Cytoreductive Surgery with Bidirectional Intraoperative Chemotherapy (BDIC) Using Intravenous Ifosfamide Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Peritoneal Sarcomatosis: A Retrospective Cohort Study.

BACKGROUND: Peritoneal sarcomatosis (PS) is a rare tumor with limited therapeutic options. Bidirectional intraoperative chemotherapy (BDIC) using intravenous ifosfamide and doxorubicin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is an emerging treatment for peritoneal malignancies. PATIENTS AND METHODS: Patients with PS who underwent CRS/BDIC using intravenous ifosfamide and HIPEC from January 2017 to July 2021 were retrospectively analyzed. The last follow-up date was May 2022. RESULTS: A total of 29 patients were included. Overall survival (OS) rates at 6, 12, 24, and 48 months after CRS/BDIC were 93.1%, 89.2%, 81.4%, and 73.3%, respectively. As of May 2022, 6 patients (20.6%) had died, including four (13.8%) with a proven recurrent tumor and two with incomplete tumor resection [completeness of cytoreduction (CC)-2 or CC-3]. Of the 20 patients (68.9%) with CC-0 or CC-1, 7 had locoregional tumor recurrence without distant metastasis, whereas the other 13 were alive with no evidence of recurrent tumor in May 2022. Disease recurrence rates were 15% at 6 months and 35% at 12, 24, and 48 months after CRS/BDIC. Clavien-Dindo class ≥ IIIa complications developed in 9 patients (31.0%) with no deaths. Leukopenia occurred in 5 patients (17.2%) and thrombocytopenia in 12 patients (41.3%); these hematologic abnormalities resolved. A total of 9 (31.0%) patients developed nephrotoxicity; all recovered except one, who progressed to chronic kidney disease. CONCLUSIONS: CRS/BDIC using intravenous ifosfamide and doxorubicin-based HIPEC is a potentially effective treatment for PS and has an acceptable rate of complications.

A 51-Year-Old Woman with Advanced Peritoneal Mesothelioma and Stage 3b Chronic Kidney Disease Treated with Cytoreductive Surgery and Bidirectional Intraperitoneal Cisplatin and Ifosfamide Chemotherapy: A Case Report.

BACKGROUND Malignant mesotheliomas are rare, yet highly malignant tumors. Mesotheliomas are tumors that develop from mesothelial surfaces, with the pleura being the most common, followed by the peritoneum. The diagnosis of malignant peritoneal mesothelioma (MPM) is usually established when the disease is advanced, owing to the nonspecific clinical appearance and abdominal symptoms. Initially, MPM was treated with palliative systemic chemotherapy, with or without palliative surgery. However, cytoreductive surgery (CRS) combined with bidirectional intraoperative chemotherapy (BDIC) has recently emerged as a treatment option for MPM. BDIC creates a bidirectional chemotherapy gradient in the peritoneal tumor cells through the simultaneous use of intraperitoneal and intravenous chemotherapy. CRS, combined with BDIC (CRS-BDIC), allows the complete elimination of residual tiny tumor cells after complete removal of the visible tumor nodules. CASE REPORT Herein, we present a case of a 51-year-old woman with MPM and chronic kidney disease (CKD) stage 3b. Her treatment consisted of neoadjuvant chemotherapy and immunotherapy, followed by CRS-BDIC using intraperitoneal cisplatin and doxorubicin, and intravenous ifosfamide. The surgery was successful, with no immediate complications or decline in the patient's kidney function. On follow up 2 months later, the patient denies suffering any chemotherapy-related adverse effects, and her kidney profile remains stable. CONCLUSIONS In conclusion, nephrotoxicity, a known adverse effect of cisplatin and ifosfamide, might not be a contraindication for the use of these potentially nephrotoxic drugs in CRS-BDIC in patients with renal impairment.

Bidirectional Intraoperative Chemotherapy Using Cisplatin and Ifosfamide for Intraperitoneal Mesothelioma in Severe Renal Impairment: A Case Report.

