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.

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.

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.

Spiliotis-Farfarelos Maneuver for the Management of Small Bowel Obstruction and Frozen Pelvis in Patients With Peritoneal Metastasis.

The management of the advanced peritoneal disease is demanding especially in cases of extensive bowel infiltration and the obstruction of the gastrointestinal tract in different sites. Patients with bowel obstruction due to peritoneal carcinomatosis have an overall survival that ranges from three to eight months to four to five weeks based on the operability or not of the disease, respectively. The decision to operate should carefully consider the balance between the probability of symptomatic relief and the risk of severe perioperative complications and survival after surgery. The extent of the disease and postoperative malnutrition could further complicate patients' postoperative course. We aim to present an operative maneuver of bowel preparation and fixation in cases of extensive infiltration of the small bowel by peritoneal carcinomatosis (PC) in order to eliminate the risk of postoperative fistula formation or anastomotic leakage.

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.

Intestinal preconditioning ameliorates ischemia-reperfusion induced acute lung injury in rats: an experimental study.

BACKGROUND: Phospholipases A(2) (PLA(2)) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) induced by intestinal ischemia-reperfusion (IIR). Intestinal ischemic preconditioning (IIP) has been shown to improve intestinal tolerance to subsequent sustained ischemia and limit the systemic inflammatory response. We tested the effect of IIP on the intestinal ischemia-reperfusion-induced ARDS, with particular focus on PLA(2). METHODS: Rats were randomized into three groups: (1) sham surgery group (sGroup), 45 min sham intestinal ischemia-4 h reperfusion, (2) IIR group (IIRGroup), 45 min intestinal ischemia-4 h reperfusion, (3) IIP group (ipGroup), three cycles of intestinal ischemia for 4 min and reperfusion for 10 min followed by 45 min intestinal ischemia-4 h reperfusion. At the end of each experiment, blood gases were obtained and bronchoalveolar lavage (BAL) followed. Biochemical (total protein, PLA(2), PAF-AcH) and cytological parameters of the BAL fluid were quantified. Plasma MDA was measured as an indicator of systemic oxidative stress. Comparisons between groups were made using one-way ANOVA followed by post hoc comparison with a Tukey test or Mann-Whitney test when appropriate. Differences were considered significant if P < 0.05. RESULTS: Alveolar-arterial O(2) gradient values and wet to dry lung ratio were significantly (P < 0.05) increased in the IIRGroup and this increase was prevented in the ipGroup. Following the same pattern, BAL total protein, PLA(2), and PAF-AcH were significantly lower in the ipGroup. Ischemic preconditioning significantly abolished neutrophil count in BAL fluid. Plasma MDA was significantly lower in the ipGroup. Despite a significant tissue polymorphonuclear reduction, no significant lung or intestinal histologic damage score changes were revealed. CONCLUSIONS: Intestinal preconditioning protects IIR-induced lung injury, partly by modulating the arachidonic acid cascade.

Anatomic Variations of the Deep Femoral Artery and Its Branches: Clinical Implications on Anterolateral Thigh Harvesting.

The deep femoral artery (DFA) is the largest branch of the common femoral artery (CFA), supplying with its branches, the medial circumflex femoral artery (MCFA) and lateral circumflex femoral artery (LCFA), the thigh muscles, the hip joint, and the femur. Their anatomical variations have a great impact on both interventional and surgical procedures. The anterolateral thigh (ALT) flap, a versatile soft tissue with highly increasing use in reconstructive surgery, is noticeably influenced by this variability. A total of 25 articles were incorporated into the review. Studies conducted after the year 2009 were included. After the assessment of all studies included, we concluded that the DFΑ arises from the CFA with a varying site of origin, the posterolateral being the prevalent one found in 51.32% of cases. Of all cases studied, the MCFA and the LCFA most often originated from the DFA in 63.125% and 74.92%, respectively, but the CFA constitutes another frequent source of origin in 27% and 12.12% of cases, respectively. The descending branch of the lateral circumflex femoral artery (dLCFA) is the prominent pedicle in the ALT flap, originating from the LCFA in 83.55% of cases. However, the presence of an oblique lateral circumflex femoral artery (oLCFA) branch with changeable origination was observed. Knowledge of the anatomical variants in the deep femoral artery is imperative both for interventional radiologists and surgeons. Especially in reconstructive surgery, the possibility for different sources supplying the skin and the pedicle compel surgeons to acquire an awareness of this subject.

