Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant. METHODS: A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease. RESULTS: Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years; p = 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years; p = 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI; p = 0.015), CC status of resection (p < 0.0001), and Ki67 (p = 0.04) as predictors of survival. Systemic chemotherapy before (p = 0.55) or after (p = 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (p = 0.03) and CC (p = 0.04) remained significant. CONCLUSIONS: Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.

Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective Italian Multicenter Observational Study of 511 Cases.

PURPOSE: The aim of this study was to help with the process of selecting patients with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at distinct clinical time points reflecting the natural history of the disease. METHODS: In a retrospective Italian multicenter study investigating patients with advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we analyzed data for consecutive patients at eight treatment time points: primary debulking surgery (PDS); interval debulking surgery after partial response, after no response, and after a pathologic complete response to neoadjuvant chemotherapy; first recurrence with a progression-free interval >12, <12 months, or >12 months in patients who underwent further chemotherapy before CRS and HIPEC; and patients who underwent two or more CRS procedures and chemotherapy lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373 procedures; 72.6% achieved complete cytoreduction, with an overall major morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS) was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS) survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer showed significant differences in OS and PFS according to the time points analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer Index, and the times when patients underwent CRS plus HIPEC as independent prognostic factors. CONCLUSIONS: This selective information on survival should help in interpreting the findings from ongoing randomized studies focusing on CRS plus HIPEC in patients with advanced ovarian cancer.

Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented. METHODS: Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2. RESULTS: Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy. CONCLUSIONS: These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.

Iterative procedures combining cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated peritoneal recurrence.

PURPOSE: The aim of this study was to analyse feasibility, morbidity and outcome of repeat complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). CRS combined with HIPEC is becoming the gold standard treatment for resectable peritoneal carcinomatosis in highly selected patients. As yet treatment of isolated peritoneal recurrence with iterative CRS and HIPEC has not been thoroughly explored. MATERIALS AND METHODS: We selected 16 patients presenting isolated peritoneal recurrence who had undergone iterative CRS and HIPEC from a dataset of 322 CRS associated with HIPEC performed between 1996 and 2012. RESULTS: Peritoneal carcinomatosis (PC) was due to colorectal and ovarian cancer, peritoneal mesothelioma and pseudomyxoma peritonei (PMP). Disease-free survival (DFS) was 13 months after the first procedure and 13.7 months after the second one. Overall morbidity rate was 43.7% (7/16) for all patients, with grade III-IV complications in three patients (18.7%). CONCLUSIONS: Iterative procedures combining cytoreductive surgery and HIPEC are feasible with acceptable morbidity and mortality rates in strictly selected patients. DFS following repeated CRS and HIPEC is comparable to that registered after the first procedure.

Radiofrequency vessel-sealing system versus the clamp-crushing technique in liver transection: results of a prospective randomized study on 100 consecutive patients.

BACKGROUND: Liver transection is considered a critical factor influencing intra-operative blood loss. A increase in the number of complex liver resections has determined a growing interest in new devices able to 'optimize' the liver transection. The aim of this randomized controlled study was to compare a radiofrequency vessel-sealing system with the 'gold-standard' clamp-crushing technique. METHODS: From January to December 2012, 100 consecutive patients undergoing a liver resection were randomized to the radiofrequency vessel-sealing system (LF1212 group; N = 50) or to the clamp-crushing technique (Kelly group, N = 50). RESULTS: Background characteristics of the two groups were similar. There were not significant differences between the two groups in terms of blood loss, transection time and transection speed. In spite of a not-significant larger transection area in the LF1212 group compared with the Kelly group (51.5 versus 39 cm(2) , P = 0.116), the overall and 'per cm(2) ' blood losses were similar whereas the transection speed was better (even if not significantly) in the LF1212 group compared with the Kelly group (1.1 cm(2) /min versus 0.8, P = 0.089). Mortality, morbidity and bile leak rates were similar in both groups. CONCLUSIONS: The radiofrequency vessel-sealing system allows a quick and safe liver transection similar to the gold-standard clamp-crushing technique.

MACC1 mRNA levels predict cancer recurrence after resection of colorectal cancer liver metastases.

