Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases – The Hong Kong experience and literature review

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used to treat peritoneal metastases from appendiceal or colorectal origin. We evaluate our institution's experience and survival outcomes with this procedure, and its efficacy in symptom relief.MethodsThis is a single-centre retrospective observational study on patients with peritoneal metastases (PM) from appendiceal neoplasm or colorectal cancer who underwent CRS/HIPEC in Queen Mary Hospital. Our primary endpoints were overall survival (OS) and morbidity and mortality of this procedure; secondary endpoints included disease-free survival (DFS) and symptom-free survival.ResultsBetween 2006 and 2018, thirty CRS/HIPEC procedures were performed for 28 patients – 17 (60.7%) had appendiceal PM while 11 (39.9%) had colorectal PM. The median peritoneal cancer index was 20; complete cytoreduction was achieved in 83.3% patients. High-grade morbidity occurred in 13.3% cases. There was no 30-day mortality. Two-year OS were 71.6% and 50% for low-grade appendiceal PM and colorectal PM patients (p = 0.20). Complete cytoreduction improved OS (2-year OS 75.4% vs 20%, p = 0.04). Median DFS was 11.8 months. Median symptom-free duration was 36.8 months; patients with complete cytoreduction were more likely to remain asymptomatic (82.9% at 1 year, vs 60% in incomplete cytoreduction group, p < 0.01). 91.7% low-grade appendiceal PM patients and 58.4% colorectal PM patients remained asymptomatic at post-operative one year (p = 0.31).ConclusionCRS/HIPEC is beneficial to appendiceal PM and selected colorectal PM patients – improving survival and offering prolonged symptom relief, with reasonable morbidity and mortality. Complete cytoreduction is key to realising this benefit.     

The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases

Background

Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases.

Methods

This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection.

Results

These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes.

Conclusions

Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.

     

The role of single-incision laparoscopic peritoneal exploration in the management of patients with peritoneal metastases

The outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) depends on the extent of peritoneal metastases (PM) and the completeness of cytoreduction (CCR). The role of preoperative assessment of PM is to identify potential candidates for CRS/HIPEC and to prevent unwarranted laparotomy for those who are not. Laparoscopy has been utilized for that purpose but with concerns related to technical difficulties and risk of trocar site metastases. Single-incision laparoscopic peritoneal exploration (SILPE) has not yet been evaluated in this setting. This single-center retrospective study examined patients from January 2011 to December 2015 who underwent SILPE for diagnosis and staging of PM. Preoperative, intraoperative, and postoperative data were collected. For the patients who underwent subsequent laparotomy, a comparison between SILPE and laparotomy findings was made. A total of 183 SILPE were performed. Primary sites were mostly colorectal in 72 cases (39.3%) and gastric in 47 (25.7%). Overall, 157 patients (85.8%) had at least one prior abdominal surgery and 48 (26.2%) had 3 or more. SILPE was successfully achieved in 90.2% of the cases. Two (1.2%) intraoperative complications and five (3%) postoperative complications were observed. Eighty-one patients had laparotomy, with a median of 27 days between SILPE and laparotomy (4–162 days). The peritoneal carcinomatosis index PCI was 9.7 ± 7.5 at SILPE, and 13.5 ± 9.6 at laparotomy. The positive predictive value of SILPE to predict CCR was 79.5%. SILPE sensitivity was 75% and specificity 97%. The lowest sensitivity was in regions 9–12 ranging from 44 to 53%. SILPE can be safely incorporated in the management of patients with PM. It is a safe and feasible staging tool, allowing for preventing unwarranted laparotomy for patients not deemed candidate for CRS/HIPEC. Even though it may underestimate PCI, SILPE accurately predicts the possibility of CCR.     

Peritoneal Surface Disease Severity Score as a predictor of resectability in the treatment of peritoneal surface malignancies

Background

We evaluated the clinical utility of the Peritoneal Surface Disease Severity Score (PSDSS) as a preoperative predictor of resectability in the treatment of peritoneal surface malignancies.

Methods

Forty-nine patients were selected for cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and were stratified according to the PSDSS retrospectively.

