Synchronous Peritoneal Research Articles

Palliative surgery for Krukenberg tumors - 12-year experience and review of the literature.

AIMTo determine the clinical characteristics of patients undergoing palliative surgery for Krukenberg tumors, including disease presentation, outcomes, and prognostic factors.METHODSThis was a retrospective clinical study of all patients who underwent palliative surgery for Krukenberg tumors between January 2004 and December 2015. Patient information was obtained from inpatient and outpatient case notes as well as the hospital electronic records. Patients who underwent potentially curative resection, and patients with Krukenberg tumors who did not undergo surgery were also excluded from the study. Palliative surgery was defined as those performed for either alleviation of symptoms or for asymptomatic patients for whom surgical removal of the tumors were deemed necessary following a multidisciplinary consensus. Tumors were diagnosed pre-operatively by computed tomography scans and all had histologic confirmation of the surgical specimens.RESULTSOver the study duration, 38 female patients underwent palliative surgery for Krukenberg tumors at our institution. Mean age was 54.2 ± 11.7 years. The colon was the most frequent primary source of metastases (n = 21) followed by the stomach (n = 4). Prophylactic palliative surgery was performed for eight (21.1%) asymptomatic patients. Median post-operative length of stay was 8 d (IQR 6-12 d). Five patients (13.2%) experienced post-operative complications, although high grade morbidity was only seen in one patient (2.6%). Median overall survival from surgery was 17 mo (95%CI: 12.1-21.9) at a median follow-up duration of 12 mo (IQR 8-17 mo). The median survival was shorter for patients who underwent emergency surgery, younger patients, those with a colorectal primary, larger tumors, or synchronous peritoneal or hepatic metastases.CONCLUSIONPalliative surgery for Krukenberg tumors can be performed safely with acceptable complication rates. Bilateral oophorectomy should be performed to prevent the risk of symptomatic contralateral tumors.

Hepatectomy increases metastatic graft and growth in an immunocompetent murine model of peritoneal metastases

BackgroundCurative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis. MethodsMurine model of colorectal PM in Balb/C mice was developed by intraperitoneal injection of different CT-26 tumour cell concentrations. Five days after the injection, mice were randomized into three groups: 68% hepatectomy group, sham laparotomy and control group without surgery. On post-operative days 1, 5 and 20, PM was evaluated macroscopically, tumour growth and liver regeneration by immunohistochemistry, and angiogenesis by immunofluorescence. Circulating progenitor cells, plasmatic cytokines and digestive arterial blood flow velocity measurements were also analysed. ResultsReproducible murine model of limited colorectal PM was obtained. Surgery induced PM increases and promoted neo-angiogenesis. Major hepatectomy influence the tumour growth in the late phase after surgery, the extent of extra-peritoneal metastasis and the increase of Ki-67 expression in the remnant liver. ConclusionsThis animal model confirms the pro-tumoural and pro-angiogenic role of surgery, laparotomy and major LR, which promotes the increase of angiogenic factors and their participation in PM growth. These results suggest that peritoneal resection should be first step in the case of two-step liver and peritoneal surgery for patients with colorectal PM and LM.

A large multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancers with microsatellite instability.

3536 Background: Deficient Mismatch Repair (dMMR) in colorectal cancers (CRC) represent 12% of all tumors. In non-metastatic CRC setting, dMMR are associated with good prognosis but also with resistance to adjuvant 5-FU chemotherapy. In metastatic CRC (mCRC) setting, dMMR is found in less than 5% and its influence on prognosis and treatment response is little known. Methods: This multicenter retrospective study included all consecutive patients with dMMR mCRC treated between 2005 and 2015 in 17 centers. The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Prognostic variables were evaluated in univariate analysis using the Log rank test and in multivariate analysis using the Cox regression model. Results: A total of 198 patients with dMMR mCRC were included (median age 64.6 years). dMMR mCRC were mostly diagnosed with synchronous metastases (59%) and frequent peritoneal carcinosis (43%). Lynch syndrome was found in 34% of cases and 36% of tumors had a BRAFV600E mutation. Median OS was 20.6 months. A low risk Kohne's prognostic index (HR = 0.40 [0.22-0.72], p = 0.02) and absence of peritoneal carcinosis (HR = 0.51 [0.29-0.90], p = 0.02) were associated with better OS in multivariate analysis. Main first-line regimens were 5FU-based (n = 20), oxaliplatin-based (n = 75) or irinotecan-based (n = 46) chemotherapy. Median PFS on first-line treatment was 5.9 months. The objective response rate (ORR) was 0%, 19% and 36% for 5FU-based, oxaliplatin-based and irinotecan-based chemotherapies, respectively (p = 0.02). A trend for a longer PFS (3.3, 5.5 and 10.2 months, respectively, p = 0.06) and OS (17.7, 21.1 and 34.2 months, respectively, p = 0.05) was also observed for irinotecan-based chemotherapy. The addition of bevacizumab to chemotherapy was associated with a significant increase of ORR (p = 0.01) and PFS (p = 0.04) as compared to the addition of an anti-EGFR therapy. Conclusions: This study suggests that dMMR mCRC are associated with poor prognosis and chemoresistance, especially to 5FU-based chemotherapy. Efficacy of irinotecan and bevacizumab should be evaluated in a prospective trial in combination with immune checkpoint inhibitors.

