alone results in high recurrence rates, and the survival benefit remains questionable. In recent years, the emphasis has been on surgery combined with adjuvant therapies. In this article, the present state of surgical management of MPM will be reviewed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment strategy for pseudomyxoma peritonei (PMP) with curative intent. The aim of this study was to ...determine the patterns of failure in patients who underwent such a procedure and to evaluate management and outcome of progressive disease.
After exclusion of patients with overt malignancy, progression was studied in 96 PMP patients treated primarily by CRS with HIPEC. Location, pathology, management and outcome were recorded.
Median follow-up was 51.5 months (0.1-99.5). Median progression free survival (PFS) was 28.2 months (95% CI 18.3->). Progressive disease was mainly located sub hepatic (38%) or in multiple regions (36%). Pathological dedifferentiation was observed in 8 patients (20%). The choice of treatment depended on pathology, extent of disease and PFS. Seventeen patients were treated for progression by second CRS with (n=8) or without HIPEC (n=10). The 3-years overall survival (OS) probability after this treatment was 100% and 53.3% (95% CI 28.2-100%), respectively. Fifteen patients with (slow) progression were observed. Three-years OS probability of these patients was 66.0% (95% CI 43.4-100%). All patients treated for progression by systemic chemotherapy only (n=6) had died of disease after a median follow up of 14.8 (9.8-33.6) months. A longer PFS after primary treatment was associated with longer OS after progression (P = 0.04).
Progressive PMP after primary CRS with HIPEC is probably the result of technical failure and/or tumor biology. Management of progressive PMP can be valuable for selected patients and should depend primarily on the PFS.
The incidence of plantar fibromatosis (PF) is unknown. Sometimes PF tends to recur repetitively after surgical treatment. In our institute we have used postoperative radiotherapy in an attempt to ...diminish the change on recurrence.
The Dutch Network and National Database for Pathology (PALGA) was consulted to establish the incidence of plantar fibromatosis (PF). Data from 9 patients (11 feet) with PF referred to our institute for recurrent disease were analyzed and the role of postoperative radiotherapy in prevention of recurrence was studied.
An average of 1.2 operations for PF was performed per 100,000 citizens yearly in the Netherlands. Twenty-six operations were performed and postoperative radiotherapy was used in 6 cases. Plantar fasciectomy was associated with the lowest recurrence rate. After microscopically incomplete excision or excision of early recurrence (≤6 months) alone all tumors recurred, while recurrence was rarely observed after adjuvant radiotherapy. However, radiotherapy was associated with significantly impaired functional outcome in 3 cases.
Plantar fibromatosis is relatively rare. Plantar fasciectomy seems to be the operation of choice. Although effective in decreasing the recurrence rate, adjuvant radiotherapy should be used very selectively because of its serious side effects.
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.
Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded.
The Netherlands Cancer Institute.
Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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, dependant 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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