Postoperative Complications Result in Poor Oncological Outcomes: What Is the Evidence?

The majority of patients with solid tumors undergo a curative resection of their tumor burden. However, the reported rate of postoperative complications varies widely, ranging from 10% to 70%. This narrative review aims to determine the impact of postoperative complications on recurrence and overall survival rates following elective cancer surgeries, thereby providing valuable insights into perioperative cancer care. A systematic electronic search of published studies and meta-analyses from January 2000 to August 2023 was conducted to examine the effect of postoperative complications on long-term survival after cancer surgeries. This comprehensive search identified fifty-one eligible studies and nine meta-analyses for review. Recurrence-free survival (RFS) and overall survival (OS) rates were extracted from the selected studies. Additionally, other oncological outcomes, such as recurrence and cancer-specific survival rates, were noted when RFS and OS were not reported as primary outcomes. Pooled hazard ratios and 95% confidence intervals were recorded from the meta-analyses, ensuring the robustness of the data. The analysis revealed that long-term cancer outcomes progressively worsen, from patients with no postoperative complications to those with minor postoperative complications (Clavien-Dindo grade ≤ II) and further to those with major postoperative complications (Clavien-Dindo grade III-IV), irrespective of cancer type. This study underscores the detrimental effect of postoperative complications on long-term oncological outcomes, particularly after thoracoabdominal surgeries. Importantly, we found a significant gap in the data regarding postoperative complications in surface and soft tissue surgical procedures, highlighting the need for further research in this area.

Realizing Textbook Outcomes Following Liver Resection for Hepatic Neoplasms with Development and Validation of a Predictive Nomogram.

BACKGROUND: 'Textbook Outcome' (TO) represents an effort to define a standardized, composite quality benchmark based on intraoperative and postoperative endpoints. This study aimed to assess the applicability of TO as an outcome measure following liver resection for hepatic neoplasms from a low- to middle-income economy and determine its impact on long-term survival. Based on identified perioperative predictors, we developed and validated a nomogram-based scoring and risk stratification system. METHODS: We retrospectively analyzed patients undergoing curative resections for hepatic neoplasms between 2012 and 2023. Rates of TO were assessed over time and factors associated with achieving a TO were evaluated. Using stepwise regression, a prediction nomogram for achieving TO was established based on perioperative risk factors. RESULTS: Of the 1018 consecutive patients who underwent liver resections, a TO was achieved in 64.9% (661/1018). The factor most responsible for not achieving TO was significant post-hepatectomy liver failure (22%). Realization of TO was independently associated with improved overall and disease-free survival. On logistic regression, American Society of Anesthesiologists score of 2 (p = 0.0002), perihilar cholangiocarcinoma (p = 0.011), major hepatectomy (p = 0.0006), blood loss >1500 mL (p = 0.007), and presence of lymphovascular emboli on pathology (p = 0.026) were associated with the non-realization of TO. These independent risk factors were integrated into a nomogram prediction model with the predictive efficiency for TO (area under the curve 75.21%, 95% confidence interval 70.69-79.72%). CONCLUSION: TO is a realizable outcome measure and should be adopted. We recommend the use of the nomogram proposed as a convenient tool for patient selection and prognosticating outcomes following hepatectomy.

Acute kidney injury after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy - A systematic review.

The use of nephrotoxic chemotherapeutic agents during hyperthermic intraperitoneal chemotherapy (HIPEC), carries the risk of postoperative acute kidney injury (AKI). The available evidence on this subject is sparse with variability in the reported incidence of AKI. In this systematic review, the aim was to analyse the incidence, risk factors, and preventive measures for AKI after cytoreductive surgery and HIPEC. A systematic literature search was conducted using the terms 'Acute kidney injury', 'Acute kidney failure', 'Acute renal failure', 'Acute renal impairment', 'HIPEC Surgery', 'Cytoreductive Surgery', 'Heated Chemotherapy' on PubMed, Scopus, clinical trial.gov, POPLINE and Google Scholar. Randomized controlled trials, cohort studies and observational studies published from January 2000-December 2020 were included. The systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021247781). Data from 16 articles, which included 1622 patients, was included. The incidence AKI by any definition, was 23.36 %. The highest incidence of AKI (45.45 %) was reported after paclitaxel-HIPEC. The incidence of AKI after cisplatin-HIPEC was 34.7 %. Cisplatin HIPEC was the most common factor associated with AKI in 7/16 studies followed by pre-existing comorbidities and low intraoperative diuresis in 4 and 3 studies respectively. The perioperative use of sodium thiosulfate and amifostine led to a significant reduction in the incidence of AKI. The reported incidence of AKI after CRS-HIPEC is high. Identifying preoperative risk factors, optimising comorbidities, maintaining perioperative haemodynamic stability, perioperative use of sodium thiosulfate, maintaining adequate diuresis could reduce the incidence of AKI.

