Pancreatic cancer with synchronous peritoneal and hepatic metastases: A case report.

Introduction and importance: There is evidence that patients with limited peritoneal carcinomatosis of pancreatic cancer or those with low burden of hepatic metastases are amenable to surgical resection. A case report of a patient with cancer of the pancreatic tail and synchronous peritoneal and hepatic metastases is presented. CASE PRESENTATION: A male patient, 66 years old, underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and radio-frequency ablation (RFA) for synchronous hepatic metastases simultaneously to distal pancreatectomy for adenocarcinoma of the pancreas. Adjuvant chemotherapy followed the R0 surgery. The patient remained disease free for 18 months, developed liver recurrence and died 28 months after the initial operation. DISCUSSION: CRS plus HIPEC with synchronous ablation or resection of hepatic metastases may be used for the treatment of pancreatic cancer with synchronous peritoneal and hepatic metastases in highly selected patients. CONCLUSION: Further studies are needed to confirm whether patients with synchronous peritoneal and hepatic metastases are offered survival benefit from complex surgical intervention (CRS plus HIPEC combined with hepatic resection or RFA).

Morbidity and mortality of patients with peritoneal malignancy following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The purpose of this study was to record the incidence, and identify the prognostic variables of morbidity and mortality in patients with peritoneal malignancy undergoing cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The files of patients with peritoneal malignancy who underwent CRS + HIPEC from 2015-2022 were retrieved. Morbidity and hospital mortality were recorded and correlated to a variety of clinical variables. RESULTS: A total of 44/192 (22.9%) patients were recorded with postoperative complications. Grade 3 and 4 complications were 12.5%. The possible prognostic variables of morbidity were the extent of peritoneal malignancy and the number of suture lines. The mortality rate was 2.5% (5 patients). The number of FFP units, and peritonectomy procedures were identified as possible prognostic variables of hospital mortality. CONCLUSIONS: The morbidity rate in patients undergoing CRS + HIPEC is acceptable compared to morbidity of previous publications or major gastrointestinal surgical operations. The possible prognostic variables of morbidity are the extent of peritoneal malignancy, and the number of suture lines. The mortality rate is low. The possible prognostic variables of mortality are the number of FFP units, and the number of peritonectomy procedures.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer: 18 years of experience.

AIM: To identify the clinical and pathological factors associated with relapse in women who had undergone secondary cytoreductive surgery due to locally advanced recurrent ovarian cancer. METHODS: Women with locally advanced recurrent ovarian cancer who had undergone cytoreduction between 2000 and 2018 were included in this study. Demographic, clinical and biochemical intraoperative findings were recorded for each woman. All factors were assessed in order to identify which correlated with the outcomes of interest (i.e. disease relapse, mortality and morbidity). RESULTS: In total, 181 women who had undergone secondary cytoreduction were analysed. The hospital mortality rate was 1.7 % (n = 3) and the morbidity rate was 32.1 % (n = 58). Recurrence was recorded in 101 (55.8 %) women. Infiltration of large bowel lymph nodes was a negative prognostic indicator of morbidity (p = 0.029). A prior surgical score of 1 (PSS-1) [odds ratio (OR) 0.465] and complete cytoreduction (OR 0.518) were found to be significant independent predictors for disease relapse. Median overall survival was greater for patients with PSS-1 (151.3 vs 59.4 vs 44.1 months; p = 0.049) and patients with complete cytoreduction (137.6 vs 36.2 vs 10.0 vs 27.4 months; p < 0.001). CONCLUSION: Complete cytoreduction and PSS-1 are associated with reduced disease relapse and increased overall survival. Infiltration of large bowel lymph nodes is associated with increased morbidity.

Ovarian cancer: 20-year experience with cytoreductive surgery and perioperative intraperitoneal chemotherapy.