Results

Of 52 cytoreductive surgeries performed in 49 patients, HIPEC was performed in 33 cases (63%). We analyzed 31 cases of appendiceal and colorectal cancer patients who underwent CRS and HIPEC and 12 who underwent CRS only. 68% of the patients in whom CRS and HIPEC was performed were classified as PSDSS stage I or II. Contrastingly, all patients in whom CRS and HIPEC was unachievable were scored as PSDSS stage III or IV.

Conclusions

The outcomes of this study suggest that the PSDSS can be used as a preoperative assessment tool to predict disease resectability in the treatment of peritoneal surface malignancies.     

Trends in the indications for and short-term outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

BackgroundCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM).MethodsThe US HIPEC Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ± HIPEC between 2000 and 2012 (P1) versus 2013–2017 (P2).ResultsAmong 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045).ConclusionCRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.     

Hepatobiliary Procedures in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

The long-term prognosis of patients with peritoneal malignancies has greatly improved since the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, CRS can be associated with high postoperative morbidity. In this retrospective study, we analyzed the influence of hepatobiliary surgery as part of CRS on postoperative short-term patient outcome.

Methods

Between 2005 and 2008, a total of 63 (25%) of 252 patients with peritoneal surface malignancies undergoing CRS and HIPEC required hepatobiliary surgery. Liver resection was performed in 22, resection of Glisson capsule in 39, and bile duct resection in 2 patients. The mean age of the study population was 49.3 years. Thirty-four patients (54%) were women.

Results

Complete macroscopic cytoreduction (CC-0/1) was reached in 59 patients (93.7%). The median hospital stay was 18 days. Twenty-two patients developed minor complications (35%), such as moderate fever, pain, or secondary wound healing. In 21 patients (33%), severe complications occurred, most commonly pancreatitis and abdominal abscess. Three patients (4.8%) developed a biliary leakage. Of these, 2 had to be reoperated.

Conclusions

In our experience, hepatobiliary procedures have to be performed in up to one-third of patients and are associated with a low rate of specific complications, such as biliary leakages.     

Survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A systematic review and discussion of latest controversies

IntroductionPeritoneal metastases confer the worst survival amongst all sites of metastatic colorectal cancer. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for patients with isolated colorectal peritoneal metastases (CRPM). The aim of this study was to evaluate the outcomes following CRS and HIPEC for CRPM from published high volume cohort studies and to highlight the latest controversies and future directions of CRPM treatment.Materials and methodsA systematic review was performed on published studies on the treatment outcomes of CRS and HIPEC for colorectal peritoneal metastases.ResultsTwenty studies met the inclusion criteria for the systematic review. The median survival for all patients ranged from 14.6 to 60.1 months. The 5-year overall survival ranged from 23.4% to 52%. For patients with complete cytoreduction, the median survival was 25 to 49 months. Major morbidity and mortality ranged from 15.1% to 47.2% and 0% to 4.5%, respectively.ConclusionCRS and HIPEC for the treatment of CRPM is safe and current evidence suggests it improves both median and disease-free survival. However, the efficacy of intraperitoneal chemotherapy, in particular oxaliplatin, has recently come under scrutiny. Accordingly, higher quality evidence is urgently required to contribute to multidisciplinary and international consensus on CRPM treatment strategies.     

Feasibility and benefits of an enhanced recovery after surgery protocol for patients undergoing cytoreductive surgery and heated intraperitoneal chemotharpy: A single institution experience

BackgroundCytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is reported to have a prolonged length of stay (LOS). We incorporated an enhanced recovery after surgery (ERAS) protocol to examine whether we could reduce our LOS.MethodsPatients were identified who underwent CRS/HIPEC from 2015 to 2018 before and after initiation of ERAS protocol. The protocol included pre-operative, peri-operative and post-operative interventions. Primary end point was LOS. Secondary endpoints were morbidity and mortality.ResultsForty patients were identified, thirty-one of which underwent CRS/HIPEC: 16 before and 15 after ERAS. The median LOS prior to ERAS was 11 days (5–20) and 7 days (5–27) after ERAS (P < 0.05). There was no significant difference in 30-day morbidity (Clavien-Dindo ≥3) or mortality between the groups.ConclusionsAn ERAS protocol can safely be implemented in patients undergoing CRS/HIPEC with earlier return of bowel function and decrease in LOS without increasing morbidity or mortality.     

