Cytoreductive surgery and HIPEC for peritoneal metastasis. Justified hope or desperate illusion? Fifteen years of experience from a Greek Peritoneal Surface Malignancy center.

PURPOSE: Peritoneal spread of neoplastic diseases is considered a fatal condition with a dismal prognosis. Few therapeutic options were offered to these patients and surgery had only palliative character. However, advances in surgical techniques and new drugs development, have changed the management of this terminal stage disease. Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC), has been proposed as a promising alternative to palliative surgery and systemic chemotherapy, since 1980s. Many changes through all these years have refined the technique and standardized indications and limits. METHODS: A retrospective study was performed in our medical records, of all patients treated with CRS and HIPEC since 2006. Survival, complications and prognostic factors were studied in a total of 632 patients. RESULTS: Female patients were 419 and males were 213. Mean age was 52.6 years. Peritoneal metastases secondary to colorectal cancer were the most frequent treated disease (87 patients), whereas hepatobilliary-pancreatic neoplastic diseases and sarcomas were the less frequent causes of peritoneal carcinomatosis. Patients with peritoneal metastases from ovarian cancer, treated with systemic chemotherapy and then received interval cytoreductive surgery with HIPEC, were the largest group that are still alive (43%), while only 35% of patients with hepatobilliary-pancreatic cancer and peritoneal disease are alive at present. Gender, age, peritoneal cancer index (PCI), completeness of cytoreduction score (CCs), and number of complications were important prognostic factors of overall survival. CONCLUSIONS: Peritoneal carcinomatosis is still considered a final stage disease with a poor prognosis. The confinement of the neoplastic disease in the peritoneal cavity has led to the development of local therapies with promising results. CRS and HIPEC have evolved significantly over the past several years and are at the present the most valuable treatment in highly selected patients with peritoneal carcinomatosis.

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.

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.

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.

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.

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.

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.

Hepatocellular Carcinoma Peritoneal Metastasis: Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

INTRODUCTION: Peritoneal dissemination of hepatocellular carcinoma (HCC) is a rare presentation with an incidence of 2-6%. The most common cause of peritoneal deposits is a ruptured HCC that results in tumor spillage into the peritoneal cavity. The overall incidence of spontaneous ruptures of HCC ranges from 5 to 15% and carries a high mortality rate of up to 50%. Other factors influencing peritoneal dissemination are the lymph node metastasis and the direct diaphragmatic invasion and there is no significant association with past history of FNAB, or percutaneous RFA or ethanol injection and lung or adrenal metastasis. Clinical Study: We present our experience with 4 patients with localized peritoneal metastases from HCC controlled and managed with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The mean peritoneal cancer index (PCI) was 10.2. In two cases there is a history of rupture at the onset of diagnosis and in one case dissemination of peritoneal cavity after FNB procedure. All patients after CRS and HIPEC received Sorafenib. RESULTS: In our study the mean time of onset of peritoneal metastasis was 13.5 months from initial operation and the mean survival was 30 months. Our results are comparable with other studies. CONCLUSION: Peritoneal metastasis of hepatocellular carcinoma is rare and the benefit of systemic chemotherapy is poor and from Sorafenib is not well described. Surgical resection of extrahepatic HCC metastasis remains challenging. However several case reports and a few case series have provided that surgical resection of HCC peritoneal implants may benefit. We believe from our experience in well-selected patients with peritoneal metastasis from HCC, cytoreductive surgery with HIPEC and Sorafenib may prolong survival compared to systemic chemotherapy alone.

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.

Locoregional treatment of peritoneal sarcomatosis A single-centre experience.

