BEV-IP : perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis

Background: Selected patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) benefit from cytoreductive surgery (CRS) combined with intraperitoneal chemoperfusion (IPC). However, even after optimal cytoreduction, systemic and locoregional recurrence are common. Perioperative chemotherapy with bevacizumab (BEV) may improve the outcome of these patients. Methods/Design: The BEV-IP study is a phase II, single-arm, open-label study aimed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC. This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality (primary composite endpoint). Secondary endpoints are treatment completion rate, chemotherapy-related toxicity, pathological response, progression free survival, and overall survival. Discussion: The BEV-IP trial is the first prospective assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and IPC for colorectal peritoneal metastases

Using Pharmacologic Data to Plan Clinical Treatments for Patients with Peritoneal Surface Malignancy

The surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of gastrointestinal and gynecologic malignancy. This transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis which, without special treatments, is a fatal manifestation of these diseases. In order to control peritoneal carcinomatosis cytoreductive surgery to remove gross disease is combined with perioperative intraperitoneal and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the intraperitoneal or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia (41-42ºC) of the intraperitoneal chemotherapy solution. A constant dose of chemotherapy agent and volume of carrier solution based on body surface area allows prediction of systemic drug exposure and systemic toxicity. Timing of the chemotherapy as a planned part of the surgical procedure to maximize exposure of all peritoneal surfaces is crucial to success

Consensus statement for treatment protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Objectives: Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics. Methods: The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance). Results: Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m(2)) and cisplatin (10.5 mg/m(2)) was endorsed by 20/ 22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m(2) (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of >= 8/10. Conclusions: The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research

A bronchogenic cyst, presenting as a retroperitoneal cystic mass

Bronchogenic cysts are mostly benign, congenital abnormalities originating from the remnants of the primitive foregut. A retroperitoneal location is rare. Due to the mostly asymptomatic behavior and the historical confusion regarding histology, an exact prevalence is not known. We present here a case report of a retroperitoneal bronchogenic cyst. A literature review was performed for cases of retroperitoneal bronchogenic cysts written in English. Anatomopathological criteria for inclusion were pseudo stratified, ciliated, columnar epithelium together with the presence of at least one of the following: cartilage, smooth muscle or seromucous glands. In addition, the embryology, pathogenesis, radiological, clinical and suggested treatment modalities are reviewed. We report the surgical excision of a retroperitoneal bronchogenic cyst that presented as a non-functioning left adrenal mass. Our review of literature revealed only 62 potential cases of retroperitoneal bronchogenic cysts. After applying the strict anatomopathological criteria, only 30 cases of true retroperitoneal bronchogenic cysts could be identified. Retroperitoneal location of a bronchogenic cyst is rare. Despite the rarity of this pathologic entity, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal cystic lesions. Only histology can confirm definitive diagnosis. Surgery remains the recommended treatment of choice

A Pharmacokinetic and Pharmacodynamic Rationale for Perioperative Cancer Chemotherapy in Patients with Peritoneal Carcinomatosis

