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Background: Patients with colon cancer may present at multiple different stages of the disease process. Many patients can be cured of colon cancer as a result of a simple surgical procedure usually performed by minimally invasive techniques. However, there are a variable number of patients, estimated at approximately 10%, who have a more advanced disease. If these patients are treated by the current conventional standard of care, the likelihood for treatment failure is extremely high. Methods: These are not patients with known disseminated disease but patients who are at high risk of recurrent disease unless special treatments are initiated preoperatively and intraoperatively. The identification of these patients is by (1) a high-quality CT scan, (2) tumor markers found preoperatively, (3) colonoscopic findings, and (4) symptoms. Results: Patients identified as being at high risk require special preoperative treatments which include neoadjuvant chemotherapy. Intraoperative chemotherapy with HIPEC should occur as part of the treatment if peritoneal metastases are documented by biopsy. In the operating room, a thorough exploration of all possible occult peritoneal spaces for metastatic disease needs to be performed. A modified cytoreductive surgical procedure along with a colon resection is performed in order to minimize sites of occult peritoneal metastases. This includes the greater omentum, ovaries, and tubes in postmenopausal women. Peritonectomy is used to create a shroud around the tumor so that all peritoneum that has been in direct contact with the tumor surface is resected and is used as a barrier against tumor cell dissemination in the process of colon cancer resection. If peritoneal metastases are visualized at any site, HIPEC should be included as part of the treatment package. Conclusions: I am convinced that patients at high risk of recurrence will have an improved outcome with proper preoperative evaluation, preoperative neoadjuvant chemotherapy, and a revised intraoperative management strategy. [ABSTRACT FROM AUTHOR]

Sclerosing encapsulating peritonitis (SEP) is a rare entity characterized by encapsulation of the small bowel and/or the colon by a fibrous tissue that forms a shell. Intraperitoneal chemotherapy (IPC) has been reported to be a potential causative factor of secondary SEP. However, few studies have reported on secondary SEP related to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Here, we review results from four clinical cases of SEP associated with CRS and HIPEC. In all four patients, additional surgery was necessary to alleviate recurrent episodes of small bowel obstruction. These obstructions can occur as early as several weeks after CRS plus HIPEC or as late as 3 years after treatment. Of utmost importance is the prevention of fistulization which can result in enteric contamination of the peritoneal space. To date, no solution to SEP has been identified except additional surgery but it is evident that these reoperative experiences are difficult for both surgeon and patient. The etiopathogenesis of SEP in this setting remains unknown but it is clear that it is related to chronic inflammation of the peritoneum. Large studies are needed to identify the incidence and potential common causes of SEP after CRS and HIPEC. [ABSTRACT FROM AUTHOR]

Background: Mucinous appendiceal neoplasms have a pattern of metastases that is different from the other gastrointestinal cancers. The first site for cancer dissemination is the peritoneal space surrounding the primary tumor and this is followed by increasingly extensive peritoneal spread. Invasion of the psoas and iliacus muscle is an unusual phenomenon. Method: From a prospective database of appendiceal mucinous neoplasms treated by cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC), patients with psoas muscle invasion were reviewed. Their clinical features and treatments were tabulated. Results: Three patients with ages 33, 60, and 63 were identified. Two patients had disease progression into the psoas muscle 33 and 95 months after CRS plus HIPEC. One had dissecting mucinous tumor into psoas, iliacus and quadratus lumborum muscle at the time of diagnosis of the appendiceal mucinous neoplasm. All three survived at least five years from their initial treatment. Conclusion: Despite the fact that mucinous tumor invasion was outside the peritoneal cavity, long term benefit from psoas muscle resection with a mucinous appendiceal neoplasm is possible and resection possibly with HIPEC should be considered. [ABSTRACT FROM AUTHOR]

Background:During the Fifth International Workshop on Peritoneal Surface Malignancy in Milan in 2008, a consensus was reached that contrast-enhanced CT (ceCT) was the principal imaging modality for patients being evaluated for treatment of peritoneal metastases. This fact being accepted, the radiologic criteria for that may exclude patients from a high value cytoreductive surgery (CRS) plus hyperthermic perioperative chemotherapy (HIPEC) have not been reliably determined. Methods:From a consensus of surgeons and radiologists, radiologic images were selected and their determinant radiologic characteristics described. The anatomic pathology causing the abnormal images were identified and characterised. The cytoreductive surgical procedures that may, in selected patients, result in a complete resection of the pathology identified were presented. Results:Radiographs of 15 CT images that cause concern when a patient is being evaluated for CRS were listed. The anatomic pathology these images define and possible surgical resections they require were reviewed. The surgical implications of the absence or presence of a single, or of multiple concerning CT features was extracted from the surgical and radiologic literature. Conclusions:There is a definite need to identify new pre-operative imaging parameters to define optimal indication of CRS with HIPEC. The presence of a single concerning radiologic feature is associated with the possibility of an adverse outcome or technically more complex resections associated with increased morbidity and mortality. If two or more of the concerning radiologic features are described from the CT, suboptimal cytoreduction will usually occur. [ABSTRACT FROM AUTHOR]