PURPOSE: Complete cytoreduction has been established as the most significant factor of long-term survival in epithelial ovarian cancer. Perioperative intraperitoneal chemotherapy has been added in the treatment of ovarian cancer the last 20 years. The purpose of the study was to determine the outcome of women with ovarian cancer using the data of one surgical team. METHODS: Women with ovarian cancer treated from 2000 to 2019 by the same surgical team were enrolled in the study. The patients underwent cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Clinical and histopathological variables were correlated to hospital mortality, morbidity, survival and recurrences. RESULTS: The mean age of 350 women was 59.5+11.7 years. The hospital mortality and morbidity rate were 2.0% and 28.3%, respectively. Complete cytoreduction was possible in 60% of the cases. The overall 5- and 10-year survival rate was 47% and 39%, respectively. The prognostic variables of survival were the extent of peritoneal malignancy, the extent of previous surgery, the grade of differentiation, the use of adjuvant chemotherapy, the lymphadenectomy of the resected large bowel, and the postoperative morbidity. The recurrence rate was 45.7%. The extent of peritoneal carcinomatosis, the extent of previous surgery, and the grade of differentiation were the prognostic variables of recurrence. CONCLUSIONS: The limited extent of peritoneal carcinomatosis in women with well differentiated ovarian cancer that do not have history of previous surgery, who undergo standard pelvic peritonectomy procedure, and receive adjuvant chemotherapy are expected to be long-term survivors.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in the treatment of rare tumors with peritoneal metastases.

PURPOSE: Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) is the standard treatment for tumors presented with peritoneal metastases (PM). Data in the literature about the treatment of rare tumors with PM are limited and of low-quality. The aim of the study was to assess the outcome and safety of CRS and HIPEC for these tumors. METHODS: Patients with rare tumors with PM that underwent CRS and HIPEC between 2005-2018, were retrospectively analyzed. Clinical and histopathological variables were correlated to survival. RESULTS: 43 patients, mean age 55.7 ± 12.9 years, underwent 48 cytoreductions. The most frequent histopathologic type was sarcomatosis (31.3%). The majority of the patients (70.8%) had limited extent of peritoneal disease. Complete or near-complete cytoreduction was achieved in 83.3% of the cases. Severe morbidity was recorded in 12.6%. The median disease-free survival and overall survival were 11 and 63 months, respectively. Although the completeness of cytoreduction was found to be significantly related to survival, the extent of peritoneal carcinomatosis was the single prognostic factor. CONCLUSIONS: CRS followed by HIPEC is an effective and safe method in the treatment of rare tumors with PM. Further large, well-designed prospective studies are needed to validate these results.

Twenty-years' experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP).

PURPOSE: Pseudomyxoma peritonei is treated with cytoreductive surgery (CRS) combined and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). The purpose of this study was to report the20-year experience of one surgical team inCRS and HIPEC for PMP of appendiceal origin. METHODS: Retrospective study of the files of patients with PMP of appendiceal origin that underwent CRS+HIPEC. Morbidity and hospital mortality were recorded. Clinical and histopathologic variables were correlated to survival and recurrence. RESULTS: The files of 41 patients with PMP of appendiceal origin that underwent CRS+HIPEC from 1999-2018 were retrieved. The mortality and the morbidity rates were 2.4% and 29.3%, respectively. The 5- and 8-year survival rate was 68.3%. The completeness of cytoreduction, and the extent of previous surgery were identified as the prognostic indicators of survival. The recurrence rate was 32.5% with the completeness of cytoreduction, the histologic type of the tumor being the prognostic indicator. CONCLUSIONS: CRS in combination with perioperative intraperitoneal chemotherapy is a safe and effective treatment in the management of PMP of appendiceal origin.

Hyperthermic intra-operative intraperitoneal chemotherapy as an adjuvant to pancreatic cancer resection.

BACKGROUND: Even after potentially curative resection the long-term survival of pancreatic cancer is poor. The local-regional failures are frequent. Previous studies have shown that adjuvant treatment with hyperthermic intra-operative intraperitoneal chemotherapy (HIPEC) may effectively control local disease. The objective of the study is to update the results of the prior publications by integrating data from recently accrued cases. Also, to revisit the clinical and pharmacological rationale for the intraperitoneal administration of chemotherapy in pancreatic cancer patients undergoing potentially curative resection. METHODS: This is a prospective study of pancreatic cancer patients that underwent R0 resection in combination with HIPEC-gemcitabine. Morbidity and mortality were recorded. Survival was calculated and the sites for recurrent disease were recorded. RESULTS: The updated results for 33 patients that underwent treatment until 2016 and for 6 more patients that were included until 2018 were presented. The hospital mortality and morbidity rate were 5.1% (2 patients), and 28.2% (11 patients) respectively. The median and 5-year survival rate was 17 months and 24% respectively. With a median follow-up time of 13 months 23 patients (59%) were recorded with recurrence. Local regional failures were recorded in 4 patients (10.3%). CONCLUSIONS: HIPEC following R0 resection is a feasible and safe adjuvant treatment for pancreatic cancer. The local-regional failures appear to be significantly decreased and to result in an increased overall survival. Further studies with combined intraperitoneal and systemic perioperative chemotherapy may serve to supplement our data with an increased benefit for patients having pancreas cancer resection.

Ten-year experience with peritoneal mesothelioma.

PURPOSE: Peritoneal mesothelioma is a rare disease that remains confined to the peritoneal surfaces for long. Cytoreductive surgery (CRS) combined with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is the most effective treatment and complete cytoreduction is the most significant prognostic indicator of long-term survival. This study attempted to present the results of CRS in combination with hyperthermic intraperitoneal chemotherapy in patients with peritoneal mesothelioma and identify the prognostic indicators of survival. METHODS: The files of patients with peritoneal mesothelioma were retrospectively reviewed. Morbidity, hospital mortality, recurrences, and the sites of recurrence were recorded. Survival and recurrence were correlated to performance status, age, extent of peritoneal dissemination, tumor grade, tumor volume, and completeness of cytoreduction. RESULTS: From 2005-2017, 29 patients underwent 33 cytoreductions for peritoneal mesothelioma. Hospital mortality and morbidity were 3% and 27.3% respectively. The median and 8-year survival were 66 and 62% months, respectively. The completeness of cytoreduction was the single prognostic indicator of survival, and the tumor grade the single prognostic indicator of recurrence. CONCLUSION: CRS combined with HIPEC is the therapeutic strategy that may provide long-term survival.

Cytoreductive Surgery in Combination with HIPEC in the Treatment of Peritoneal Sarcomatosis.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal carcinomatosis, but it has been debated for peritoneal sarcomatosis. The purpose of the study is the presentation of perioperative and long-term results of CRS and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal sarcomatosis. Retrospective study in a prospectively maintained database of 20 patients that underwent 29 CRS + HIPEC for peritoneal sarcomatosis. Clinical and histopathologic variables were correlated to survival. Complete cytoreduction was possible in 86.2% of the cases. The hospital mortality and morbidity rate were 0 and 20.7%, respectively. The median follow-up was 26 months, and recurrence was recorded in 20 cases (69%). The median and 5-year survival was 55 ± 13 (34-58) months and 43%, respectively. Prior surgical score (PSS) was the single variable related to survival (p = 0.018). The histologic subtype of the tumor was related to recurrence (p < 0.001). CRS and HIPEC in peritoneal sarcomatosis may offer a survival benefit in selected patients with low hospital mortality. The variety of histologic types of sarcomatosis has not made possible the identification of subgroups of patients that may be offered significant benefit by CRS and HIPEC. Further studies are required.

Cytoreduction and HIPEC for peritoneal carcinomatosis of pancreatic cancer.

