Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy (HIPEC) by Minimally Invasive Approach,an Initial Experience

Background

The cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard treatment in patients with carcinomatosis peritoneal from different origins. The use of a minimally invasive approach for this high complex procedure might be an alternative that provides them less morbidity and faster recovery with similar oncologic outcomes.

Methods

We describe the initial experience of CRS and HIPEC done via the laparoscopic route in patients with minimal peritoneal metastases in our Unit from March 2016 to January 2018.

Results

A total of eight patients were operated by this minimally invasive approach. The different diagnoses were low-grade pseudomyxoma peritonei (2), benign multicystic mesothelioma (2), primary epithelial ovarian carcinomatosis (2) and locally advanced colon carcinoma T4 (2). The median age was 54 (20–62) years, the median PCI was 3 (2–4), the median operative time was 287 min (240–360), complete cytoreduction CC0 was achieved in all the patients, and no major morbidity was observed. The median length of stay was 4.75 days (4–5). After a median follow-up of 9.5 months, no relapse has been observed.

Conclusion

The results suggest that this minimally invasive approach for CRS and HIPEC is feasible and safe in a highly selected group of patients with peritoneal surface malignancies.

     

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.

     

Effects of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the Treatment of Goblet Cell Carcinoma: A Prospective Cohort Study

Background

Goblet cell carcinoma (GCC) of the appendix is a rare disease. Treatment options vary according to disease staging. Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) may improve survival in patients with peritoneal spreading.

Objective

The aim of this study was to examine the prognosis of patients with appendiceal GCC treated per protocol, and to evaluate the results of CRS+HIPEC in cases of peritoneal spreading.

Methods

From 2009 to 2016, a total of 48 GCC patients were referred to the European Neuroendocrine Tumour Center of Excellence, Aarhus University Hospital. All patients received treatment per protocol according to disease staging. In patients with localized disease, the treatment was a right hemicolectomy. Patients with peritoneal spread who met the inclusion criteria for CRS + HIPEC, as well as patients with high-risk features of developing peritoneal spread, received CRS + HIPEC. If too-extensive disease was found, palliative chemotherapy was offered.

Results

Overall survival for patients with localized disease (n = 6) or deemed at risk of peritoneal spread (n = 8) was 100% after a median follow-up of 3.5 years. In patients with peritoneal spread and eligible for CRS+HIPEC(n = 27), the median survival was 3.2 years [95% confidence interval (CI) 2.3–4.1] and the 5-year survival rate was 57%. In contrast, the median survival for patients with too-extensive intraperitoneal disease (n = 7) was 1.3 years (95% CI 0.6–2.0), with a 3-year survival rate of 20%.

Conclusions

Long-term survival can be achieved in patients with peritoneal spread treated with CRS + HIPEC. CRS+HIPEC was associated with a favorable outcome in GCC patients at high-risk of developing peritoneal spread.

     

Where Oncologic and Surgical Complication Scoring Systems Collide: Time for a New Consensus for CRS/HIPEC

Introduction

Morbidity and mortality rates after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are important quality parameters to compare peritoneal surface malignancy centers. A major problem to assess postoperative outcomes among centers is the inconsistent reporting due to two coexisting systems, the diagnose-based common terminology criteria for adverse events (CTCAE) classification and the therapy-oriented Clavien-Dindo classification. We therefore assessed and compared both reporting systems.

Patients and Methods

Complications after CRS/HIPEC were recorded in 147 consecutive patients and independently graded by an expert board using both systems. In a next step, a group of residents, experienced surgeons, and medical oncologists evaluated a set of twelve real complications, either with the Clavien-Dindo or CTCAE classification.

Results

The postoperative complication rate after CRS/HIPEC was 37 % (54/147), 6.8 % (10/147) were reoperated, and three (2 %) patients died. The most frequent complications were intestinal fistula or abscess, pulmonary complications, and ileus. Grading of complications with the CTCAE classification resulted in a significantly higher major morbidity rate compared to the Clavien-Dindo classification (25 vs. 8 %, p = 0.001). Evaluating a set of complications, residents, surgeons, and oncologists correctly assessed significantly more complications with the Clavien-Dindo compared to the CTCEA classification (p < 0.001). In addition, all participants evaluated the Clavien-Dindo classification as more simple. Residents (p < 0.001) and surgeons (p < 0.01) required less time with the Clavien-Dindo classification; there was no difference for oncologist.

