Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Long term oncologic outcomes from the international PSOGI registry.

The laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) in highly selected patients was previously reported from the PSOGI registry with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to update this international PSOGI registry with a larger cohort of patients and a longer follow-up period. METHODS: An international registry was designed through a networking database (REDCAP®). All centers performing L-CRS + HIPEC were invited through PSOGI to submit data on their cases. Variables such as demographics, clinical outcomes, and survival were analyzed. RESULTS: A total of 315 L-CRS + HIPEC cases were provided by 14 worldwide centers. A total of 215 patients were included in the L-CRS + HIPEC group. The median peritoneal cancer index (PCI) was 3 (3-5). The median length of stay was 7 days (5-10) and the major morbidity (Clavien-Dindo ≥3) was 6.1% after 30 days. The 5-year disease-free survival (DFS) per tumor origin was: 94% for PMP-LG, 85% for PMP-HG, 100% for benign multicyst peritoneal mesothelioma (MPM), 37.4% for colonic origin, and 54%(at 3 years) for ovarian origin. The 5 years overall survival (OS) per tumor origin was: 100% for PMP-LG, PMP-HG and MPM; 61% for colonic origin, and 74% (at 3 years) for ovarian origin. In addition, a total of 85 patients were analyzed in the laparoscopic risk-reducing HIPEC (L-RR + HIPEC). The median length of stay was 5 days (4-6) and the major morbidity was 6% after 30 days. The 5-year DFS per tumor origin was: 96% for perforated low grade appendiceal mucinous neoplasm (LAMN II) and 68.1% for colon origin. The 5 years OS per tumor origin was: 98% for LAMN II and 83.5% for colonic origin. CONCLUSIONS: Minimally invasive CRS + HIPEC is a safe procedure for selected patients with peritoneal carcinomatosis in specialized centers. It improves perioperative results while providing satisfactory oncologic outcomes. L-RR + HIPEC represents a promising strategy that could be evaluated in patients with high risk of developing peritoneal carcinomatosis into prospective randomized trials.

Establishment of a desirable dose using neutral argon plasma to eradicate miliary peritoneal implants: A phase I/II controlled trial.

INTRODUCTION: Neutral argon plasma (NAP) system could meet the requirements to achieve oncological cytoreduction of peritoneal carcinomatosis with miliary lesions, minimizing the associated morbidity. This phase I/II trial aims to establish the desirable dose that is safe and effective in eliminating tumor cells with lower penetration. METHODS: Patients diagnosed with different origins for peritoneal carcinomatosis and miliary implants were selected for the study. The safe and potentially effective dose (desirability) of NAP was evaluated according to three factors: distance (mm), application time (s) and power (%), to evaluate the response variables such as the presence of tumor cells (Y/N) and the depth of penetration. RESULTS: Ten patients and 120 samples were evaluated and treated with NAP. There was no vascular or organ injury intraoperative using a pre-established dose of 100% (coagulation mode) at a distance of 2-3 cm. The distance was found to be correlated with the presence of the tumor cells in ex-vivo analysis, with an OR of 15.4 (4.0-111.4). The time and energy used were protective factors to eliminate tumor cells with an OR of 0.4 (0.1-0.9) and 0.8 (0.8-0.9), respectively. The safest and most effective desirability results were as follows i) energy 80% during 2-4 s with a distance of 2 cm (0.89), and ii) energy 100% during 2-4 s with a distance of 3 cm (0.90). CONCLUSIONS: The use of NAP during a CRS and HIPEC is safe and effective for eradicating tumor cells on the peritoneal surface at suggested doses of energy, distance and duration. TRIAL IDENTIFICATION: ClinicalTrials.gov Identifier: NCT04904042.

External multicentre validation of pseudomyxoma peritonei PSOGI-Ki67 classification.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.