Ovarian preservation with subcutaneous transposition in the setting of cytoreductive surgery

INTRODUCTIONIn recent years, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance as a treatment modality for peritoneal carcinomatosis. In female patients, this procedure involves a total hysterectomy and bilateral saphingo-oophorectomy to remove the pelvic peritoneum. We present a case of an unfortunate female adolescent with peritoneal carcinomatosis who underwent cytoreductive surgery and HIPEC. In view of the compelling circumstance, an innovative surgical technique was used to attempt ovarian preservation.PRESENTATION OF CASEA 14 year old girl with carcinoma of the sigmoid colon and peritoneal metastases was offered cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. In view of her age, ovarian preservation with subcutaneous transposition was performed during cytoreductive surgery. She is currently well 6 months post surgery and has resumed normal menstruation. We review the literature regarding ovarian preservation with subcutaneous transposition and discuss its benefit in pre-menopausal women undergoing peritonectomy and cytoreductive surgery for peritoneal carcinomatosis.DISCUSSIONSubcutaneous transposition of the ovary in pre-menopasual patients requiring cytoreductive surgery spares them the sequelae of surgical castration. The subcutaneous location of the transposed ovary conveys advantages such as the ease of ultrasound surveillance and removal in event of disease recurrence. It also retains the possibility of future conception as the transposed ovary can easily be accessed for ovum extraction with assisted reproductive techniques.CONCLUSIONOvarian preservation with subcutaneous transposition is a technique worth considering in the treatment of pre-menopausal women who require cytoreductive surgery for peritoneal carcinomatosis.     

Assessment of Neoadjuvant Chemotherapy on Operative Parameters and Outcome in Patients with Peritoneal Dissemination from High-Grade Appendiceal Cancer

Background

High-grade appendiceal adenocarcinoma is a rare malignancy with propensity for peritoneal metastases (PM). The impact of neoadjuvant chemotherapy on operative cytoreduction (CRS) and intraperitoneal chemotherapy (HIPEC) and patient survival was reviewed.

Methods

A total of 45 patients with PM from high-grade appendiceal adenocarcinoma were identified from a prospective database. All patients had laparotomy with intent to undergo CRS and HIPEC. Operative parameters, complications, and survival outcomes were analyzed.

Results

Of the 45 patients (male: 27, female: 18; median age: 55 years), 26 received neoadjuvant chemotherapy ± bevacizumab. Of the 26, 15 (58 %) had a response based on improvement in imaging, biomarkers, or both and 9 (34 %) had stable disease. The median peritoneal cancer index (PCI) was 27. Also, 30 (67 %) had a completeness of cytoreduction score (CCR) of ≤1 and 37 (82 %) received HIPEC. There were no differences in PCI, CCR score, operative blood loss, or major organ resection between those who received or did not receive neoadjuvant chemotherapy. Operative time was significantly shorter in those who did not receive neoadjuvant chemotherapy. Major complications and length of hospital stay were similar between the groups. The median actuarial overall survival calculated from the date of initial therapeutic intervention was not different in those treated with or without neoadjuvant therapy.

Conclusions

Neoadjuvant chemotherapy has marked clinical activity in patients with PM from high-grade appendiceal adenocarcinoma and does not adversely affect operative outcomes. These data support conducting a prospective clinical trial to define the role of neoadjuvant chemotherapy in this clinical setting.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in recurrent epithelial ovarian cancer with peritoneal metastases: a single centre experience

Background

This investigation aims to assess morbidity, mortality and postoperative outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (REOC) with peritoneal metastases (PM).

Methods

Consecutive patients with radiographic evidence of REOC with PM were scheduled for CRS and HIPEC at the Comprehensive Cancer Center, University Hospital Tübingen, Germany. Clinical data were retrospectively analyzed.