Objective: Appendectomy is an extremely common surgical procedure usually performed for an inflammatory process within this organ. Upon occasion, the pathology within the appendix is a neoplastic process which requires definitive oncologic management. Methods: The optimal management strategies for appendiceal neoplasms were reviewed and pertinent literature critically evaluated. The technology for appendectomy for an inflammatory process and an appendectomy for a neoplastic process were compared and contrasted. Results: A new surgical procedure called "radical appendectomy" was described and its merits for optimizing the management of an appendiceal neoplasm enumerated. The technology of radical appendectomy was described. The possible shortcomings that may be encountered in performing a new surgical methodology for appendectomy was presented and the results of a technically perfect radical appendectomy enumerated. The integration of a radical appendectomy with perioperative hyperthermic chemotherapy was described. Conclusions: When a malignancy exists as the cause of appendiceal pathology, the radical appendectomy will provide the maximal amount of information required for optimal decisions regarding patient management. [ABSTRACT FROM AUTHOR]

Background: Only approximately one in ten pancreas cancer patients is a candidate for potentially curative resection of this disease. Even this small fraction of patients has a poor prognosis following pancreatico-duodenectomy. The disease has an anatomic location that makes it difficult for the surgeon to maintain adequate margins of resection and prevent tumor spillage at the time of resection. Also, the disease is biologically aggressive and even with a complete visible resection of the disease, micrometastases are likely to remain behind. Methods: A survey of the sites for surgical treatment failure of resected pancreas cancer was performed. Also, the multiple modalities used in an attempt to improve the results of cancer resection are scrutinized. Results: The surgical treatment failures are regional in nature and occur at the resection site and on peritoneal surfaces, within the liver, and within the regional lymph nodes. These anatomic sites account for nearly 100% of the initial sites of disease progression. Current hypothesis suggests that micrometastases released from the cancer specimen by the trauma of surgery account for the high incidence of resection site progression and peritoneal metastases. Although surgical trauma may contribute to micrometastases within the liver and lymph nodes, these are most likely present though not detected by preoperative radiologic studies. Adjuvant treatments such as neoadjuvant chemotherapy or combination systemic chemotherapy have not been associated with improved survival. Extended resections such as total pancreatectomy or extended lymphadenectomy have not been associated with benefit. However, resection with a negative margin of excision along with the removal of at least 12 lymph nodes in and around the pancreaticoduodenectomy specimen is associated with superior outcomes. A regional chemotherapy treatment that consists of hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine and long-term normothermic intraperitoneal chemotherapy (NIPEC-LT) gemcitabine for 6 months postoperatively is suggested as a new treatment that has demonstrated decreases in localregional failure and promises to more adequately target micrometastases in the peritoneal space, in the liver and lymph nodes. Conclusions: Pancreas cancer surgery should attempt to achieve negative margins of resection with the removal of at least 12 lymph nodes. Hyperthermic intraperitoneal gemcitabine can adequately eradicate malignant cells dislodged from the cancer specimen into the bed of the resection at high density and on distant peritoneal surfaces as peritoneal metastases. Long-term intraperitoneal gemcitabine may act on micrometastases in the liver through absorption into the portal vein blood and the lymph nodes as a result of gemcitabine absorption by subperitoneal lymphatic channels. The use of HIPEC and NIPEC-LT gemcitabine may improve local control of resected pancreas cancer. [ABSTRACT FROM AUTHOR]

Malignant peritoneal mesothelioma is a rare disease, with approximately 800 new patients per year in the United States. Its natural history is defined by progression restricted to the peritoneal space. In the past, patients with this disease had a limited lifespan of approximately 1 year. Numerous single-institution studies as well as a systematic review have reported median survival of 3 to 5 years with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy. These markedly improved survival statistics were achieved in experienced centers with 1% mortality and 20% morbidity rates. Data have shown that knowledgeable patient selection is required to prevent patients unlikely to benefit from undergoing these interventions. The conclusion is that patients with peritoneal mesothelioma can experience long-term progression-free survival or significant palliation with cytoreductive surgery plus hyperthermic perioperative chemotherapy. This management plan should be considered the standard of care for properly selected patients with malignant peritoneal mesothelioma at experienced centers around the world. [ABSTRACT FROM AUTHOR]