Artificial Intelligence in Perioperative Planning and Management of Liver Resection.

Artificial intelligence (AI) is a speciality within computer science that deals with creating systems that can replicate the intelligence of a human mind and has problem-solving abilities. AI includes a diverse array of techniques and approaches such as machine learning, neural networks, natural language processing, robotics, and expert systems. An electronic literature search was conducted using the databases of "PubMed" and "Google Scholar". The period for the search was from 2000 to June 2023. The search terms included "artificial intelligence", "machine learning", "liver cancers", "liver tumors", "hepatectomy", "perioperative" and their synonyms in various combinations. The search also included all MeSH terms. The extracted articles were further reviewed in a step-wise manner for identification of relevant studies. A total of 148 articles were identified after the initial literature search. Initial review included screening of article titles for relevance and identifying duplicates. Finally, 65 articles were reviewed for this review article. The future of AI in liver cancer planning and management holds immense promise. AI-driven advancements will increasingly enable precise tumour detection, location, and characterisation through enhanced image analysis. ML algorithms will predict patient-specific treatment responses and complications, allowing for tailored therapies. Surgical robots and AI-guided procedures will enhance the precision of liver resections, reducing risks and improving outcomes. AI will also streamline patient monitoring, better hemodynamic management, enabling early detection of recurrence or complications. Moreover, AI will facilitate data-driven research, accelerating the development of novel treatments and therapies. Ultimately, AI's integration will revolutionise liver cancer care, offering personalised, efficient and effective solutions, improving patients' quality of life and survival rates.

Postoperative Hyperbilirubinemia and Acute Liver Dysfunction after Cytoreductive Surgery and HIPEC.

How to cite this article: Kannancheeri A, Solanki SL, Kazi M, Saklani A. Postoperative Hyperbilirubinemia and Acute Liver Dysfunction after Cytoreductive Surgery and HIPEC. Indian J Crit Care Med 2024;28(1):80-81.

Acute postoperative pain management techniques, their efficacy and complications after major gastrointestinal and hepato-pancreato-biliary cancer surgeries: An observational study.

BACKGROUND: Patients undergoing major gastrointestinal (GI) surgery including hepato-pancreato-biliary (HPB) surgeries have large incisions, which cause severe acute postoperative pain that, if untreated, is associated with a higher incidence of postoperative morbidity and delayed recovery. METHODOLOGY: Our study included all patients who underwent elective major upper GI and HPB surgeries from 1 January 2018 to 31 December 2018. The patients were divided into two groups: the epidural and the non-epidural group. The average and worst pain scores at rest and movement were compared between both groups. We also studied the effect of pain relief in the two groups and associated postoperative outcomes, resumption of feeding, ambulation, hospital stay and intensive care unit stay. RESULTS: A total of 566 patients were included in the study, out of which 490 received epidurals, and the rest, 76, belonged to the non-epidural group (transversus abdominis plane, rectus sheath block or no regional analgesia technique). The median average pain score at rest and movement was 2.0 and 3.0, respectively, in the epidural and non-epidural groups. The postoperative outcomes showed no statistical difference. CONCLUSION: The epidural group and the non-epidural group had similar pain scores, and the postoperative outcomes were also comparable.

Impact of fluid and haemodynamic management in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy on postoperative outcomes - A systematic review.