Conclusion

In conclusion, our data indicate that there is a different interpretation of severity grades of complications after CRS/HIPEC between the two classifications. There is a need for a common language in the field of CRS/HIPEC, which should be defined by a new consensus to compare surgical outcomes.

     

PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival.

Methods

Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction.

Results

Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0–36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21.

Conclusions

The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

     

Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry

Background

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant.

Methods

A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease.

Results

Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years; p = 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years; p = 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI; p = 0.015), CC status of resection (p < 0.0001), and Ki67 (p = 0.04) as predictors of survival. Systemic chemotherapy before (p = 0.55) or after (p = 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (p = 0.03) and CC (p = 0.04) remained significant.

Conclusions

Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.

     

Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): a Single-Center Experience in Austria

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly influence overall and disease-free survival in selected patients suffering from peritoneal surface malignancies (PSM) of various tumor entities. Because of the extent of the therapeutic approach, the associated morbidity and mortality and the multidisciplinarity needed, implementation of a CRS + HIPEC program at an institution is often challenging.

Methods

This single-center analysis included all patients (n?=?60, 34 female, 26 male) with PSM from various tumor primaries [colorectal cancer (15/60; 25%), appendix neoplasia (21/60; 35%), and others (24/60; 40%)] treated with CRS + HIPEC at our institution between 2006 and 2014. Charts were reviewed for preoperative patient evaluation, procedure-specific and tumor-specific parameters, morbidity, mortality, tumor recurrence and patients’ overall (OS), and disease-free survival (DFS).

Results

In 57 of the 60 patients included in the investigation (57/60; 95%), a radical resection (CC 0/1) was achieved. Median operating time was 559 min (253–900) with a median need of packed red blood cells of 1.1 (0–7) or fresh frozen plasma of 4.4 (0–20) concentrates. Twenty (33.3%) patients experienced 24 Dindo-Clavien grade III/IV complications (24/63; 38.1%). Postoperative 30- and 90-day mortality was 0% in our study population. Five-year OS was 43%, 5-year DFS 33%.

Conclusions

Due to thorough preoperative patient evaluation, strict inclusion and exclusion criteria, and intense collaboration with other specialties, we were able to achieve an excellent 5-year OS of 43% with a CC score of 0/1 in 95% of our patient population. We were able to demonstrate the feasibility, efficacy, and safety of CRS + HIPEC in patients suffering from PSM at our institution.

     

Prediction of Resectability in Pseudomyxoma Peritonei with a New CT Score

Background

Curative treatment of pseudomyxoma peritonei (PMP) is complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC).

Objective

The aim of this study was to build and evaluate a preoperative imaging score to predict resectability.

Patients and methods

Between 2007 and 2014, all PMP patients in two tertiary reference centers who underwent laparotomy with intent to undergo CRS and HIPEC were included in this study retrospectively. Thickness of tumor burden was measured on preoperative multidetector-row computed tomography (MDCT) by two radiologists blinded to surgical results in five predetermined areas. Patients were divided into two cohorts with the same resectability rate (building and validation). The performances of the scores were assessed using receiver operating characteristic (ROC) curve analyses.

Results

Overall, 126 patients were included, with compete CRS being achieved in 91/126 patients (72.2%). Two cohorts of 63 patients matched by age, sex, burden of disease, resectability rate, and pathological grade were constituted. The MDCT score was the sum of the five measures, and was higher in unresectable disease [median 46.2 mm (range 27.9–74.6) vs. 0.0 mm (range 0.0–14.0), p < 0.001]. Area under the ROC curve was 0.863 (range 0.727–0.968) and 0.801 (range 0.676–0.914) in the building and validation cohorts, respectively. A threshold of 28 mm yielded a sensitivity, specificity, positive predictive and negative predictive value of 94, 81, 81 and 94% in the building cohort, and 80, 68, 59 and 85% in the validation cohort, respectively. Using our score, overall and disease-free survival were increased in the group classified as resectable.