This paper compared the similarities and differences of the two most common types of colorectal cancer metastases. The treatment of liver metastases by surgery combined with systemic chemotherapy was explained. The different natural history of liver metastases as compared to peritoneal metastases and the possibility for prevention of peritoneal metastases were emphasized. Perioperative cancer chemotherapy or second-look surgery must be considered as individualized treatments of selected patients who have small volume peritoneal metastases or who are known to be at risk for subsequent disease progression on peritoneal surfaces. However, the fact that peritoneal metastases, when diagnosed in the follow-up of colorectal cancer patients, can be cured with a combination of cytoreductive surgery and hyperthermic perioperative chemotherapy cannot be ignored. Careful follow-up and timely intervention in colorectal cancer patients with progressive disease are a necessary part of the management strategies recommended by the multidisciplinary team. After a critical evaluation of the data currently available, these strategies for prevention and management of colorectal metastases are presented as the author's recommendations for a high standard of care. As more information becomes available, modifications may be necessary. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases. The optimal agents for HIPEC have not been established.Melphalan is a drug with broad activity and a favorable profile for intraperitoneal application. The purpose of this study is to review our experience using melphalan for HIPEC. Pharmacologic data was obtained. Thirty four patients who underwent CRS for peritoneal metastases received melphalan for HIPEC between 2003 and 2011. The first 10 patients received 70mg/m2; subsequent 24 received 60 or 70mg/m2. The mean PCI was 21}7. Twenty-eight patients (83%) had a CC score of 1 or 2. The mean length of stay was 18 } 2 days. Nine patients (26%) had a grade 3 and 6 (17%) had grade 4 morbidity. There were no postoperative deaths. The pharmacologic analysis of plasma to peritoneal fluid levels of melphalan showed an AUC ratio of 33 while the tumor nodules to peritoneal ratio was 8. Melphalan is an acceptable agent for use in HIPEC. The morbidity of intraperitoneal melphalan at the dose of 60-70 mg/m2 appears acceptable. Further studies comparing the effectiveness of melphalan and other HIPEC agents are needed. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for selected patients with pseudomyxoma peritonei (PMP) and diffuse malignant peritoneal mesothelioma (DMPM). Tumor infiltration of the hemidiaphragm requiring partial resection occurs as a result of large volume and/or invasive disease at this anatomic site. Transmission of disease from abdomen to chest is a great danger in this group of patients. From a prospective database, patients who had diaphragm resection and then hyperthermic thoracoabdominal chemotherapy (HITAC) as a component of a cytoreductive surgical procedure were identified. Data from control patients receiving HIPEC or hyperthermic intrathoracic chemotherapy (HITOC) were analyzed for comparison. The morbidity, mortality, survival, and recurrence rate within the thoracic space were presented. Thirty patients had partial resection of a hemidiaphragm as part of a cytoreductive surgical procedure that utilized HITAC. The pharmacologic benefit of intracavitary chemotherapy administration was documented with an area under the curve ratio of intracavitary concentration times time to plasma concentration times time of 27 ± 10 for mitomycin C and 75 ± 26 for doxorubicin. Comparing percent chemotherapy absorbed for a ninety-minute treatment showed the largest for HIPEC, then for HITAC, and lowest for HITOC. The incidence of grade 3 and 4 adverse events was 43%. There was no mortality. Adjustments in the chemotherapy dose are not necessary with HITAC. The morbidity was high, the survival was acceptable, and intrathoracic recurrence was low. [ABSTRACT FROM AUTHOR]

In patients with pseudomyxoma peritonei or peritoneal mesothelioma, direct extension of disease through the hemidiaphragm may result in an isolated progression of tumor within the pleural space. We monitored the intrapleural and plasma levels of mitomycin C and doxorubicin by HPLC assay in order to determine the pharmacokinetic behavior of this intracavitary use of chemotherapy. Our results showed a persistent high concentration of intrapleural drug as compared to plasma concentrations. The increased exposure for mitomycin C was 96, and the increased exposure for doxorubicin was 241. When the clearance of chemotherapy from the thoracic cavity was compared to clearance from the abdomen and pelvis, there was a considerably more rapid clearance from the abdomen as compared to the thorax. The pharmacologic study of intrapleural chemotherapy in these patients provides a strong pharmacologic rationale for regional chemotherapy in this group of patients. [ABSTRACT FROM AUTHOR]

Peritoneal metastases (PM) are a common presentation for patients with metastatic colorectal cancer (CRC), and the median survival of patients with PM is approximately one year. In a majority of patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery (CRS) and heated perioperative chemotherapy (HIPEC) as a standard approach for selected patients with PM from CRC. These investigators have demonstrated a very promising long-term survival in a subset of patients with a limited amount of isolated peritoneal metastatic disease. This paper presents the data that supports CRS and HIPEC as a treatment option for CRC patients with PM. These results of treatment are compared and contrasted to the results that can be expected with systemic chemotherapy alone. [ABSTRACT FROM AUTHOR]

Background: Peritoneal surface malignancy resulting from local dissemination is a common manifestation of treatment failure of gastrointestinal cancers. Although the management of carcinomatosis has been improved with an aggressive surgical approach of extensive cytoreduction followed by heated intraoperative intraperitoneal chemotherapy, no patients are cured when there is residual disease after surgery. Melphalan ( l-phenylalanine mustard) is a well-known antineoplastic alkylating agent which has markedly increased pharmacological activity with heat. The use of heated intraoperative intraperitoneal melphalan may provide a pharmacokinetic and clinical advantage in this group of gastrointestinal cancer patients who cannot be made cancer-free with cytoreductive surgery. Methods: Thirteen patients with residual disease following cytoreductive surgery for peritoneal carcinomatosis were included in this study. After surgical resection and prior to anastomotic reconstruction, patients received intraperitoneal melphalan (70 mg/m2) in 3 l of 1.5% dextrose peritoneal dialysis solution at 41–42°C for 90 min. Concentrations of melphalan were assessed in the peritoneal fluid, blood, urine and tumor nodules using high-performance liquid chromatography. Results: During the 90 min of treatment 87.2±4.3% of the drug was absorbed from the perfusate/peritoneal fluid and 11.9±2.1% was excreted in the urine. The area-under-the-curve ratio of peritoneal fluid to plasma was 33.3±11.8 with an average peak plasma concentration of 0.82±0.24 μg/ml occurring at 28.5±13.1 min. Concentrations of melphalan in tumor nodules on the peritoneal surface were approximately ten times higher than in plasma with an average peak concentration of 7.2±4.2 μg/gm. The grade III/IV morbidity was 38%; there was no mortality. Conclusion: Approximately 90% of the drug was absorbed during the 90-minute procedure with a 30 times greater exposure of drug at the peritoneal surfaces than in the blood. Concentrations of the drug in peritoneal surface tumor nodules were approximately ten times greater than concentrations in the blood. These data demonstrate that heated intraoperative intraperitoneal melphalan could have a significant impact on the treatment of peritoneal surface malignancies. [ABSTRACT FROM AUTHOR]

