Hyperthermic intraperitoneal chemotherapy

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Hyperthermic intraperitoneal chemotherapy
Schema HIPEC.png
Schematic overview of HIPEC
Other namesHyperthermic intraperitoneal chemotherapy (HIPEC), intra-abdominal hyperthermic chemoperfusion, intraoperative chemohyperthermic peritoneal perfusion (CHPP), or the Sugarbaker technique
Specialty Surgical oncology

Intraperitoneal hyperthermic chemoperfusion (HIPEC or IPHC) is a type of hyperthermia therapy used in combination with surgery in the treatment of advanced abdominal cancers. [1] In this procedure, warmed anti-cancer medications are infused and circulated in the peritoneal cavity (abdomen) for a short period of time. The chemotherapeutic agents generally infused during IPHC are mitomycin-C and cisplatin.

Contents

Medical uses

IPHC is generally used after surgical removal of as much cancer as possible (debulking), which may include the removal of all involved peritoneal areas. Evidence supports a benefit in certain cases of ovarian cancer. [2]

Evidence is insufficient as of 2020 to support its use in primary advanced epithelial ovarian, fallopian tube or primary peritoneal carcinoma, recurrent ovarian cancer, peritoneal colorectal carcinomatosis, gastric peritoneal carcinomatosis, malignant peritoneal mesothelioma, or disseminated mucinous neoplasm of the appendix. [3]

These procedures can be 8–10 hours long and carry a significant rate of complications. [4]

The chest counterpart of HIPEC is the hyperthermic intrathoracic chemotherapy (HITOC).

Chemotherapy agents

Various chemotherapies are used [5] and there is no clear consensus on which drugs should be used. Mitomycin C and oxaliplatin are the most commonly used agent for colorectal cancer, while cisplatin is used in ovarian cancer. [6]

History

In 1934, Joe Vincent Meigs in New York originally described tumor debulking surgery (cytoreductive surgery) for ovarian cancer under the premise of reducing macroscopic disease. [7] In the 60s and 70s this aggressive cytoreductive approach began to be accepted. During this time, Dr. Kent Griffith at the National Cancer Institute also reported on prognostic indicators of survival in stage II and III ovarian cancer patients, importantly noting that residual tumor mass size (<1.6 cm) after cytoreductive surgery was significantly associated with extended survival. [7] During this time research started to show hyperthermia as well as intraperitoneal chemotherapy was effective in killing cancer cells. Spratt et al. in the 1980s, at the University of Louisville in Kentucky combined these concepts into a thermal transfusion infiltration system (TIFS) for delivery of heated chemotherapy into the peritoneal space of canines. [8] The first human was subjected to TIFS with administration of hyperthermic chemotherapy for locally advanced abdominal malignancy in 1979. [9] Further studies in the 1980s delivered chemotherapeutic agents at concentrations up to 30 times greater than those safely administered via IV route. In the mid to late 1980s, Sugarbaker led the Washington Cancer Institute further investigation into therapy for gastrointestinal malignancies with peritoneal dissemination and was able to report survival benefits. [10] It became apparent early that completeness of cytoreduction was associated with survival benefits. [7] In 1995, Sugarbaker created a stepwise approach to cytoreduction, in an attempt to standardize and optimize this process. [11]

The HIPEC technique was also further improved upon by suggesting multiple modalities of delivery. The "Coliseum" technique as well as a similar approach described by Dr. Paul Sugarbaker in 1999 were open abdominal techniques where heated chemotherapy was poured in. Benefits of this open approach included direct access by the surgeon to the cavity during administration of the hyperthermic agents to manipulate the fluid and bowel in order to achieve a quick and homogeneous temperature and distribution of drug within the abdomen. Additionally, care can be taken to ensure that all peritoneal surfaces are exposed equally throughout the duration of the therapy as well as avoid dangerous temperatures or over-exposure to normal tissues. In comparison, the closed technique involves the closure of the abdominal wall prior to infusion of the chemotherapy reducing the issue of heat loss from peritoneal surfaces. In attempts to combine potential advantages of these two techniques, Sugarbaker employed a semi-open method by developing a new containment instrument (Thompson retractor) described in 2005 to support watertight elevation of the abdominal skin edges. More recently, a laparoscopic approach for CRS with HIPEC in highly selected patients with minimal disease burden has been described.