Conclusion

A simple preoperative MDCT score measuring tumor burden in the perihepatic region is able to predict resectability and survival of PMP patients.

     

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Elderly: Is It Reasonable? A Meta-Analysis

Background

Whether cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is safe and worthwhile for elderly patients remains unclear. This meta-analysis of outcomes after CRS plus HIPEC for the elderly aimed to generate a higher level of evidence and precise indications for these patients.

Methods

A systematic literature search for studies reporting postoperative outcomes after CRS plus HIPEC for elderly patients was performed in the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Knowledge Conference Proceedings Citation Index-Science, and Google Scholar databases. The included studies evaluated the overall 30-day postoperative morbidity, 90-day postoperative mortality, grade 3 or higher postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay.

Results

The inclusion criteria were met by 13 retrospective studies involving 2544 patients. Considering only comparative studies, the 90-day postoperative mortality was significantly increased for elderly patients [odds ratio (OR), 0.49; 95% confidence interval (CI), 0.27–0.88; I ² = 79%]. The 30-day grade 3 or higher postoperative morbidity was increased in the patients 70 years of age or older (14.5%; 95% CI 8.1–24.4 vs. 32.3%; 95% CI 22.4–44.0%; p = 0.004; I ² = 85%). The overall 30-day postoperative morbidity, rates of anastomotic leaks, reoperation and readmission, and length of hospital stay were not affected by age.

Conclusions

Treatment of the elderly with CRS plus HIPEC was associated with increased severe postoperative morbidity and mortality. However, these conclusions should be weighted given the existence of major biases in the included studies. Age alone probably would not be a formal contraindication, but frailty should be taken into account. Further prospective studies are needed.

     

SSAT State-of-the-Art Conference: Current Surgical Management of Gastric Tumors

Introduction

The current era of gastric surgery is marked by low morbidity and mortality rates, innovative strategies to approach resections with a minimally invasive fashion or hyperthermic intraperitoneal chemotherapy (HIPEC), as well as improved understanding of the biology of sporadic and hereditary stromal, neuroendocrine, and epithelial malignancies.

Methods

In 2017, the Society for Surgery of the Alimentary Tract convened a State-of-the-Art Conference on Current Surgical Management of Gastric Tumors with both international experts and emerging leaders in the field of gastric surgery.

Results

Martin D. McCarter, MD of the University of Colorado discussed the current management of gastric gastrointestinal stromal tumors (GIST). Kaitlyn J. Kelly, MD of the University of California, San Diego discussed the management of gastric carcinoid tumors. Jeffrey A. Norton of Stanford University discussed recent advances in the management of gastric adenocarcinoma including a focus on hereditary diffuse gastric cancer (HDGC). Joseph Kim, MD of Stony Brook University discussed a systematic approach to minimally invasive gastrectomy for cancer. Joyce Wong, MD of Pennsylvania State University discussed the role for cytoreductive surgery (CRS) and HIPEC for gastric adenocarcinoma.

Conclusions

This review provides gastrointestinal surgeons with a concise update on the current surgical management of gastric tumors.

     

Implications of Stoma Formation as Part of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Formation of protective stoma as part of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC) may be an effective tool in reducing anastomotic leak incidence. Our aim was to evaluate the incidence and implications of stoma formation during CRS–HIPEC and to examine whether a creation of protective stoma reduces the postoperative morbidity.

Methods

A cohort retrospective analysis of all CRS–HIPEC procedures performed between 2004 and 2016 was conducted. Predicting factors for stoma formation were assessed by comparing all patients who underwent stoma formation to those who did not; both groups were then restricted to cases with ≥2 bowel anastomoses and compared in terms of perioperative outcomes in order to determine whether protective stoma confers a morbidity benefit.