PURPOSE: Peritoneal carcinomatosis of pancreatic cancer is generally considered for palliative treatment. The purpose of this study was to report the outcome of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in patients with pancreatic cancer and peritoneal carcinomatosis. METHODS: Patients with documented resectable peritoneal carcinomatosis of pancreatic cancer underwent cytoreductive surgery in combination with HIPEC from 2008-2016 by the same surgical team. RESULTS: Six patients underwent 8 cytoreductions. Complete or near-complete cytoreduction was possible in 7 cases, and palliative surgery in one case. Gemcitabine was used in 5 cases during HIPEC, and cisplatin+mitomycin-C in 2 others. All patients received adjuvant chemotherapy with gemcitabine. Four patients survived without evidence of recurrence for more than 12 months. CONCLUSIONS: Cytoreductive surgery with HIPEC may be considered a treatment option in highly selected patients with pancreatic cancer and peritoneal carcinomatosis.

Cytoreductive surgery and hyperthermic intraperitenoal chemotherapy (HIPEC) for colorectal and appendiceal carcinomas with peritoneal carcinomatosis.

PURPOSE: Cytoreductive surgery combined with intraperitoneal chemotherapy has been established as the standard treatment for selected patients with peritoneal malignancy. The purpose of the study was the presentation of the 10- year experience with cytoreductive surgery and intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal and appendiceal origin. METHODS: Clinical and histopathological variables were retrospectively reviewed in a prospectively maintained database. All patients underwent cytoreductive surgery with the purpose of complete or near-complete cytoreduction. The variables were correlated to survival, and recurrences. Morbidity and hospital mortality were recorded. RESULTS: From 2006-2016 100 patients underwent cytoreductive surgery for colorectal and appendiceal carcinomas with peritoneal carcinomatosis. The hospital mortality and morbidity were 2% and 43% respectively. Completeness of cytoreduction (CC) 0 surgery was possible in 51% of the patients. The median and 10-year survival were 13 months and 23% respectively. The completeness of cytoreduction, performance status and the lymph node status were identified as prognostic indicators of survival. The recurrence rate was 55%. The completeness of cytoreduction, the lymph node status, and the use of postoperative adjuvant systemic chemotherapy were identified as prognostic variables of recurrence. CONCLUSION: Nearly half of the patients with peritoneal carcinomatosis of colorectal and appendiceal origin may undergo complete cytoreduction and nearly half of them may enjoy long-term survival.

The effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) as an adjuvant in patients with resectable pancreatic cancer.

Background - aims: The long-term survival of pancreatic cancer is poor even after potentially curative resection. The incidence of local-regional failures is high. There is evidence that hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) is effective in controlling the local-regional failures. The purpose of the study is to identify the effect of HIPEC after surgical removal of pancreatic carcinoma. Patients - Methods: Prospective study including 33 patients with resectable pancreatic carcinomas. All patients underwent surgical resection (R0) and ΗIPEC as an adjuvant. Morbidity and hospital mortality were recorded. The patients were followed-up for 5 years. Survival was calculated. Recurrences and the sites of failure were recorded. RESULTS: The mean age of the patients was 67.8 ± 11.1 years (38-86). The hospital mortality was 6.1% (2 patients) and the morbidity 24.2% (8 patients). The overall 5-year survival was 24%. The mean and median survival was 33 and 13 months, respectively. The median follow-up time was 11 months. The recurrence rate was 60.6% (20 patients). Three patients were recorded with local-regional failures (9.1%) and the others with liver metastases. CONCLUSIONS: It appears that HIPEC as an adjuvant following potentially curative resection (R0) of pancreatic carcinoma may effectively control the local-regional disease. Prospective randomised studies are required.

Lack of significant intraoperative coagulopathy in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) indicates that epidural anaesthesia is a safe option.

