PrimerX: A Bayesian Multistage Cohort Embedded Randomised Trial to Evaluate the Role of Deferred Local Therapy of the Primary Tumour in Combination with Immune Checkpoint Inhibitor-based First-line Therapy in Metastatic Renal Cell Carcinoma Patients.

Background: Historically, patients with metastatic renal cell carcinoma (mRCC) have been offered upfront cytoreductive nephrectomy (CN) followed by systemic therapy. Currently, CN is no longer the standard of care (SOC) based on the randomised phase 3 CARMENA study performed in the vascular endothelial growth factor receptor tyrosine kinase inhibitor era. With the advent of immune checkpoint inhibitor (ICI) combination therapy in first line, the role of CN needs to be reassessed. There is indirect evidence from small retrospective series that deferred CN after ICI combination therapy may lead to better outcomes. To reassess the role of CN, we designed PrimerX, a randomised controlled trial following the Trial within Cohorts (TwiCs) study design. The primary objective of this study is to re-evaluate the benefit of deferred local treatment in the current era of immunotherapy. Study design: This PrimerX study has been designed as a TwiCs study within the Dutch Prospective Renal Cell Carcinoma (PRO-RCC) cohort. The PRO-RCC cohort includes patients with mRCC and nonmetastatic RCC, and has been set up for prospective collection of long-term clinical data and as an infrastructure for initiating TwiCs studies. The PrimerX TwiCs trial follows a Bayesian adaptive multistage design to allow for early discontinuation due to futility or efficacy. PrimerX has appropriate ethics approval and is registered at clinical.trials.gov (NCT05941169). End points: The primary clinical endpoint is overall survival, defined as the time from randomisation to death from any cause. The secondary endpoint is the objective response rate within the primary tumour prior to local therapy, as assessed by a computed tomography scan. Patients and methods: A maximum of 700 patients with synchronous mRCC and absence of progression at metastatic sites following at least 6 mo of standard first-line ICI combination therapy will be assigned randomly to receive local treatment of the primary tumour (experimental arm) or SOC (control arm). The experimental intervention consists of (partial) CN, any form of ablative local therapy, or magnetic resonance imaging guided ablative stereotactic radiotherapy, performed within 6 mo and 1.5 yr after the start of systemic treatment.

Relevant Ongoing Clinical Trials to Investigate Local-Regional Treatment Strategies for Peritoneal Surface Malignancies.

BACKGROUND AND OBJECTIVES: The multimodal therapy of peritoneal metastases of common cancers (i.e. colorectal, gastric, and ovarian), including CRS plus HIPEC, is still subject to several clinical studies. METHODS: This paper presents the ongoing studies regarding HIPEC, as found on clinicaltrials.gov. The emphasis was set on Phase III recruiting trials, including the newest information from principal investigators who answered the call of the authors. RESULTS: Ninety trials have been identified, and the protocols of 15 studies have been presented in detail. CONCLUSIONS: There are interesting ongoing trials investigating the role of CRS plus HIPEC.

Intraoperative hyperthermia is associated with increased acute kidney injury following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is common after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal surface malignancies. Herein we analyzed the association between intraoperative hyperthermia and AKI following CRS-HIPEC. METHODS: In this retrospective cohort study, we collected baseline and perioperative data from patients who underwent CRS-HIPEC mainly for pseudomyxoma peritonei between 2014 and 2020. Nasopharyngeal temperature was recorded at 5-min intervals. The area above the threshold was calculated for intraoperative hyperthermia (>37.0 °C). AKI was diagnosed and classified according to the KDIGO creatinine criteria. A multivariable logistic regression model was established to assess the association between hyperthermia and AKI. RESULTS: A total of 480 patients were included in the analysis. Of these, 10.6% (51/480) developed AKI within 7 postoperative days. After correction for confounding factors, a larger area above the threshold of hyperthermia was significantly associated with an increased risk of AKI (odds ratio [OR] 1.36, 95% CI 1.14-1.63, p = 0.001). Among other factors, older age (OR 1.05, 95% CI 1.02-1.09, p = 0.002), postoperative hypotension requiring vasopressors (OR 2.09, 95% CI 1.02-4.27, p = 0.042), and intraperitoneal chemotherapy containing cisplatin (OR 2.75, 95% CI 1.20-6.33, p = 0.017) were also associated with an increased risk of AKI. Patients with AKI required longer mechanical ventilation, stayed longer in the intensive care unit and hospital, developed more complications, and required more intensive care unit readmission. CONCLUSIONS: Among patients undergoing CRS-HIPEC, intraoperative hyperthermia was independently associated with a higher risk of AKI; this effect was additive to other risk factors including cisplatin-containing chemotherapy.