Pancreatic leak related hemorrhage following pancreaticoduodenectomy. A case series.

CONTEXT: Delayed arterial hemorrhage, secondary to pancreaticojejunal leakage, is an infrequent complication (2-4%) of pancreaticoduodenectomy but it carries a high mortality rate with more than half of the patients dying from overwhelming sepsis and/or bleeding. Its ideal management remains unclear. CASE REPORTS: We hereby present our experience with respect to the presentation and management of this severe post-pancreaticoduodenectomy complication which occurred in 3/149 patients (2.1%) operated on between 1996 and 2008 in our department and we review the role of endoscopy, interventional radiology and surgery in its management. CONCLUSIONS: The severity of the underlying sepsis and the prompt identification of the sentinel bleed determine surgical and angiographic intervention and define the outcome in the treatment of a pancreatic leak-related hemorrhage. Endoscopy has no role in this setting.

Secondary debulking for ovarian carcinoma relapse: The R-R dilemma ­ is the prognosis different for residual or recurrent disease?

Objective: To analyze the kind of ovarian cancer relapse by separating residual from recurrent disease and correlating them with patient survival. Material and Methods: This was a retrospective study of 200 women with ovarian carcinoma relapse between 2005 and 2017. Results: The main sites of residual disease included the great omentum, epiploic appendices, liver round ligament, gallbladder, and cervical/vaginal stump. The median survival for women with residual disease treated with cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) + systemic chemotherapy was 38 months compared with the control group, which reached 23.8 months. The morbidity rates were 18% vs 7%, respectively, and the mortality rates were 2.5% vs 1.3%. The main sites of recurrent disease included the mesenterium, pelvic floor, diaphragm, and Glisson's capsule. Women with recurrent disease treated with CRS + HIPEC + systemic chemotherapy had median survival rates of 26 months vs 16 months in the control group. The morbidity rates were 22% vs 15%, respectively, and the mortality rates were 3.3% vs 0%. Conclusion: Patients undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse have a different prognosis when compared with patients with residual and recurrent disease. A different prognosis is presented in women undergoing secondary debulking plus HIPEC for ovarian carcinoma relapse when comparing patients with residual and recurrent disease.

CRS and HIPEC in patients with peritoneal metastasis secondary to colorectal cancer: The small-bowel PCI score as a predictor of survival.

BACKGROUND: Combining cytoreductive surgery (CRS) with Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) can benefit patients with peritoneal metastasis from colorectal cancer. The present study evaluates the small bowel subset of the Peritoneal Cancer Index (Small-Bowel-PCI score (SB-PCI), min-max 0-12) as a prognostic factor in such patients. METHODS: We retrospectively analyzed patients that underwent CRS and HIPEC for recurrent colorectal cancer with peritoneal metastasis. Patient characteristics, procedure details, and clinical outcomes were evaluated. RESULTS: Eighty patients were included. The mean intraoperative PCI-score was 16.8, with a mean SB-PCI score of 5.9. CC0/1 was achieved in 62/80 patients. The mean follow-up period was 26.3 months. Univariate regression analysis showed that the ECOG status, the presence of severe complications, the HIPEC regimen (oxaliplatin vs. mitomycin-C), the PCI score, the SB-PCI score and the completeness of cytoreduction correlated significantly with overall survival. In multivariate analysis, the SB-PCI and CC score were identified as independent prognostic factors of survival. When the SB-PCI was stratified in three groups (0-4, 5-8 and 9-12), Kaplan-Meier curve analysis showed significant difference in survival (p<0.001). CONCLUSIONS: The SB-PCI correlates with overall survival in patients with peritoneal metastases secondary to colorectal cancer in this retrospective cohort. Its use should be validated in prospective patient series.