Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy

Witkamp, Arjen J.; Bree, Eelco de; Goethem, R Van; Zoetmulder, F.A.N.

doi:10.1053/ctrv.2001.0232

Cited by 207 publications

(132 citation statements)

References 61 publications

(47 reference statements)

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“…The two principal methods to deliver intraoperative intraperitoneal chemotherapy are the open abdomen and the closed abdomen technique [50]. In a pig model, the open technique had significantly increased absorption of oxaliplatin to the systemic compartment and enhanced penetration of oxaliplatin into abdominal tissues when compared to the closed abdomen method [51].…”

Section: Mode Of Action: Open Vs Closed Abdominal Lavagementioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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Intraperitoneal chemotherapy is associated with a significant pharmacokinetic and pharmacodynamic benefit and can, alone or in combination with systemic chemotherapy (bidirectional chemotherapy), be used for treating primary and secondary peritoneal surface malignancies. Due to the peritoneal-plasma barrier, high intraperitoneal drug concentration can be achieved by intraperitoneal chemotherapy, whereas systemic concentration remains low. Bidirectional chemotherapy may provide in addition adequate drug concentrations from the side of the subperitoneal space to the peritoneal tumour nodules. Major pharmacological problems of intraperitoneal chemotherapy are limited tissue penetration and poor homogeneity of drug distribution to the entire seroperitoneal surface. Significant pharmacological determinants of intraperitoneal chemotherapy are choice of drug, drug dosage, solution volume, carrier solution, intra-abdominal pressure, temperature, duration, mode of administration, extent of peritonectomy and interindividual variability. Drugs most commonly applied for intraperitoneal chemotherapy include mitomycin C, cisplatin, carboplatin, oxaliplatin, irinotecan, 5-fluoruracil, gemcitabine, paclitaxel, docetaxel, doxorubicin, premetrexed and melphalan. The drugs and their doses that are used vary widely among centres. While the adequate drug choice for intraperitoneal and bidirectional chemotherapy is essential, randomized clinical trials to determine the most optimal drug or drug combination are lacking, and only eight retrospective comparative clinical studies are available. Further clinical pharmacological studies are required to determine the most effective drug regimen for intraperitoneal and bidirectional chemotherapy in various indications. In the future, reliable drug sensitivity testing and genetic profiling of peritoneal metastases will be needed for enabling patient-specific therapy.

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Section: Mode Of Action: Open Vs Closed Abdominal Lavagementioning

confidence: 99%

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Bree

Michelakis

Stamatiou

et al. 2017

Pleura and Peritoneum

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“…Pseudomyxoma peritonei can take on a protracted course if the histopathology is that of disseminated peritoneal adenomucinosis (DPAM), or rapidly evolve as a highly malignant tumor with peritoneal mucinous carcinomatosis (PMCA) histopathology. Current treatment combines cytoreductive surgery (resection of the tumor and peritoneal implants) and intraperitoneal hyperthermic chemotherapy (5)(6)(7)(8). Despite extensive resections, pseudomyxoma peritonei frequently relapses and 5-year survival is only 53% (9), although survival is significantly better if lymph nodes are negative (5-year survival is 76% for lymph node-negative patients and 11% for lymph node-positive patients; P < 0.001; ref.…”

Section: Introductionmentioning

confidence: 99%

Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution

Semino–Mora

Testerman

Liu

et al. 2013

Clinical Cancer Research

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Purpose: Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors and mucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and b-catenin expression within pseudomyxoma peritonei samples.Experimental Design: The study included 48 patients: 19 with disseminated peritoneal adenomucinosis (DPAM) and 29 with peritoneal mucinous carcinomatosis (PMCA). Fourteen patients were given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry.Results: ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased b-catenin levels in the cytoplasm, the cell nuclei, and mucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane b-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics.Conclusions: Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant b-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis.