Efficacy and safety of intraperitoneal chemotherapy for pancreatic cancer.

Pancreatic cancer is a highly aggressive cancer with unfavorable prognosis despite the therapeutic interventions. Intraperitoneal chemotherapy has recently shown potential outcomes in the presence of peritoneal metastases. However, a consensus is still lacking on different methods for intraperitoneal chemotherapy in pancreatic cancer. A variety of drugs and doses via three types of intraperitoneal chemotherapy have been studied. The prognosis and treatment strategies for pancreatic ductal adenocarcinoma (PDAC) will be significantly influenced by peritoneal dissemination and resectability of the macroscopic disease. Normothermic intraperitoneal chemotherapy (NIPEC) has been used for the treatment of peritoneal metastases of pancreatic carcinomas. Intraperitoneal chemotherapy is often combined with systemic therapies or surgical procedures which may lead to favorable combination therapies such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a relatively new approach that provides a homogenous and deep penetration of the chemotherapy into the peritoneum by producing aerosols. The present study aims to review the literature for recent evidence on intraperitoneal chemotherapy in pancreatic cancer.

Overall survival and prognostic factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with intraoperative radiation therapy in patients with advanced abdominopelvic malignancies: A single center retrospective analysis of 159 patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to look at the overall survival (OS), progression-free survival (PFS), and prognostic factors associated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraoperative radiation therapy (IORT). METHODS: This study is a single center retrospective study performed on 159 patients who underwent treatment with CRS and HIPEC combined with IORT for abdominopelvic malignancies. OS and PFS were used to evaluate the efficacy of this treatment strategy amongst patients with abdominopelvic malignancies. RESULTS: The cohort's median age was 53 years, with a male predominance (58.5%). The median OS was not reached, but the mean OS was 76.87 months. In univariate analysis, several factors, including synchronous organ metastasis, Pathologic Peritoneal Carcinomatosis Index (pPCI) ≥10, increased estimated blood loss, and severe postoperative complications, were associated with worse OS. However, multivariate analysis identified pPCI ≥ 10 as the sole independent predictor of worse OS. The 1- and 3-year survival rates were 83% and 70.4%, respectively. pPCI ≥ 10 and severe postoperative complications were significant predictors of worse survival outcomes. CONCLUSIONS: Radical surgery alone is not enough, and CRS combined with HIPEC and IORT, when indicated, was proven to be safe and effective with no added morbidity or mortality.

The Predictive Value of the Fibrinogen-Albumin-Ratio Index on Surgical Outcomes in Patients with Advanced High-Grade Serous Ovarian Cancer.

BACKGROUND/OBJECTIVES: The present study evaluates predictive implications of the pretherapeutic Fibrinogen-Albumin-Ratio Index (FARI) in high-grade serous ovarian cancer (HGSOC) patients undergoing primary cytoreductive surgery. METHODS: This retrospective study included 161 patients with HGSOC International Federation of Gynecology and Obstetrics (FIGO) stage ≥ IIb, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Associations between the FARI and complete tumor resection status were described by receiver operating characteristics, and binary logistic regression models were fitted. RESULTS: Higher preoperative FARI values correlated with higher ascites volumes (r = 0.371, p < 0.001), and higher CA125 levels (r = 0.271, p = 0.001). A high FARI cut at its median (≥11.06) was associated with lower rates of complete tumor resection (OR 3.13, 95% CI [1.63-6.05], p = 0.001), and retrained its predictive value in a multivariable model independent of ascites volumes, CA125 levels, FIGO stage, and Charlson Comorbidity Index (CCI). CONCLUSIONS: The FARI appears to act as a surrogate for higher intra-abdominal tumor load. After clinical validation, FARI could serve as a readily available serologic biomarker to complement preoperative patient assessment, helping to identify patients who are likely to achieve complete tumor resection during primary cytoreductive surgery.

Robotic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is there a benefit?

BACKGROUND: Open cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option for the management of malignancies with peritoneal carcinomatosis and of peritoneal origin. Robotic surgery shows promise as a minimally invasive approach for select patients. We aimed to evaluate the differences in outcomes between robotic versus open CRS/HIPEC and hypothesized less morbidity and faster recovery in the robotic approach group. METHODS: We conducted a retrospective cohort study from our HIPEC database including all tumor origins. We included patients aged 18-89 years who underwent CRS/HIPEC for curative intent at a single institution between January 1, 2017, and December 31, 2023. Patients were stratified by open versus robotic-assisted surgery. Mann-Whitney U and Fisher Exact tests were used to compare differences in patient characteristics and outcomes. RESULTS: A total of 111 patients underwent CRS/HIPEC for curative intent, with 95 (85.6%) cases performed open and 16 (14.4%) robotically. The groups were demographically similar, except patients undergoing robotic CRS/HIPEC had a significantly higher median income ($83,845 vs. $70,519, p < 0.001). Rate of comorbidities and cancer type, including appendiceal, colorectal, and ovarian, were the same. The peritoneal carcinomatosis index and completion of cytoreduction score were similar between groups. Robotic approach was associated with statistically significant lower estimated blood loss (113 vs. 400 mL, p < 0.001) and postoperative transfusions (6.3% vs. 23.2%, p = 0.036). Total complications, readmission rates, and 30-day mortality were similar among groups, but the robotic group had a significantly shorter length of stay (5.5 vs. 9 d., p < 0.001). CONCLUSION: Robotic CRS/HIPEC holds promise to decrease intraoperative blood loss, blood transfusions, and hospital stay while providing similar immediate postoperative outcomes in select patients. These results should be validated in the setting of a prospective trial and effects on long-term oncologic outcomes should be investigated.

Does maximal effort cytoreductive surgery after 6-cycles of chemotherapy play a role in the management of advanced ovarian cancer?

BACKGROUND: The current gold standard in the surgical management of advanced ovarian cancer recommended by ESGO and ASCO is complete resection of all visible disease. If this is not deemed possible in the upfront setting, then interval cytoreductive surgery should be undertaken after 3-4-cycles of neo-adjuvant chemotherapy. Occasionally, surgery in the interval setting may not be possible either due to factors associated with patient fitness, or due to persistence of disease in sites deemed unresectable on interval scanning. Limited published data assessing outcomes from surgery delayed to after 6-cycles of NACT (delayed cytoreductive surgery) suggests a potential benefit over no surgery and suggests that if interval cytoreductive surgery is not possible, then the clinician might consider delayed surgery on a case by case basis. We sought to review the outcomes of patients with Advanced Ovarian Cancer presenting to the Northern Gynaecological Oncology Centre who underwent delayed surgery. METHODOLOGY: This study is a retrospective analysis looking at patients with epithelial ovarian cancer of FIGO stage IIIC and above, who were not deemed suitable to undergo either primary or interval cytoreductive surgery, referred to the Northern Gynaecological Oncology Centre Gateshead, UK, between January 2014 and December 2020. We compared survival outcomes in women receiving non-standard treatment for advanced ovarian cancer, comparing two groups of patients; those completing at least six cycles of platinum-based chemotherapy as part of their first-line treatment and not having surgery with those who received delayed cytoreductive surgery after completing of 6-cycles of primary chemotherapy. RESULTS: A total of 89 cases were included in the analysis and 78/89 patients had completed at least 6-cycles of primary chemotherapy in the first-line treatment setting without any attempt at surgical cytoreduction. 11/89 patients underwent DDS after completion of 6-cycles of primary chemotherapy. The majority of included cases 87/89 (98%) were high-grade serous ovarian cancer (HGSOC). Surgery and no-surgery groups were well matched in terms of stage comparison at presentation with an overall stage distribution of 62% FIGO stage IIIC, 10% stage IVA and 28% stage IVB. The surgery group were significantly younger than the no-surgery group with median age of 68 (interquartile range (IQR) 59-71 years) and 77 years (IQR 70-82 years) (p < 0.01), respectively. The overall survival (OS) of the surgery and no-surgery groups was 25 months and 23 months, respectively (p = 0.38) with a median follow-up of 20 months (IQR 11-29 months). The 1 year disease-specific mortality for both groups was 18%. CONCLUSION: Maximal effort cytoreductive surgery after 6-cycles is not associated with a survival benefit (even with complete cytoreduction) but may be considered in the context of symptomatic disease or for palliation of symptoms amenable to surgery.

