Outcome of management of pseudomyxoma peritonei national cancer institute

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Outcome of management of pseudomyxoma peritonei national cancer institute
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   J Cancer Sci Clin Ther 2018; 2 (1): 025-037  DOI: 10.26502/jcsct.0006 Journal of Cancer Science and Clinical Therapeutics 25 Research Article Outcome of Management of Pseudomyxoma Peritonei: National Cancer Institute Gad Z 1* , Nassar O 1 , Soliman H 1 , Mohamed S 2  and Mohamed M 3   1 Surgical Oncology Derpartment, National Cancer Institute, Cairo University, Giza, Egypt 2 Medical Oncology Derpartment, National Cancer Institute, Cairo University, Giza, Egypt 3 Ain Shams University, Cairo, Egypt * Corresponding Author:  Dr. Zeiad Samir Gad, Surgical Oncology Derpartment, National Cancer Institute, Cairo University, Giza, Egypt, Tel: 002023635083; E-mail: raniamounir@kasralainy.edu.eg  Received:  14 February 2018; Accepted:  26 February 2018; Published:  28 February 2018 Abstract Background:  The current treatment for pseudomyxoma peritonei (PMP) consists of radical cytoreductive surgery (CRS) followed by hyperthermic intra-peritoneal chemotherapy (HIPEC). Aim:  To assess PMP patients regarding the clinical and pathological characteristics, the treatment including surgery (CRS) and chemotherapy either HIPEC type or post-operative systemic chemotherapy aiming to evaluate end results regarding recurrence and survival. Patients and Methods:  This retrospective study included 39 patients with PMP who were diagnosed, treated and followed-up from 2009-2014 at National Cancer Institute, Cairo, Egypt. Results:  High grade mucinous adenocarcinoma was found in 23.1% of patients. Patients with low grade tumor showed higher survival rate compared with patients with high grade disease. The mean operative PCI score all patients who were explored was 15.81. Our study reported success to achieve complete cytoreduction that was combined with HIPEC in 44% of patients who were planned for this modality. Treatment related postoperative grade (3-5) complications mainly surgery related developed in 17.3 of patients. Operative mortality was 22.2%. The follow up period in our study was quite short (mean 22.9). However the overall survival at the end of the follow up in our study was 48.7%, 1 year survival was 82%, and 2 year survival was 41%. The overall survival in patients treated with CRS and HIPEC was 66.6%, with 1 year and 2 year survival of 91% and 66.6% respectively. Only 2 patients developed recurrent disease during the follow up period.   J Cancer Sci Clin Ther 2018; 2 (1): 025-037  DOI: 10.26502/jcsct.0006 Journal of Cancer Science and Clinical Therapeutics 26 Conclusion:  The outcome of PMP treatment process is extremely variable. Combined CRS and HIPEC were considered the best therapeutic approach for patients with PMP. Surgical experience combined with proper patient selection have to be built up together to improve the outcome. That could only be achieved through more centralization of patients’ treatment in specialized units or center. Keywords:  Pseudomyxoma peritonei; Hyperthermic intra-peritoneal chemotherapy; Tumor; Chemotherapy 1.   Introduction Pseudomyxoma peritonei (PMP) is a rare intraperitoneal tumor, characterized by disseminated intraperitoneal tumor implants on peritoneal surfaces. The disseminated neoplastic cells produce mucin, which leads to the characteristic mucinous ascites [1]. Traditionally PMP has been treated with serial debulking procedures. This technique can provide relief for some time; however repeated debulking procedures become increasingly difficult, and lead to more complications [2].A more aggressive approach combining Cytoreductive Surgery (CRS) and Intraperitoneal Chemotherapy (IPEC) is being used. CRS is performed to remove as much macroscopic disease as possible often undertaken according to Sugarbaker’s protocol. This is combined with IPEC that targets the microscopic residual disease and free neoplastic cells in the peritoneal cavity. This chemotherapy may be heated (hyperthermic) (HIPEC), which is used intra-operatively; or this can be used either preoperatively or early postoperative [3]. Retrospective studies have shown that debulking procedures alone can provide 5- year survival rates of 55% -75%, however, around 90% of patients have disease recurrence within 2 years and will often require multiple debulking procedures [4]. Combining CRS and HIPEC can greatly improve survival with average 5 year survival rate around 76% [5]. However other studies have shown that 5 year disease free survival can range from 37.4% to 74%. This difference between studies may be a reflection of patient selection and experience of the centers than an evaluation of the treatment regimen [6]. The aim of this work was to assess patients with PMP regarding the clinical and pathological characteristics, the treatment including surgery (CRS) and chemotherapy either HIPEC type or post-operative systemic chemotherapy aiming to evaluate end results regarding recurrence and survival. 