Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer with Peritoneal Metastasis—Indian Experience

Introduction Peritoneal metastasis secondary to gastric cancer is associated with poor prognosis. Recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may be an efficacious treatment option for an otherwise palliative condition. Methods A retrospective single institutional study of patents diagnosed with gastric carcinoma and peritoneal metastasis and treated with CRS and HIPEC from February 2015 to December 2019. Results Sixteen patients with gastric cancer and peritoneal carcinomatosis were treated with CRS and HIPEC. Three patients underwent upfront surgery, and five patients underwent interval surgery. The mean peritoneal cancer index (PCI) was 3.5, and adequate complete cytoreduction (CC) score of 0/1 was achieved in all patients. All patients received HIPEC with mitomycin C. Major surgical complications were in 12.5% of patients. Grade I surgical site infection was present in one patient. Three patients had prolonged gastrointestinal (GI) recovery. The 30-day mortality was zero. Median follow-up time was 39 months. The median progression-free survival (PFS) was 12 months (95% confidence interval [CI] 6.86–17.13). The median overall survival (OS) was 17 months (95% CI 6.36–27.64). Conclusion Multidisciplinary treatment of perioperative chemotherapy with CRS and HIPEC is a promising treatment option, which may prolong survival in selected patients, and large randomized clinical trials are warranted for it to become standard of care.

Antibiotic Prophylaxis for Surgical Site Infection in General Surgery: Oncological Treatments and HIPEC

The procedure of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a combined surgical and oncological treatment for peritoneal carcinomatosis of various origins. Antibiotic prophylaxis is usually center-related and should be discussed together with the infectious disease specialist, taking into account the advanced oncologic condition of the patient, the complexity of surgery—often requiring multiorgan resections—and the risk of post-HIPEC neutropenia. The incidence of surgical site infection (SSI) after CRS and HIPEC ranges between 11 and 46%. These patients are also at high risk of postoperative abdominal infections and septic complications, and a bacterial translocation during HIPEC has been hypothesized. Many authors have proposed aggressive screening protocols and a high intra and postoperative alert, in order to minimize and promptly identify all possible infectious complications following CRS and HIPEC.

Communicating imaging findings in peritoneal mesothelioma: the impact of ‘PAUSE’ on surgical decision-making

The peritoneal cavity is the second commonest site of mesothelioma after the pleural cavity. There are five histological types of peritoneal mesothelioma with variable symptomatology, clinical presentation and prognosis. Cystic mesothelioma is a borderline malignant neoplasm with a favourable prognosis, well-differentiated papillary mesothelioma is generally a low-grade malignancy, and all other varieties such as epithelioid, sarcomatoid and biphasic mesothelioma are highly malignant types of peritoneal mesothelioma with poor prognosis. Malignant peritoneal mesothelioma was considered inevitably fatal prior to the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in selected cases where long-term survival and cure could be achieved. However, the survival benefits following CRS and HIPEC mainly depend on completeness of cytoreduction, which come at the cost of high morbidity and potential mortality. Using the acronym ‘PAUSE’, we aimed at describing the key imaging findings that impact surgical decision-making in patients with peritoneal mesothelioma. PAUSE stands for peritoneal cancer index, ascites and abdominal wall disease, unfavourable sites of involvement, small bowel and mesenteric disease and extraperitoneal disease. Reporting components of ‘PAUSE’ is crucial for patient selection. Despite limitations of CT in accurately depicting the volume of disease, describing findings in terms of PAUSE plays an important role in excluding patients who might not benefit from CRS and HIPEC.

P093 RESULTS OF CYTOREDUCTION SURGERY AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) WITH SIMULTANEOUS COMPLEX RECONSTRUCTION OF THE ABDOMINAL WALL

Aim “Cytoreductive surgery (CRS) together with the application of hyperthermic intraperitoneal chemotherapy (HIPEC) has proven to be a feasible and effective method in the management of selected patients with peritoneal metastases and/or primary peritoneal tumors. Infiltration of the abdominal wall is a frequent finding in these patients, which often leads to extensive resections and complex parietal reconstructions in the same surgical act. This may be associated with wound complications and the consequent delay in postoperative therapy of the patient. For this reason, an exquisite management of the abdominal wall is required. Our goal is to evaluate the technique and results of two clinical cases that required simultaneous complex reconstructions.” Material and Methods “Review patients undergoing CRS and HIPEC and simultaneous complex abdominal wall reconstruction between 2015 and 2020. Analysis of oncological history, description of the defect resulting from cytoreduction and the reconstruction technique used, postoperative course and medium-term results.” Results “Different techniques were used to reconstruct the abdominal wall according the caracteristics of the defect after cytoreduction. The simultaneous performance of reconstruction techniques did not increase the hospital stay nor the rate of complications of the surgical wound. Systemic chemotherapy was continued without delay and we have no evidence of incisional hernias in the medium term.” Conclusions “In our experience, the use of abdominal wall reconstruction techniques in the same surgical time after performing CRS and HIPEC is safe and with good results in the medium term.”

Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis

Background Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. Methods A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41–43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1–2), and severe neutropenia (grade 3–4). Results In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) Conclusions Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases: analysis of short- and long-term outcomes

Background Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer (CRC) metastases. In recent years, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with limited peritoneal involvement. We report the evolution of CRS and HIPEC for colorectal peritoneal metastases at a tertiary referral center over a 10-year period. Methods Patients with colorectal peritoneal metastases undergoing CRS and HIPEC were included and retrospectively analyzed at a tertiary referral center from January 2006 to December 2015. Main outcomes included evaluation of grade III/IV complications, mortality rate, overall and disease-free survival, and prognostic factors influencing survival on a Cox multivariate analysis. Results Sixty-seven CRSs were performed on 67 patients during this time for colorectal peritoneal metastases. The median patient age was 57 years with 55.2% being female. The median peritoneal carcinomatosis index (PCI) was 7, with complete cytoreduction achieved in 65 (97%) cases. Grade > 2 complications occurred in 6 cases (8.9%) with no mortality. The median overall survival for the entire cohort was 41 months, with a 3-year overall survival of 43%. In case of complete cytoreduction, median overall and disease-free survival were 57 months and 36 months respectively, with a 3-year disease-free survival of 62%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival. Conclusions CRS and HIPEC for limited peritoneal metastases from CRC are safe and effective, with acceptable morbidity. In selected patients, it offers a highly favorable long-term outcomes.

Case Report: Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Application in Intraperitoneally Disseminated Inflammatory Myofibroblastic Tumor and in the Youngest Patient in the World: New Indication and Modification of Technique

Introduction: Peritoneal metastases occur in cancers that spread to the peritoneal cavity and indicate the advanced stage of the disease. In children they are mainly seen in sarcomas, Gastrointestinal Stromal Tumors and primary disseminated ovarian tumors. Inflammatory Myofibroblastic Tumor (IMT) is a very rare lesion, characterized by an unpredictable clinical course. The absorption of chemotherapeutic agents through the peritoneal-plasma barrier (PPB) is minimized, thus HIPEC procedure limits the systemic exposure to chemotherapy and permits the administration of its higher doses. The main purpose of HIPEC is to remove the visible macroscopic disease in order to achieve complete cytoreduction (CRS).HIPEC Procedure in Children: Several papers deal with the CRS and HIPEC in children and adolescents, however pediatric experience is still limited. Thus far, the HIPEC procedure has been carried out on patients over 2 years old. The most common indication for the surgery and the best outcome was experienced by patients with desmoplastic small round cell tumor (DSRCT). Most patients received intraperitoneal cisplatin.HIPEC Modification: A 5-month-old infant was admitted to the Department of Pediatric Oncology due to the abdominal distention and blood in the stool. The Computed Tomography (CT) revealed a solid-cystic mass in the right abdominal area. The primary tumor and numerous peritoneal metastasis were removed and the Inflammatory Myofibroblastic Tumor (IMT) was diagnosed. The patient underwent subsequently CRS and modified HIPEC procedure. To avoid overheating of the infant, the intraperitoneal normothermic chemoperfusion was performed. Due to the low body weight a modified dosage of intraperitoneal doxorubicin was used. The child underwent standard postoperative chemotherapy and received crizotinib therapy. At 12 months follow-up since treatment completion the patient remains in complete remission. To our knowledge this is the youngest patient, the only infant and the first pediatric patient with IMT who underwent the modified HIPEC procedure in the world.Conclusions: CRS and HIPEC is technically possible also in infants. For its safe course patients selection and technique modification are necessary. Use of HIPEC should be also considered in intraperitoneally disseminated IMT. A complete cytoreductive surgery as the first HIPEC step seems to be the key factor in survival.

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin: A Single Center Experience

Background: Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal accumulation of mucus leading to death if left untreated. In recent years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) offered increased survival rates. This study aims to identify the clinical, pathological, and surgical features influencing safety and survival outcomes of patients undergoing CRS and HIPEC for PMP of appendiceal origin.Methods: A retrospective analysis of all patients undergoing CRS and HIPEC for PMP of appendiceal origin from January 2015 to May 2019 was conducted at our institution.Results: Study population included 50 patients (74% female, 26% male). The median age at CRS was 60 (38–84). The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC 0–1) was achieved in 47 patients (94%). HIPEC chemotherapeutic regimen was based on oxaliplatin for 13 (28%) patients and mitomycin for 34 (72%) patients. We experienced a total of 19 (38%) postoperative complications, of which 14 (74%) of grade I-II and 5 (26%) of grade III-IV, according to the Clavien-Dindo classification. The median follow-up period was 27 months (12–107) from the date of cytoreductive surgery. The mean survival rate was 100 months, with a 5-year OS of 91%. The mean progression-free survival rate was 77 months (0–107), with a 5-year PFS of 63%. Multivariate analysis identified adenocarcinoma histotype and incomplete cytoreduction to significantly worsen progression-free survival, while incomplete cytoreduction was the only independent predictor of poorer overall survival.Conclusion: Complete cytoreduction and appendiceal neoplasm histotype play a crucial role in the survival of patients affected by PMP of appendiceal origin. The rates of morbidity associated with CRS and HIPEC for PMP are acceptable.

Feasibility and outcomes of cytoreductive surgery and HIPEC for peritoneal surface malignancies in low- and middle-income countries: a single-center experience of 232 cases

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). Methods A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. Results Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. Conclusions Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.