Results

In total, 90 patients were analyzed. Complete cytoreduction and HIPEC could be performed in 69 % of patients. When categorizing patients with respect to the completeness of cytoreduction (CC-0/1 vs CC-2/3), there was no difference considering baseline demographic characteristics. Cumulative morbidity was 42 %. Morbidity rates did not statistically differ between CC-0/1 patients with HIPEC and CC-2/3 patients without HIPEC. No surgery-related and 90-day postoperative mortality was observed. In CC-0/1 patients, median overall survival was 35 months as opposed to 14 months in CC-2/3 patients. There was no difference in survival with respect to the peritoneal carcinomatosis index (PCI) as long as complete cytoreduction could be achieved.

Conclusions

CRS and HIPEC can be performed with acceptable morbidity and low mortality in specialized centres. Our data do not suggest that HIPEC necessarily increases the risk of postoperative adverse events.     

Is the measurement of sarcopenia associated with oncological disease in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

Background

Peritoneal malignancies are challenging cancers to manage. While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC), may offer a cure, it is a radical procedure associated with significant morbidity. Pre-emptive identification of deconditioned patients for optimization may mitigate surgical risk. However, the difficulty lies in identifying a cost-effective predictive tool. Recently, there has been interest in sarcopenia, which may occur due to malignancy. The purpose of this study was to assess the utility of sarcopenia at predicting post-operative outcomes.

Methods

A quaternary-centre retrospective study of CRS and HIPEC patients (2017–2020), were conducted to determine the association between pre-operative sarcopenia on oncological (peritoneal carcinomatosis index (PCI)) and surgical outcomes (complications). Sarcopenia from lumbar CT-images were measured using Slice-o-matic™. Statistical differences were analysed using Mann–Whitney U and Chi-squared test.

Results

Cohort analysis (n = 94) found 40% had sarcopenia, majority were female (53.2%), and average age of 55 years. The major pathologies was colorectal cancer (n = 39, 41.5%), appendix adenocarcinoma (n = 21, 22.3%), and pseudomyxoma peritonei (PMP) (n = 19, 20.2%). Sarcopenia was associated with decreased weight, 72.7 versus 82.2 kg (P = 0.014) and shorter survival, 1.4 versus 2.1 years (95% CI, 1.09–3.05, P = 0.032). Median PCI (excluding PMP) was 11 (6–18) and median PCI (only PMP) was 25 (11–32). Post-operatively, sarcopenia patients experienced more complications (72.5% vs. 64.8%, P = 0.001).

Conclusion

Pre-emptive identification of sarcopenia may be a useful prognostic indicator and predictor of post-operative outcomes in CRS and HIPEC. For oncological patients, sarcopenia may be an indicator of patients requiring targeted pre-operative rehabilitation, or advanced disease requiring further treatment.     

Morbidity Associated with Colostomy Reversal After Cytoreductive Surgery and HIPEC

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the survival in selected colorectal cancer patients with peritoneal metastases. In these patients, the risk of a low anastomosis is sometimes diminished through the creation of a colostomy. Currently, the morbidity and mortality associated with the reversal of the colostomy in this population is unknown.

Methods

Our study involved two prospectively collected databases including all patients who underwent CRS–HIPEC. We identified all consecutive patients who had a colostomy and requested a reversal. The associations between four clinical and ten treatment-related factors with the outcome of the reversal procedure were determined by univariate analysis.

Results

21 of 336 patients (6.3 %) with a stoma with a mean age of 50.8 (standard deviation 10.2) years underwent a reversal procedure. One patient was classified as American Society of Anesthesiologists (ASA) grade III, 6 as ASA grade II, and the remaining as ASA grade I. Median time elapsed between HIPEC and reversal was 394 days (range 133–1194 days). No life-threatening complications or mortality were observed after reversal. The reversal-related morbidity was 67 %. Infectious complications were observed in 7 patients (33 %). Infectious complications after HIPEC were negatively correlated with the ultimate restoration of bowel continuity (P = 0.05). Bowel continuity was successfully restored in 71 % of the patients.

Conclusions

Although the restoration of bowel continuity after CRS–HIPEC was successful in most patients, a relatively high complication rate was observed. Patients with infectious complications after HIPEC have a diminished chance of successful restoration of bowel continuity.     