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“…El tiempo medio de todo el procedimiento fue de 6,36 horas [5][6][7][8]15 . Todos los pacientes permanecieron en la Unidad de Cuidados Intensivos durante, como mínimo, los 5 días que duraba la quimioterapia peritoneal postoperatoria.…”

Section: Experiencia En El Hospital San Jaimeunclassified

“…Estos son potenciados por el calor, que también tiene un efecto citotóxico por sí mismo, se elimina el atrapamiento celular, y se consiguen niveles altos de fármaco en la zona a tratar, imposibles de lograr por vía sistémica debido a su toxicidad [5][6][7][8] . Debido a la barrera peritoneo-plasmática, las sustancias de alto peso molecular como mitomicina C, 5-fluorouracilo, cisplatino o doxorubicina, permanecen largo tiempo dentro del abdomen antes de su eliminación a través de la sangre, lo que las hace especialmente indicadas en esta modalidad terapéutica.…”

Section: Introductionunclassified

Carcinomatosis peritoneal: Quimioterapia intraperitoneal con hipertermia

et al. 2004

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IntroducciónLa diseminación peritoneal constituye uno de los principales patrones de recaída tras cirugía en los tumores de localización abdominal y pélvica. Ha sido considerada clásica-mente como un signo de enfermedad generalizada, tratada de forma paliativa y de desenlace inevitablemente fatal. En un reciente estudio multicéntrico en el que se incluían pacientes con carcinomatosis de origen no ginecológico, la supervivencia media era de 3.1 meses 1 . En estudios en los que se ha tratado con quimioterapia sistémica, se han obtenido buenas respuestas tumorales, aunque sin mejoría en la supervivencia.La diseminación de las células tumorales en el peritoneo puede ser espontánea o producirse durante la cirugía, por mecanismos como la formación de émbolos tumorales por presión, la fuga de células malignas al cortar los vasos linfá-ticos o la siembra de las mismas en la cavidad peritoneal durante la disección quirúrgica. Va seguida habitualmente de la invasión o perforación de la serosa.Una vez extirpado el tumor primario, los factores de crecimiento celular involucrados en la cicatrización estimulan el crecimiento de las células malignas viables atrapadas o en coágulos sanguíneos intraabdominales, o por la fibrina en superficies peritoneales traumatizadas. Paralelamente, el atrapamiento de dichas células dificulta el acceso a ellas de la quimioterapia sistémica, disminuyendo o anulando su eficacia 2,3 . Desde 1980 han aparecido en la literatura nuevas propuestas para el tratamiento de los pacientes afectos de diseminación tumoral peritoneal, un grupo de difícil manejo terapéutico y emocional, derivado de la perspectiva de fracaso terapéutico con perdida rápida y progresiva de la calidad de vida 4 . La administración de drogas antitumorales por vía intraperitoneal, la inmunoterapia intracavitaria, la terapia fotodinámica o la quimioterapia e hipertermia intraperitoneal constituyen una muestra de las líneas de trabajo en esta dirección 4 . La perfusión intraperitoneal con quimioterapia e hipertermia ha ofrecido hasta el momento resultados esperanzadores. Consiste en realizar la cirugía de exéresis máxima o debulking, seguida de dosis altas de quimioterapia regional en perfusión hipertérmica durante el mismo acto operatorio. En ocasiones se completa la técnica con la administración de dosis altas de quimioterapia en la cavidad peritoneal los dí-as posteriores a la cirugía, a través de catéteres provisionales implantados a tal efecto.La cirugía posibilita la reducción de la enfermedad peritoneal a un tamaño mínimo y libera todas las adherencias, creando las condiciones óptimas para obtener mayor eficacia de los citostáticos. Estos son potenciados por el calor, que también tiene un efecto citotóxico por sí mismo, se elimina el atrapamiento celular, y se consiguen niveles altos de fármaco en la zona a tratar, imposibles de lograr por vía sistémica debido a su toxicidad [5][6][7][8] . Debido a la barrera peritoneo-plasmática, las sustancias de alto peso molecular como mitomicina C, 5-fluorouracilo, cisplatino o doxorubici...

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Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy

Cited by 207 publications

References 61 publications

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Pharmacological principles of intraperitoneal and bidirectional chemotherapy

Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution

Carcinomatosis peritoneal: Quimioterapia intraperitoneal con hipertermia

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