BACKGROUND Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm with a poor prognosis. Bidirectional intraoperative chemotherapy (BDIC) using concurrent intraperitoneal and intravenous chemotherapy in combination with cytoreductive surgery (CRS) is an emerging treatment option for selected cases of MPM. It is a locoregional treatment that involves intraoperative chemoperfusion of heated chemotherapy. The administration of systemic along with intraperitoneal chemotherapy allows for a bidirectional chemotherapy gradient in peritoneal tumor cells. The aim of this treatment is eradication of microscopic residual cancer cells after major removal of macroscopic tumor nodules. To date, there is no consensus on the chemotherapeutic regimen that can be used in BDIC to manage MPM in patients with severe renal impairment. Administering intravenous ifosfamide with hyperthermic intraperitoneal cisplatin and doxorubicin is a promising regimen in treating peritoneal mesothelioma. Nephrotoxicity is a dose-limiting adverse effect of cisplatin and ifosfamide. Therefore, dose adjustment is required in patients with renal impairment. CASE REPORT In this report, we describe a 46-year-old female patient with recurrent MPM and severe renal impairment. Her treatment was managed with hyperthermic intraperitoneal cisplatin and doxorubicin along with intravenous ifosfamide following CRS. The cisplatin dose was reduced to 50% and the ifosfamide dose was reduced by 25%. The patient tolerated the procedure well, without deterioration in her renal function. At her 9-month follow-up, she did not report experiencing chemotherapy-related adverse effects, and her kidney function remained stable. CONCLUSIONS Severe renal impairment might not be a contraindication to using potentially nephrotoxic chemotherapeutic agents in CRS-BDIC.

Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy For Recurrent Ovarian Cancer: The First Reported Experience From Saudi Arabia.

OBJECTIVES: To report our pilot experience (feasibility, morbidity and postoperative outcomes) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of patients with recurrent ovarian cancer and peritoneal carcinomatosis. METHODS: Thirty nine patients were retrospectively analyzed for perioperative details. RESULTS: The vast majority of patients had platinumsensitive disease (69.2%). Complete (CC-0) and incomplete (CC-1/2) resections were achieved in 24 (61.5%) and 15 (38.5%) patients, respectively. The median peritoneal cancer index (PCI) was 14 (range: 2-28). Cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) was the most frequently used HIPEC regimen (87.2%). No intraoperative morbidity/mortality happened. A total of eight patients developed III-IV postoperative complications (20.5%). Median follow-up time was 41 months (range:3-106). No 60 day readmission/mortality happened. At the last date of follow-up, there were 13 patients who were alive without disease (33.4%); mortality occurred in 10 patients (25.6%). For all patients, the mean diseasefree survival (DFS) and overall survival (OS) were 46.3 months (95% CI: 33.7-58.9) and 81 months (95% CI: 68.6-93.3) respectively. PCI >14 was correlated with statistically significant poor DFS and OS at univariate analysis (p=0.046). When compared to CC-0, CC-1/2 was correlated with poor DFS and OS, however, without statistical significance. Cox multivariate analyses of DFS and OS failed to demonstrate PCI score, CC score and platinum-sensitivity as independent prognosticfactors of DFS and OS. CONCLUSIONS: Our study demonstrated the feasibility, safety and favorable clinical outcomes of CRS and HIPEC in patients with recurrent ovarian cancer and peritonealcarcinomatosis.

Combined Intraoperative Radiotherapy (IORT) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Cytoreduction Surgery (CRS) as a Novel Approach in the Management of Resectable Pancreatic Cancer.

BACKGROUND: Pancreatic cancer is leading cause of cancer related deaths. The prognosis is usually very poor. In spite of the advances in modern surgery, the outcome is still poor. IORT was recently introduced with recorded improvement in both locoregional tumor control and patient survival. Prophylactic HIPEC was introduced during the initial surgery in order to prevent subsequent peritoneal cancer or tumor recurrence which showed some encouraging results. AIM OF WORK: Evaluation of the perioperative results of the combination of IORT and HIPEC with CRS as a novel approach in the management of resectable pancreatic cancer. PATIENTS AND METHODS: This study was conducted at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. Data were collected retrospectively. A total of five patients were included in the study, during the period from November 2017 to August 2018. All surgeries were done by the same surgeon. RESULTS: The average age was 51 years (25-63). The patients were two males and three females. All the patients underwent complete surgical resection combined with IORT then HIPEC. All patients were discharged home in good condition. They were regularly followed up without any evidence of local recurrence or metastases. CONCLUSION: The combination of IORT and HIPEC with CRS gives the addition of the benefits of each procedure alone without affecting the postoperative morbidity or mortality. This combination appeared to be feasible, safe and well tolerated. However, this need to be applied on a larger number of patients with longer periods of follow-up to reach sound conclusions.