Background and Aims: Cytoreduction surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an extensive surgery associated with significant fluid shift and blood loss. The haemodynamic management and fluid therapy protocol may impact postoperative outcomes. This systematic review was conducted to find the effect of haemodynamic monitoring and perioperative fluid therapy in CRS-HIPEC on postoperative outcomes. Methods: We searched PubMed, Scopus and Google Scholar. All studies published between 2010 and 2022 involving CRS-HIPEC surgeries that compared the effect of fluid therapy and haemodynamic monitoring on postoperative outcomes were included. Keywords for database searches included a combination of Medical Subject Headings terms and plain text related to the CRS-HIPEC procedure. The risk of bias and the certainty assessment were done by Risk of Bias-2 and the methodological index for non-randomised studies. Results: The review included 16 published studies out of 388 articles. The studies were heterogeneous concerning the design type and parameter measures. The studies with goal-directed fluid therapy protocol had a duration of intensive care unit (ICU) stay that varied from 1 to 20 days, while mortality varied from 0% to 9.5%. The choice of fluid, crystalloid versus colloid, remains inconclusive. The studies that compared crystalloids and colloids for perioperative fluid management did not show a difference in clinical outcomes. Conclusion: The interpretation of the available literature is challenging because the definitions of various fluid regimens and haemodynamic goals are not uniform among studies. An individualised approach to perioperative fluid therapy and a justified dynamic index cut-off for haemodynamic monitoring seem reasonable for CRS-HIPEC procedures.

Evaluation of perioperative routine coagulation testing versus thromboelastography for major liver resection - A single-arm, prospective, interventional trial (PORTAL trial).

Background and Aims: The International Normalised Ratio (INR), which assesses the loss of procoagulant factors in the extrinsic pathway, fails to evaluate the coagulation abnormalities comprehensively after a major liver resection, which often leads to reduced synthesis of procoagulant and anticoagulant-factors. This study was conducted with an aim to study the trend and compare the results of routine coagulation tests and thromboelastography (TEG) during the perioperative period in patients undergoing major liver resections (≥3 segments). Methods: Twenty-five patients who underwent a major liver resection were enrolled. This prospective, single-arm, interventional study was performed with the primary objective of determining the serial changes in conventional coagulation tests and TEG during the perioperative period in patients undergoing major liver resections, at the preincision period, intraoperative period, postoperatively, at 48 h and on the fifth postoperative day. Transfusion requirements of blood components were also assessed with a TEG-guided replacement strategy. Spearman rank-order correlation was used to study the relationships of coagulation tests (both TEG and conventional tests) at each time point. Results: The prothrombin time (PT)-INR was elevated in 14 patients (56%) at the intraoperative, immediate postoperative and 48-h time points in contrast to the TEG parameters, which remained normal in all patients. Blood component transfusion was avoided in 4, 11 and 10 patients at the intraoperative, immediate postoperative and 48-h time points, respectively. Conclusion: International Normalised Ratio overestimates the coagulopathy in patients undergoing major liver resection, and a thromboelastography-guided transfusion strategy reduces overall transfusion requirements.

Postoperative complications and critical care management after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy: A systematic review of the literature.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment option performed for peritoneal surface malignancies. Postoperatively almost all patients are transferred to the intensive care unit electively. AIM: To describe the common and rare postoperative complications, postoperative mortality and their critical care management after CRS-HIPEC. METHODS: The authors assessed 54 articles for eligibility. Full text assessment identified 14 original articles regarding postoperative complications and critical care management for inclusion into the final review article. RESULTS: There is an exaggerated metabolic and inflammatory response after surgery which may be termed as physiological in view of the nature of surgery combined with the use of heated intraperitoneal chemotherapy with/out early postoperative intravenous chemotherapy. The expected postoperative course is further discussed. CRS-HIPEC is a complex procedure with some life-threatening complications in the immediate postoperative period, reported morbidity rates between 12%-60% and a mortality rate of 0.9%-5.8%. Over the years, since its inception in the 1980s, postoperative morbidity and survival have significantly improved. The commonest postoperative surgical complications and systemic toxicity due to chemotherapy as reported in the last decade are discussed. CONCLUSION: CRS-HIPEC is associated with a varying rate of postoperative complications including postoperative deaths and needs early suspicion and intensive care monitoring.