Tratamiento quirúrgico de los leiomiosarcomas de vena cava. Serie de casos en un hospital de tercer nivel y revisión de la literatura / Surgical treatment of vena cava leiomyosarcomas: Series of cases in a referral center and literature review

Introducción Los tumores primarios de vena cava inferior son tumores raros de origen mesenquimal que surgen de la musculatura lisa de la pared. Debido a su escasa prevalencia, existen pocos datos definitivos sobre su tratamiento y pronóstico. Su tratamiento se basa en principios oncológicos generales. Métodos Se ha analizado una serie de 6 casos intervenidos desde 2010 a 2020, evaluando distintos parámetros relacionados con las características demográficas del tumor, del tratamiento recibido y de los resultados obtenidos en supervivencia y morbilidad. Además, se ha llevado a cabo una revisión bibliográfica de la evidencia disponible actualmente. Resultados En todos los pacientes se llevó a cabo una resección quirúrgica óptima con R0 en 4/6 y R1 en 2/6. La mayor morbilidad sucedió en un paciente fallecido en periodo intraoperatorio. Se realizó cavorrafia en un paciente y cavoplastia en 5/6 utilizando injerto criopreservado en 3/6 y prótesis en 2/6. Al final del seguimiento de nuestra serie (con una media de seguimiento de 10,7 meses), el 50% de los pacientes continúan vivos. La media de supervivencia fue de 11,3±9,07 meses. De los 6 pacientes, 3 presentaron recidivas hematógenas con un intervalo libre de enfermedad de 9±2 meses. Conclusión El diagnóstico y tratamiento del leiomiosarcoma de vena cava inferior continúa siendo un reto. Debido a su baja prevalencia, resultará difícil establecer un tratamiento totalmente estandarizado, y se recomienda su abordaje en centros especializados. Por otra parte, se deberían intentar aunar los casos intervenidos de cara a avanzar en el conocimiento del abordaje de esta enfermedad (AU)

Introduction Primary tumors of the inferior vena cava are rare tumors of mesenchymal origin. They arise from the smooth muscles of the vena cava wall. Due to its low prevalence, there are few definitive data on its treatment and prognosis. Its treatment is based on general oncological principles. Methods A series of six cases operated from 2010 to 2020 were analyzed. Different parameters related to the demographic characteristics, the tumor, the treatment received, and the results obtained in survival and morbidity were analyzed. In addition, a bibliographical review of the currently available evidence was carried out. Results Optimal surgical resection was accomplished in all patients with R0 in 4/6 and R1 in 2/6. The greatest morbidity occurred in a patient who died in the intraoperative period. Cavography was performed in one patient and cavoplasty in 5/6 using cryopreserved graft in 3/6 and prothesis in 2/6. The 50% were still alive at the end of the follow-up (with a mean follow-up of 10.7 months). The mean survival was 11.3±9.07 months. 3/6 patients presented hematogenous recurrences with a disease-free interval of 9±2 months. Conclusion The diagnosis and treatment of inferior vena cava leiomyosarcoma is still a challenge. Due to its low prevalence, it will be difficult to establish a totally standardized treatment and its approach is recommended in specialized centers. On the other hand, a multicentric study should be made to collect the most cases as possible in order to advance in the understanding of the approach to this disease (AU)

Laparoscopic cytoreductive surgery and HIPEC: a comparative matched analysis.

BACKGROUND: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a procedure that has had encouraging results for peritoneal metastases (PM) from diverse tumour origins, but it is not exempt from high morbidity. Recently, the important role of laparoscopy in oncologic surgeries and its benefits have been evaluated for CRS + HIPEC in selected patients, which has yielded promising results. The aim of our study is to analyse the use of laparoscopy for CRS + HIPEC in patients with limited peritoneal disease. METHODS: We have conducted a retrospective study from a prospective database in our tertiary referral hospital within the period of January 2009 to July 2019, which includes 825 patients who had PM from varying tumour origins. We have compared the patients treated with the laparoscopic approach (L-CRS-HIPEC) to a matched population who have undergone the open approach (O-CRS-HIPEC) and fulfil the same selection criteria. We have analysed the postoperative outcomes and survival results. RESULTS: We have confirmed the homogeneity between the sample of the O-CRS + HIPEC (n = 42) and the L-CRS + HIPEC (n = 18) regarding preoperative and intraoperative features. The L-CRS + HIPEC group had shorter hospital stays, (median of 4 [2-10] days versus 9 [2-19] days) and reduced wait time to return to chemotherapy (median of 4 [3-7] weeks and a median of 8 [4-36] weeks) than the O-CRS + HIPEC group. No differences were found regarding the need for perioperative blood transfusion, surgery time or postoperative morbi-mortality. No early locoregional relapse occurred in the L-CRS + HIPEC group and short term disease-free survival did not differ between groups. CONCLUSIONS: Laparoscopy for CRS + HIPEC is feasible and safe in highly selected patients, with no significant differences concerning postoperative morbi-mortality or early oncological results. We have found that patients who have undergone laparoscopic operations have shorter hospital stays and that they return to adjuvant chemotherapy sooner. Further investigation is required to confirm the benefits of minimally invasive procedures for the management of PM.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry.