2.   Patients and Methods 2.1   Patients   This is a retrospective study that was conducted at National Cancer Institute (NCI) in Cairo, Egypt. The study included patients with PMP who were diagnosed (radiologically and pathologically), treated and followed up in the period from 2009 to 2014.   J Cancer Sci Clin Ther 2018; 2 (1): 025-037  DOI: 10.26502/jcsct.0006 Journal of Cancer Science and Clinical Therapeutics 27 2.2 Methods Histologically proven PMP were identified at the Histopathology department database. Patients’ files were retrieved from the Biostatistics department. Data were extracted from the medical records, and selected variables were collected including; Demographic characteristics included age and gender, patient medical history regarding diabetes mellitus and hypertension, history and number of previous surgeries that were related to PMP diagnosis and management, time between disease diagnosis and definitive surgery, number and types of lines of preoperative and  postoperative systemic chemotherapy, and patients’ response, pathological features of the disease including type, grade, margins and lymph nodes involvement, preoperative evaluation including laboratory, radiological investigations including CT scan for the chest and abdomen, MRI, and PET CT if available, to estimate the preoperative PCI and metastasis, presence of extra-peritoneal metastasis, Operative data (operative PCI score, whether complete or incomplete cytoreduction was done, data about hyperthermic intra peritoneal chemotherapy and type of chemotherapy, intraoperative morbidity, operative mortality), post-operative data (ICU admission and duration of ICU admission, hospital stay was calculated starting from date of operation till date of discharge, follow up data including disease progression and recurrence), survival data (event free survival was calculated from date of surgery till date of recurrence, progression or date of last follow up, overall survival was calculated from date of diagnosis of the primary cancer till date of death or date of last follow up if not died). Date of diagnosis was determined by the date of the operation or by the date of the first pathology report if biopsy was taken. Histopathology of the tumor was classified according to the WHO classification, to low grade mucinous carcinoma and high grade mucinous carcinoma. Tumor markers included in the study were CA125, CA19-9 and CEA. Data about completeness of cytoreduction was not documented according the CC score, so it was estimated according to R score; where R0 means no microscopic residuals at the end of the operation, R2 means macroscopic residual, while R1 means microscopic residuals detected as positive margin. Operative complications were considered as any deviation from the ideal operative and postoperative course, while operative mortality was defined as death within one month of the operation. Progression and recurrence was diagnosed in case of marked rise of tumor markers and/or evidence of relapse in abdominal CT scan, or during laparotomy for any cause. 3.   Results This study included 39 patients with pseudomyxoma peritonei. Their mean age was 53.8 years (Table 1). Female to male ratio was about 1:1 [20 females (51%): 19 males (49%)]. Diabetic patients represented 5.6% of patients and 12.5% of patients were hypertensive. Twenty eight patients (71.7%) were diagnosed outside NCI, while 11 patients (28.2%) were diagnosed at NCI. The circumstances leading to the discovery of PMP were; open biopsy during abdominal surgery in 84.6% (n=33) of patients, core biopsy in 10.2% (n=4), laparoscopic in 2.6% (one patient), and cytology in 2.6% (one patient). These abdominal surgeries included Panhystrectomy in 11 patients (33.3%), exploration in 13 patients (39.3%), appendectomy in 4 patients (30.3%), hernioplasty in 3 patients (9.1%), during   J Cancer Sci Clin Ther 2018; 2 (1): 025-037  DOI: 10.26502/jcsct.0006 Journal of Cancer Science and Clinical Therapeutics 28 caesarian section in one patient (3%), and iliopsoas mass in one patient (3%). Twenty three patients (58.9%) were presented with abdominal or pelvic mass, 6 patients with abdominal or pelvic cysts while ascites was manifested in 66.7% of patients ranging from mild to massive. Extra-peritoneal metastasis was reported in 4 patients (10.2%) that included liver metastasis in 3 patients and one patient presented with spread along the insertion of iliopsoas muscle at the upper thigh. Descriptive Statistics Range Mean ± SD Age (years) 25-70 53.846 ± 12.014 Time between diagnosis 15-Jan 4.577 ± 3.880 and operation (months) ICU stay (days) 21-Jan 6.368 ± 5.387 Total hospital stay (days) Jan-68 11.115 ± 13.698 Follow up time (months) Jan-63 22.974 ± 15.875 Table 1:  Descriptive