Impact of tigecycline versus imipenem-cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study.

The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem-cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem-cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem-cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p < 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p < 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p < 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p < 0.001). In conclusion, compared to imipenem-cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.

Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: Cytopenia after hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported in non-comparative studies with various chemotherapeutic regimens. This study compared the incidence of leukopenia and thrombocytopenia in patients who underwent CRS/HIPEC and received melphalan or cisplatin plus mitomycin-c (CIS + MMC). METHODS: This retrospective study included patients who underwent CRS/HIPEC at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from March 2011 to March 2017 and received melphalan 60 mg/m2 or CIS 100 mg/m2 combined with MMC 30 mg/m2. Incidences and severity of leukopenia, neutropenia, thrombocytopenia, and anemia were compared between groups. RESULTS: This study included 46 patients who received CIS + MMC and 35 patients who received melphalan. The leukopenia incidence was 25.7% in the melphalan group and 17.3% in the CIS + MMC group (P = 0.362), with one patient (2.8%) in the melphalan group developed grade V leukopenia. The number of days to leukocyte nadir was 32.8 days for CIS + MMC group compared to 9.8 days for melphalan group(P = 0.035). Thrombocytopenia occurred at a similar rate in the melphalan (60%) and CIS + MMC (68.8%) groups (P = 0.4). Grade III thrombocytopenia developed in 3.2% and 5% of patients in the melphalan and the CIS + MMC groups, respectively. Neutropenia did not occur in any patient. In multivariate analysis, leukopenia predictors were female gender (P = 0.047) and baseline leukocyte counts (P = 0.029). Baseline platelet count predicted thrombocytopenia (P < 0.001). CONCLUSIONS: Melphalan and CIS + MMC regimens were associated with comparable incidences of leukopenia and thrombocytopenia. Severe leukopenia and severe thrombocytopenia were rare following CRS/HIPEC using both chemotherapy regimens.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of pseudomyxoma peritonei: A single-center experience.

BACKGROUND AND AIMS: Pseudomyxoma peritonei (PMP) results from perforated appendiceal tumors. It is usually diagnosed preoperatively by imaging. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), although aggressive long procedure with high complications rate, was considered the optimal treatment. This study is aiming to study the role of CRS and HIPEC in the management of PMP and assess the outcome. METHODS: This is a retrospective study which was conducted at King Faisal Hospital and Research Center, a tertiary care hospital during the period from November 2008 to June 2016. Approval of the Research Advisory Council was obtained. Forty-one procedures of CRS and HIPEC were performed in 38 patients. Using the open abdomen technique, CRS was performed using standard peritonectomy procedures and visceral resections directed toward the complete elimination of tumors from abdominopelvic cavity. HIPEC was performed using mitomycin C in a dose of 30 mg/m2 and allowed to circulate in abdominopelvic cavity for 90 min at 41.0 to 42.2 °C. RESULTS: Forty-one procedures were performed in 38 patients. Three procedures were done as repeat CRS and HIPEC. No perioperative mortality. Cystoscopy and bilateral ureteric stents in 35 procedures (85.5%). Hospital stay (range 9-85 days) average is 21 days. Follow up period is 1-84 months, and median follow up is 54 months. Five-year survival rate is 92%. Median 5-year disease-free survival rate is 60%. Two patients died during the follow up period by septic shock and one patient died from disease progression. CONCLUSION: CRS and HIPEC is well-tolerated and feasible management for PMP.

Glargine Insulin Use Versus Continuous Regular Insulin in Diabetic Surgical Noncritically Ill Patients Receiving Parenteral Nutrition: Randomized Controlled Study.

BACKGROUND: Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE-in-PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI-in-PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN. METHODS: This prospective randomized open-label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI-in-PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5-9. The percentages of blood glucose measurements at goal were compared between groups. RESULTS: Sixty-seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day ( P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI-in-PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI-in-PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI-in-PN (11.4%; P > .1). CONCLUSION: Both glargine insulin and RI-in-PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for management of recurrent/relapsed ovarian granulosa cell tumor: a single-center experience.