INTRODUCTION: A laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS+HIPEC) in highly selected patients has been reported in small cohorts with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to analyse individual patient data from these international centres collected through the Peritoneal Surface Oncology Group International (PSOGI) L-CRS+HIPEC registry. METHODS: An international registry was designed through a networking database (REDCAP®). All centres performing L-CRS+HIPEC were invited through PSOGI to submit data on their cases. Patient's characteristics, postoperative outcomes and survival were analysed. RESULTS: Ten international centres contributed a total of 143 L-CRS+HIPEC patients during the study period. The most frequent indication was low grade pseudomyxoma peritonei in 79/143 (55%). Other indications were benign multicyst mesothelioma in 21/143(14%) and peritoneal metastasis from colon carcinoma in 18/143 (12,5%) and ovarian carcinoma in 13/143 (9%). The median PCI was 3 (2-5). The median length of stay was 6 (5-10) days, with 30-day major morbidity rate of 8.3% and 30-day mortality rate of 0.7%. At a median follow-up of 37 (16-64) months 126/143 patients (88.2%) were free of disease. CONCLUSIONS: Analysis of these data demonstrates that L-CRS+HIPEC is a safe and feasible procedure in highly selected patients with limited peritoneal disease when performed at experienced centres. While short to midterm outcomes are encouraging in patients with less invasive histology, longer follow up is required before recommending it for patients with more aggressive cancers with peritoneal dissemination.

Complete laparoscopic pelvic peritonectomy plus hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of our study was to present the technique for, and early results of complete laparoscopic pelvic peritonectomy (LPP) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a study on consecutive patients who had LPP for limited peritoneal carcinomatosis (peritoneal carcinomatosis index < 10) from ovarian cancer, colon cancer and benign multicystic mesothelioma, from January 2017 to November 2019 at 2 referral centers in Spain. Perioperative, pathologic, 30-day major morbidity and mortality characteristics were analyzed. The surgical technique is shown in the attached video. RESULTS: Twelve LPP + HIPEC were performed. Complete cytoreduction was achieved in 100% of the patients, the median duration of the operation was 450 min (range 360-600 min). There were 2 cases (16%) of IIIa morbidity (trocar hernia and pleural effusion), and no mortality. The median length of hospital stay was 5.5 days (range 4-10 days). The median length of follow-up was 10 months (range 2-30 months). There was a recurrence at the splenic hilum in 1 patient which was treated by laparoscopic splenectomy and one nodal recurrence at 13 months while all other patients are alive and free of disease at last follow-up. CONCLUSIONS: This is the first technical video of a minimally invasive approach for complete pelvic peritonectomy plus omentectomy associated with HIPEC. For highly selected patients, this procedure presents a feasible and safe alternative to the maximally invasive approach.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

"Super-rapid" Technique in Donation After Circulatory Death Liver Donors: Advantages and Disadvantages.

In recent years, donation after circulatory death (DCD) has increased as an option to overcome the organ donor shortage crisis and to decrease the large number of patients on liver transplant waiting lists. The "super-rapid" technique is now the "gold standard" procurement method because of its availability, reproducibility, low cost, and extensive experience. Recently, extracorporeal support has been implemented, with encouraging results. Strict donor acceptance criteria have proven to be essential to optimize the DCD liver graft outcomes and minimize biliary complication rates. In this study we assessed the state of the art of DCD liver transplantation with regard to its development and the actual strategies to prevent graft complications, with aim of expanding the pool of marginal liver donors.

Intraoperative Heparinization During Simultaneous Pancreas-Kidney Transplantation: Is It Really Necessary?