PURPOSE: The purpose of this study is to evaluate the fluctuations of coagulation parameters during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) and confirm beyond doubt that epidural anaesthesia is safe with this type of operations. MATERIALS AND METHODS: This is a prospective clinical study of consecutive patients who had cytoreductive surgery and HIPEC. An epidural catheter was inserted into all patients. Peripheral venous blood samples in specific time points of the procedure were tested for complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), fibrinogen, D-dimer, and expression of the GpIIb/IIIa platelet receptor. RESULTS: A total of 51 consecutive patients were included in this study. The initial mean (SD) platelet count decreased significantly to a mean of 250.6 (105.4) 10(9)/L (p < 0.001). Fibrinogen levels decreased to 295.9 (127.4) mg/dL (p = 0.009). D-dimer levels increased to 5.3 (3.1) mg/dL (p < 0.001). APTT increased from 30.8 (5.8) s to 35.1 (4.6). The mean INR increased significantly to 1.5 (0.5) (p < 0.001). The total number of GpIIb/IIIa platelet receptors showed no significant variation throughout the measurements and was 72603.2 before HIPEC, 80772.4 during, and 77432.1 after. All the parameters examined, despite significant fluctuations remained in levels that would permit perioperative epidural analgesia. No related complications were recorded. CONCLUSION: Our results support the belief that epidural analgesia is a safe option in cytoreductive surgery and HIPEC despite certain intraoperative fluctuations in coagulation parameters. It is of major importance to regulate any abnormalities observed during surgery. There are no available data regarding the occurrence of coagulopathy in the post-operative period.

Treating peritoneal mesothelioma with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. A case series and review of the literature.

BACKGROUND: Encouraging results on survival of patients with malignant peritoneal mesothelioma have been shown with the use of cytoreductive surgery and perioperative intraperitoneal chemotherapy. This study explores the impact of aggressive surgical treatment on overall survival of peritoneal mesothelioma. METHODS: This is a retrospective analysis of prospectively collected clinical data of all patients with diagnosis of malignant peritoneal mesothelioma treated in a designated referral centre in Greece. All patients were offered cytoreductive surgery and intraperitoneal chemotherapy. Patient's characteristics, operative reports, pathology reports, and discharge summaries were stored in an electronic database and later reviewed and analysed. RESULTS: Cytoreduction for peritoneal mesothelioma was performed on 20 patients (15 men and 5 women) with a mean age of 59.4 years (SD 16.1). Mean peritoneal cancer index was 16.1 (SD 10.4) and the median completeness of cytoreduction score was 2 (range 1-2). Mean overall survival was 46.8 months (SE 4.03) with a mean of 21.4 and median of 18 months of follow-up. Disease-specific survival was 100% for the observed period. Univariate analysis showed the completeness of cytoreduction as the only possible predictor of survival. A median of 10 (range 4-14) peritonectomy procedures were performed per patient. Median hospital stay was 14 (range 10-57 days). Grade III and IV complications occurred post-operatively in 5 patients (25%). Two patients died in the post-operative period of pulmonary embolism and myocardial infarction. CONCLUSION: Cytoreductive surgery with HIPEC has proved the most effective treatment even when taking account of the cost of significant morbidity.

HIPEC in controversial digestive tumors.

Local-regional and peritoneal metastases still develop despite improvements in surgical techniques. Intraperitoneal chemotherapy has been proved to be effective in reducing the rate of local-regional and peritoneal metastases in many malignancies. There is adequate evidence that intraperitoneal perioperative chemotherapy after aggressive resection of locally advanced tumors of the digestive system may be helpful in decreasing the rate of local-regional and peritoneal metastases. Prospective trials and meta-analyses have shown that patients with locally advanced gastric or colorectal carcinomas are offered significant survival benefit and develop reduced number of local-regional metastases with surgery combined with perioperative intraperitoneal chemotherapy. In pancreatic cancer the preliminary results have shown that these patients do not develop local-regional recurrences with R0 resection in combination with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). Further studies are required to document these findings.

The relationship between E2F family members and tumor growth in colorectal adenocarcinomas: A comparative immunohistochemical study of 100 cases.