A further advance was made in 2016, when Lotti M. et al. described a new technique, the Laparoscopy-Enhanced HIPEC (LE-HIPEC) technique, in which the hyperthermic chemotherapy is delivered after the closure of the abdominal wound, and a laparoscopic approach is used to stir the abdominal content during the perfusion. [12] [13] Lotti M called into question the statement that the Coliseum technique could achieve the homogeneous distribution of heat. [14] [15] The aim of the LE-HIPEC is to achieve a better heat delivery and preservation (as is in the closed technique) and a better circulation of the perfusion fluid (as is in the open technique). [16] Compared to the standard closed-abdomen technique, the LE-HIPEC technique allows the surgeon to open the abdominal compartments to let the inflow of the heated perfusion fluid. Moreover, it allows the identification and division of the early intra-abdominal adhesions that can hamper the circulation of the perfusion fluid during a standard closed-abdomen perfusion. In a further study, Lotti M et al. showed that after CRS early intra-abdominal adhesions occur in 70% of the patients, soon after the closure of the wound. [17] [18]

Mechanism

Infused chemotherapy diffuses from the intraperitoneal fluid into tissue, interstitial space, and plasma, similar to peritoneal dialysis. The plasma-peritoneum barrier prevents systemic absorption of the chemotherapy into the bloodstream thereby limiting toxicity and side effects. Certain agents, like cisplatin or mitomycin C, are heated to 41 °C-43 °C for an enhanced cytotoxic effect. [19]

Anesthetics

It has been reported that goal-directed therapy may contribute to individually adjusting fluid therapy and drugs, this might allow to avoid overhydration and to ensure hemodynamic stability. [20]

Controversy

While potentially curative, CRS plus HIPEC is associated with substantial perioperative morbidity and mortality and a short-term decline in the quality of life. [21] Skeptics of this procedure argue there is no multi-centered randomized Phase 3 trial comparing CRS+HIPEC with complete cytoreduction followed by systemic therapy. Hence this therapy has not met the scientific bar to be considered standard of care. However, proponents of CRS+HIPEC argue that until now, there has been no systemic therapy that has provided prolonged survival for peritoneal metastases. Peritoneal metastases, based on the primary tumor and extent of the disease, has a median overall survival of less than 36 months based on systemic therapy alone. [22] The treatment of peritoneal carcinomatosis of colorectal origin with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has a 5-year recurrence-free or cure rate of at least 16%. [23]

Related Research Articles

<span class="mw-page-title-main">Colorectal cancer</span> Cancer of the colon or rectum

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and fatigue. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.

<span class="mw-page-title-main">Krukenberg tumor</span> Medical condition

A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often found in both ovaries, consistent with its metastatic nature.

<span class="mw-page-title-main">Ovarian cancer</span> Cancer originating in or on the ovary

Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.

<span class="mw-page-title-main">Pseudomyxoma peritonei</span> Medical condition

Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity. This will result in compression of organs and will destroy the function of the colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death occurring via cachexia, bowel obstruction, or other types of complications.

<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

<span class="mw-page-title-main">Omental cake</span> Medical condition

Omental cake is a radiologic sign indicative of an abnormally thickened greater omentum. It refers to infiltration of the normal omental structure by other types of soft-tissue or chronic inflammation resulting in a thickened, or cake-like appearance.

Carcinosis, or carcinomatosis, is disseminated cancer, forms of metastasis, whether used generally or in specific patterns of spread.

Hepatic arterial infusion (HAI) is a medical procedure that delivers chemotherapy directly to the liver. The procedure, mostly used in combination with systemic chemotherapy, plays a role in the treatment of liver metastases in patients with colorectal cancer (CRC). Although surgical resection remains the standard of care for these liver metastases, majority of patients have lesions that are unresectable.

<span class="mw-page-title-main">Intraperitoneal injection</span> Injection of substances into peritoneum (body cavity)

Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum. It is more often applied to non-human animals than to humans. In general, it is preferred when large amounts of blood replacement fluids are needed or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection.

<span class="mw-page-title-main">Peritoneal mesothelioma</span> Medical condition

Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.

Hyperthermic intrathoracic chemotherapy (HITOC) is part of a surgical strategy employed in the treatment of various pleural malignancies. The pleura in this situation could be considered to include the surface linings of the chest wall, lungs, mediastinum, and diaphragm. HITOC is the chest counterpart of HIPEC. Traditionally used in the treatment of malignant mesothelioma, a primary malignancy of the pleura, this modality has recently been evaluated in the treatment of secondary pleural malignancies.

Cytoreductive surgery (CRS) is a surgical procedure that aims to reduce the amount of cancer cells in the abdominal cavity for patients with tumors that have spread intraabdominally. It is often used to treat ovarian cancer but can also be used for other abdominal malignancies.

<span class="mw-page-title-main">Farrer Park Hospital</span> Hospital in Connexion, Singapore

Farrer Park Hospital is a private tertiary healthcare institution in Farrer Park, Singapore. Located above the Farrer Park MRT station at the Connexion building, the hospital has a capacity of 220 beds across four inpatient suites and 18 operating theaters including major surgery, cardiovascular and endoscopic suites. It is interconnected with the Farrer Park Medical Centre, where there are 10 floors of suites for over 200 medical specialists, as well as One Farrer Hotel.