Results

One hundred and ninety-nine CRS–HIPEC procedures were performed on 186 patients. Thirty-four patients (17%) underwent stoma formation, 24 of them as protective stoma. Formation of a stoma was correlated with higher peritoneal carcinomatosis index score (13.6 ± 8 vs. 9.5 ± 7.7, p = 0.007), larger number of organs resected (p < 0.001), greater number of anastomoses (p < 0.001), prolonged operative time (8.1 ± 2.7 vs. 6.6 ± 2.2 h, p = 0.002), and prolonged hospital stay (12 vs. 8.5 days, p = 0.001). In procedures requiring ≥2 anastomoses, formation of protective stoma reduced the anastomotic leak rate (6 vs. 37%, p = 0.025), the morbidity rate (6 vs. 41%, p = 0.017), and reoperation rate (0 vs. 28%, p = 0.03). Overall, 15 patients (44%) underwent stoma reversal, 3 of whom had a complication treated non-operatively.

Conclusions

Protective stoma should be considered in extensive CRS–HIPEC procedures requiring two or more bowel anastomoses in order to reduce the postoperative morbidity rate.

     

Validation of the Recent PSOGI Pathological Classification of Pseudomyxoma Peritonei in a Single-Center Series of 265 Patients Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Background

Controversies still persist regarding the terminology and pathologic classification of appendiceal mucinous neoplasms and associated pseudomyxoma peritonei (PMP). We assessed reproducibility and prognostic significance of the classification recently proposed by the Peritoneal Surface Oncology Group International (PSOGI).

Methods

A prospective database of 265 PMP patients uniformly treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) from 1995 to 2017 was reviewed. According to the PSOGI, peritoneal disease was retrospectively classified into three categories: low-grade (LG-PMP), high-grade (HG-PMP), and signet-ring cells (SRC-PMP). Acellular mucin (AC) was classified separately. The extent of peritoneal involvement was quantified by the peritoneal cancer index (PCI).

Results

Twenty-six patients were diagnosed with AC (9.8%), 197 with LG-PMP (74.4%), 38 with HG-PMP (14.3%), and 4 with SRC-PMP (1.5%). In the overall series, median follow-up was 65.5 months (95% confidence interval 53.7–78.8) and 10-year overall survival was 62.9% (median 148.7 months). Operative death occurred in 10 patients (3.8%) and major complications occurred in 89 patients (33.6%). Ten-year survival was 89.6% for AC, 63.2% for LG-PMP, 40.1% for HG-PMP, and 0 for SRC-PMP. In a multivariate model, the World Health Organization (WHO) pathological classification independently correlated with survival (p = 0.028). In a separate model, the PSOGI classification did not reach statistical significance (p = 0.149). Completeness of cytoreduction and PCI > 22 correlated with prognosis in both models.

Conclusions

AC and SRC-PMP pathological categories of the PSOGI classification identified two subsets of patients with favorable and exceedingly dismal prognosis, respectively. It remains unclear whether the PSOGI classification might provide better prognostic stratification than the current WHO classification. Further studies in larger prospective series are needed.

     

Marrow Fat—a New Target to Treat Bone Diseases?

Purpose of Review

The goal of this review is to summarize recent findings on marrow adipose tissue (MAT) function and to discuss the possibility of targeting MAT for therapeutic purposes.

Recent Findings

MAT is characterized with high heterogeneity which may suggest both that marrow adipocytes originate from multiple different progenitors and/or their phenotype is determined by skeletal location and environmental cues. Close relationship to osteoblasts and heterogeneity suggests that MAT consists of cells representing spectrum of phenotypes ranging from lipid-filled adipocytes to pre-osteoblasts. We propose a term of adiposteoblast for describing phenotypic spectrum of MAT. Manipulating with MAT activity in diseases where impairment in energy metabolism correlates with bone functional deficit, such as aging and diabetes, may be beneficial for both. Paracrine activities of MAT might be considered for treatment of bone diseases.

Summary

MAT has unrecognized potential, either beneficial or detrimental, to regulate bone homeostasis in physiological and pathological conditions. More research is required to harness this potential for therapeutic purposes.