Eighteen-Months Safety and Efficacy Following Intraperitoneal Treatment With 224Radium-Labeled Microparticles After CRS-HIPEC in Patients With Peritoneal Metastasis From Colorectal Cancer.

BACKGROUND AND OBJECTIVES: Peritoneal metastasis from colorectal cancer carries a high risk for relapse after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). A novel alpha-emitting radiopharmaceutical (Radspherin) has been designed to deliver short-range radiation to micrometastases and free-floating tumor cells. METHODS: A Phase 1/2a study evaluated the safety, tolerability, and signal of efficacy of escalating doses of Radspherin injected intraperitoneally after CRS-HIPEC. RESULTS: Eleven patients received 1-4 MBq (Group 1) whereas 12 patients received 7 MBq; nine patients single dose/three patients split-dose (Group 2). Median age was 66.5 and 61.5 years, and median peritoneal cancer index 6 and 7, respectively. One hundred and seventy-eight adverse events were reported, only seven were deemed related to Radspherin. Thirteen serious adverse events (SAEs) were reported in eight patients and no SAEs were related to Radspherin. At 18-months, none of the 12 patients receiving 7 MBq experienced peritoneal recurrences, however four had non-peritoneal recurrences. Across both groups (n = 22), 41% had recurrent disease, only 14% of them in the peritoneum. CONCLUSIONS: Radspherin was well tolerated. At 18 months, median disease-free survival has not been reached, and none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. The results are encouraging and warrant further clinical evaluation.

Review of Options to Traditional HIPEC for Prevention and Treatment of Peritoneal Metastases.

Cytoreductive surgery with HIPEC has definite application to the management of selected patients with peritoneal metastases. Patients who profit most have a complete cytoreductive surgery. Higher-grade tumors such as colorectal cancer, gastric cancer, and ovarian malignancy are benefited by CRS and HIPEC only under limited circumstances. High-grade tumor invades subperitoneal lymphatics where HIPEC is not effective. Options to traditional HIPEC for treatment of invasive intraabdominal malignancies with peritoneal metastases must be explored.

When Benchmarks Fail Us: A Case Study in Cytoreductive Surgery.

INTRODUCTION: Relative Value Units (RVUs) are utilized to measure physician work effort and create national benchmarks. Physicians are often measured against national benchmarks to determine compensation. Using a case study in cytoreductive surgery, we explored variability in coding that can impact national benchmarks. METHODS: A survey was conducted amongst surgeons in the peritoneal surface malignancies consortium (PSM). Data was collected on clinical experience, clinical full time equivalent, wRVUS and institutional coding practice. RESULTS: Coding of the same procedure resulted in significantly varying RVUs (IQR 60-101) across institutions. Higher volume (> 50% practice) appeared to have better coding practices with higher wRVU/case (Median 102 vs 62, p = 0.04). CONCLUSIONS: There is significant variability in the measurement of similar effort across institutions due to coding variability. Such variability creates flaws in measurement necessary for benchmarks.

Gastroenteropancreatic Neuroendocrine Tumor with Peritoneal Metastasis: A Review of Current Management.

Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival-particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed.

HIPEC as Up-Front Treatment in Locally Advanced Ovarian Cancer.

