Laparoscopic Hyperthermic Intraperitoneal Chemotherapy Research Articles

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy plus Neoadjuvant Intraperitoneal and Systemic Chemotherapy for Gastric Cancer with Malignant Ascites

Abstract Background: Patients with gastric cancer (GC) and malignant ascites (MA) usually have poor outcomes and a high risk of recurrence and mortality, even after curative gastrectomy or chemotherapy. Systemic chemotherapy has been prescribed for patients with GC and MA; however, most of these patients expire within 1 year. Aim: To evaluate the outcomes of laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in the outcomes of GC patients with MA. Methods: We enrolled 62 patients with GC and MA between January 1, 2016, and March 1, 2021. Four patients were excluded because of extraperitoneal metastasis, and two patients were ineligible. A total of 56 patients underwent biweekly staging laparoscopy and LHIPEC with NIPS. We also performed staging laparoscopy to evaluate the effectiveness of LHIPEC + NIPS. Results: The mean survival time of the 56 patients was 20.8 months. The overall complication rate was 33.93%. After the LHIPEC + NIPS intervention, the peritoneal cancer index score (P < 0.001), ascites volume (P = 0.003), and cytology (P < 0.001) significantly improved compared to before the intervention; quality of life (Eastern Cooperative Oncology Group) was also better than before the intervention (P = 0.002), and no discomfort was noted postintervention. Conclusion: LHIPEC + NIPS is feasible for the treatment of GC with MA and may improve patients’ quality of life.

Initial Experience Using Laparoscopic HIPEC for Gastric Cancer with Peritoneal Metastasis: Safety and Outcomes.

Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.

Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity. We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90min from June 2019 to December 2022. Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4-8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0-4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4-7.5) days. There were six (27%) 90-day major complications (Clavien-Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively. CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.

Japanese practice of comprehensive treatment for peritoneal metastasis of gastric cancer

Patients with peritoneal metastasis (PM) from gastric cancer (GC) have a poor prognosis. Surgery or systemic treatment alone hardly improves the prognosis and overall survival (OS). A newly developed comprehensive treatment involving a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used to treat patients with PM from GC. The Peritoneal Dissemination Center of Kishiwada Tokushukai Hospital in Japan has been committed to treating patients with PM from GC. Selected patients undergo laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), preoperative intraperitoneal (IP) chemotherapy, and systemic chemotherapy that includes intravenous and oral chemotherapy prior to surgery. CRS plus HIPEC is then performed to achieve complete cytoreduction. Postoperative IP chemotherapy or systemic chemotherapy is also administered to nearly all patients. The results demonstrate that comprehensive treatment, including neoadjuvant chemotherapy and CRS plus HIPEC, can significantly improve the prognosis and OS of selected patients with PM from GC.

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

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

Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery

Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11–20) and severe cases (PCI 21–39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

Peritoneal Mesothelioma in a High Volume Peritoneal Surface Malignancies Unit.

Diffuse malignant peritoneal mesothelioma (PM) is a rare neoplasm, traditionally associated with a poor prognosis. There are other varieties of PM that are even less frequent and of uncertain malignancy. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved prolonged survival in selected patients. The aim of this study is to analyze the patients with PM assessed in our center. Clinicopathological characteristics, diagnostic procedures and survival results from patients with PM appraised at our unit, according to the applied treatment, were analyzed. Seventeen patients were assessed between 2007 and 2019. Three cases had multicystic PM that were treated with complete CRS + HIPEC; all patients are alive and free of disease after a long follow-up. Three other cases had biphasic PM; a curative treatment could be performed in none of them, and their survival was minimal (<6 moths). Lastly, 11 cases with epithelioid PM were treated. Two cases were considered unresectable at laparoscopy (PCI 39); one of them had a long survival (67 months) with three iterative laparoscopic palliatives HIPECs for refractory ascites. The other nine cases were treated with curative CRS + HIPEC, with a median PCI of 14 (range 4-25), and a median overall survival (OS) of 58 months, with a 5-year OS of 47.4%. In conclusion, CRS + HIPEC, when possible, appears to be the optimal treatment for patients with PM. Knowledge of this therapeutic option is crucial, both to offer it to patients and to avoid delays in their referral to appropriate centers for treatment.

An Asian Tertiary Centre's Early Experience with Laparoscopic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis.

The use of open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown improved oncological survival in terms of treating peritoneal surface malignancies (PSM). However, this procedure often comes with associated morbidity. The move towards use of laparoscopic surgery in this field is postulated to lead to a reduction in morbidity and earlier return to function, but literature on its use for CRS and HIPEC has been scarce. We performed a retrospective review of 6 patients with PSM who underwent laparoscopic CRS and HIPEC in our institution and analysed the patient characteristics, oncological history, perioperative and postoperative outcomes. Median peritoneal cancer index (PCI) score was 0 (IQR 0-1.25). All 6 patients had appendiceal primaries. Median operative time was 285min (IQR 228.8-300); median length of stay was 7.5days (IQR 5-8.8). All patients achieved complete cytoreduction, and there was no conversion to open surgery. One patient developed port site infection and another 2 patients subsequently developed adhesions. Median follow-up time was 35 (IQR 17.5-41) months. No patients had developed recurrence at the time of data collection. We conclude that in patients with limited PCI sore (< 2), laparoscopic CRS and HIPEC are safe and feasible. With increasing experience, a select group of patients with limited PSM may be treated via minimally invasive surgery, minimising the morbidity of a traditional laparotomy.

Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study.

Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration. From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC. Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months. Cytoreduction and HIPEC for selected patients with low-volume PMfrom PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients.

Initial experience in laparoscopic peritonectomy and Hipec for the treatment of peritoneal metastasis in a newly establish center

Background: Laparoscopic peritonectomy has been described as a feasible and reproducible technique, however it is technically challenging and requires specific training, Our aim is to present our experience on laparoscopicperitonectomy and laparoscopic HIPEC in a newly stablish center.

Impact of hyperthermic intraperitoneal chemotherapy on genomic heterogeneity of peritoneal metastases in stage IV gastroesophageal adenocarcinoma.

312 Background: Programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are potential biomarkers for response to therapy. Heterogeneity of PD-L1 and TMB has been demonstrated in gastroesophageal adenocarcinoma (GEA) in response to systemic chemotherapy. With the increased use of hyperthermic intraperitoneal chemotherapy (HIPEC) for GEA peritoneal metastases (PM), we aimed to determine the effects of HIPEC on genomic heterogeneity of PM. Methods: This is a retrospective review of a prospectively maintained database of patients with stage IV GEA who underwent iterative laparoscopic HIPEC (mitomycin C 30 mg + cisplatin 200 mg, 60 minutes) between 2017 and 2021. PD-L1 status and TMB levels were reviewed from peritoneal tumor specimens collected prior to each HIPEC. PD-L1 status was defined as positive if combined positive score (CPS) was 1 or greater using the 22C3 pharmDx assay. TMB levels were defined as low, intermediate, or high for up to 5, 5 to 15, or over 15 mutations per megabase (m/MB), respectively. Potentially actionable and biologically relevant variants were reviewed, as well as overall survival, defined as time from diagnosis with stage IV disease to death from any cause. Results: 16 patients completed at least one HIPEC during the study period. Median age was 55.5 years (range 43-79), 50% were female, and 62.5% were Caucasian. All patients received at least one line of systemic chemotherapy after stage IV diagnosis and prior to first HIPEC. Median peritoneal cancer index at first HIPEC was 15 (range 3-39). Three patients completed only one HIPEC. Of the 13 who completed at least two HIPECs, 5 had sufficient tumor tissue for genomic analysis at two timepoints. Of those 5 patients, one exhibited a change in PD-L1 expression from positive to negative after HIPEC, and one exhibited an increase in TMB from low to intermediate. All 5 patients exhibited a change in the profile of potentially actionable or biologically relevant genetic variants, including gain or loss of mutations in DNA repair genes (RAD51), proto-oncogenes (MET), and tumor suppressor genes (ERBB3, IRS2). Median overall survival amongst the full cohort was 27.4 months, with median follow-up of 26.1 months. Overall survival was higher amongst those who underwent at least 2 HIPECs compared to only one, but this was not statistically significant. Conclusions: Amongst our cohort, only one patient exhibited a change in PD-L1 expression and one in TMB after HIPEC. However, HIPEC was associated with a change in genetic variant profiles in all evaluable patients. If confirmed in larger studies, this temporal genomic heterogeneity could inform the role of PD-L1, TMB, and other genetic variants as predictive biomarkers for therapy after HIPEC. Iterative laparoscopic HIPEC warrants further investigation as a treatment option after systemic therapy for GEA with peritoneal metastases.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with improved perioperative outcomes: a single-center early experience propensity-matched analysis.

The role of laparoscopy in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not well established. Herein, we describe our early experience of laparoscopic CRS/HIPEC in patients with low-volume peritoneal disease compared to patients who underwent open CRS/HIPEC during the same time period. Using a prospectively maintained database, patients who underwent laparoscopic CRS/HIPEC were compared to a control cohort of patients who underwent open CRS/HIPEC, matched for peritoneal carcinomatosis index (PCI), completeness of cytoreduction, and tumor histology. Between 2008 and 2017, 16 patients underwent laparoscopic CRS/HIPEC and were compared to a matched control cohort of 32 patients who underwent open CRS/HIPEC. Clinical and demographic data were similar between the groups. PCI, number of resected organs, and optimal cytoreduction rates were comparable. Patients who underwent laparoscopic experienced a lower estimated blood loss, (median, [IQR 1-3]); 150mL, [50-300] vs. 100mL, [50-125], p = 0.04, shorter length of stay (median [IQR 1-3]; 4days [3-6] vs. 6days [5-8], p < 0.01, and a lower 30-day complication rate (6.3% vs. 56.3%, p < 0.01). There was no difference in progression-free survival (p = 0.577) and overall survival (p = 0.472) between the groups. This preliminary study demonstrates that laparoscopic CRS/HIPEC is feasible and safe for curative treatment in selected patients with low tumor volume. Minimally invasive CRS/HIPEC is associated with fewer postoperative complications and shorter length of stay. There was no difference in long-term oncological outcomes between the groups.

Laparoscopic cytoreductive surgery and HIPEC in LAMN with small volume of peritoneal disease: a valuable option of treatment for good patient-related experience measures (PREMs).

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the best effective treatment for pseudomyxoma peritonei (PMP). In the last years, the advances in histopathology have stratified PMP lesions in different degrees of aggressivity suggesting the possibility of a tailored treatment. In a subset of patients with small volume peritoneal disease, laparoscopic CRS and HIPEC is feasible. The aim of this study is to analyze the results of laparoscopic CRS + HIPEC in a monocentric series of patients under patient-related experience measures (PREMs). All consecutive patients who underwent laparoscopic CRS-HIPEC with curative intent at Cancer Institute of Montpellier were retrieved from a prospectively maintained database and analyzed. Selection criteria for laparoscopic approach were low-grade PMP with pathological confirmation prior to CRS-HIPEC, age < 75years, no extra-peritoneal disease, peritoneal cancer index (PCI) < 10, and a limited history of abdominal surgery. A PREMS interview was conducted before analysis with all the included patients. Outcomes of interest included postoperative morbidity, medium-term survival, and PREMs. Fourteen patients were operated on for low-grade PMP with a laparoscopic approach at our institution. Conversions to laparotomy were necessary in three patients, and postoperative complications were observed in three patients (Clavien 3b in one patient). In-hospital postoperative median stay was 9.5days. No death or recurrence was observed during the study period. Laparoscopic CRS-HIPEC for LAMN in presence of small peritoneal disease is feasible in terms of postoperative morbidity and mortality. According to our PREMs questionnaire, patients' expectations were satisfied.

Conversion Surgery for Patients with Advanced Gastric Cancer with Peritoneal Carcinomatosis.

Background Patients with advanced gastric cancer (AGC) with peritoneal carcinomatosis (PC) usually have poor outcomes and high mortality risk, even with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study analyzed the prognostic factors of AGC with PC and evaluated laparoscopic HIPEC (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) as a conversion surgery for AGC patients with PC with a poor initial prognosis. Patient and Methods. We retrospectively evaluated 127 patients with AGC and PC from January 1, 2012, to March 1, 2020. After the exclusion of 32 ineligible patients, the conversion group comprised 34 patients who underwent LHIPEC + NIPS as a conversion surgery followed by CRS plus HIPEC. The CRS + HIPEC group included 15 patients who underwent CRS with HIPEC alone. Additionally, the C/T group comprised 23 patients who received systemic chemotherapy, and the palliative group comprised 23 patients who received only conservative therapy or palliative gastrectomy. Results The conversion group demonstrated a significantly better mean overall survival compared to the CRS + HIPEC, C/T, and palliative groups (p < 0.001). Patients in the conversion group who underwent LHIPEC + NIPS had significantly decreased peritoneal cancer index (PCI) scores (p < 0.001) and ascites (p=0.003). Malignant ascites amount also significantly decreased after treatment in the LHIPEC + NIPS group (p < 0.001). Conclusions LHIPEC + NIPS can significantly improve the overall survival, the PCI score, and malignant ascites amount in peritoneal cytology-positive gastric cancer with PC, and an initially high PCI score. Therefore, it may be a feasible conversion strategy for AGC patients with PC.

Review of management and treatment of peritoneal metastases from gastric cancer origin.

Gastric cancer (GC) is the third cause of cancer-related deaths in the world, with less than 25% survivors at 5 years. These results are largely related to the high incidence of peritoneal metastases (PM) in these patients. Nowadays, the standard treatment for GC with PM is palliative systemic chemotherapy (SCT) with a survival of 6 months. From the 2000s, the combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been gaining popularity for different neoplastic diseases that involve the peritoneal surface. The use of CRS and HIPEC has been studied for GC with PM, with promising results in selected patients, obtaining survival rates never seen before. Moreover, HIPEC and other intraperitoneal chemotherapy techniques have been used to prevent peritoneal recurrences in patients diagnosed on locally advanced GC without macroscopic PM (adjuvant or prophylactic HIPEC). Even, intraperitoneal chemotherapy [laparoscopic HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy (NIPS)] has been used as neoadjuvant treatment to reduce peritoneal disease burden in order to improve the rate of patients in whom complete cytoreduction can be achieved. Finally, patients with high volume peritoneal disease can be treated by palliative intraperitoneal chemotherapy to control the symptoms resulting from malignant ascites, using laparoscopic HIPEC or pressurized intraperitoneal aerosol chemotherapy (PIPAC). This review aims to update the management of PM from GC origin in these different clinical scenarios, based on the literature and the experience of the authors.

Surgery with hyperthermic intraperitoneal chemotherapy after response to induction chemotherapy in patients with peritoneal metastasis of gastric cancer.

Gastric cancer (GC) with peritoneal metastases (PM) has a dismal prognosis and to date only a few management options have been reported. Of those, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after induction bidirectional intraperitoneal and systemic chemotherapy (BIPSC) appear as a promising treatment option for these patients. Outcome data including safety and efficacy of CRS with radical Gastrectomy and HIPEC after response to combination of laparoscopic HIPEC (LHIPEC) with BIPSC as an induction therapy in patients with PM of GC was evaluated in this retrospective observational study. Diagnostic Laparoscopy was performed in 53 patients with PM of GC who admitted to the Center for Treatment of Peritoneal Surface Malignancies, Istanbul, between 2013 and 2016. Peritoneal cancer index (PCI), ascites status and cytology were determined. The patients underwent LHIPEC and then, BIPSC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2) and intravenous Docetaxel/Cisplatin/5-Fluorouracil (DCF) for 3 cycles. In selected patients, CRS with radical gastrectomy and HIPEC were performed after the response to induction therapy. BIPSC was continued for 3 more cycles with a dose reduction in an adjuvant setting. All LHIPEC procedures were uneventful with Grade 1-2 side effects (11/53, 20,8%). As a response to induction chemotherapy PCI was reduced from 19.6±8 (range, 6-39) to 13.6±9.8 (range, 1-39) (P<0.001). Ascites was detected in 55% (29 out of 53) and cytology was positive in 51% (27 out of 53) of the patients before induction chemotherapy. Ascites was completely abolished and all cytology became negative. Then, 34 of 53 (64.15%) patients underwent CRS with radical gastrectomy and HIPEC. CC0/1 resection was achieved in 22 (64.70%) of patients (P<0.05). The median survival time was 18.9±13.4 (95% CI: 15.2-22.6 months. Combined surgery and HIPEC related mortality occurred in 1 out of 34 patients (2.9%) due to developed diffuse intravascular coagulation at postoperative day 2. Grade 2 operative complications included biliary fistula in one, and duodenal stump leakage in two patients (8.7%). All of the fistula closed with conservative management. The median survival time was 18.9±13.4 months and the median progression-free survival time was 15.6±12.9 with 1-, 2-, and 5-year survival rates of 82.4%, 59% and 17.6% in patients with PM of GC. Multivariate analysis identified high peritoneal cancer index (P=0.000) and complete resection (P<0.05) as independent predictors for better progression-free and overall survival. The best outcomes can be expected with optimal cytoreduction and limited peritoneal dissemination in response to induction chemotherapy. Knowledgeable selection of patients with PM of GC is essential to perform surgery with HIPEC safely with acceptable mortality and morbidity.

Laparoscopic cytoreductive surgery and HIPEC for advanced ovarian cancer

Laparoscopic cytoreductive surgery and HIPEC for advanced ovarian cancer

Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei-A Novel Treatment Approach.

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m2, 60 min, 43 °C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m2 + cisplatin 40 mg/m2, accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m2) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

Factors Associated with Resection and Survival After Laparoscopic HIPEC for Peritoneal Gastric Cancer Metastasis.

Although laparoscopic hyperthermic intraperitoneal chemotherapy (LS-HIPEC) has been proven safe in patients with gastric adenocarcinoma and carcinomatosis or positive cytology, patient selection criteria remain unclear. Thus, we perform a retrospective analysis to identify factors associated with improved survival and resection rates. Data for all patients undergoing LS-HIPEC for stage IV gastric adenocarcinoma between June 2014 and November 2018 were collected prospectively and analyzed for associations with survival and resection using uni- and multivariate logistic regression, Cox proportional hazards models, and Kaplan-Meier survival functions. Of 70 patients who underwent LS-HIPEC, 43 (61%) received two drugs (mitomycin C and cisplatin), and 27 (39%) received three drugs (mitomycin C, cisplatin, and paclitaxel). The two groups' demographic and oncologic differences were not significant, although the three-drug group had a significantly lower rate of radiation therapy use (58% vs. 15%; p < 0.01). Univariate analysis revealed that poor differentiation [Cox hazard ratio (HR) 2.75; 95% confidence interval (CI) 1.34-5.63; p < 0.01], gross carcinomatosis (HR 3.10; 95% CI 1.52-6.30; p = 0.03), and ascites (HR 3.43; 95% CI 1.88-6.26; p < 0.01) were associated with shorter median survival. Gastrectomy was associated with improved overall survival (HR 0.32; 95% CI 0.15-0.70; p < 0.01). The resection rate of the 45 patients without ascites (38%) was significantly higher than that of the 25 patients with ascites (0%; p < 0.01). Our findings identify ascites as a significant prognostic factor for gastric cancer patients with peritoneal metastases undergoing LS-HIPEC. Our findings can be used to help identify patients who are unlikely to proceed to resection after LS-HIPEC and are good candidates for novel therapeutic approaches or clinical trials.