INTRODUCTION: The use of intraoperative sodium heparin during simultaneous pancreas-kidney transplantation (SPKT) remains as a routine practice in some referral centers to minimize pancreatic graft thrombosis rate. One of its disadvantages is the theoretical increased risk of postoperative bleeding. In our center, we have abandoned its use since 2011. MATERIALS AND METHODS: We performed a retrospective analysis among 198 SPKTs performed in our center between the years 1989 and 2017. The variables of our study were vascular thrombosis of the pancreatic graft and hemoperitoneum and upper gastrointestinal bleeding in the mediate postoperative period (up to 2 months after the transplant). We compared these results between SPKT recipients who had undergone intraoperative heparinization (n = 157) and those who had not (n = 51). To avoid bias, a second comparison was performed using propensity score matching on the following characteristics: sex, recipient age, recipient body mass index, cold ischemia time, preoperative hemodialysis or peritoneal dialysis, time of diabetes, and Pancreas Donor Risk Index. Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas χ2 or Fisher exact test was used to compare categorical data. RESULTS: No statistically significant differences were found when comparing the use of intraoperative heparin, even after the homogenization of both groups. CONCLUSIONS: In our experience, intraoperative heparinization during SPKT surgery was not useful because it did not significantly decrease the graft thrombosis rate, and its withdrawal did not enhance hemoperitoneum or upper gastrointestinal bleeding postoperative rates.

Pancreas Donor Hypernatremia: Is it Really a Risk Factor for Simultaneous Pancreas-kidney Transplantation?

INTRODUCTION: Solid organ donor hypernatremia has been classically reported to be a risk factor for cell lysis and graft damage. National criteria for pancreatic donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be relative exclusion criteria. The aim of our study is to review the postoperative outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas graft thrombosis, early pancreatectomy, and reoperation rates regarding different ranges of donor sodium levels. MATERIAL AND METHODS: We performed a retrospective analysis among 161 SPKTs performed in our center between the years 2001 and 2017. We compared the aforementioned postoperative variables in two situations: 1) Whether the donor pancreas sodium levels were inferior to 149 mEq/L, or equal to or greater than 150 mEq/L; and 2) If they had severe hypernatremia (considering sodium levels greater than or equal to 160 mEq/L as threshold) or not. To ensure the comparability of the groups, a second comparison was performed on new samples after using propensity score matching. A Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas a χ2 test or Fisher's exact test was used to compare categorical data. RESULTS: No statistically significant differences were found between the groups that relate high donor serum sodium levels with the morbidity variables included in our study or with early pancreatic graft loss. CONCLUSIONS: In our cohort, early postoperative main morbidity and pancreas graft loss of SPKT recipients do not differ significantly regarding donor serum sodium levels.

Validation in colorectal procedures of a useful novel approach for the use of C-reactive protein in postoperative infectious complications.

AIM: Our aim was to validate a novel use of C-reactive protein (CRP) measurement to identify postoperative infectious complications in patients undergoing colorectal surgery, and to compare the predictive value in this setting against white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR). METHOD: This was a retrospective study of CRP, NLR and WBC measurements in patients undergoing colorectal surgery. CRP, NLR and WBC were recorded on the second postoperative day and on the day of infectious complication (patients who developed infectious complications) or within 3 days prior to discharge (subjects with no complications). The test for detecting infectious complications consisted of comparing the value of the inflammatory marker on the day on which a complication was suspected against the value recorded on the second postoperative day. The test was considered positive if a given value was higher than the registered peak at postoperative day 2. Factors influencing the postoperative peak CRP were also studied. RESULTS: A total of 254 patients were retrospectively studied. Patients whose CRP value was higher than on the second postoperative day had a diagnostic accuracy for infectious complications of up to 94.4% and sensitivity, specificity, positive predictive value and negative predictive value of up to 97.4%, 93.4%, 85.7% and 99.1%, respectively. Poorer results were observed when WBC count and NLR were used rather than CRP measurement. Multiple linear regression analysis showed that surgical procedure and approach, as well as additional resections, were independent factors for 48 h peak CRP. CONCLUSION: C-reactive protein is a better parameter than WBC count and NLR for detecting infectious complications. Our proposed methodology presents good diagnostic accuracy and performance and could potentially be used for any surgical procedure.