BACKGROUND: Peritoneal sarcomatosis appears to be responding poorly to systemic chemotherapy. Treatment options traditionally include surgical ressections, chemotherapy and radiation therapy. Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) offers a promising alternative locoregional treatment option. PATIENTS AND METHODS: We examine retrospectively 8 patients (4 females, 4 males) with peritoneal sarcomatosis. The most common histology type was the liposarcoma (4/8). The chemotherapeutic agents that were administered were mitomycin, cisplatin and doxorubicin. We analyse our cases with regard to the PCI, the CC score, the complications that occurred and the overall survival. RESULTS: A complete level of cytoreduction (CC0/1) was feasible in 5/8 of patients. We report post-operative complications such as GI leaks and fistulas in 3 cases and infections in 2 cases. Overall survival was proved to depend on the PCI (better overall survival rate when PCI<20) DISCUSSION: We identify acceptable morbidity, comparable to other series of patients undergoing CRS+HIPEC for other histologies. The specific sarcoma type and the previous treatment received prove to be factors that alter significantly the prognosis and the survival rates: therefore, conclusions cannot be safely excluded in such small patient series. On the whole, we conclude that, given the already positive and promising results from CRS+HIPEC in sarcomatosis, more studies need to be performed, in order to determine the role of all the aforementioned factors. KEY WORDS: Fibrosarcoma, HIPEC, Leiomyosarcoma, Liposarcoma, Rabdomyosarcoma, Sarcomatosis.

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.

Male breast cancer originating in an ectopic breast tissue in the umbilicus A Case Report.

INTRODUCTION: Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. Carcinomas of accessory breast tissue account for ∼0.3% of breast cancers, 5% of which are arising within a supernumerary breast. They are usually diagnosed at a later stage compared with breast cancer, due to their rarity and low clinical suspicion. CASE PRESENTATION: We present the case of a 58 years old male who was admitted to our hospital for an umbilical hernia, surgical repair. During surgery a small skin biopsy was excised and sent for pathological examination as routine procedure. The histological report revealed the presence of a poorly differentiated carcinoma. Immunochemical analysis confirmed adenocarcinoma of breast origin. CONCLUSION: Carcinomas of accessory breast tissue are rare and therefore they are usually of advanced stage in time of diagnosis. Few cases have been reported in literature of accessory breast tissue carcinomas in men. To the best of our knowledge, this is the only case in the literature, of ectopic breast tissue cancer in the umbilicus. KEY WORDS: Ectopic breast, Male breast cancer, Umbilicus.

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.

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.

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.

Short bowel syndrome after cytoreductive surgery and HIPEC: nutritional considerations.

PURPOSE: The aim of this study was to present a group of patients with <150 cm of small intestine after cytoreductive surgery (CRS)+hyperthermic intraperitoneal chemotherapy (HIPEC) and the special problems arising from this condition. METHODS: From November 2005 to November 2013, 130 patients were treated for peritoneal carcinomatosis (PC) with CRS+HIPEC. Ten patients (7.7%) were left with a short bowel due to anatomical and surgical reasons. All these patients were subjected to ileostomy. Four patients (40%) were treated for ovarian carcinoma, 4 (40%) for colon and appendiceal carcinoma, 1 for peritoneal mesothelioma and 1 patient for primary peritoneal carcinoma. The completeness of cytoreduction (CC) score was CC-0 in 4 patients (40%), CC-1 in 3 (30%) and CC-2 in 3 (30%). RESULTS: The mean length of the remaining small bowel was 105 cm (range 80-150). Mean hospitalization was 42 days vs 24 days in other patients with CRS+HIPEC (p<0.002). The daily ileostomy output increased between the 3rd to 4th week as a result of oral feeding and decreased at the 4th week due to somatostatin analogue administration and possible intestinal adaptation. The mean ileostomy output at 6 months was 810±100 ml vs 1590±210 ml the first month after CRS+HIPEC (p<0.001). The overall morbidity and mortality rate was the same as in patients without extensive resection. The impact of small bowel syndrome (SBS) on overall survival was very important, as the mean overall survival in the SBS group was 28.6 months vs 41 months in other CRS+HIPEC patients (p<0.001). CONCLUSIONS: SBS is sometimes inevitable in order to perform optimal cytoreduction. Special management is required for these patients, including special nutritional efforts and home total parenteral nutrition (TPN). Extensive small bowel resection may constitute a contraindication in the management of peritoneal carcinomatosis.

Management of diaphragmatic peritoneal carcinomatosis: surgical anatomy guidelines and results.

Surgical resections, such as peritoneal stripping (peritonectomy) or full-thickness resection of the diaphragm (FTDR), are performed for disseminated diaphragmatic lesions in patients with peritoneal carcinomatosis (PC). This article presents the anatomical steps of diaphragmatic surgery in order to avoid intraoperative and postoperative complications and to decrease the morbidity and mortality of cytoreductive surgery in patients with PC.