Background: Although lymph node and liver metastases are recognized as indications for resection of metastatic disease from colorectal cancer, carcinomatosis has not traditionally been regarded as having surgical treatment options. Reports have suggested that complete surgical removal of carcinomatosis combined with thorough irrigation of the peritoneal cavity with chemotherapy could result in longterm survival in selected patients. Proper selection factors are important because palliative surgery in these patients has not proved beneficial. Study design: From a database of 156 patients with carcinomatosis from colorectal cancer, a retrospective analysis of data prospectively recorded in 70 patients with complete cytoreduction was performed. Eleven clinical and treatment factors were studied in univariate and multivariable analyses using survival as an end point. Results: By univariate analysis, patients with peritoneal cancer index (PCI) of<20 had a median survival of 41 months compared with 16 months for patients with PCI>20 (p=0.004). The difference in negative versus positive lymph nodes was also significant; differences in survival that were improved but not significant were present for age greater than 30 years, mucinous histology, location within the colon versus rectum, and absence of an adverse factor such as cancer perforation or obstruction present at the time of primary cancer resection. Only PCI<20 versus PCI>20 and lymph node status were significant in the multivariable analysis. Conclusions: Favorable longterm results of complete cytoreduction in patients treated for carcinomatosis are associated with a limited volume of carcinomatosis observed at the time of cytoreduction and in patients with negative lymph nodes at the time of primary operation. [Copyright &y& Elsevier]

Summary: Appendiceal mucinous neoplasms sometimes present with peritoneal dissemination, which was previously a lethal condition with a median survival of about 3 years. Traditionally, surgical treatment consisted of debulking that was repeated until no further benefit could be achieved; systemic chemotherapy was sometimes used as a palliative option. Now, visible disease tends to be removed through visceral resections and peritonectomy. To avoid entrapment of tumour cells at operative sites and to destroy small residual mucinous tumour nodules, cytoreductive surgery is combined with intraperitoneal chemotherapy with mitomycin at 42°C. Fluorouracil is then given postoperatively for 5 days. If the mucinous neoplasm is minimally invasive and cytoreduction complete, these treatments result in a 20-year survival of 70%. In the absence of a phase III study, this new combined treatment should be regarded as the standard of care for epithelial appendiceal neoplasms and pseudomyxoma peritonei syndrome. [Copyright &y& Elsevier]

Background. A prominent part of treatment failure of gastrointestinal and gynecologic malignancy is dissemination to peritoneal surfaces. This has been associated with a limited survival and no reliable treatment strategies. Methods. A review of the natural history of carcinomatosis was performed and a rationale for intraperitoneal chemotherapy was sought. The pharmacology of chemotherapy administration into the peritoneal cavity was reviewed. Results. The technology of perioperative intraperitoneal chemotherapy requires the administration of drugs along with moderate hyperthermia in the operating room as a planned part of the surgical procedure. The solution in which the chemotherapy is diluted has an effect upon the drug clearance from the peritoneal cavity. Also, the volume of the carrier solution affects the exposure of cancer nodules on peritoneal surfaces. Conclusions. New combinations of intraperitoneal chemotherapy administration when combined with optimal surgical technology for maximal chemotherapy effects should result in benefit to patients with peritoneal surface dissemination of gastrointestinal and gynecologic malignancy. [ABSTRACT FROM AUTHOR]

Background. Peritoneal surface malignancy can result from full thickness invasion of gastrointestinal cancer through the bowel wall or from dissemination of cancer cells from the trauma of cancer surgery. In the past, this clinical situation was treated only with palliative intent. Methods. An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. Results. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. Conclusions. Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in both phase II studies and phase III studies. All historical controls show 0% long-term survival. Surgical interventions combined with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs must be considered a treatment option. [ABSTRACT FROM AUTHOR]