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion: The University of Arizona early experience

AIM:To evaluate the safety and effectiveness of our new cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemoperfusion(HIPEC)program.METHODS:Retrospective review of patients with gastrointestinal malignancies who were suitable candidates for CRS and HIPEC between 12/1/2009 and 10/1/2010.All clinicopathologic data were reviewed with a special focus on the surgical outcome and the postoperative morbidity and mortality.RESULTS:Fourteen patients were identified.Median age was 64 years;seven were female.The primary tumors were:colonic(29%),appendiceal(36%),peritoneal mesothelioma(14%),gastric(7%),adenocarcinoma of unknown primary(7%),and gastrointestinal stromal tumor(7%).Eleven patients(79%)received CRS/HIPEC,three for palliation.Three patients that did not undergo CRS/HIPEC had an average peritoneal cancer index(PCI)of 25.The eight patients that underwent curative CRS/HIPEC had an average PCI of 10 and a completeness of cytoreduction score of 0(87.5%) or 1(12.5%).Postoperative morbidity was 36%;the worst adverse event was Grade 3 ileus.Mortality rate was 0%.CONCLUSION:CRS with HIPEC is safe and feasible at tertiary institutions with fledgling programs.PCI is an accurate predictor of surgical outcomes.     

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.

     

The role of molecular biomarkers in outcomes and patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases of colorectal origin

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal metastases of colorectal (CRC) origin. The impact of different biomarkers in predicting recurrence after CRS/HIPEC is unclear.MethodsRetrospective review of patients who underwent CRS/HIPEC for PC of CRC origin from 03/2007–08/2017. Molecular profile of the primary tumor was obtained from pathology reports, whenever available.ResultsOverall, 100 patients underwent CRS/HIPEC for peritoneal metastases of CRC origin. Most patients presented high grade tumor histology (G2/G3, n = 97, 97%), and a majority showed mucinous features (n = 61, 61%). At a median follow-up of 18 months, median DFS for the overall population was 13 months (95% CI 9.6, 16.4). Data reporting at least one mutational analysis was available in 64 patients. Microsatellite stability was detected in 42/50 (84%) patients, mKRAS in 25/51 (49%), and mBRAF in 5/35 (14.3%). On Kaplan–Meier analysis, BRAF was the only mutation associated with poor DFS (16 months, CI 95% 11.7–43.3 vs. 7 months, CI 95% 2.1–11.9, p = .008). On multivariate analysis, mBRAF independently predicted earlier recurrence (p = .032).ConclusionsIn this analysis, mBRAF was independently associated with earlier recurrence in patients undergoing CRS/HIPEC for CRC, leading to dismal median DFS (7 months). Strict patient selection is advisable in these patients.     

Does hyperthermic intraoperative chemotherapy lead to improved outcomes in patients with ovarian cancer? A single center cohort study in 111 consecutive patients

Background

For recurrent disease or primary therapy of advanced ovarian cancer, cytoreductive surgery (CRS) followed by adjuvant chemotherapy is a therapeutic option. The aim of this study was to evaluate the outcome for patients with epithelial ovarian cancer treated with hyperthermic intraoperative chemotherapy (HIPEC) and completeness of cytoreduction (CC).

Methods

Data were retrospectively collected from 111 patients with recurrent or primary ovarian cancer operated with the contribution of visceral surgical oncologists between 1991 and 2006 in a tertiary referral hospital.

Results

Ninety patients received CRS and 21 patients CRS plus HIPEC with cisplatin. Patients with complete cytoreduction (CC0) were more likely to receive HIPEC. Overall, 19 of 21 patients (90.5?%) with HIPEC and 33 of 90 patients (36.7?%) with CRS had a complete cytoreduction (P?Conclusions Completeness of cytoreduction was proved to be crucial for long-term outcome. HIPEC procedures in ovarian cancer should be performed in clinical trials to compare CRS, HIPEC and systemic chemotherapy against CRS with systemic chemotherapy. Concerning the safety of HIPEC with cisplatin, the risk of persistent renal failure must be considered when dosage is based on body surface.     

