Surgical oncology in patients aged 80 years and older is associated with increased postoperative morbidity and mortality: A systematic review and meta-analysis of literature over 25 years.

BACKGROUND: The study aim is to analyze the evolution over the last 25 years of the results reported after abdominal oncological surgery in patients aged 80 years of age and older. The primary endpoint was morbidity and mortality in this group of patients; the secondary endpoint was overall survival. METHODS: A systematic search strategy was used to browse through Medline/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials using a combination of standardized index terms. Studies published between 1997 and 2017 were selected. Only those studies that showed morbidity and mortality after digestive and hepatobiliary tract oncological surgery in individuals aged 80 years and older were included. The PROSPERO registration number is CRD42018087921. PRISMA and MOOSE guidelines were applied. RESULTS: A total of 79 studies were included, categorized by origin of malignancy: esophageal (7), stomach (26), liver (4), pancreas (19), and colorectal (23). Compared with the non-elderly group, the elderly group had similar esophageal morbidity with higher mortality (RR 2.51, 1.50 to 4.21; P = 0.0005); higher gastric morbidity (RR 1.25, 1.09 to 1.43; P = 0.001), and mortality (RR 2.51, 1.81 to 3.49; P = 0.0001); similar liver morbidity and mortality; higher pancreatic morbidity (RR 1.17, 1.03 to 1.33; P = 0.02) and mortality (RR 2.37, 1.86 to 3.03; P < 0.00001); and similar colorectal morbidity with higher mortality (RR 4.44, 1.91 to 10.32; P = 0.005). CONCLUSION: Oncological surgery of most abdominal visceral tumors is associated with increased morbidity and mortality in patients older than 80 years.

Psoas Muscle Index Does Not Predict Post-Transplant Outcomes: A Series of 57 Liver Transplant Recipients.

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function. Our aim is to evaluate the degree of sarcopenia by measuring the patients on the waiting list for liver transplantation and its influence on the different post-liver transplant outcomes in our group. METHODS: The psoas muscle index (PMI, cm2/m2) was calculated (right psoas muscle area [cm2]/the square of the body height [m2]) in 57 patients on the waiting list for liver transplantation in our center, and the post-transplant variables relevant to our study were collected. RESULTS: The 57 recipients had a mean age of 57 years (range, 35-73) and had a mean of 7.4 months (range, 0-39) on the liver transplant waiting list. The mean psoas muscle index was 2.39 (range, 1-4), and the mean body mass index was 28.01kg/m2 (range, 22-36). After multivariate analysis we found a positive correlation between the PMI and the body mass index of the recipients (r = 0.320, P = .017), intensive care unit length of stay, and donor age (r = 0.319, P = .042), and between cold ischemia time and graft survival (r = 0.366, P = .009). We found no correlation in our sample between PMI and post-liver transplant complications either in terms of graft or patient survival. CONCLUSION: PMI is not representative of total muscle mass and sarcopenia and is not effective in adequately predicting the survival of patients on the waiting list for liver transplantation.

Survival outcomes in patients aged 75 years and over with peritoneal colorectal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): multicenter study of the Spanish Group of Peritoneal Cancer Surgery (GECOP).

BACKGROUND: The attitude toward cytoreductive surgery with HIPEC in peritoneal carcinomatosis from colorectal cancer is unclear. The aim of this study is to report the perioperative outcomes after cytoreductive surgery with HIPEC in patients ≥ 75 years. METHODS: This retrospective multicenter study collected the data the Spanish Group of Peritoneal Cancer Surgery. Thirty-six patients with peritoneal carcinomatosis from colorectal cancer met the selection criteria for the study. Morbidity, mortality, disease-free and overall survival were analyzed. RESULTS: Morbidity (grade III-IV) was 17% and 2 patients died of complications related to the procedure (5.4%). Median disease-free survival (DFS) was 16 months. DFS at 1 and 3 years was 81% and 42%, respectively. Overall survival at 1 and 3 years was 96% and 75%. In the univariate analysis, preoperative comorbidities (p = 0.01), liver metastases (p = 0.02), blood transfusion (p = 0.001) and postoperative complications (p = 0.001); and in the multivariate analysis, perioperative blood transfusion (OR 2.56, 95% CI 1.95-6.24, p = 0.03) and postoperative complications (OR 3.25, 95% CI 2.35-7.56, p = 0.02) were associated with a lower overall survival. CONCLUSIONS: Age is not an absolute contraindication to perform cytoreduction surgery with HIPEC in highly selected elderly patients with colorectal peritoneal carcinomatosis.

Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model.

BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model. METHODS: After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals' peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically. RESULTS: Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups). CONCLUSION: Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

Molecular Adsorbent Recirculating System Treatment Can Reduce Blood Levels of N-Acetylcysteine in Patients With Acetaminophen Overdose: Case Reports.

BACKGROUND: Acetaminophen poisoning continues to be a major cause of liver failure that can lead to liver transplantation. N-acetylcysteine (NAC) is the cornerstone of treatment. Some authors use a Molecular Adsorbent Recirculating System (MARS) system in acetaminophen poisoning. It is reported that the MARS system eliminates acetaminophen more efficiently than conventional dialysis. It is theoretically possible that treatment with MARS administered after NAC will increase the effectiveness of treatment. CASE REPORTS: The first patient, a woman of 14 years old, presented blood levels of 112 mg/dL 12 hours after ingestion of 15 g of acetaminophen. Treatment with NAC was initiated. At 17 and 23 hours after ingestion, blood levels were 23.5 µg/mL and 5.9 µg/mL, respectively. The second patient, a woman of 28 years old, presented blood levels of 115 mg/dL 4 hours after ingestion of 40 g of acetaminophen. Treatment with NAC was initiated. At 14 and 23 hours after ingestion, blood levels were 15.8 µg/mL and <2 µg/mL, respectively. In both patients, we performed MARS after completing treatment with NAC, and after the first session, blood levels were below the lower limit of detection (≤2 µg/mL). DISCUSSION: The correct timing of MARS to avoid interactions with the administered dose of NAC in acetaminophen overdose is essential so as to not impair the effectiveness of this treatment. These considerations in the management of this entity help in the resolution of liver failure, thus avoiding the need for a liver transplant.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies.

BACKGROUND: The aim of this study was to analyze the results short term perioperative of patients with peritoneal surface malignancies undergoing cytoreduction with peritonectomy and HIPEC under a controlled fast track protocol and evaluate the factors related to the failure of implementation of the protocol. PATIENTS AND METHOD: We prospectively analyzed a consecutive series of patients (N = 156) with peritoneal surface malignancies treated by cytoreductive surgery with peritonectomy procedures and HIPEC from September 2008 until December 2014, in whom a fast track protocol was implemented. We limited the protocol to patients who had optimal cytoreduction, HIPEC administration, and not more than one digestive anastomosis. All patients signed informed consent for surgery and the perioperative multimodal recovery program. RESULTS: A total of 156 consecutive patients, with a median age of 57 years were included in the study. Median PCI was 8 (IQR: 0-32). Morbidity rate (Clavien-Dindo) was 25.6%, with a major morbidity rate (Clavien-Dindo III-IV) of 11.5%. One hundred and three patients (66%) completed the protocol. Multivariate analysis identified the following independent factors, which were related to failure of the protocol: age over 57 years (OR = 3.159, 95% CI: 1.286-7.758, p < 0.05), the realization of a digestive anastomosis (OR = 3.834, 95% CI: 1.562-9.414, p < 0.005) and occurrence of postoperative complications (OR = 18.704, 95% CI: 6.888-50.790, p < 0.001) CONCLUSIONS: Our data support the idea that in selected patients undergoing cytoreductive surgery and HIPEC, with a low PCI and especially no necessity to perform a digestive anastomosis, the implementation of a fast track program is feasible.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in elderly patients. A systematic literature review.