Role of prophylactic HIPEC in non-metastatic, serosa-invasive gastric cancer: a literature review.

The role of prophylactic hyperthermic intraperitoneal chemotherapy (p-HIPEC) in serosa invasive gastric cancers without gross or microscopic peritoneal disease, to reduce the rate of peritoneal relapse is an area of ongoing research. Although p-HIPEC is effective in reducing the rate of peritoneal relapse and improving disease free and overall survival with or without adjuvant chemotherapy, when added to curative surgery in locally advanced, non-metastatic gastric cancers, the available literature is at best, heterogeneous, centre-specific and skewed. Apart from that, variations in the systemic therapy used, and the presence of the associated nodal disease further complicate this picture. To evaluate the role of p-HIPEC the PubMed, Cochrane central register of clinical trials, and the American Society of Clinical Oncology (ASCO) meeting library were searched with the search terms, "gastric", "cancer", "hyperthermic", "intraperitoneal", "chemotherapy", prophylactic", "HIPEC" in various combinations, and a critical review of the available evidence was done. Although p-HIPEC is a promising therapy in the management of locally advanced gastric cancers, the current evidence is insufficient to recommend its inclusion into routine clinical practice. Future research should be directed towards identification of the appropriate patient subset and towards redefining its role with current peri-operative systemic therapies.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in a 2-YearOld Child with Abdominopelvic Rhabdomyosarcoma: A Case Report of Anaesthetic Concerns.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-established multimodal treatment in patients with peritoneal surface malignancies in adults. Children younger than 3 years rarely undergo such extensive surgeries with heated chemotherapy infusion intraoperatively. Only one such case is reported in the literature for CRS-HIPEC for an abdominopelvic rhabdomyosarcoma in a child of 2 years or less. We present the case of a 2-year-old child with abdominopelvic rhabdomyosarcoma undergoing CRS-HIPEC and discuss the perioperative concerns and challenges.

Multimodal opioid sparing onco-anesthesia: A consensus practice guideline from Society of Onco-Anesthesia and Perioperative Care (SOAPC).

Opioids are an indispensable part of perioperative pain management of cancer surgeries. Opioids do have some side effects and abuse potential, and some laboratory data suggest a possible association of cancer recurrence with perioperative opioid use. Opioid-free anesthesia and opioid-sparing anesthesia are emerging new concepts worldwide to safeguard patients from adverse effects of opioids and potential abuse. Opioid-free anesthesia could lead to ineffective pain management, leaving the perioperative physician with limited options, while opioid-sparing anesthesia may be a rational approach. This consensus guideline includes general considerations of the safe use of perioperative opioids along with concomitant use of central neuraxial or regional blockade and systematic nonopioid analgesics. Region-specific onco-surgeries with their specific recommendations and consensus statements for judicious use of opioids are suggested. Use of epidural analgesia or regional catheter during thoracic, abdominal, pelvic, and lower limb surgeries and use of regional nerve blocks/catheter in head neck, neuro, and upper limb onco-surgeries, wherever possible along with nonopioids analgesics, are suggested. Short-acting opioids in small aliquots may be allowed to control breakthrough pain for expedient control of pain. The purpose of this consensus practice guideline is to provide the practicing anesthesiologists with best practice evidence and consensus recommendations by the expert committee of the Society of Onco-Anesthesia and Perioperative Care for safe opioid use in onco-surgeries.