Peritoneal carcinomatosis from gastrointestinal cancer has new treatment options for surgical management. The approach uses cytoreductive surgery which combines peritonectomy and visceral resection in an effort to remove all visible cancer within the abdomen and pelvis. Then the peritoneal cavity is flooded with chemotherapy solution in an attempt to eradicate residual disease. In order to select patients for this approach the quantitative prognostic indicators for carcinomatosis were reviewed, compared and contrasted. Prognostic indicators to be used to select patients for this aggressive approach at the initiation of surgery and after completion of cytoreduction were studied. Four quantitative assessments to be used at the time of abdominal exploration were the Gilly staging, Japanese gastric cancer P score, peritoneal cancer index (PCI), and the simplified peritoneal cancer index (SPCI). All have value with the PCI being the most validated and most precise. Preoperative assessments include the tumor histopathology and the prior surgical score. The completeness of cytoreduction score is an assessment of residual disease after a maximal surgical effort. An opportunity for long-term survival following treatment for carcinomatosis requires a complete cytoreduction in all reports for gastrointestinal cancer. Quantitative prognostic indicators need to be knowledgeably employed when patients with carcinomatosis are being treated. Improved patient selection with greater benefit and reduced morbidity and mortality should result. [ABSTRACT FROM AUTHOR]

The initial dissemination of colon cancer occurs through three routes: the lymphatics, the portal blood, and the peritoneal surfaces. Dissemination to peritoneal surfaces may be only superficial contamination of the parietal and visceral peritoneum that may be treatable for cure. Unfortunately, surgery may have an adverse impact on peritoneal surface dissemination. Surgical interventions may convert a superficial process into an invasive condition with a greatly reduced prognosis. In patients with peritoneal seeding, peritonectomy procedures and perioperative intraperitoneal chemotherapy should be performed concomitantly. By use of a quantitative scoring system, the mass of cancer present in the abdomen and pelvis at the time of treatment of carcinomatosis correlated directly with survival. Aggressive treatment of patients with peritoneal carcinomatosis requires consideration in the management of colorectal cancer. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery and perioperative intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil may be considered as an accepted treatment for appendiceal malignancy with mucinous peritoneal carcinomatosis or for pseudomyxoma peritonei. This aggressive approach has been successfully utilized in approximately 500 patients with an acceptable mortality (1.5%) and morbidity (27%). Although pulmonary complications are frequently recorded, life-endangering acute respiratory failure in the absence of pulmonary infection or an obvious source of systemic sepsis has not been previously described. An extensive clinical review of two patients who had a clinical course compatible with acute respiratory distress syndrome without obvious cause except for the cytoreductive surgery and perioperative intraperitoneal chemotherapy itself was undertaken. These two patients developed gradually increasing respiratory distress in the postoperative period. No bacterial or fungal infections of lungs or intra-abdominal sites or sepsis were discovered. These two patients were unusual in that they had extensive cytoreduction, maximal heat with the mitomycin C chemotherapy, and perfusion of both the abdominal cavity and the right pleural space. Reoperation in both patients failed to show a septic source within the abdomen for progressive adult respiratory distress syndrome. We conclude that aggressive cytoreductive surgery plus perioperative intraperitoneal and intrapleural chemotherapy was associated with life-endangering respiratory failure in two patients. No other cause for this condition was evident from an exhaustive review of the clinical course of these two patients. It is possible that this aggressive approach to appendix malignancy with carcinomatosis is sufficiently traumatic to be considered a cause of adult respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Peritoneal seeding from primary gastric cancer occurs in 10–20% of patients. The diagnosis of this advanced disease is usually not provided by clinical studies prior to abdominal exploration. From the data available in the literature, the surgeon is forced to make an intraoperative judgement concerning the risks and benefits of an aggressive management plan versus supportive care. A strategy has evolved that utilizes peritonectomy and extended gastrectomy to maximally cytoreduce tumor combined with perioperative intraperitoneal chemotherapy. In the current state of the art, the perioperative intraperitoneal chemotherapy is heated and manually distributed to provide uniform treatment to all peritoneal surfaces and the resection site. The pharmacologic parameters have been established and the results of phase II studies are reported. Five-year survival of patients in whom a complete cytoreduction was possible is approximately 10% with a median survival of 12 months. Gastrectomy with peritonectomy to eliminate all visible implants combined with perioperative intraperitoneal chemotherapy should be used in selected patients with primary gastric cancer and carcinomatosis.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Use of regional chemotherapy in addition to cytoreductive surgery in patients with established gastric cancer peritoneal metastases should have limited expectations for an improved outcome. 10.1245/s10434-016-5306-0 4 Bonnot P.E., Piessen G., Kepenekian V., Decullier E., Pocard M., Meunier B., Bereder J.M., Abboud K., Marchal F., Quenet F. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): A propensity score analysis. Common knowledge would suggest that regional treatments for peritoneal metastases from gastric cancer would not be successful. [Extracted from the article]

Complex surgical procedures in the upper abdomen require clear exposure. To improve exposure xiphoidectomy is indicated; however, in the past there was an extensive time commitment and unpredictable bleeding. We describe a rapid and bloodless approach to xiphoidectomy, utilizing a self-retaining retractor, controlled osteotomy, and complete removal to the xiphisternal junction. The xiphoid bone is dissected with high-voltage electrosurgery, denatured, and resected completely. Bleeding points are easily controlled with electrocoagulation. This procedure allows optimal exposure to the most superior aspect of the abdominal cavity. [ABSTRACT FROM AUTHOR]

Summary: Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue. [ABSTRACT FROM AUTHOR]

The author reflects on the article by Akaishi and colleagues titled "Peritonectomy for peritoneal carcinomatosis: long-term outcomes from a single Brazilian institution," which discusses treatment strategies for patients with carcinomatosis. He congratulates the authors for their work at Hospital Sirio Libanes in São Paulo, Brazil, and calls on others professionals to follow their example and conduct research in treating carcinomatosis throughout South America.