AIM: The aim of this study was to retrospectively report our experience (efficacy/morbidity) with cytoreductive surgery+hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) for the management of recurrent/relapsed ovarian granulosa cell tumors (OGCT). MATERIAL AND METHODS: From 2010 to 2013, six patients underwent CRS+HIPEC. CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m²) and doxorubicin (15 mg/m²) and allowed to circulate in the abdominopelvic cavity for 90 min at 41.0-42.2°C. RESULTS: Cytoreduction completeness (CC-0) was achieved in all except one patient (CC-1). Five patients had OGCT recurrences in abdomen+pelvis and one patient in abdomen only. No grade V morbidity (Clavien-Dindo classification) occurred. Two patients developed lung atelectasis, which was managed by mere chest physiotherapy (grade I). One patient developed urinary tract infection (grade II) and another patient developed pneumonia (grade II) - both of which were managed by antibiotics. One patient developed splenic bed and anterior abdominal wall collections requiring ultrasound-guided aspiration without general anesthesia (grade III). One patient developed pulmonary embolism requiring intensive care-unit management (grade IV). Four chemo-naïve patients received adjuvant chemotherapy whereas the remaining two previously chemo-exposed patients received no adjuvant therapy. All patients were alive and disease-free without proof of recurrence/relapse at 40, 32, 27, 24, 20 and 16 months. The average interval of follow-up after CRS+HIPEC was roughly 27 months (range: 16-40 months). CONCLUSION: CRS+HIPEC appears to be an efficacious and morbidly well-tolerated therapeutic modality for recurrent/relapsed OGCT. Long-term follow-up data and further research are needed.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for managing peritoneal carcinomatosis from endometrial carcinoma: a single-center experience of 6 cases.

BACKGROUND AND OBJECTIVES: Endometrial carcinoma is the most common gynecologic malignancy worldwide. Prognosis of patients with peritoneal carcinomatosis (PC) from endometrial carcinoma is deadly, with an estimated median survival not exceeding 12 months. The objective of this study was to report our experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for managing PC from primary and recurrent endometrial carcinoma. DESIGN AND SETTINGS: A retrospective analysis of 6 patients with PC arising from endometrial cancer, who were managed with CRS and HIPEC at our referral tertiary care center, from November 2010 to August 2013. MATERIALS AND METHODS: Six patients underwent CRS and HIPEC. CRS was performed using standard peritonectomy procedures and visceral resections directed toward the complete elimination of tumors from ab.dominopelvic cavity. HIPEC was performed with cisplatin (50 mg/m2) and doxorubicin (15 mg/m2) and allowed to circulate in abdominopelvic cavity for 90 minutes at 41.0 to 42.2°C. RESULTS: Two patients with primary endometrial carcinoma and 4 patients with recurrent endometrial carcino.ma confined to peritoneal cavity were studied. Complete cytoreduction (CC-0) was achieved in 5 patients. The International Federation of Gynecology and Obstetrics (FIGO) stages and histopathological types were as follows: IB endometrioid adenocarcinomas (n=1), IC mesonephric carcinomas (n=1), IIIA endometrioid adenocarcino.mas (n=2), IIIA papillary serous carcinomas (n=1), and IIIC clear-cell carcinomas (n=1). Anastomotic leak (grade I) was the most commonly encountered postoperative complication. Two patients developed grade IV compli.cations due to septicemia and pulmonary embolism. No intraoperative mortality occurred. Postoperatively, all patients received chemotherapy (carboplatin and paclitaxel). In 1 patient, the clear-cell carcinoma histologic lesion relapsed within 6 months; the metastases spread to hepatic, pelvic, and mesenteric lymph nodes, and the patient died 5 months later. One patient with cytoreduction completeness of CC-2 developed hepatic metastases within 3 months and is still alive at a follow-up up 6 months. Remaining patients (n=4) are alive and disease free without evidence of recurrence of follow-ups at 35, 34, 19, and 7 months. CONCLUSION: CRS and HIPEC are well-tolerated and feasibly promising management modalities in PC from primary and recurrent endometrial carcinoma. Further research is needed for in-depth analysis.