OBJECTIVE: Upon colon cancer metastasis resection in liver, disease outcome is heterogeneous, ranging from indolent to very aggressive, with early recurrence. The aim of this study is to investigate the capability of metastasis associated in colon cancer 1 (MACC1) levels measured in liver metastasis specimens to predict further recurrence of the disease. METHODS: Gene expression and gene dosage of MACC1, hepatocyte growth factor (HGF), and hepatocyte growth factor receptor (MET) were assessed using quantitative realtime polymerase chain reaction on a cohort of 64 liver metastasis samples from patients with complete follow-up of 36 months and detailed clinical annotation. The most relevant mutations associated to prognosis in colorectal cancer, KRAS, and PIK3CA were assessed on the same specimens with Sanger sequencing. RESULTS: Receiver operating characteristic (ROC) analysis revealed that MACC1 mRNA abundance is a good indicator of metastatic recurrence (AUC = 0.65, P < 0.05), whereas no such results were obtained with MET and HGF, nor with gene dosage. Generation of MACC1-based risk classes was capable of successfully separating patients into poor and good prognosis subgroups [hazard ratio (HR) = 5.236, 95% confidence interval (CI) = 1.2068-22.715, P < 0.05]. Also KRAS mutation was significantly associated with higher risk of recurrence (HR = 2.07, 95% CI = 1.048-4.09, P < 0.05). Cox regression multivariate analysis supported the independence of MACC1, but not KRAS, from known prognostic clinical information (Node Size HR = 3.155, 95% CI = 1.4418-6.905, P < 0.001, Preoperative carcinoembryonic antigen HR = 2.359, 95% CI = 1.0203-5.452, P < 0.05, MACC1 HR = 7.2739, 95% CI = 1.6584-31.905, P < 0.01). CONCLUSIONS: MACC1, a new easily detectable biomarker in cancer, is an independent prognostic factor of recurrence after liver resection of colorectal cancer metastasis.

Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence.

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.

Diagnostic and Therapeutic Pathway in Diffuse Malignant Peritoneal Mesothelioma.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare form of mesothelioma that carries a very poor prognosis. The 5-year overall survival is about 20% (±5.9). Survival is optimal for patients suitable for cytoreductive surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC), with a median OS ranging from 34 to 92 months. However, selecting patients for surgery remains a complex task and requires a careful preoperative workup, rational analysis of prognostic profiles, and risk prediction models. Systemic chemotherapy could be offered: (1) in the adjuvant setting for high-risk patients; (2) for patients not eligible for CRS; and (3) for those with recurrent disease. It mainly includes the combination of Platin compound with Pemetrexed or immunotherapy. The biology of DMPM is still largely unknown. However, progress has been made on some fronts, such as telomere maintenance mechanisms, deregulation of apoptosis, tyrosine kinase pathways, and mutation of BRCA1-associated protein 1 (BAP1). Future perspectives should include translational research to improve our understanding of the disease biology to identify druggable targets. We should also clear the role of immune checkpoint inhibitors and investigate new locoregional technologies, such as pressurized intraperitoneal aerosol chemotherapy (PIPAC) or normothermic intraperitoneal chemotherapy (NIPEC).

Diagnostic and Therapeutic Pathway of Advanced Ovarian Cancer with Peritoneal Metastases.

Over two thirds of ovarian cancer patients present with advanced stage disease at the time of diagnosis. In this scenario, standard treatment includes a combination of cytoreductive surgery and carboplatinum-paclitaxel-based chemotherapy. Despite the survival advantage of patients treated with upfront cytoreductive surgery compared to women undergoing neo-adjuvant chemotherapy (NACT) and interval debulking surgery (IDS) due to high tumor load or poor performance status has been demonstrated by multiple studies, this topic is still a matter of debate. As a consequence, selecting the adequate treatment through an appropriate diagnostic pathway represents a crucial step. Aiming to assess the likelihood of leaving no residual disease at the end of surgery, the role of the CT scan as a predictor of cytoreductive outcomes has shown controversial results. Similarly, CA 125 level as an expression of tumor load demonstrated limited applicability. On the contrary, laparoscopic assessment of disease distribution through a validated scoring system was able to identify, with the highest specificity, patients undergoing suboptimal cytoreduction and therefore best suitable for NACT-IDS. Against this background, with this article, we aim to provide a comprehensive review of available evidence on the diagnostic and treatment pathways of advanced ovarian cancer.