Enhanced recovery after surgery (ERAS) in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a cross-sectional survey.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols have been questioned in patients undergoing cytoreductive surgery (CRS) with/without hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies. This survey was performed to study clinicians' practice about ERAS in patients undergoing CRS-HIPEC. METHODS: An online survey, comprising 76 questions on elements of prehabilitation (n=11), preoperative (n=8), intraoperative (n=16) and postoperative (n=32) management, was conducted. The respondents included surgeons, anesthesiologists, and critical care specialists. RESULTS: The response rate was 66% (136/206 clinicians contacted). Ninety-one percent of respondents reported implementing ERAS practices. There was encouraging adherence to implement the prehabilitation (76-95%), preoperative (50-94%), and intraoperative (55-90%) ERAS practices. Mechanical bowel preparation was being used by 84.5%. Intra-abdominal drains usage was 94.7%, intercostal drains by 77.9% respondents. Nasogastric drainage was used by 84% of practitioners. The average hospital stay was 10 days as reported by 50% of respondents. A working protocol and ERAS checklist have been designed, based on the results of our study, following recent ERAS-CRS-HIPEC guidelines. This protocol will be prospectively validated. CONCLUSIONS: Most respondents were implementing ERAS practices for patients undergoing CRS-HIPEC, though as an extrapolation of colorectal and gynecological guidelines. The adoption of postoperative practices was relatively low compared to other perioperative practices.

Hyperammonemia after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Report of Three Cases with Unusual Presentation.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for peritoneal surface malignancies. A variety of metabolic derangements have been reported in the perioperative period in these patients, most of which are a result of the complex interaction of peritoneal denudation, chemotherapy bath, and fluid imbalance. We report three cases of hyperammonemia-related neurological dysfunction seen in HIPEC patients. To the best of our knowledge, this is the first report of this presentation. Timely recognition of this condition needs a high degree of suspicion, and unless aggressively treated, is likely to be associated with poor outcome. How to cite this article: Sharma V, Solanki SL, Saklani AP. Hyperammonemia after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Report of Three Cases with Unusual Presentation. Indian J Crit Care Med 2021;25(5):590-593.

Artificial intelligence in perioperative management of major gastrointestinal surgeries.

Artificial intelligence (AI) demonstrated by machines is based on reinforcement learning and revolves around the usage of algorithms. The purpose of this review was to summarize concepts, the scope, applications, and limitations in major gastrointestinal surgery. This is a narrative review of the available literature on the key capabilities of AI to help anesthesiologists, surgeons, and other physicians to understand and critically evaluate ongoing and new AI applications in perioperative management. AI uses available databases called "big data" to formulate an algorithm. Analysis of other data based on these algorithms can help in early diagnosis, accurate risk assessment, intraoperative management, automated drug delivery, predicting anesthesia and surgical complications and postoperative outcomes and can thus lead to effective perioperative management as well as to reduce the cost of treatment. Perioperative physicians, anesthesiologists, and surgeons are well-positioned to help integrate AI into modern surgical practice. We all need to partner and collaborate with data scientists to collect and analyze data across all phases of perioperative care to provide clinical scenarios and context. Careful implementation and use of AI along with real-time human interpretation will revolutionize perioperative care, and is the way forward in future perioperative management of major surgery.

Cancer related nutritional and inflammatory markers as predictive parameters of immediate postoperative complications and long-term survival after hepatectomies.

BACKGROUND: The overall survival (OS), disease-free survival (DFS) and complications after liver resections is unsatisfactory. Cancer-related malnutrition and inflammation have an effect on survival but not studied/not clear on postoperative complications. METHODS: We retrospectively analyzed prospectively maintained database of 309 patients. The outcome variables included complications in terms of Clavien-Dindo (CD) Score, OS and DFS; We studied effect of preoperative albumin globulin ratio (AGR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and aspartate transaminase to platelet ratio index (APRI) and dynamic change from pre-operative to postoperative value (Delta-AGR, Delta-NLR, Delta-PLR and Delta-APRI) on complications, OS and DFS. RESULTS: Total 98 patients (31.71%) had postoperative complications. Fifty patients had CD 1 & 2 and 35 (11.33%) had CD 3 & 4, and 13 (4.12%) had mortality (CD 5). Low AGR, high NLR, high PLR and high Delta-AGR and high Delta-APRI predicted increased major complications. Preoperative high NLR predicted worse OS and low AGR predicted worse OS and DFS. Delta-APRI showed trends towards worse OS and DFS. CONCLUSION: These serum inflammatory markers can predict immediate postoperative complications. Preoperative AGR and preoperative NLR can predict survival after liver resections. High Delta-AGR, which is a new entity, is predicting more postoperative complications and needs further detailed studies.