The objective of this review was to evaluate morbidity, mortality and survival outcomes of elderly patients with peritoneal carcinomatosis. A systematic literature search and standardized data collection of primary research publications until June 2016 on morbidity, mortality and survival outcomes in adults aged 65 and older with peritoneal carcinomatosis treated with cytoreduction and HIPEC was performed, using PubMed, EMBASE, Scopus, ClinicalTrials.gov and Cochrane. Bibliographies of relevant reports were also hand-searched to identify all potentially eligible studies. Nine studies were included. Severe morbidity of all elderly patients ranges from 17% to 56% in centers with high experience. In-hospital and 30-day mortality ranges from 0% to 8%. In only two studies were the differences in morbidity and mortality statistically significant related to the control group. However, older adults undergoing cytoreductive surgery and HIPEC consistently had lower survival rates across all study settings and procedure types than younger individuals. In studies that stratified for elderly patients, PCI, completeness of cytoreduction, tumor histology and albumin levels were predictive factors of survival. None of these studies examined quality of life, which precludes including functional outcomes in this review. Differences in exposures, outcomes, and data presented in the studies did not allow for quantification of association using a meta analysis.

Use of (18)F-FDG PET/CT in the preoperative evaluation of patients diagnosed with peritoneal carcinomatosis of ovarian origin, candidates to cytoreduction and hipec. A pending issue.

PURPOSE: To evaluate the clinical usefulness of the results obtained with (18)F-FDG PET/CT in relation to CT in the preoperative staging of patients with peritoneal carcinomatosis secondary to primary or recurrent ovarian cancer candidates to cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). MATERIAL AND METHODS: A retrospective study comparing the results obtained with CT and (18)F-FDG PET/CT in the preoperative evaluation of a series of 59 patients was performed. In all patients the peritoneal carcinomatosis index (PCI) was determined by preoperative radiological CT and 18F-FDG PET/CT and compared with surgical PCI, which was considered as reference. RESULTS: Of the 59 patients studied, in 55 peritoneal carcinomatosis presences were confirmed (4 patients had complete responses to neoadjuvant chemotherapy). The mean surgical, CT and 18F-FDG PET/CT PCI was 9.46±7.70, 3.69±3.96 and 2.25±1.02, respectively. In the global disease detection, CT showed a higher positive likelihood ratio (LR+) than (18)F-FDG PET/CT (15.3, 95% CI 8.35-28.04 vs. 3.47, 95% CI 3.36-5.11) and a lower negative likelihood ratio (LR-) than 18F-FDG PET/CT (0.67, 95% CI 0.61-0.73 vs. 0.82, 95% CI 0.76-0.88). In every region of the abdomen the CT showed a greater LR+ than 18F-FDG PET/CT and a lower LR- than 18F-FDG PET/CT. CONCLUSIONS: CT showed the best diagnostic results compared to (18)F-FDG PET/CT to confirme the presence of peritoneal disease. The lower performance of the (18)F-FDG PET/CT suggests that the main utility of (18)F-FDG PET/CT is to evaluate a possible metastatic extraperitoneal spread of the disease.

Hyperthermic intraperitoneal chemotherapy with paclitaxel or cisplatin in patients with stage III-C/IV ovarian cancer. Is there any difference?