PURPOSE: The main objective of the study is to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of naïve ovarian cancer women undergoing complete or near-complete cytoreduction by assessing the overall survival, the disease-specific survival, and the disease-free survival. The secondary objective is the identification of prognostic indicators of survival and recurrence of these patients. PATIENTS-METHODS: Retrospective study of treatment in naïve women with locally advanced ovarian cancer treated with cytoreductive surgery (CRS) and HIPEC and compared with those who were treated with cytoreduction alone. Clinicopathologic variables were correlated to overall survival, disease-specific survival, and disease-free survival using Kaplan-Meier method, and the multivariate Cox proportional hazards regression models. RESULTS: 5- and 10-year overall survival, disease-specific survival, and disease-free survival rates were significantly higher in patients treated with CRS and HIPEC. These patients were 67% less likely to die from any cause (adjusted hazard ratio, aHR = 0.33, p = 0.001), 75% less likely to die from cancer (aHR = 0.25, p = 0.003), and 46% less likely to develop recurrence (aHR = 0.54, p = 0.041) compared to patients treated with CRS alone. Moreover, the poor performance status (aHR = 2.96, p < 0.001), the serous carcinomas (aHR = 0.14, p = 0.007), and the morbidity (aHR = 6.87, p < 0.001) were identified as independent indicators of poor overall survival. The degree of differentiation (aHR = 8.64, p = 0.003) was identified as the independent indicator of disease-specific survival (aHR = 4.13, p = 0.002), while the extent of peritoneal carcinomatosis (aHR = 2.32, p < 0.001) as the independent indicator of disease-free survival. CONCLUSIONS: Treatment in naïve patients with locally advanced ovarian cancer undergoing CRS plus HIPEC appears to have improved overall, disease-specific, and disease-free survival.

Insight into Predictors of Cytoreduction Score Following Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy for Gastric Peritoneal Carcinomatosis Improves Patient Selection and Prognostic Outcomes.

BACKGROUND: Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes. PATIENTS AND METHODS: In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression. RESULTS: We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0). CONCLUSIONS: We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

The role of cytoreductive nephrectomy in the era of immune checkpoint inhibitors: A review of current evidence and ongoing trials.

Renal cell carcinoma (RCC) was diagnosed in over 400 000 individuals globally in 2020, making it a significant global health concern. The incidence of RCC varies by region and overall mortality rates have been declining. This decline is attributed in part to advancements in early cancer detection through imaging and the development of more effective systemic therapies. Cytoreductive nephrectomy (CN) was adopted as a standard treatment for metastatic RCC (mRCC) based on clinical experience and early clinical trials. However, the treatment landscape has shifted with the introduction of tyrosine kinase inhibitors (TKI) in 2007 and, more recently, immune checkpoint inhibitors (ICIs). Dual ICI therapy and combinations of ICIs with TKIs are collectively referred to as immuno-combination therapies and have become standard first-line treatments. This review examines the evolving role of CN in the era of immuno-combination therapies, with a focus on patient selection and the timing of surgery. The immunogenic nature of RCC, characterized by spontaneous tumor regression and immune cell infiltration, suggests a potential benefit from combining CN with ICI therapy to enhance treatment outcomes. This is supported by several clinical studies that reported improved outcomes; however, these were limited by their retrospective nature. Ongoing clinical trials, such as NORDIC-SUN, PROBE, and SEVURO-CN, are expected to provide critical insights into the role of CN in the ICI era. Their findings will ultimately guide future clinical decision-making and further refine treatment strategies for mRCC.

Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial.

INTRODUCTION: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. METHODS AND ANALYSIS: The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. ETHICS AND DISSEMINATION: The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. TRIAL REGISTRATION: ChiCTR2200057258. Registered on March 5, 2022.

Utilization of Partial Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma.