Peritoneal carcinomatosis (PC) is a common manifestation of both gastrointestinal and gynecologic malignancies. Until recently, this condition was considered beyond curative intent treatment. Since the 1980s, new treatment strategies combining cytoreductive surgery (CRS) with perioperative intraperitoneal and intravenous chemotherapy have emerged. The underlying hypothesis considers CRS responsible for the removal of the macroscopic disease and that perioperative chemotherapy should address the residual microscopic disease. These new treatment regimens have presented encouraging clinical results that contrast with prior failure. The parameters for perioperative chemotherapy are mainly extrapolated from literature on peritoneal dialysis and data from systemic chemotherapy. The overall aim of this thesis was to provide a pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal (IP) and intravenous (IV) chemotherapy in PC patients and, to assess its toxicity. After intraoperative IV administration of 5-fluorouracil or ifosfamide, substantial levels of these drugs were found inside the peritoneal fluid and tumor nodules (Papers I and II). This created a pharmacologically advantageous situation whereby a normothermic administered IV drug was subject to the effect of the local hyperthermia in the peritoneal fluid and tumor nodule. High levels of 5-fluouracil, ifosfamide and doxorubicin were observed inside the tumor nodules (Papers I, II and III) and, the identical pharmacokinetic advantage (expressed as Area Under the Curve (AUC) IP/IV ratios)) resulted in different drug levels of doxorubicin according to the density of the tumor nodules (Paper III). These data stressed the importance of pharmacodynamic variables such as tumor nodule density, size, and, vascularity. Therefore, the tumor nodule is proposed as a more appropriate pharmacological endpoint than AUC ratios. After IP Mitomycin C administration in PC patients with a contracted abdomen, mitomycin clearance from the abdomen decreased (Paper IV), which indicated  these patients at risk of under-treatment. Consequently, these pharmacologic data indicate a change in dosimetry for these treatment protocols might be warranted according to the diffusion area. Although diffusional vectors are viewed the main driving force for these treatment protocols, only pharmacokinetic variables such as dose, volume and duration are considered. As pharmacodynamic variables are equally important in the pharmacological assessment of cytotoxic effect, the tumor nodule was proposed as the center of a new conceptual model (Paper I). Mitomycin C data on non-metabolizers ( Paper IV) indicated the cytotoxicity of these cancer chemotherapy protocols is at the level of the individual tumor nodules. The morbidity and mortality of a new bidirectional intraoperative chemotherapy regimen in PC patients was analyzed (Paper V) which provided a means for identifying subsets of patients at risk for increased toxicity. This thesis provides pharmacokinetic and pharmacodynamic guidance for improving perioperative chemotherapy treatment strategies in PC patients and reports its toxicity

An Unusual Case of Peritoneal Carcinomatosis

The peritoneal surface remains an important failure site for patients with gastrointestinal and gynecologic malignancies. In the past, oncologists regarded peritoneal carcinomatosis as an incurable component of an intra-abdominal malignancy. During the last two decades, novel therapeutic approaches have emerged for peritoneal carcinomatosis patients. We report the first case of peritoneal carcinomatosis emerging from an extra-adrenal, intra-abdominal paraganglioma. This 49-year-old male was treated with cytoreductive surgery and hyperthermic intraperitoneal perioperative chemotherapy. Paragangliomas are rare tumors of neural crest-derived chromaffin cells and can originate either from the sympathetic or from the parasympathetic ganglia. It has been estimated that as many as 10% of the paragangliomas arise outside the adrenal glands. This case represents an unreported presentation of paraganglioma. Two possible origins of this malignancy, and the applied therapy, are discussed. We report the feasibility of cytoreductive surgery plus hyperthermic intraperitoneal perioperative chemotherapy in the treatment of this malignancy

Rhabdomyolysis after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Case Report

Gastric cancer with peritoneal carcinomatosis is a disease with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) can improve prognosis, although in most cases this should still be considered as a palliative treatment. Therefore, morbidity has to be avoided at all cost as quality of life is of utmost importance. We describe the case of a 64-year-old female with an adenocarcinoma of the stomach that was initially treated with a Billroth II gastrectomy, adjuvant chemotherapy and radiotherapy. During follow-up, the diagnosis of peritoneal carcinomatosis was made, and the patient was referred for CRS and HIPEC. Postoperatively, she developed rhabdomyolysis in both gastrocnemius muscles. Renal function remained within normal limits, but ultrasonography of the lower legs suggested the presence of bilateral abscesses. Drainage with pigtail catheters was necessary for more than 1 month, significantly impairing quality of life. The objective of this case report is to heighten awareness for this complication. Rhabdomyolysis is a rare complication of CRS and HIPEC, with a significant impact on quality of life. Prevention is necessary and can be achieved by adequate surgical positioning, using the altered lithotomy position, sufficient padding and by preventing hypovolemia

An Unusual Location of Extraosseous Ewing's Sarcoma

Ewing's sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen