Upfront or intermediate treatment of advanced ovarian cancer patients with cytoreduction plus HIPEC: Results of a retrospective study.

BACKGROUND: Newly diagnosed advanced-stage ovarian cancer patients are treated with neoadjuvant chemotherapy, primary or intermediate cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to evaluate the optimal timing of cytoreduction plus HIPEC for advanced ovarian cancer patients. METHODS: Advanced ovarian cancer patients treated with cytoreductive surgery plus HIPEC at three different hospitals between 2005 and 2019 were subgrouped regarding their time of management with cytoreduction plus HIPEC, upfront or intermediate. We retrospectively assessed the overall survival (OS), the progression-free survival (PFS), and the disease-free survival (DFS) of these groups. RESULTS: A total of 112 ovarian cancer patients were contained. Of whom, 47 patients were in the upfront group with 24 (51.1%) to be alive, while 65 patients were included in the intermediate group with 34 (52.3%) to be alive. OS (48 vs. 30 months) and DFS (42 vs. 20 months) indicated no significant difference. Although the same median PFS was observed in both groups (10 months), a higher mean PFS was observed in the upfront group (11.9 vs. 9 months, p = 0.023). CONCLUSION: The treatment of advanced ovarian cancer patients with upfront cytoreductive surgery plus HIPEC is feasible with the same survival results. Further, larger prospective studies need to verify our results.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Metastases from Endometrial Cancer.

BACKGROUND: More information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome. RESULTS: A total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3-35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2 for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan-Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor. CONCLUSIONS: For selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.

Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases From a Small Bowel Adenocarcinoma: Multi-Institutional Experience.

BACKGROUND: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA). METHODS: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC. RESULTS: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS. CONCLUSION: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

Survival and nutritional factors on home parenteral nutrition (HPN): Our initial experience.

PURPOSE: Home parenteral nutrition (HPN) has been proposed as the treatment of choice in patients suffering from intestinal failure (IF) and has been claimed to improve survival and quality of life either in patients with benign disorders or even in those with malignancies. The purpose of the present analysis was to report characteristics and outcomes of adult patients with IF receiving HPN in Greece. METHODS: Patients that received HPN between 2011 and 2017 were included in this retrospective analysis. Characteristics of the included patients, cause of HPN, duration of HPN, route of HPN administration, complications as well as survival rates were recorded. RESULTS: A total of 189 patients were included in the present analysis. Of these, 163 (86.3%) suffered from cancer while 26 (13.7%) received HPN due to non-malignant diseases. The reported mortality was 74.6% while overall severe complications rate was 77%. CONCLUSIONS: According to the findings of our study, HPN seems to have beneficial effect but it should be considered with caution by the physicians who should take into account the indications of each patient to receive parenteral nutrition, the underlying disease and prognosis and the access of each patient to home care services.

Quality of life after cytoreductive surgery and HIPEC: A single centre prospective study.

PURPOSE: Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has become a crucial method in the management of peritoneal metastasis. This study evaluated the Quality of Life (QoL) post CRS plus HIPEC. METHODS: 80/95 patients underwent CRS plus HIPEC at the Metaxa Cancer Hospital, Piraeus, Greece from 06/2011 to 06/2015 and completed the colorectal version of the Functional Assessment of Cancer Therapy questionnaire (FACTC, version 4) at 1 week pre-operatively and at 1, 3, 6, 12, 18, 24 months post-operatively. The subscales assessed were the physical, social/family, emotional and functional wellbeing. RESULTS: In all subscales, fluctuations in the scores indicated a worsening of QoL in the first 3 post-operative months, followed by improvement back to pre-operative levels and even better scores later on. Statistical improvement was proven for the physical and emotional well-being subscales. CONCLUSIONS: The significant improvement in the physical well-being is attributed to the eradication of symptoms, whereas the relevant improvements in the emotional wellbeing subscale are explained both by the pre-operative desperation of the diagnosis or relapse of malignancy, and the post-operative hopefulness after a successful operation.

Does upfront therapy with cytoreductive surgery and HIPEC confer a survival benefit in patients with synchronous gastric peritoneal carcinomatosis when compared with patients with metachronous gastric peritoneal carcinomatosis?

Gastric cancer (GC) remains the second leading cause of cancer death worldwide, accounting for 8% of the total cases and 10% of total deaths in 2008. Surgery remains the curative treatment option for GC and the main reason for treatment failure is peritoneal recurrence which, according to the literature, occurs in 40-60% of the cases, despite extensive surgery including D2 lymph node dissection. The hyperthermic intraperitoneal chemotherapy (HIPEC) technique is increasingly used in the treatment of primary and digestive peritoneal carcinomatosis (PC), in association with cytoreductive surgery (CRS). We retrospectively analyzed 14 patients with gastric peritoneal carcinomatosis (GPC) undergoing CRS/HIPEC in the last 10 years. Six patients already had GPC at the time of diagnosis (group A) and 8 developed metachronous GPC (group B). Treatment with CRS and HIPEC didn't seem to confer a survival benefit to patients with synchronous PC from gastric cancer.

Perioperative systemic chemotherapy for peritoneal mucinous appendiceal carcinomas treated with cytoreductive surgery & HIPEC.

PURPOSE: To identify the role of systemic chemotherapy in the management of appendiceal malignancies. METHODS: Over a 10-year period (2005 -2014), 52 patients with appendiceal neoplasms were treated at our Peritoneal Surface Malignancy Unit [14 (26.9%) disseminated peritoneal adenomucinosis (DPAM), 30 (57.7%) peritoneal mucinous carcinomatosis of appendiceal origin (PMCA) and 8 (15.4%) PMCA-I]. All patients (100%) underwent cytoreductive surgery (CRS) & hyperthermic intraperitoneal chemotherapy (HIPEC), while 20 (38.5%) of them also received perioperative systemic chemotherapy. RESULTS: Mean peritoneal cancer index (PCI) was 23.6. Completeness of cytoreduction score (CC-S) was: CC-0 in 26 patients (50%), CC-1 in 20 patients (38.5%) and CC-2 in 6 patients (11.5%). High grade malignancy was reported in 27 patients (51.9%) and low grade malignancy in 25 patients (48.1%). More than half of the patients developed recurrence (n=36, 69.2%), while death was reported in 40.4% (n=21). Median overall survival (OS) in all histologic groups was 24 months for patients who received perioperative systemic chemotherapy and 14 months for patients who did not (p=0.048). Median disease free survival (DFS) in all histologic groups was 19 months for patients who received perioperative systemic chemotherapy and 10 months for patients who did not (p=0.034). CONCLUSION: We suggest that perioperative systemic chemotherapy serves as a helpful therapeutic tool in the management of peritoneal mucinous appendiceal carcinomas treated with cytoreductive surgery & HIPEC.

Hepatobiliary and pancreatic procedures during cytoreductive surgery and HIPEC.

PURPOSE: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used as locoregional treatment in selected patients with peritoneal malignancy. The purpose of this study was to report on the outcomes of patients undergoing hepatobiliary and pancreatic procedures during CRS and HIPEC. METHODS: A prospectively maintained database was used to identify patients that underwent hepatobilliary and/or pancreatic procedures during CRS and HIPEC. Outcome variables included morbidity, 30-day or in-hospital mortality, return to operating theatre, and complications. RESULTS: Sixty eight patients were included in the study, in whom 67 hepatobiliary and 15 pancreatic procedures were performed. Complete cytoreduction (CC-0/1) was achieved in 64 patients (94.8%). Twelve patients underwent liver resections, 50 underwent resection of Glisson's capsule, 5 underwent procedures of the biliary tree and 15 patients underwent pancreatic procedures. Major complications were encountered in 30/68 patients (44.1%). Pancreatic fistulas (PFs) were observed in 42.8% of the patients that underwent distal pancreatectomy. Reoperation rate was 8.8%, while 2.9% of the patients died during their hospital stay. CONCLUSION: The need for hepatobiliary procedures bears a significant - but acceptable - rate of morbidity. However, it should not represent a definitive contraindication for CRS and HIPEC.

Intensive care unit hospitalization after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: Peritoneal metastasis (PM) is nowadays treated with the complex procedure of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS+HIPEC). Given the fact that the procedure presents high morbidity and mortality rates, admitting patients to the Intensive Care Unit (ICU) seems inevitable. In our study, we have tried to determine the factors that indicate when admission in the ICU is necessary. METHODS: We retrospectively analyzed 230 patients (140 females, 90 males) with PM, who were operated on from November 2005 until October 2015, and underwent CRS+HIPEC. The patients were divided into two groups, based on whether they were extubated after the operation or not, thus being admitted to the ICU. We also distinguished a group of patients who, after the initial extubation, had to be re-intubated and transferred to the ICU. We assessed morbidity and mortality rates for each of the aforementioned groups, along with the complications developed in each case (thoracic, gastrointestinal, renal). RESULTS: We found that morbidity and mortality rates in both examined groups were approximately similar; the course changed when a complication occurred, and this increased mortality, especially if the onset of the symptoms was delayed. Also, these rates were much worse for the group that had to be re-intubated and transferred to the ICU. CONCLUSIONS: On the whole, we conclude that the decision of immediate admission to the ICU post-operatively is hard, as it depends on multiple factors; therefore, the use of an easy predictive method is not realistic and a more individualized and patient-to-patient approach is preferable.

The role of cytoreductive surgery and HIPEC in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer in the Western world. The current standard treatment of these patients consists of cytoreduction and systemic chemotherapy. One of the most distinct features of EOC is the tendency to disseminate into the peritoneal cavity and remain confined to the peritoneum and intra-abdominal viscera. This makes it an ideal target for loco-regional therapy. Improved long-term results can be achieved in highly selected patients using cytoreductive surgery (CRS), in combination with intra-operative hyperthermic intra-peritoneal chemotherapy (HIPEC). Optimal cytoreduction of advanced ovarian cancer is currently the most relevant prognostic factor. However, even when a complete resection is possible, the appearance of recurrences during follow-up is very common, due to the presence of microscopic residual disease, not visible to the surgeon. HIPEC has become a useful therapeutic strategy to obtain a higher degree of debulking by trying to eliminate the residual microscopic component responsible for recurrences. A summary of the current clinical evidence suggests that the most interesting settings first to explore in randomized trials are secondary CRS after upfront incomplete CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure to initial standard therapy. There is much less indirect evidence for a potential benefit of HIPEC for less advanced stages (I - II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation). CRS and HIPEC offer a significant survival benefit in patients with recurrent EOC. This observation applies to both platinum-sensitive and platinum-resistant disease.

Digestive fistulas after cytoreductive surgery & HIPEC in peritoneal carcinomatosis.

PURPOSE: The development of digestice fistulas is a complication of gastrointestinal operations during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In this article we present the incidence, management and outcome of enterocutaneous digestive fistulas after CRS and HIPEC. METHODS: Over the past 10 years (2005-2014), 184 patients with peritoneal carcinomatosis underwent CRS and HIPEC. HIPEC was administered in the operating room immediately after CRS, but in 48 (26%) patients this happened before the formation of intestinal anastomosis or repair of seromuscular tears, using the open (coliseum) technique; in the remaining 137 (74%) patients the anastomoses were performed before HIPEC. All patients were operated on by the same surgical team. RESULTS: Of the 185 patients 16 (8.6%) developed an enterocutaneous digestive fistula. Spontaneous fistula closure was observed in 14 (87.5%) patients. The median duration of spontaneous closure was 18 days (range 9-56). Reoperation was needed in 2 (12.5%) patients. There were 2 (12.5%) deaths. CONCLUSION: CRS and HIPEC is a well-known treatment modality for peritoneal carcinomatosis. The incidence of digestive fistulas is increased a little compared to that of conventional digestive surgery.

Cytoreductive surgery and HIPEC for peritoneal carcinomatosis. A review on morbidity and mortality.

PURPOSE: To review morbidity and mortality of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. METHODS: A literature search was conducted to identify studies from centers that perform CRS and HIPEC, and to collect and analyse data about morbidity and mortality. RESULTS: Twenty-five articles, published from 2006 to 2014 were reviewed. The studies included 24-1069 patients that had been treated with CRS and HIPEC for peritoneal carcinomatosis. The overall rate of severe perioperative morbidity ranged from 0 to 62% and the mortality rate varied from 0 to 10%. Major morbidity was correlated with age, peritoneal carcinomatosis index (PCI), comorbidities, number of digestive anastomoses and institution where the treatment was performed. CONCLUSION: Although the resultant morbidity is not negligible, with good patient selection this modality appears to be overall safe and effective in experienced hands. The results indicated that this treatment should be practised by institutions with expertise in the management of peritoneal carcinomatosis.

Clinical history of patients with peritoneal carcinomatosis exluded from cytoreductive surgery & HIPEC.

PURPOSE: The aim of this study was to explore the natural course of peritoneal carcinomatosis (PC) in patients who are not fit to undergo cytoreductive (CRS) surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Over an 8-year period (2006-2013) 320 patients were excluded from CRS and HIPEC at our center. Exclusion criteria were: (a) age >75 years; (b) ASA score ≥ 3; (c) extraperitoneal disease; (d) massive disease involvement of the small bowel; (e) disease involvement of the hepatic pedicle or the pancreas; (f) invasion of retroperitoneal space; (g) more than two stenoses of the small bowel. Another 130 patients underwent CRS and HIPEC. RESULTS: In the HIPEC group (N=130), the mean overall survival was 26.2±11.7 months, while from the non- HIPEC group (N=320), 200 patients underwent palliative surgery, with a mean overall survival of 11.7±8.3 months. Only 120 patients received palliative chemotherapy with a mean overall survival of 7.2±4.3 months. CONCLUSION: Our study suggests that, in patients unfit to undergo CRS & HIPEC, an exploratory laparotomy and palliative surgery should be performed, offering a survival benefit and improved quality of life.

Mapping the location of peritoneal metastases using the peritoneal cancer index and the correlation with overall survival: a retrospective study.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors within the Peritoneal Cancer Index (PCI) score in PC patients. METHODS: 140 patients (60 ovarian, 45 colon, 14 gastric, 10 pseudomyxoma peritonei, 5 mesothelioma, 6 sarcoma) with PC treated with CRS+HIPEC from 2007 to December 2013 were retrospectively included. Tumor extent and location were assessed by the PCI and residual disease was recorded using the Completeness of Cytoreduction (CC) score. All clinical data were computed in univariate and multivariate analysis using survival as primary endpoint. RESULTS: The PCI remains the most important factor concerning the long-term survival. Involved areas 4, 5 and 8 are more favorable in survival vs areas 9, 10 and 11, which predict a significantly worse outcome (p<0.002). Prognosis varies not only depending on how many peritoneal areas are involved but also on the location of the primary tumor. CONCLUSION: We demonstrated that the involvement of different areas in the PCI system has a significant impact on the final prognosis and survival.