177P New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese Classification of Colorectal Carcinoma: A multi-institutional study.

177P New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese Classification of Colorectal Carcinoma: A multi-institutional study.

177P New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese Classification of Colorectal Carcinoma: A multi-institutional study.

177P New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese Classification of Colorectal Carcinoma: A multi-institutional study.

The role of surgery in the therapeutic approach of gastric cancer liver metastases.

Gastric cancer (GC) currently prevails as the second cause of death by malignancy worldwide. Estimations suggest that 35% of affected patients appear with synchronous distant metastases. The vast majority of patients present with hepatic metastatic disease, sometimes accompanied by synchronous peritoneal and lung dissemination. The disease mostly remains asymptomatic at an early stage, with few reported cases of incidental abdominal discomfort. As the cancer advances, symptoms such as nausea or vomiting arise, along with indigestion and dysphagia, blood loss in the form of melena or hematemesis, as well as anorexia and weight loss. Having spread to the liver, it also causes jaundice due to hepatomegaly and general inanition. Despite recent research on the therapeutic strategies against GC metastatic disease, surgical resection appears the only potentially curative approach. Unfortunately, the majority of patients are not eligible to undergo surgical intervention. With regard to treatment modalities of the advanced stage disease, the role of metastasectomy is still debatable and quite unclear, while prolonged survival was succeeded only under certain specific circumstances. Systemic chemotherapy remains however another option, as well as local management in the form of cryotherapy, radiofrequency ablation, or transcatheter arterial chemoembolization. The aims of this review were to evaluate the results of surgical treatment for metastatic GC with special reference to the extent of its histological spread and to present the recent literature in order to provide an update on the current concepts of advanced surgical management of this entity. Relevant publications in the last two decades are briefly reviewed.

Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases.

The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases. Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed. Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%. Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

New Staging System for Colorectal Cancer Patients with Synchronous Peritoneal Metastasis in Accordance with the Japanese Classification of Colorectal Carcinoma: A Multi-Institutional Study

Background: Peritoneal metastasis of colorectal cancer (CRC) is often discovered during initial surgery. The aim of this study is to propose a new staging system that could be used to help determine the management of CRC patients. Methods: We evaluated a total of 766 Stage IV CRC patients with synchronous peritoneal metastasis. According to the Japanese classification, we divided the peritoneal metastasis into P1, P2, and P3. We distinguished distant metastasis from liver metastasis and peritoneal metastasis. According to the Cox proportional hazard model, we constructed a new staging group. Results: According to a comparison of the R² statistics, the combination of liver metastasis and peritoneal metastasis was selected as the final variables. Next, we defined P1H(-) as Grade A, P2H(-) as Grade B, and other groups as Grade C. Our proposed new stage (Akaike Information Criteria [AIC] 7,338.82; concordance index [c-index] 0.644; R² 0.123) could thus divide the patients into different prognostic groups more clearly than the current Japanese classification (AIC 7,373.89; c-index 0.619; R² 0.097). Conclusion: Our proposed new staging system is very simple and easy for general surgeons to follow. This system is useful for determining the appropriate operative strategy for CRC patients with peritoneal metastasis and for estimating the patients' prognosis.

Prognoses and treatment strategies for synchronous peritoneal dissemination of colorectal carcinoma.