The mammalian E2F family of transcription factors comprises a group of 8 proteins, which either activate or repress transcription of numerous target genes, playing a role in cell-cycle progression and apoptosis. We have collectively investigated the immunohistochemical expression of E2F1, E2F2, and E2F4 transcription factors and their relation to cell kinetic parameters using serial section analysis in a series of 100 cases of human colorectal adenocarcinomas. E2F1 and E2F4 expressed nuclear immunopositivity in all cases. The range of their expression was 2% to 80% (mean 21% ± 15%) and 2% to 90% (mean 66% ± 20%), respectively. E2F2 was expressed in 41 cases at low levels (range, 1% to 5%, mean 2% ± 9%). A statistically significant direct association between E2F4 and cell proliferation, as expressed by high levels of Ki-67 labeling index, was shown. A mutually exclusive immunostaining pattern between E2F1 and E2F4 and a direct correlation of E2F1 and apoptosis were also highlighted. Our results point to a possible direct tumor-promoting role for E2F4 in the context of colorectal carcinogenesis. The inverse immunohistochemical relationship between E2F1 and E2F4 indicates a possible mechanistic interlink in colorectal cancer. Low expression of E2F2 may reflect functional redundancy between members of the E2F family, in this case between E2F1 and E2F2.

Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival.

BACKGROUND: DNA methylation represents one of the most common epigenetic changes in human cancer providing important information regarding carcinogenesis. A possible role as a prognostic indicator has also been proposed. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation status in patients with operable gastric cancer. METHODS: Using methylation-specific PCR (MSP) we examined the incidence and prognostic significance of SOX17 methylation status in cell free circulating DNA in the serum of 73 patients with operable gastric cancer. Fifty-one patients were male (69.9%), their median age was 65 years, 43 patients (58.9%) had regional lymph node involvement and all had a Performance Status (WHO) of 0-1. RESULTS: SOX17 promoter was found to be methylated in 43 out of 73 gastric cancer serum samples examined (58.9%). All 20 control serum samples from healthy individuals were negative. Overall survival (OS) was found to be significantly associated with SOX17 methylation (p=0.049). A significant correlation between methylation status and differentiation (p=0.031) was also observed. No other significant associations between different tumor parameters examined and SOX17 methylation status were observed. CONCLUSIONS: SOX17 promoter methylation in cell free DNA of patients with operable gastric cancer is a frequent event and may provide important information regarding prognosis in this group of patients.

Preliminary results of hyperthermic intraperitoneal intraoperative chemotherapy as an adjuvant in resectable pancreatic cancer.

Background and Aims. 5-year survival in patients with pancreatic cancer is poor. Surgical resection is the only potentially curative resection. The results of adjuvant treatment either with chemotherapy or with radiotherapy have been contradictory and the incidence of local-regional recurrence remains high. If local-regional recurrence is controlled survival may be expected to increase. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) may be used in order to control local-regional recurrences. The purpose of the study is to identify the effect of HIPEC in patients with pancreatic cancer undergoing potentially resection. Patients and Methods. From 2007-2011, 21 patients, mean age 69.4 ± 9.5 (50-86) years, underwent tumor resection, and HIPEC with gemcitabine. The hospital mortality and morbidity rate was 9.5% and 33.3%, respectively. 5-year and median survival was 23% and 11 months, respectively. The recurrence rate was 50% but no patient developed local-regional recurrence. No patient was recorded with gemcitabine-induced toxicity. Conclusions. This clinical study of 21 patients is the first to combine an R(0) pancreas cancer resection with HIPEC. Increased morbidity and mortality from intraoperative gemcitabine was not apparent. Patients with pancreatic cancer undergoing potentially curative resection in combination with HIPEC may be offered a survival benefit. Data suggested that local-regional recurrences may be greatly reduced. Further studies with greater number of patients are required to confirm these findings.