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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. 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]

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]

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]

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]

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]

Rare diseases are often associated with uninformed medical decisions and poorly executed treatments because of inexperience of the physicians. Desmoplastic small round-cell tumor is a rare disease that is a form of peritoneal surface malignancy usually affecting young males, with a mean survival of 29 months. In order to begin to build a more knowledgeable clinical pathway all 7 patients treated at the Washington Hospital Center were studied and compared to patients described in the medical literature. Clinical and pathological data, tumor distribution, cytoreductive surgery, completeness of cytoreduction and survival were recorded and analyzed. The first most common symptoms were pain, increased abdominal girth and palpable abdominal mass in our patients and in the literature review. The overall survival did not improve with cytoreductive surgery plus intraperitoneal chemotherapy (mean survival 32 months); however, 2 long-term survivors who responded to systemic chemotherapy of 55 and 101 months were recorded. The latter may be the longest survivor reported in the literature. No consistent response to chemotherapy was observed in our patients or in any literature review. Complete surgical removal of this malignancy did not correlate with survival in our patients. The absence of improved survival of our aggressively treated patients as compared to the literature was thought to be a consequence of an advanced stage of the disease. A new comprehensive approach that uses complete clearing of cancer by surgery and perioperative systemic and perioperative intraperitoneal chemotherapy as early as is possible in the natural history of the disease emerged as goals for future management. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose. To measure the clearance intraperitoneal mitomycin C and doxorubicin in patients having peritonectomy and analyze the impact of the extent of peritoneal resection on pharmacokinetics. Methods. A group of 15 patients with peritoneal carcinomatosis were submitted to cytoreductive surgery and heated intraperitoneal chemotherapy. Ten patients received mitomycin C and five, doxorubicin. Six patients underwent total parietal peritonectomy and nine had less-extensive peritonectomy. Pharmacokinetics were determined by sampling peritoneal fluid and blood. Drug concentrations over time, area under the curve ratios and the amount of drug recovered from the peritoneal cavity were calculated and compared between the groups. Results. The concentrations of mitomycin C over time in the peritoneal fluid and plasma were similar in five patients with total parietal peritonectomy as compared to five patients with less-extensive peritonectomy (P=0.5350 and 0.6991; Mann-Whitney test). Mitomycin C area under the curve ratio in total peritonectomy patients was 20.5 and 25.7 in patients with less-extensive peritonectomy. The difference in total amount of drug recovered from the peritoneal cavity was not significant (30.6±6.188% versus 22.6±3.84%, P=0.095). In the studies with doxorubicin, one patient underwent total parietal peritonectomy with similar pharmacokinetics to four patients submitted to partial peritonectomy. Conclusions. The extent of parietal peritoneal resection did not affect the pharmacokinetics of intraoperative intraperitoneal chemotherapy. The pharmacological barrier between the abdominopelvic cavity and plasma is not directly related to an intact peritoneum. [ABSTRACT FROM AUTHOR]

Simple Summary: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal metastases from colorectal cancer (CRC). However, the characteristics of long-term survivors are not well documented. This study set out to investigate the patient characteristics associated with the long-term survival of peritoneal metastases from CRC. We retrospectively analyzed 206 long-term survivors who underwent CRS for peritoneal metastases from CRC. We found that most long-term survivors showed low peritoneal cancer index (PCI), low PCI of small bowel subsets, and complete cytoreduction (CC-0), while some exhibited characteristics considered associated with poor prognosis. Background: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). Methods: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. Results: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2–7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0–2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2–2.6) years. Conclusions: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to report the pharmacokinetics of heated intraoperative intraperitoneal mitomycin C (MMC) and to analyze the impact of heat, extent of peritoneal resections, and effect of intraoperative hyperthermic chemotherapy on the pharmacological properties of the peritoneal plasma barrier. Methods: Sixty patients with peritoneal carcinomatosis were included in a phase I/II study combining cytoreductive surgery with 2 h of heated intraperitoneal mitomycin C in an intraoperative lavage technique and one cycle of early postoperative 5-fluorouracil (5-FU) given on postoperative days 1–5. Three pharmacokinetic analyses were performed: (1) pharmacokinetics of heated intraoperative intraperitoneal MMC was determined for 18 patients by sampling peritoneal fluid, plasma, and urine during the 2-h procedure; (2) impact of peritoneal resections on MMC pharmacokinetics was assessed by comparing a group of patients who underwent ≤1 peritonectomy procedure (minimal surgery) to a group of patients who underwent ≥2 peritonectomy procedures (extensive surgery), and (3) effects of heated intraoperative intraperitoneal chemotherapy on the pharmacokinetics of early postoperative intraperitoneal 5-FU by comparing a group of patients treated with heated intraoperative intraperitoneal MMC to a control group who did not receive heated intraoperative intraperitoneal chemotherapy. Results: The mean dose of heated intraoperative intraperitoneal MMC per patient was 22.5 ± 7.1 mg (12.9 ± 3.8 mg/m[sup 2] ). Drug absorption from perfusate was 14.3 ± 2.7 mg. The mean aeras under the curve (AUC) for perfusate and plasma were, respectively, 340 ± 138 and 15 ± 4 µg/ml × min. The mean AUC peritoneal fluid/plasma ratio was 23.5 ± 5.8. Patients who underwent extensive peritoneal resections exhibited a significantly (p = 0.037; Wilcoxon rank test) increased peak plasma concentration of MMC, a significantly (p = 0.029) increased AUC of plasma concentrations and a significantly (p = 0.034) decreased peritoneal fluid/plasma AUC ratio. Pharmacokinetic studies of early postoperative intraperitoneal 5-FU showed no significant difference in plasma AUC, perfusate AUC and AUC ratio between patients who received and those who did not receive heated intraoperative intraperitoneal MMC. Conclusions: Heated intraoperative intraperitoneal chemotherapy achieves high peritoneal concentrations of MMC with limited systemic absorption. Systemic drug absorption during heated intraoperative intraperitoneal chemotherapy is increased when extensive peritoneal resections are performed, but such slight increases are unlikely to change the risk of systemic drug toxicities. Heated intraoperative intraperitoneal chemotherapy does not alter the pharmacokinetics of early postoperative intraperitoneal 5-FU. [ABSTRACT FROM AUTHOR]