We devised a simple dichotomous classification system and showed sufficient reproducibility to indicate treatment strategies for peritoneal metastasis of colorectal cancer. We included 67 patients with peritoneal metastasis of colorectal cancer and classified them according to the largest lesion size, number of lesions and number of regional peritoneal metastases. The oncological data were recorded and compared. According to the univariate analyses, the prognoses were significantly better in patients with≤3 disseminated lesions than in those with≥4, and in patients with disseminated lesions in only one region than in those with≥2 lesions. A multivariate analysis showed that primary tumor resection and the presence of peritoneal metastases in only one region were favorable factors for the patient survival. Patients with disseminated lesions in only one region (localized group) and those with nonlocalized lesions had three-year survival rates of 45.6 and 12.2%, respectively. Finally, primary tumor resection improved the prognoses in both the localized and nonlocalized groups. Colorectal cancer patients were categorized into localized and nonlocalized groups according to the number of regions with peritoneal metastasis, and significant prognostic associations were demonstrated. Subsequent analyses of the oncological data suggested that primary tumor resection contributes to an improved prognosis in all patients with synchronous peritoneal metastases.

Factors affecting recurrence and prognosis after R0 resection for colorectal cancer with peritoneal metastasis

Peritoneal metastases (PM) are a well-known poor prognostic factor. The aim of this study was to investigate the factors affecting recurrence and prognosis after R0 resection for colorectal cancer with synchronous peritoneal metastases. We conducted a multi-institutional retrospective analysis of 72 patients without distant metastases who underwent R0 surgery between 1991 and 2007 for colorectal cancer with PM localized to the adjacent peritoneum. Clinicopathological variables were analyzed for their significance to recurrence and prognosis. Recurrence was found in 51 patients (70.8%) after R0 surgery. In logistic regression analyses, lymph node metastasis was shown to be an independent factor affecting recurrence. Non-intensive or no postoperative chemotherapy and eight or fewer dissected lymph nodes were identified as independent poor prognostic factors using the Cox proportional hazards model. Among patients who received postoperative chemotherapy, prognosis was significantly better in those who received intensive adjuvant chemotherapy using camptothecin-11 or oxaliplatin after R0 surgery than in those who received non-intensive chemotherapy. Among 47 patients whose recurrence date was known, 33 patients (70.2%) experienced recurrence within 18 months after R0 surgery for peritoneal metastases, and hematogenous recurrence was observed significantly more often than peritoneal recurrence. Harvesting of more than eight lymph nodes and administration of intense adjuvant chemotherapy after R0 surgery are recommended for greater prediction accuracy and improved prognosis. Intensive follow-up should be performed within 18 months after R0 surgery for colorectal cancer with synchronous peritoneal metastases.

Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database.

Peritoneal metastasis is recognized as a predictor of poor prognosis in patients with colorectal cancer, and whether surgical intervention for peritoneal metastasis has any clinical benefit has remained controversial. The purposes of this study were to identify prognostic factors in cases of unresectable colorectal cancer with synchronous peritoneal metastasis and to clarify the impacts of primary tumor resection with high tie lymph node dissection. A multi-institutional retrospective analysis was conducted of 579 patients who underwent resection of the primary tumor for unresectable colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579 patients, clinicopathological variables were analyzed for prognostic significance using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. Multivariate analysis revealed hematogenous metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent prognostic factors. In the propensity-matched cohort, patients treated with high tie lymph node dissection showed a significantly better overall survival than those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5 months; p = 0.041). It is suggested that primary tumor resection with high tie lymph node dissection favorably affects survival, even in unresectable colorectal cancer with peritoneal metastasis.

The modified Glasgow prognostic score for early mortality in patients with synchronous peritoneal carcinomatosis from colorectal cancer.

Few studies have investigated the risk factors in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) who die within 3 months of undergoing surgical intervention and systemic chemotherapy. This study aimed to identify the risk factors associated with the post-treatment 3-month mortality rate. Retrospectively collected data from Hiroshima University were analyzed for patients presenting with synchronous PC from CRC between 1992 and 2012. The clinical, histological and survival data were evaluated and correlated with the overall survival rate at 3 months after surgical intervention. In patients who underwent surgical intervention with systemic chemotherapy for synchronous PC from CRC (N = 65), a Kaplan-Meier analysis and the log-rank test revealed that systemic chemotherapy (P = 0.023) and the modified Glasgow Prognostic Score (mGPS) (P = 0.00001) were associated with the 3-month mortality rate. Multivariate analyses using these two factors revealed that the mGPS (0/1, 2) (odds ratio 8.087; 95 % CI 1.512-43.25; P = 0.015) was an independent risk factor for the 3-month mortality rate. The mGPS is an important independent predictor of the 3-month mortality rate in patients who undergo surgical intervention with systemic chemotherapy for synchronous PC from CRC. The mGPS could aid surgeons in choosing the appropriate treatment strategy and best care for patients.

Oxaliplatin and molecular-targeted drug therapies improved the overall survival in colorectal cancer patients with synchronous peritoneal carcinomatosis undergoing incomplete cytoreductive surgery.