The article shares the perspectives of the author on the study regarding the applicability of cytoreductive surgery and perioperative intraperitoneal chemotherapy for the management of patients who have a peritoneal surface malignancy. The manuscript focuses on an evolution of treatment strategies used over an 8-year time period. For him, the researchers made the important observation that most of the patients who succumb to cancer after these treatments die as a result of continued carcinomatosis.

An abstract of the article "Clinical Experience With A New Technique Of Hyperthermic Intraoperative Intraperitoneal Chemotherapy" by Paul H. Sugarbaker and colleagues is presented.

An abstract of the article "Feasibility Study Of External Capacitance Hyperthermia With A Thermatron RF-8 For Unresectable Cancers Of Low Malignant Potential" by Paul H. Sugarbaker and colleagues is presented.

An abstract of the article "Multiple Surgical Options In The Prevention And Treatment Of Cancer Seeding Into The Abdomen And Pelvis" by Paul H. Sugarbaker and colleagues is presented.

An abstract of the article "Risk Factors Of Morbidity And Mortality Associated With Cytoreductive Surgery And Heated Intraoperative Intraperitoneal Chemotherapy For Peritoneal Carcinomatosis" by Pierre Jacquet and colleagues is presented.

Cytoreductive surgery (CRS) with hyperthermic perioperative chemotherapy (HIPEC) has become a treatment option for selected patients with peritoneal metastases (PMs) from gastrointestinal malignancies. The purpose of this study is to evaluate our most recent data regarding pulmonary complications (respiratory distress, pleural effusion, and pneumonia) and attempt to identify risk factors associated with this management plan. This study includes the most recent 4-year experience with appendiceal and colorectal carcinomatosis patients treated in a uniform manner between January 1, 2006 and December 31, 2009. A prospective morbidity and mortality database was maintained and pulmonary adverse events were analyzed with special attention to subphrenic peritonectomy. There were 147 consecutive patients with a mean age of 49.9 years. Fourteen patients (10%) presented grades I-IV pulmonary complications for a total of 26 events. The peritonectomy of right upper quadrant was performed in 74% and right plus left in 49% of the patients. Statistically, there were no more pulmonary complications among patients submitted to peritoneal stripping of right or right and left hemidiaphragm as compared to no subdiaphragmatic peritonectomy (P = 1.00 and P = 0.58, resp.). In an analysis of 18 quantitative indicators and clinical variables with pulmonary adverse events, only blood replacement greater than six units showed a significant correlation (P = 0.0062). Pulmonary adverse events were observed in 10% of patients having CRS and HIPEC. Subphrenic peritonectomy was not a specific risk factor for developing these adverse events. [ABSTRACT FROM AUTHOR]

Background: The incidence of cancer during pregnancy is approximately 1 in 1000. The most common types encountered during pregnancy are cervical, breast and ovarian. Epithelial tumors of the appendix on the other hand are rare and account for only approximately 1% of all colorectal neoplasms; the occurrence of this neoplasm during pregnancy is extremely rare. Case Presentation: The medical history of a 30 year old woman diagnosed at 17 weeks gestation with an appendiceal mucinous tumor with large volume pseudomyxoma peritonei was presented. Her pregnancy was preserved and she had an early vaginal delivery of a healthy baby at 35 weeks. At 2 1/2 weeks postpartum the patient underwent extensive cytoreductive surgery and intraperitoneal chemotherapy. She remains disease-free 5 years after her initial diagnosis. A literature review of this clinical situation and a discussion of treatment plans were presented. Conclusion: The management of an appendiceal tumor with pseudomyxoma peritonei diagnosed during pregnancy requires full knowledge of the natural history of this disease to achieve a balance of concern for maternal survival and fetal health. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: Diethylhexylphthalate (DEHP) is a lipid-soluble plasticizer commonly used in the manufacture of polyvinyl chloride-(PVC-) based plastics. Previous studies have documented the leaching of DEHP from PVC-based containers and extension sets during the IV administration of paclitaxel. Design: Study of the leaching of DEHP from infusion bags and peritoneal dialysis solution transfer sets and clinical study of DEHP was proposed. Setting: The experiments were performed in a laboratory with plastic ware normally used for intraperitoneal chemotherapy delivery. Sample: Samples were taken from fluids that had been in contact with the plastic ware. Also, blood, peritoneal fluid, and urine were collected from a patient. Methods: In a controlled laboratory environment, the authors used an established high-performance liquid chromatography assay to determine the rate and extent of DEHP leaching from infusion bags and in the solution transfer set used for early postoperative intraperitoneal chemotherapy (EPIC) administration of paclitaxel. Paclitaxel was tested at a concentration of 40 mg/L to simulate the median dose used for EPIC. In a single patient receiving 34 mg paclitaxel in 1 liter of 1.5% dextrose peritoneal dialysis solution (Dianeal ®), the presence and concentration of DEHP in samples of peritoneal fluid and urine were determined during the first 24-hour EPIC administration. Main Research Variables: DEHP levels in fluids exposed to plastic ware and in the patient's blood, peritoneal fluid, and urine were determined. Findings: The in vitro studies showed that a solution of 40 mg paclitaxel dissolved in a 1 liter bag of Dianeal resulted in the extraction of approximately 26 mg DEHP over 24 hours. Approximately 2 mg DEHP was leached during the first hour and approximately 1 mg per hour over the following 23 hours. Equivalent results were obtained when 20 mg paclitaxel was dissolved in a 500 ml bag of 6% hetastarch (Hespan ®) with a leaching... [ABSTRACT FROM AUTHOR]

: BackgroundIntraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. Using a rat model we compared the pharmacokinetics and tissue absorption of docetaxel infused intraperitoneally in two isotonic carrier solutions; 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution.: Materials and methodsSixty Sprague–Dawley rats were randomized into groups according to the carrier solution administered. Rats were given a single dose of intraperitoneal docetaxel (80 mg/m2) in 0.1 ml/g body weight of each carrier solution. Each group was further randomized according to the intraperitoneal dwell period (3, 6, 12, 18, and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and the volume recorded. Blood and tissues were sampled using a standardized protocol. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high-performance liquid chromatography.: ResultsHetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volumes remaining in the peritoneal cavity were significantly higher with hetastarch at 6 h (P = 0.022) and 12 h (P = 0.0012). Plasma docetaxel concentrations were similar for both carrier solutions. The mean total amount of docetaxel remaining in the peritoneal cavity was significantly greater with hetastarch at 3 h (P = 0.0022), 6 h (P = 0.0043), and 12 h (P = 0.0023). There was a 39% increase in the area under the curve ratio of peritoneal fluid to plasma docetaxel concentrations with hetastarch (227) versus peritoneal dialysis solution (163). Docetaxel concentrations were significantly greater with hetastarch in colonic tissue at 18 and 24 h, and in gastric tissue at 6, 12, and 18 h.: ConclusionThe use of intraperitoneal docetaxel with a hetastarch carrier solution provides a pharmacologic advantage for a local-regional killing of residual intraperitoneal tumor cells without increasing systemic toxicity. [Copyright &y& Elsevier]

Granulosa cell tumors of the ovary (GCT) are the most common type of sex cord stromal tumors. Although most of patients are diagnosed at early stage and has favorable 5‐year overall survival rate, 16–23% of GCT ultimately develop recurrent disease. Recurrences are characterized by disseminated peritoneal metastasis. The treatment options include systemic chemotherapy, secondary CRS or palliative localized radiation therapy have not yet standardized due to the rarity of disease. Aggressive CRS followed up by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefit in other peritoneal disease but limited data available for recurrent GCT. We have a case of recurrent Adult‐type GCT (AGCT) who was treated with CRS followed by HIPEC with mitomycin C and doxorubicin. The patient has no evidence of recurrence for approximately 11 years. An electronic search of the PubMed database with the following search terms: GCT, HIPEC showed that there were total 21 patients with recurrent GCT treated in seven different studies and 13 of 21 (61.9%) patients had no evidence of disease during follow‐up ranging from 6 to 100 months. Three patients (14.2%) died of the disease. Six studies used cisplatin for HIPEC. At least 76.2% (16 of 21, data not available for five patients) had complete cytoreduction with total 16 cases of perioperative complications but no perioperative mortality was observed. Although further investigation is needed, we propose that CRS and HIPEC can be an effective therapeutic option for recurrent GCT at experienced institutions. [ABSTRACT FROM AUTHOR]

Background: With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy. Patients and methods: This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study. Results: In the period 1995-2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26-74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI >20 (p = 0.014). Conclusions: In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors. [ABSTRACT FROM AUTHOR]

Aim:The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from peritoneal metastases (PM) from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma. Patients and methods:A questionnaire concerning patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for PM arising from unusual cancer sites of origin was sent to all centres, which routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network. Results:Between September 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centres worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n = 224), sarcoma (n = 189) and neuroendocrine tumours (n = 127). The median PCI was 12 [0–39]. Grade III–IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively. After a median follow-up of 46 months, median overall survival (OS) was 39 months [33.18–44.05]. Five-year OS rate was 38.7%. For the three main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumours (39.9%), and from sarcoma (29.3%) (p < 0.0001). Conclusions:CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin, especially from rare ovarian carcinomas, PM from neuroendocrine tumours. The respective roles of CRS and HIPEC remain unclear and should be evaluated. [ABSTRACT FROM AUTHOR]

Purpose:There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM. Materials and methods:The published clinical trials on CRS + HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised. Results:The natural course of GC PM is <5 months. CRS + HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS + HIPEC groupvs.5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS + HIPEC groupvs.7.9 months in the CRS alone group. In cohort studies, the median OS after CRS + HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS + HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS + HIPEC. Conclusions:The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs). [ABSTRACT FROM AUTHOR]

In this article, the authors discuss various articles on pharmacokinetics during intrapertieoneal chemotherapy published in this issue of the periodical.