Safety of Epidural Analgesia in the Perioperative Care of Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

Background

The perioperative coagulopathy, hemodynamic instability, and infectious complications that may occur during cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has raised concerns about the safety of epidural analgesia in patients undergoing such procedures.

Methods

We conducted a retrospective review of the perioperative anesthetic management of 215 adult patients who had undergone CRS with HIPEC with epidural analgesia. We reviewed epidural-related complications and analyzed the effect of early initiation of continuous epidural analgesia on estimated blood loss, intraoperative fluid administration, blood transfusion and vasopressor requirements, time to extubation, and length of stay.

Results

No epidural hematomas or abscesses were reported. Two patients (0.9 %) had delays in epidural removal because of thrombocytopenia, and two had epidural-site erythema (0.9 %). The majority of postoperative epidural-related hypotensive episodes were successfully treated with fluid boluses. Early initiation of epidural analgesic infusions (before HIPEC) was associated with significantly less surgical blood loss and fluid requirements (P = 0.005 and 0.02, respectively). Pre-HIPEC initiation of epidural infusions was not associated with a statistically significant difference in the following: volume of blood transfused, intraoperative vasopressors use, time to extubation, and length of hospital stay.

Conclusions

With close hematologic monitoring and particular attention to sterility, epidural analgesia can be safely provided to patients undergoing CRS with HIPEC. Early initiation of continuous epidural infusions during surgery could lead to decreased blood loss and less intraoperative fluid administration. Prospective randomized studies are required to further investigate these potential benefits.     

Re-do cytoreductive surgery for peritoneal surface malignancy: Is it worthwhile?

Background and objectivesCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers selected patients with peritoneal surface malignancies (PSM) an improved survival. However, a substantial proportion of patients develop peritoneal recurrence. There is limited data on the efficacy of iterative CRS and HIPEC in such patients. This study evaluates the safety, efficacy and outcomes after re-do CRS and HIPEC for PSM at a tertiary institute.MethodsPatients undergoing re-do CRS and HIPEC for recurrent PSM were included. Cases were grouped into the first and iterative cases and compared to evaluate differences in morbidity, survival and factors influencing survival.ResultsOne hundred and forty patients developed peritoneal recurrence after CRS and HIPEC. Thirty-seven patients underwent re-do CRS and HIPEC. The most common indication for iterative surgery was pseudomyxoma peritonei in 27 patients (73.0%). Median survival was 97 months for patients undergoing iterative surgery compared to 40 months for those who did not. Median survival following first and iterative surgery was 97 and 89 months, respectively (p = 0.15). Median progression-free survival after first and iterative surgery was 23 and 19 months, respectively (p = 0.47). At iterative CRS and HIPEC, incomplete cytoreduction (HR 12.82, 95% CI 1.64–100.35), increasing PCI (HR 1.13, 95% CI 1.04–1.22), in particular PCI >20 (HR 10.90, 95% CI 1.37–86.66) were factors associated with worse overall survival.ConclusionIn well selected patients, iterative CRS and HIPEC is safe, and can provide favorable survival with low morbidity. Completeness of cytoreduction and PCI are factors that influence overall survival.     

Cytoreductive Surgery Under Aminolevulinic Acid-Mediated Photodynamic Diagnosis Plus Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Ovarian Cancer and Primary Peritoneal Carcinoma: Results of a Phase I Trial

Background

We conducted a phase I clinical trial to evaluate the sensitivity, specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from ovarian cancer and primary peritoneal carcinoma (PPC).

Patients and Methods

Patients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50 mL of water 2 h before surgery. During surgery, the abdominal cavity was observed under blue light (wavelength of 440 nm) before and after CRS plus HIPEC. Specimens were excised and submitted for pathological examination to evaluate the specificity of ALA-PDD. Postoperative course was closely monitored and detailed information was recorded.

Results

CRS under ALA-PDD plus HIPEC was performed 21 times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All specimens from red fluorescent lesions were invaded by cancer cells, with a specificity of 100 %. No severe adverse events occurred during the perioperative period, with the exception of some abnormal laboratory results and mild complications. All patients were alive until the last follow-up.

Conclusion

ALA-PDD provided a high sensitivity and specificity in detecting peritoneal metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC from ovarian cancer and PPC.