     

Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration

Background

Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications.

Patients and Methods

Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2–10 mmHg, n = 28), target IAP group (10–20 mmHg, n = 71), and high IAP group (20–34 mmHg, n = 16) as well as with CBT as a continuous variable.

Results

115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035).

Conclusions

IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

     

Coagulation after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a retrospective cohort analysis

Purpose

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) benefit patients with peritoneal carcinomatosis. Nevertheless, this therapy is associated with considerable postoperative pain due to the extensive abdominal incision. While epidural analgesia offers efficacious pain control, CRS and HIPEC therapy is associated with perioperative coagulopathy that may impact its use. The purpose of this retrospective study is to characterize the postoperative coagulopathy in this patient subset and to develop a model that will help predict those at risk.

Methods

Our database of patients treated with CRS and HIPEC (n = 171) was reviewed to assess perioperative changes in platelet count, international normalized ratio (INR), and partial thromboplastin time (PTT). Abnormal coagulation was defined by platelet count < 100 × 10^?9·L^?1, INR ≥ 1.5, or PTT ≥ 45 sec. Severe abnormality in coagulation was defined by platelet count < 50 ×10^?9·L^?1, INR > 2.0, and/or PTT > 60 sec. A logistic regression model was developed to determine if patient, disease, and/or surgical factor(s) were associated with the development of postoperative coagulopathy. Epidural catheter management in this patient population was also reviewed.

Results

Significant differences (adjusted P < 0.007) were noted between median preoperative and postoperative platelet and INR values on postoperative days (POD) 0 through 6 and days 0 through 3, respectively. Highest observed median differences between preoperative and postoperative values showed a decrease in platelet count of 94 × 10^?9·L^?1 (POD 2 and POD 3), an increase in INR of 0.2 (POD 0 to POD 2), and a decrease in PTT of 3.1 sec (POD 5). Coagulopathy and severe coagulopathy occurred in 38% and 4.7% of patients, respectively. Predictors of coagulopathy included intraoperative transfusion of packed red blood cells (PRBCs) and perhaps the peritoneal carcinomatosis index (PCI). Epidural catheters were inserted in 26 patients for a median [IQR] duration of 7.0 [5.0-7.0] days without complication. At the time of their removal, no blood products were required to correct abnormal coagulation values.

Conclusions

Altered coagulation may appear during the postoperative period in approximately 40% of our patients treated with CRS and HIPEC. Intraoperative transfusion of RBCs and possibly increased PCI are associated with abnormal postoperative coagulation. Close monitoring of coagulation parameters is required to help ensure safe removal of an epidural catheter.

     

Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study

Background

Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial.

Methods

The rat colon carcinoma cell line CC-531 was injected into the peritoneal cavity of 80 WAG/Rij rats to induce PC. Animals were randomized into four treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m² at 41.5°C), CS followed by EPIC during 5 days (i.p. injection of mitomycin on day 1 and 5-fluorouracil on days 2–5), and CS followed by HIPEC plus EPIC. Primary outcome was survival.

Results

In rats treated with CS only, median survival was 53 days (95% confidence interval (CI) 49–57 days). In rats treated with CS followed by HIPEC, survival was significantly (P = 0.001) increased (median survival 94 days, 95% CI 51–137 days). In the group treated with EPIC after CS, 12 out of 20 rats were still alive at the end of the experiment (P < 0.001 as compared with CS only). In the group receiving both treatments, 11 rats died of toxicity, and therefore this group was not included in the survival analysis.

Conclusions

Both EPIC and HIPEC were effective in prolonging survival. The beneficial effect of EPIC on survival seemed to be more pronounced than that of HIPEC. Further research is indicated to evaluate and compare the possible benefits and adverse effects associated with both treatments.

     

Indications for prophylactic osteosynthesis associated with curettage in benign and low-grade malignant primitive bone tumors of the distal femur in adult patients: a case series

Background

The aim of the study was to evaluate whether the use of preventive osteosynthesis after curettage in benign and primitive low-grade malignant bone tumor localized in the distal femur in adult patients provides sufficient mechanical stability to the system as to allow weight-bearing and reduce the risk of postoperative fracture. Additionally, lower limb function after curettage and preventive osteosynthesis was evaluated.