To estimate the feasibility and limitations of incomplete cytoreductive surgery and modern systemic chemotherapy in patients with synchronous peritoneal carcinomatosis from colorectal cancer and to identify risk factors for death and factors associated with the patient prognosis. Sixty-five consecutive patients underwent surgery for synchronous peritoneal carcinomatosis from colorectal cancer at Hiroshima University, Japan between 1992 and 2012. The clinical, histological, and survival data were analyzed for independent risk factors and prognostic factors. The patients were retrospectively stratified into two groups according to the extent of surgery: complete cytoreductive surgery or incomplete cytoreductive surgery. The median survival times in the complete and incomplete cytoreductive surgery groups were 29.8 and 10.0months, respectively. Receiving systemic chemotherapy alone was an independent risk factor for death in the incomplete cytoreductive surgery group (P<0.001). Oxaliplatin and molecular-targeted drug (cetuximab or bevacizumab) therapies were also independent prognostic factors (P<0.001), whereas irinotecan therapy was not a prognostic factor (P=0.494). Oxaliplatin and molecular-targeted drug therapies improved the overall survival in patients undergoing incomplete cytoreductive surgery. Future trials for patients with synchronous peritoneal carcinomatosis from colorectal cancer should be undertaken, with patients stratified according to treatment with complete cytoreductive surgery or incomplete cytoreductive surgery with modern chemotherapy.

Enhancing the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer.

The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion. Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas.

Expression and Prognostic Significance of APE1/Ref-1 and NPM1 Proteins in High-Grade Ovarian Serous Cancer

To correlate the expression profile of human apurinic endonuclease/redox factor 1 (APE1/Ref-1) with that of nucleolar/nucleoplasmic protein nucleophosmin 1 (NPM1) in association with the aggressiveness and progression of high-grade ovarian serous cancer. Retrospective study analyzing a tissue microarray of 73 women affected by high-grade ovarian serous cancer. Protein expression was assessed by immunohistochemistry on primary tumor masses and synchronous peritoneal metastases if present. APE1/Ref-1 and NPM1 showed a significant correlation in ovarian serous cancer. Patients with a poorer outcome showed a significant overexpression of nuclear NPM1 protein. A Cox proportional hazards multivariate regression model revealed NPM1 expression to be independently significant for overall survival in high-grade ovarian serous cancers after correcting for stage, age, cytoreduction completeness, and platinum resistance. APE1/Ref-1 interacts with NPM1 to control the DNA damage repair system, and it is likely that this interaction plays a defining role in high-grade ovarian serous carcinoma. A high NPM1 immunohistochemical expression was independently correlated with a shorter survival period and thus appears to be an important prognostic factor.

Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases

The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases. Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed. Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%. Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Clinical benefit of surgery for stage IV colorectal cancer with synchronous peritoneal metastasis

Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis. We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum. Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7%, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4% had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p=0.0024) and absence of hematogenous metastases (p<0.0001) were associated with R0 resection. P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

Intraoperative radiotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Treatment of rectal cancer has markedly improved since the introduction of neoadjuvant strategies and better surgical techniques. However, treatment remains troublesome for patients with locally advanced rectal cancer (LARC) or with peritoneal carcinomatosis (PC). Patients presenting with LARC may now benefit from the integration of intra-operative radiotherapy (IORT) into multimodality treatment. Selected patients with PC now undergo cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulting in improved survival. Some patients present with locally advanced disease and synchronous peritoneal carcinomatosis and fulfill the eligibility criteria for both HIPEC and IORT, raising the question whether the combined application of both modalities within one operative procedure is feasible. This report includes five consecutive cases of rectal cancer patients presenting with LARC and synchronous PC who were treated with a multimodality treatment including IORT and HIPEC after cytoreductive surgery. Postoperative complications and survival are described. The combination of cytoreductive surgery with HIPEC and IORT appeared to be feasible and well tolerated. The observed complications did not differ from the morbidity associated with extensive pelvic surgery without HIPEC or IORT. No inhospital mortality occurred. One patient died after 11months of recurrent disease. All other patients are currently alive with one patient already surviving 38months. The current case series shows that a multimodality treatment containing IORT and HIPEC is feasible and safe with promising survival rates. This strategy may, therefore, be considered in selected rectal cancer patients presenting with both LARC and synchronous PC.

Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry

Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer. This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3). Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors. Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.

Clinical outcome of up-front surgery in patients with asymptomatic, incurable synchronous peritoneal carcinomatosis

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC. Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively. A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001). Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.