<span class="mw-page-title-main">Peritoneal carcinomatosis</span> Medical condition

Peritoneal carcinomatosis (PC) is intraperitoneal dissemination (carcinosis) of any form of cancer that does not originate from the peritoneum itself. PC is most commonly seen in abdominopelvic malignancies. Computed tomography (CT) is particularly important for detailed preoperative assessment and evaluation of the radiological Peritoneal Cancer Index (PCI).

Paul Hendrick Sugarbaker is an American surgeon at the Washington Cancer Institute. He is known for developments in surgical oncology of the abdomen, including cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy, or HIPEC, a treatment alternately referred to as the Sugarbaker Procedure.

Juan José Segura-Sampedro MBE is a Spanish surgeon and researcher at Son Espases University Hospital in Mallorca, Spain, and adjunct professor of surgery at University of the Balearic Islands. He is best known for his research in major trauma, focused on the balconing phenomenon and a preventive campaign in collaboration with the British Foreign Office.

Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma.

Andrea A. Hayes Dixon is an American surgeon. She was the first pediatric surgeon to perform a high-risk, life-saving procedure in children with a rare form of cancer and developed the first orthotropic xenograft model of metastatic Ewing's sarcoma. In 2002, she became the first African American female pediatric surgeon board-certified in the United States.

Gilles Freyer is a French professor, oncologist and medical professional who has specialised in the field of gynaecological cancers. He is currently head of the Department of Medical Oncology and Vice-Dean of the University of Lyon. He is also the current Medical Director of the Cancer Institute of the Hospices Civils de Lyon. He is known for having been the President of the cooperative group GINECO from 2013. He was also a member of the International Scientific Committee of INCa. Professor Freyer is also known for being the President of the Monaco Age Oncologie and the Co-President of the Biennale Monégasque de Cancérologie.

Somashekhar SP is an Indian robotic surgeon, author and chairman of medical advisory board at Aster DM Healthcare - GCC & India. He is also the global director of Aster International Institute of Oncology in GCC & India. He is the president of the Association of Breast Surgeons of India, editor in chief of the IJGO Springer Indian Journal of Gynec Oncology and council member of The Association of Surgeons of India. He is also the editor of Annals of Breast Diseases.