Materials and methods

We analyzed twelve cases of benign and low-grade malignant bone lesions of the distal femur in adult patients treated in our orthopedic department between 2008 and 2011 with curettage, bone filling and preventive osteosynthesis. All patients were treated with curettage with the use of high-speed cutters, plus liquid nitrogen as local adjuvant in low-grade malignant lesions, and filling of the lesion with bone graft or allograft or acrylic cement, followed by osteosynthesis.

Results

No fractures or major complications were observed; good function of the knee was observed.

Conclusion

We recommend preventive osteosynthesis after curettage in patients with very large lesions (>5 cm, >60 cm³) or high functional requirements, in obese patients, and when local adjuvants are used.

Level of evidence

Level IV retrospective case-series study.

     

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma

Purpose

Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity.

Methods

The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM.

Results

The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year.

Conclusion

The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

     

Percutaneous forefoot surgery for treatment of hallux valgus deformity: an intermediate prospective study

Background

This study aims to illustrate the results of percutaneous forefoot surgery (PFS) for correction of hallux valgus.

Materials and methods

A prospective study of 108 patients, with hallux valgus deformity, who underwent PFS was conducted. The minimum clinical and radiological follow-up was two years (mean 57.3 months, range 22–112).

Results

Preoperative mean visual analog scale was 6.3 ± 1.5 points, and AOFAS scores were 50.6 ± 11 points. At the last follow-up, both scores improved to 1.9 ± 2.4 points and 85.9 ± 1.83 points, respectively. Mean hallux valgus angle changed from 34.3° ± 9.3° preoperatively to 22.5° ± 11.1° at follow-up. At follow-up, 76.5% of the subjects were satisfied or very satisfied. Recurrence of medial 1st MT head pain happened in 22 cases (16.7%).

Conclusions

PFS, in our study, does not improve the radiological and patient satisfaction rate results compared with conventional procedures. The main advantage is a low postoperative pain level, but with an insufficient HVA correction.

Level of evidence

II, prospective study.

     

Impact of Mucinous Histology on the Prognosis of Stage I–III Adenocarcinomas of the Appendix: a Population-Based,Propensity Score-Matched Analysis

Background

Whereas the poor prognosis of signet ring cell adenocarcinomas of the appendix is well known, the significance of mucinous histology remains unclear. The aim of this population-based study was to evaluate if mucinous histology is an independent prognostic factor in appendiceal adenocarcinomas.

Methods

Patients with stage I–III adenocarcinoma of the appendix who underwent surgery between 2004 and 2012 were identified in the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods.

Results

Overall, 980 patients with appendix cancer were included, of which 449 (45.8 %) had a mucinous histology. In an unadjusted analysis, the 5-year OS and CSS in patients with a mucinous adenocarcinoma (MC) was 76.8 % (95 % confidence interval (95 %CI): 72.1–81.7 %) and 81.0 % (95 %CI: 76.6–85.6 %), respectively, compared with 70.0 % (95 %CI: 65.1–75.3 %) and 76.2 % (95 %CI: 71.5–81.2 %) in patients with non-mucinous adenocarcinoma (NMC) (P?=?0.082 and P?=?0.368). In multivariable analysis, no impact on survival was observed for OS (HR?=?1.22, 95 %CI: 0.89–1.68, P?=?0.208) and CSS (HR?=?1.21, 95 %CI: 0.84–1.74, P?=?0.296). After propensity score matching, nearly identical survival rates were observed (OS: HR?=?1.03, 95 %CI: 0.71–1.49, P?=?0.881 and CSS: HR?=?1.05, 95 %CI: 0.70–1.59, P?=?0.803).

Conclusions

The present population-based, propensity score matched analysis shows that mucinous histology does not affect survival in stage I–III appendiceal adenocarcinoma patients. Therefore, the same treatment strategies can be applied for patients with NMC and MC of the appendix.