Study Protocol: Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Metastases.

Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel laparoscopic intraperitoneal chemotherapy approach offered in selected patients affected by non-resectable peritoneal carcinomatosis. Drugs doses currently established for nebulization are very low: oxaliplatin (OXA) 120 mg/sm, cisplatin (CDDP) 10.5 mg/sm and doxorubicin (DXR) 2.1 mg/sm. A model-based approach for dose-escalation design in a single PIPAC procedure and subsequent dose escalation steps is planned. The starting dose of oxaliplatin is 100 mg/sm with a maximum estimated dose of 300 mg/sm; an escalation with overdose and under-dose control (for probability of toxicity less than 16% in case of under-dosing and probability of toxicity greater than 33% in case of overdosing) will be further applied. Cisplatin is used in association with doxorubicin: A two-dimensional dose-finding design is applied on the basis of the estimated dose limiting toxicity (DLT) at all combinations. The starting doses are 15 mg/sm for cisplatin and 3 mg/sm for doxorubicin. Safety is assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Secondary endpoints include radiological response according to Response Evaluation Criteria in Solid Tumor (version 1.1) and pharmacokinetic analyses. This phase I study can provide the scientific basis to maximize the optimal dose of cisplatin, doxorubicin and oxaliplatin applied as PIPAC.

A Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Carcinomatosis.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is an innovative laparoscopic intraperitoneal chemotherapy approach with the advantage of a deeper tissue penetration. Thus far, oxaliplatin has been administered at an arbitrary dose of 92 mg/m2, cisplatin at 7.5 mg/m2 and doxorubicin 1.5 mg/m2. This is a model-based approach phase I dose escalation study with the aim of identifying the maximum tolerable dose of the three different drugs. The starting dose of oxaliplatin was 100 mg/m2; cisplatin was used in association with doxorubicin: 15 mg/m2 and 3 mg/m2 were the respective starting doses. Safety was assessed according to Common Terminology Criteria for Adverse Events (CTCAE version 4.03). Thirteen patients were submitted to one PIPAC procedure. Seven patients were treated with cisplatin and doxorubicin and 6 patients with oxaliplatin; no dose limiting toxicities and major side effects were found. Common adverse events included postoperative abdominal pain and nausea. The maximum tolerable dose was not reached. The highest dose treated cohort (oxaliplatin 135 mg/m2; cisplatin 30 mg/m2 and doxorubicin 6 mg/m2) tolerated PIPAC well. Serological analyses revealed no trace of doxorubicin at any dose level. Serum levels of cis- and oxaliplatin reached a peak at 60-120 min after PIPAC and were still measurable in the circulation 24 h after the procedure. Cisplatin and doxorubicin may be safely used as PIPAC at a dose of 30 mg/m2 and 6 mg/m2, respectively; oxaliplatin can be used at an intraperitoneal dose of 135 mg/m2. The dosages achieved to date are the highest ever used in PIPAC.

Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience of ten years.