References

  1. ↑ Esquivel, Jesus (2010). "Technology of Hyperthermic Intraperitoneal Chemotherapy in the United States, Europe, China, Japan and Korea". In Vincent T. DeVita Jr.; Theodore Lawrence; Steven A. Rosenberg (eds.). Cancer: Principles & Practice of Oncology—Annual Advances in Oncology, Volume 1. Lippincott Williams & Wilkins. pp. 188–193. ISBN   978-1-4511-0314-4.
  2. ↑ Huo, YR; Richards, A; Liauw, W; Morris, DL (December 2015). "Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer: A systematic review and meta-analysis". European Journal of Surgical Oncology. 41 (12): 1578–89. doi:10.1016/j.ejso.2015.08.172. PMID   26453145.
  3. ↑ Auer, RC; Sivajohanathan, D; Biagi, J; Conner, J; Kennedy, E; May, T (March 2020). "Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a systematic review". European Journal of Cancer. 127: 76–95. doi:10.1016/j.ejca.2019.10.034. PMID   31986452. S2CID   210934083.
  4. ↑ "UC HealthNews : HEALTH LINE: Heated".
  5. ↑ Newton, Andrew D.; Bartlett, Edmund K.; Karakousis, Giorgos C. (2016-02-01). "Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a review of factors contributing to morbidity and mortality". Journal of Gastrointestinal Oncology. 7 (1): 99–111. doi:10.3978/j.issn.2078-6891.2015.100. ISSN   2078-6891. PMC   4754303 . PMID   26941988.
  6. ↑ Morales-Soriano, Rafael; Esteve-Pérez, Neus; Segura-Sampedro, Juan José; Cascales-Campos, Pedro; Barrios, Pedro; Spanish Group of Peritoneal Malignancy Surface (GECOP) (February 2018). "Current practice in cytoreductive surgery and HIPEC for metastatic peritoneal disease: Spanish multicentric survey". European Journal of Surgical Oncology. 44 (2): 228–236. doi:10.1016/j.ejso.2017.11.012. ISSN   1532-2157. PMID   29242018.
  7. 1 2 3 Neuwirth, Madalyn G.; Alexander, H. Richard; Karakousis, Giorgos C. (2016-02-01). "Then and now: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), a historical perspective". Journal of Gastrointestinal Oncology. 7 (1): 18–28. doi:10.3978/j.issn.2078-6891.2015.106. ISSN   2078-6891. PMC   4754315 . PMID   26941981.
  8. ↑ Spratt, John S.; Adcock, Robert A.; Sherrill, William; Travathen, S. (1980-02-01). "Hyperthermic Peritoneal Perfusion System in Canines". Cancer Research. 40 (2): 253–5. ISSN   0008-5472. PMID   7356508.
  9. ↑ Spratt, J. S.; Adcock, R. A.; Muskovin, M.; Sherrill, W.; McKeown, J. (1980-02-01). "Clinical delivery system for intraperitoneal hyperthermic chemotherapy". Cancer Research. 40 (2): 256–260. ISSN   0008-5472. PMID   6766084.
  10. ↑ Sugarbaker, P. H. (1988-01-01). "Surgical management of peritoneal carcinosis: diagnosis, prevention and treatment". Langenbecks Archiv für Chirurgie. 373 (3): 189–196. doi:10.1007/bf01274232. ISSN   0023-8236. PMID   3288830. S2CID   22833013.
  11. ↑ Sugarbaker, P. H. (1995-01-01). "Peritonectomy procedures". Annals of Surgery. 221 (1): 29–42. doi:10.1097/00000658-199501000-00004. ISSN   0003-4932. PMC   1234492 . PMID   7826158.
  12. ↑ Lotti, Marco; Capponi, Michela Giulii; Piazzalunga, Dario; Poiasina, Elia; Pisano, Michele; Manfredi, Roberto; Ansaloni, Luca (2016). "Laparoscopic HIPEC: A bridge between open and closed-techniques". Journal of Minimal Access Surgery. 12 (1): 86–89. doi: 10.4103/0972-9941.158965 . ISSN   0972-9941. PMC   4746985 . PMID   26917929.
  13. ↑ Lotti, Marco (7 January 2016). "Laparoscopy-Enhanced Closed Abdomen Hyperthermic Intraperitoneal Chemotherapy". Journal of Laparoendoscopic & Advanced Surgical Techniques Part B, Videoscopy. doi:10.1089/vor.2015.0315.
  14. ↑ Lotti, Marco (15 June 2017). "A Coliseum with frail foundations: a critical analysis of the state-o…". slideshare.net.
  15. ↑ Lotti, Marco (2017). "HIPEC and the necessary hyperthermia: do we still need the open abdomen?" (PDF). European Review for Medical and Pharmacological Sciences. 21 (20): 4473–4475. PMID   29131272.
  16. ↑ Lotti, Marco (18 September 2016). "the Laparoscopy-Enhanced HIPEC Concept". www.slideshare.net.
  17. ↑ Lotti, Marco; Giulii Capponi, Michela; Campanati, Luca; Poiasina, Elia; Ansaloni, Luca; Poletti, Eugenio; Frigerio, Luigi (December 2016). "The Onset of Intra-Abdominal Adhesions During Closed-Abdomen Hyperthermic Intraperitoneal Chemotherapy". Journal of Laparoendoscopic & Advanced Surgical Techniques. 26 (12): 997–1002. doi:10.1089/lap.2016.0396. PMID   27705085.
  18. ↑ Lotti, Marco (21 October 2016). "Intra-abdominal adhesions are formed during closed-abdomen HIPEC". www.youtube.com.
  19. ↑ van Stein, Ruby M.; Aalbers, Arend G. J.; Sonke, Gabe S.; van Driel, Willemien J. (2021-05-06). "Hyperthermic Intraperitoneal Chemotherapy for Ovarian and Colorectal Cancer: A Review". JAMA Oncology. 7 (8): 1231–1238. doi:10.1001/jamaoncol.2021.0580. ISSN   2374-2437. PMID   33956063. S2CID   233869800.
  20. ↑ Esteve-Pérez, N.; Ferrer-Robles, A.; Gómez-Romero, G.; Fabián-Gonzalez, D.; Verd-Rodriguez, M.; Mora-Fernandez, L. C.; Segura-Sampedro, J. J.; Tejada-Gavela, S.; Morales-Soriano, R. (2018-09-14). "Goal-directed therapy in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a prospective observational study". Clinical and Translational Oncology. 21 (4): 451–458. doi:10.1007/s12094-018-1944-y. ISSN   1699-048X. PMID   30218305. S2CID   52276392.
  21. ↑ "The Surgical Management of Peritoneal Carcinomatosis of Colorectal Origin | Cancer Network". www.cancernetwork.com. Retrieved 2018-04-22.
  22. ↑ Wilber, Del Quentin (2012-11-25). "Surgeon performs controversial cancer surgery named after him". Washington Post. ISSN   0190-8286 . Retrieved 2018-04-22.
  23. ↑ Simkens, Geert A; Rovers, Koen P; Nienhuijs, Simon W; de Hingh, Ignace H (2017-06-30). "Patient selection for cytoreductive surgery and HIPEC for the treatment of peritoneal metastases from colorectal cancer". Cancer Management and Research. 9: 259–266. doi: 10.2147/CMAR.S119569 . PMC   5501638 . PMID   28721098.
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