statistics. CEA was elevated in 15/22 patients (68.1%) in whom the test was done while CA 19-9 was measured in 19 patients and it was elevated in 9 patients (47%). CA125 was measured in 14 patients and it was elevated in 6 patients (42%). Low grade mucinous adenocarcinoma was reported in 30 patients (76.9%), while high grade mucinous adenocarcinoma in 9 patients (23.1%). In preoperative assessment, 32 patients (82%) had history of one previous surgery related to their illness, while 12% did not undergo any previous surgeries. The mean time between disease diagnosis and the operation was 4.6 months (range= 1-15). Twenty six patients (68%) were eligible and planned for combined CRS and HIPEC, and one patient for laparoscopic exploration. Only 12 patients (44.4%) underwent cytoreductive surgery and HIPEC, 6 patients were inoperable. Five patients had CRS without HIPEC; as their operations were aborted after completion of cytoreduction due to intraoperative complications or anesthetic limitations. However the operation was incomplete in 3 patients, and aborted before complete cytoreduction due to intraoperative morbidity. The mean operative PCI score was 15.8 (Range=0-31). The other 11 patients (28%) who were excluded from CRS and HIPEC were planned for follow up with or without systemic chemotherapy, or for best supportive care. One patient died before treatment. Among patients that underwent CRS with or without HIPEC, a macroscopic complete cytoreduction (R0) was reached in 13 patients (76.4%), R1 in 2 patients, and R2 in 2 patients. Bowel resection was done in 57.6% of patients who were planned for surgery. During the study period, 8 patients (20.5%) received one line of systemic chemotherapy, 5 patients (12.8%) received two lines. The response of the disease to chemotherapy was progressive in 5 patients and stationary in the other 8   J Cancer Sci Clin Ther 2018; 2 (1): 025-037  DOI: 10.26502/jcsct.0006 Journal of Cancer Science and Clinical Therapeutics 29 patients. The different lines of chemotherapy used in those patients are shown in Table 2. However three patients gave history of treatment with chemotherapy outside NCI but the lines used were not documented. Chemotherapy line Number of patients Taxol  –   Carboplatin 6 FOLFOX 2 Taxol  –   Gemzar 1 Cisplatin 1 FU - xeloda 1 Xeloda 1 Oxaloplatin  –   xeloda 2 IFL 1 Table 2:  Lines of chemotherapy used. 3.1   Morbidity and mortality Intraoperative complications encountered in 8 patients (29%), the most common was bleeding in 6 patients. Treatment related postoperative grade [3-5] complications mainly surgery related developed in 4 patients (17.3%) that consisted of leakage in 2 patients, pulmonary embolism, and reactionary hemorrhage. Operative mortality was 22.2% (n=6). Nineteen patients (70.4%) needed postoperative ICU admission with the mean ICU stay was 6.3 days (range 1-21), while the mean postoperative hospital stay was 11.1 days (range 1-68). 3.2   Outcome and survival The mean follow up period was 22.9 months (range 1-63). At the end of the follow up 19 patients were alive and 20 patients (51.3%) died, the overall survival was 48.7%, 1 year overall survival rate was 82%, and 2 year overall survival rate was 41%. The 1 and 2 years overall survival in patients treated with CRS and HIPEC were 91%, and 66.6% respectively. Two patients (16.7%) developed disease recurrence that needed reoperation with cytoreductive surgery and HIPEC. There was a significant relation between patients’ age and their final status or survival; young patients were associated with higher survival rates. In patients who underwent the operation after a period less than 6 months survival rate was 45%, 66.7% in operations within 6 -12 months, and 0% in operations done within a period more than a year. However these results were insignificant. Overall survival in patients with low grade mucinous adenocarcinoma was 56.6% compared to 22.2% in patients with high grade mucinous adenocarcinoma but the difference was of borderline significance (P=0.070). Patients with low grade tumor who underwent CRS and HIPEC showed significantly better overall survival when compared with those with high grade disease who underwent the same surgery (P=0.028). Correlating the number of elevated preoperative tumor markers and survival showed no significant relation between the number of elevated tumor markers and the overall survival. In all patients who were explored the mean operative PCI score was 15.81 (range 1-30).The mean PCI score of those patients who were alive at the end of the follow up period was 13, compared to 18 in patients who died. Although the mean PCI score was higher in patients who died at the end of follow up period, the correlation between the mean PCI score and survival or recurrence in our study was not significant (Table 3). Among patients who had any trial for CRS and HIPEC,
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