INTRODUCTION: Peritoneal carcinomatosis (PC) is one of the routes of dissemination of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on surgical cytoreduction of the primary tumour, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC. The rationale of this treatment, after macroscopic disease removal, is to obtain an elevated and persistent drug concentration in the peritoneal cavity, with limited systemic effects. Many studies have reported encouraging results on overall survival (OS) and the disease-free interval in patients affected by PC. PATIENTS AND METHODS: From October 1997 to November 2008, 411 operations for PC were performed in our institution; in 232 cases, cytoreduction plus HIPEC was carried out. Out of 72 operations for colonic cancer: 40 cytoreductions plus HIPEC, 12 cytoreductions+ EPIC (early postoperative intraperitoneal chemotherapy) and 16 debulking or explorative laparoscopies/laparotomies were performed. For the present study, the 40 patients who had undergone cytoreduction plus HIPEC for PC of colorectal cancer (CRC) were considered. RESULTS: The complication rate was 55% (22/40) and mortality rate 2.5% (1/40). The specific features of both groups were considered for the survival curves and complication rates, with special reference to the peritoneal carcinomatosis index (PCI; range 0, absence of disease to 39) and completeness of cytoreduction score (CCR; 0, no residual tumor, to CCR 3, residual nodules greater than 25 mm). In Group A, patients operated on prior to 2002, the median survival time was 16.7 months compared to 24.6 months for Group B, those operated on after 2002. The poor survival of Group A seemed to be related to higher PCI and CCR scores. CONCLUSION: Correct patient selection based on a maximum PCI of 16, associated with complete cytoreduction (CCR-0), produced encouraging results in our experience. To improve this encouraging survival outcome, it is very important to unify the surgical experience of expertise centres. Our results also suggest the need for an integrated approach to this condition to identify the correct aspect of the surgical domain and results that may be influencing the prognosis and the evolution of this patients.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with Oxaliplatin, Cisplatin, and Doxorubicin in Patients with Peritoneal Carcinomatosis: An Open-Label, Single-Arm, Phase II Clinical Trial.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative approach for treating peritoneal carcinomatosis that applies chemotherapeutic drugs into the peritoneal cavity as an under-pressure airflow. It improves local bioavailability of cytostatic drugs as compared to conventional intraperitoneal chemotherapy. The aim of this study is to prove feasibility, efficacy and safety of this new treatment. Patients included in the analysis underwent at least two single port PIPAC procedures; drugs used were Oxaliplatin for colorectal cancers and Cisplatin + Doxorubicin for ovarian, gastric, and primary peritoneal cancers. The primary endpoint was the Disease Control Rate according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary significant endpoints were overall and progression free survival, tumor regression on histology, and quality of life. Safety and tolerability were assessed according to the Common Terminology Criteria for Adverse Events 4. Sixty-three patients were enrolled in this trial. Forty patients (100 PIPAC) were eligible for analysis. Twenty patients were undergoing systemic chemotherapy. Fourteen patients reported an objective response (35%). Median overall survival was 18.1 months; median progression-free survival was 7.4 months. Minor morbidity was observed in seven procedures. Grade 3 complications occurred in two patients, and grade 4 in one patient submitted to reoperation. Single-port PIPAC is feasible, safe, and easy to perform. The combined treatment based on systemic chemotherapy and PIPAC does not induce significant hepatic and renal toxicity and can be considered a valid therapeutic option in patients with advanced peritoneal disease. Further studies on the use of PIPAC alone, possibly with different drug dosages, may define the real effectiveness of the procedure.

Precision oncotherapy based on liquid biopsies in multidisciplinary treatment of unresectable recurrent rectal cancer: a retrospective cohort study.

BACKGROUND: Third line innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have both been proposed for the treatment of unresectable not responsive recurrent rectal cancer (URRC). In the present study, we have compared the safety and efficacy of HPP/target therapy, using drug regimens selected by liquid biopsy precision oncotherapy, to third-line systemic therapy based on tissue specimens precision oncotherapy. METHODS: HPP/target therapy regimens were selected based on precision oncotherapy, including assays for chemosensitivity and viability, and qRT-PCR for tumor-related gene expression. In the control group, systemic third-line and further lines of therapy were defined according to clinical and biological parameters. RESULTS: From 2007 to 2019, 62 URRC patients were enrolled, comprised of 43 patients in the HPP/target-therapy group and 19 patients in the systemic therapy control group. No HPP related complications were reported and the most common adverse events were skin and bone marrow toxicity. In the HPP/target-therapy group, the ORR was 41.8% whereas in the systemic therapy control group was 15.8%. DCR of the HPP/target-therapy group was significantly improved over the systemic therapy group (P = 0.001), associated with a PFS of 8 vs 4 months (P = 0.009), and OS of 20 vs 8 months (P = 0.046). CONCLUSIONS: The present data indicate that in URCC patients, the integration of HPP/target-therapy and precision oncotherapy based upon liquid biopsy is as effective and efficacious as third-line treatment in local disease control and, therefore, deserves to be further assessed and compared to conventional systemic treatments in future prospective randomized trials.

Neither ACEIs nor ARBs are associated with respiratory distress or mortality in COVID-19 results of a prospective study on a hospital-based cohort.

Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome. Assess the effect of ACEI/ARBs on outcome in COVID-19 patients. Hospital-based prospective study. A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed. Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment. Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH. Hypertension was the single most frequent comorbidity (221/431 = 51%). Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%). In 17/221 (8%) antihypertensive medication was unknown. The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups. Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93-3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH. ACEIs and ARBs do not promote a more severe outcome of COVID-19. There is no reason why they should be withheld in affected patients.

Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience.

Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010-2018) in two different centers. Fifty patients (median age 52.5 years, range 34-75) were included; the median number of previous chemotherapy lines was three (range 1-7) and the median number of previous surgeries was one (range 1-4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC > 0 subgroup (median OS 32.9 months (95% CI 21.6-44.2) vs. 4.8 months (95% CI n.a.-9.8), hazard ratio (HR) 4.21 (95% CI 2.07-8.60), p < 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Management of pseudomyxoma peritonei by cytoreduction+HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal carcinomatosis, characterized by a slowly progressive disease process with a large amount of mucus containing occasional epithelial cells. PMP is histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA) and an intermediate or discordant feature group (ID). Recent studies have shown that most cases of PMP originate from ruptured appendiceal tumors with progressive dissemination in the peritoneal cavity of mucin-producing epithelial cells. Encouraging results in the treatment of PMP have been reported by surgical cytoreduction of the primitive cancer, peritonectomy (stripping of implants on the peritoneal surface) and intraperitoneal hyperthermic chemoperfusion (HIPEC). In recent trials, this combined approach has been proposed as the standard treatment for PMP. PATIENTS AND METHODS: In this study, the results of twelve years single-institution experience on 60 consecutive patients affected by PMP, treated by cytoreductive surgery and the original semi-closed HIPEC technique are reported with special reference to overall survival (OS) and progression-free survival (PFS). RESULTS: The postoperative morbidity rate was 45% (27 patients); surgical morbidity was observed in 19 patients and medical complications in 9 cases. No postoperative deaths were observed. The survival data, 53 patients were analized (the last 7 were considered only for the complications rate, postoperative mortality and cancer features, not for OS or PFS because they were too recent for evaluation). At the final follow-up of the 53 patients, five and ten years OS were respectively 94% and 84.6% . DFS was 80% and 70% at five and ten years respectively. The follow-up data indicated that the survival probability may be good in patients with hystological type appendicular adenoma optimally cytoreduced (CCR-0). Interestingly if preoperative chemotherapy was performed represented a negative prognostic factor with statistically significant impact both on OS and DFS. CONCLUSION: As in other similar studies, cytoreductive surgery plus HIPEC, even when combined with an aggressive surgical procedure, is associated with an acceptable risk of postoperative complications and mortality. This combined treatment results in DFS and OS rates that are not described in the literature for surgery associated with systemic chemotherapy and, in our opinion, may be considered the gold standard treatment for this rare tumor.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: morbidity and postoperative outcomes.

BACKGROUND: Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) represents a treatment option for peritoneal surface malignancies. Even if it has been reported that this new approach improved survival of selected patients, it is still associated with high morbidity and mortality rates. METHODS: From October 1995 to December 2017, over 450 patients affected by peritoneal carcinomatosis (PC) underwent in our Institute CRS associated with HIPEC. For this preliminary analysis we considered 300 patients presenting PC of different origin: pseudomyxoma peritonei (PMP, N.=98), epithelial ovarian cancer (EOC, N.=87), peritoneal mesothelioma (DMPM, N.=49) and colorectal cancer (CRC, N.=66). Postoperative morbidity and mortality were studied in order to identify possible risk factors. RESULTS: The morbidity rate was 36.3% in all procedures (109/300). According to the Clavien-Dindo Classification, 67 cases (22.3%) were associated with grade I-II complications and 35 cases (11.7%) with grade III-IV. Surgical and medical complication rates were 8.3% (25/300) and 11.3% (34/300), respectively. The mortality rate was 2.3%. Reoperation was needed in 28 patients (9.3%). The operative time, the number of anastomosis, of peritonectomy procedures, of visceral resections performed and the PCI value resulted the most statistically significant factors influencing postoperative morbidity and mortality. CONCLUSIONS: The risks of perioperative morbidity and mortality after CRS and HIPEC are analogous to any other major gastrointestinal surgery. CRS and HIPEC should remain a treatment option for highly-selected patients in whom a curative or life prolonging treatment is a pursuit and should be performed in high volume specialized institutions.