OBJETIVE: To compare the results of the administration of HIPEC with Paclitaxel or Cisplatin after cytoreduction in patients with stage IIIC-IV ovarian cancer, especially focused on disease-free survival. PATIENTS: We retrospectively analyzed a consecutive series of patients operated after being diagnosed with stage III-C/IV serous epithelial ovarian carcinoma. Patients included in the study were treated between January 2008 and March 2015. After cytoreduction, Paclitaxel (doses of 60 mg/m(2)O or Cisplatin (doses of 75 mg/m(2)) were used. RESULTS: A total of 111 patients were included. Median age was 61 years. In 60 of them (54%) Paclitaxel was used during HIPEC treatment and 51 patients (46%) were treated with Cisplatin. PCI was similar between groups (PCI = 11 in both cases). Median follow up was 34 months (12-96 months). The median disease free survival in Paclitaxel Group was 27 months and 33 months in Cisplatin Group (p = 0.551). In patients treated with Paclitaxel disease free survival rates at 1, 2, and 3 years were 79%, 60% and 46%. In patients treated with Cisplatin disease free survival at 1, 2, and 3 years were 64%, 50% and 40% respectively. After a multivariate analysis, incomplete cytoreduction (HR: 6.54, 95% CI 2.98-10.17, p < 0.01) and PCI >11 (HR: 2.15, 95% CI 1.42-6.68, p < 0.05) were identified as independent factors associated with a reduced disease-free survival. Cystotatic used was not relevant regarding disease free survival analysis. CONCLUSION: HIPEC with paclitaxel or cisplatin after cytoreduction in patients with ovarian cancer IIIC-IV has not shown different results in disease-free survival outcomes.

Morbidity and mortality outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients aged 75 years and over: Spanish group of peritoneal cancer surgery (GECOP) multicenter study.

BACKGROUND: The aim of this study is to report the perioperative outcomes of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in patients ≥75 years from a Spanish multi-institutional experience. METHODS: This multi-institutional retrospectively analyzed a prospectively collected clinical data from 10 Spanish hospitals that are part of the Spanish Group Peritoneal Cancer Surgery (GECOP). We assessed postoperative morbidity rates and performed univariate and multivariate analyses of factors associated with overall (grade I-IV) and major (grade III-IV) postoperative morbidity. RESULTS: A total of 85 patients aged ≥75 years were included. Forty six postoperative adverse events were detected in 37 patients (43.5%). Twenty five complications in 20 patients (23.5%) were mild (grade I-II) and 16 complications in 12 patients (14.1%) were moderate-severe (grade III-IV). Five patients died in the first 90 days after the procedure (5.9%). After multivariate analysis, independent factors associated with postoperative complications were: PCI> 12 (OR: 4.14, 95% CI 1.22-14.12, p = 0.043) and the need for perioperative blood transfusion (OR: 14.91, 95% CI 3.87-57.46, p < 0.001). Regarding grade III-IV complications, after multivariate analysis, the presence of preoperative albumin levels <3.5 mgr/dl (OR: 9.15, 95% CI 1.38-60.57, p = 0.017), need for diaphragmatic peritonectomy procedures (OR: 11.32, 95% CI 1.40-91.32, p = 0.023) and perioperative blood transfusion (OR: 8.58, 95% CI 1.44-51.16, p = 0.018) were independent factors. CONCLUSIONS: Cytoreductive surgery and performing HIPEC by experienced groups in selected patients aged ≥75 years can be performed with morbidity and mortality similar to that described in the literature.

Clinical Significance of Contamination of the Preservation Solution in Liver Transplantation.

INTRODUCTION: The aim of the present study was to describe the incidence and microbiological profiles of positive cultures obtained from preservation solution (PS) and correlate these findings with infectious complications detected in the liver transplant (LT) recipient. PATIENTS: We conducted a single-center, retrospective study between December 2010 and August 2014 among 178 LT. In all grafts, a PS culture was carried out. All the infections in the receipt until hospital discharge were collected. In patients with >1, infection was considered the most severe according to Clavien-Dindo classification. RESULTS: PS culture was positive for bacterial or fungal agents in 79 of 178 LT recipients (44%). The most commonly cultured organisms were coagulase-negative staphylococci (64%), Enterobacteriaceae (17%), and Staphylococcus aureus (4.7%). In the 79 patients with positive PS, 49 blood cultures were requested in the period after LT. Twenty-five postoperative infections (31.7%) were diagnosed. Only 4 of 79 patients (5%) with PS contamination had a postoperative infections related with isolated microorganism. CONCLUSIONS: Contamination of PS appears in a high percentage of liver grafts before LT, although there is a poor correlation with postoperative infections in LT recipient. In these patients, a standardized process including fungal and bacterial cultures could be useful.