Background and Objectives. Systemic chemotherapy administered prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mucinous adenocarcinoma of appendiceal origin (PMCA) is associated with a significant rate of histological response. The impact of preoperative systemic chemotherapy (PSC) on intraperitoneal tumor burden, completeness of cytoreduction, and perioperative complications is unknown. Methods. We analyzed prospectively collected data from our HIPEC database. Thirty-four patients with PMCA were prospectively recruited and treated with PSC. Perioperative variables and survival in this group of patients were compared against 24 patients with PMCA who did not receive PSC. Results. Ten of 34 patients (29%) receiving PSC had a complete or near complete histological response. Patients receiving PSC had a lower peritoneal carcinomatosis index, required fewer peritonectomies and visceral resections, and achieved complete cytoreduction more frequently compared to patients with no preoperative chemotherapy. The incidence of perioperative complications and survival were not significantly different between the two groups. However, patients with complete histological response had better overall survival compared to patients without complete response. Conclusions. Preoperative systemic chemotherapy in appendix-originated PMCA is associated with a significant rate of histological response which may reduce the tumor burden, facilitate less aggressive and more complete CRS, and improve short-term survival in patients with a significant histological response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, no tumor-node-metastasis (TNM) staging system exists for patients with diffuse malignant peritoneal mesothelioma (DMPM). The primary objective was to formulate a clinicopathological staging system through the identification of significant prognostic parameters. METHODS: Eight international institutions with prospectively collected data on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy contributed to the registry. Two hundred ninety-four patients had complete clinicopathological data and formed the basis of this staging project. RESULTS: Peritoneal cancer index (PCI) was categorized into T1 (PCI 1-10), T2 (PCI 11-20), T3 (PCI 21-30), and T4 (PCI 30-39). Twenty-two patients had positive lymph nodes (N1) and 12 patients had extra-abdominal metastases (M1). The survival for patients with T1 (PCI 1-10) N0 M0 was significantly superior to the other patients. This group of patients is therefore designated as Stage I. The survival of patients with T2 (PCI 11-20) and T3 (PCI 21-30), in absence of N1 or M1 disease, was similar. This group of patients was categorized as Stage II. The survival of patients with T4 (PCI 30-39), N1, and/or M1 was similarly poor. This group of patients was therefore categorized as Stage III. Three prognostic factors were independently associated with survival in the multivariate analysis: histological subtype, completeness of cytoreduction, and the proposed TNM staging. The 5-year survival associated with Stage I, II, and III disease was 87%, 53%, and 29%, respectively. CONCLUSIONS: The proposed TNM staging system resulted in significant stratification of survival by stage when applied to the current multi-institutional registry data. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on diagnosis and management of ASBO. Initial conservative management is usually safe, however proper timing for discontinuing non operative treatment is still controversial. Open surgery or laparoscopy are used without standardized indications. Methods: A panel of 13 international experts with interest and background in ASBO and peritoneal diseases, participated in a consensus conference during the 1st International Congress of the World Society of Emergency Surgery and 9th Peritoneum and Surgery Society meeting, in Bologna, July 1-3, 2010, for developing evidencebased recommendations for diagnosis and management of ASBO. Whenever was a lack of high-level evidence, the working group formulated guidelines by obtaining consensus. Recommendations: In absence of signs of strangulation and history of persistent vomiting or combined CT scan signs (free fluid, mesenteric oedema, small bowel faeces sign, devascularized bowel) patients with partial ASBO can be managed safely with NOM and tube decompression (either with long or NG) should be attempted. These patients are good candidates for Water Soluble Contrast Medium (WSCM) with both diagnostic and therapeutic purposes. The appearance of water-soluble contrast in the colon on X-ray within 24 hours from administration predicts resolution. WSCM may be administered either orally or via NGT (50-150 ml) both immediately at admission or after an initial attempt of conservative treatment of 48 hours. The use of WSCM for ASBO is safe and reduces need for surgery, time to resolution and hospital stay. NOM, in absence of signs of strangulation or peritonitis, can be prolonged up to 72 hours. After 72 hours of NOM without resolution surgery is recommended. Patients treated non-operatively have shorter hospital stay, but higher recurrence rate and shorter time to readmission, although the risk of new surgically treated episodes of ASBO is unchanged. Risk factors for recurrences are age <40 years and matted adhesions. WSCM does not affect recurrence rates or recurrences needing surgery when compared to traditional conservative treatment. Open surgery is the preferred method for surgical treatment of strangulating ASBO as well as after failed conservative management. In selected patients and with appropriate skills, laparoscopic approach can be attempted using open access technique. Access in the left upper quadrant should be safe. Laparoscopic adhesiolysis should be attempted preferably in case of first episode of SBO and/or anticipated single band. A low threshold for open conversion should be maintained. Peritoneal adhesions should be prevented. Hyaluronic acid-carboxycellulose membrane and icodextrin can reduce incidence of adhesions. Icodextrin may reduce the risk of re-obstruction. HA cannot reduce need of surgery. [ABSTRACT FROM AUTHOR]