OBJECTIVES: Cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) is a standard of care. Partial nephrectomy (PN) in the setting of metastatic disease is an uncommon occurrence, and we aimed to characterize its utilization in a modern cohort. METHODS: The National Cancer Database was reviewed for patients with mRCC from 2010 to 2017. Patients with cTanyNanyM1 who underwent cytoreductive surgery in the form of PN or radical nephrectomy (RN) were compiled. Our primary outcome was survival outcome for patients who underwent PN compared to RN. Secondary outcomes included 30-day readmission, length of stay, and survival outcomes. RESULTS OBTAINED: A total of 13,896 patients with mRCC who underwent cytoreductive surgery were identified. In total, 13,242 underwent RN and 654 underwent PN. The RN population was more likely to have cN positive disease, while the PN population was more likely to have cT1 disease. Length of stay, readmission and 30-day mortality were not significantly different between PN and RN, but overall mortality and 90-day mortality favored PN (p < 0.001). Cox regression for death showed PN with improved overall survival (HR 0.782, p < 0.001). Logistic regression for predictors of cytoreductive PN revealed cT1 and cN0 as significant factors. Overall survival, as seen on KM analysis, identified that PN exhibited improved 2-year (67.1% vs. 52.0%) and 5-year (40.7% vs. 29.2%) overall survival relative to RN (p < 0.001). CONCLUSIONS: PN is an infrequent treatment with mRCC and its utilization is stable from 2010 to 2017. Overall survival is significantly better for those undergoing PN, likely due to their favorable oncologic disease characteristics.

Respiratory Complications in the Immediate Postoperative Period after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Nowadays: An Observational Study.

Background and objectives: Several respiratory complications have been described after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Materials and methods: Patients admitted to intensive care unit (ICU) after CRS and HIPEC during 10 years. Data recorded were: Demographic characteristics; severity of illness; complete blood sample; chest radiographs; type of cancer and extension; HIPEC drug and temperature; ICU and hospital stay; and mortality. Results: Of the 124 patients included, 67 patients (54.0%) presented respiratory complications: 56 (83.6%) acute respiratory failure, 25 (37.3%) pleural effusion, 13 (19.4%) atelectasis, and 3 (4.5%) other; only 1 (3.0%) developed pneumonia. They had higher severity scores at ICU admission. 1 patient required initiation of invasive mechanical ventilation during ICU admission due to pneumonia, and 1 patient needed placement of a pleural chest tube due to symptomatic pleural effusion.Only the need for a high fluid balance during surgery was correlated to the development of respiratory complications on multivariate analysis.Median ICU stay was 5 (4.0-5.0) days. ICU mortality was 0.8.0%. Conclusion: In our study, 54% of patients treated with CRS and HIPEC developed respiratory complications during the postoperative period. However, the majority of these complications were not severe and did not significantly impact mortality rates or hospital stays. How to cite this article: Pintado MC, Oñoro A, Beltran D, Nevado E. Respiratory Complications in the Immediate Postoperative Period after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Nowadays: An Observational Study. Indian J Crit Care Med 2024;28(10):952-957.

Efficacy of immune checkpoint inhibitor combination therapy prior to nephrectomy in advanced renal cell carcinoma: A retrospective pilot study.

Renal cell carcinoma (RCC) affects 10%-20% of patients annually, often with metastases present. This study evaluated the impact of systemic therapy before nephrectomy in patients with unresectable or metastatic renal cell carcinoma (RCC). Patients receiving upfront immune checkpoint inhibitor (ICI) combination therapy showed significantly improved progression-free survival (PFS) compared to nephrectomy alone (2-year PFS: 62.3% vs. 17.4%; p = 0.036), while upfront tyrosine kinase inhibitor (TKI) therapy did not (2-year PFS: 18.2% vs. 12.3%; p = 0.545). Surgery-related outcomes did not differ significantly between groups. ICI therapy maintained tumour reduction rates better than TKI therapy. The study highlights the potential benefits of ICI combination therapy over TKI therapy in advanced RCC, suggesting further research is needed to confirm these findings.

Guidelines for the Prophylaxis and Treatment of Peritoneal Metastases From Colorectal Cancer: A GRADE-Approach for Evidence Evaluation and Recommendations.

Colorectal peritoneal metastases (CPM) are common in colorectal cancer patients. This article aims to provide GRADE guidelines for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in two clinical situations: (1) To determine the value of adjuvant HIPEC for the prevention of CPM in high-risk colorectal cancer patients; (2) to determine the impact on survival of cytoreductive surgery and HIPEC followed by adjuvant systemic chemotherapy as compared to systemic chemotherapy alone in patients with CPM.