Feasibility of diaphragmatic interventions in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: A 20-year experience

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Abstract

Introduction

Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an effective treatment for improving prognosis of selected patients with peritoneal carcinomatosis. The addiction of diaphragmatic procedures may increase the incidence of postoperative respiratory complications. Our goal was to evaluate the early postoperative results following diaphragmatic surgery.

Methods

Prospectively collected data of patients undergoing diaphragmatic surgery between January 2000 and January 2020 were retrospectively analyzed. Chest drains were routinely placed in all cases. Demographics, clinical and perioperative features were evaluated.

Results

The study included 222 patients. Peritoneal stripping and full-thickness resections were performed in 165 and 57 cases, respectively. Women and ovarian tumours represented the vast majority of cases. Overall postoperative mortality and morbidity rates were 1.3% (3 patients) and 43.2% (96 patients), respectively. Specific diaphragmatic surgery-related complications was 9.4% (21 patients). No pleural effusion and pneumothotrax occurred. The incidence of pneumonia was 1.8% (4 patients), each due to systemic bacterial origin, 2 (0.9%) of which required Intensive Care Unit-readmission. Postoperative bleeding was observed in 15 (6.7%) cases, 12 (5.4%) of which required reoperation. A comparison with 105 patients who operated during the same period without diaphragmatic surgery was performed and by multivariate analysis, Peritoneal Cancer Index, histology and overall morbidity resulted significantly associated with diaphragmatic surgery.

Conclusion

Diaphragmatic surgery during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is often required in order to obtain complete resection. It may be associated with higher postoperative morbidity, especially bleeding, but routine placement of chest drains may reduce the incidence of adverse respiratory events.

Introduction

Cytoreductive surgery (CRS) with hypertermic intraperitoneal chemotherapy (HIPEC) has developed over the last years as a curative treatment for selected patients with peritoneal carcinomatosis (PC). Reported postoperative 30-day mortality and morbidity rates are 0.8–4% and 22–55%, respectively [[1], [2], [3], [4]]. Complete cytoreduction is the mainstay of treatment and diaphragmatic surgery (DS) may be required to achieve this goal, resulting in increased risk of postoperative respiratory complications.

Few series reporting specific postoperative results following diaphragmatic interventions during CRS with HIPEC are present in the literature [[5], [6], [7], [8]], most being limited to extended surgery for ovarian cancer. The incidence rate of respiratory complications seems increased and the topic of chest drains is controversial. Moreover, bleeding due to diaphragmatic procedures is usually unreported. In our study, we aimed to review the feasibility of DS in patients submitted to CRS with HIPEC in terms of early postoperative results.

A retrospective analysis of a prospectively maintained database was performed including all patients who underwent CRS and HIPEC for PC at our Department, between January 2000 and January 2020. Preoperative work-up included computed tomography (CT) scan in all patients, whereas positron emission tomography (PET)/CT scan and Magnetic Resonance Imaging (MRI) were performed in selected cases. Laparoscopy was always performed in order to improve preoperative staging and patient selection [9]. CRS and open (Coliseum) HIPEC procedures were based on the technique originally described by Sugarbaker [10]. The extent of peritoneal involvement was recorded according to the Peritoneal Cancer Index (PCI), through quantitatively combining the cancer implant size with the tumor distribution throughout 13 abdominopelvic regions, producing a maximum score of 39 [10]. The completeness of cytoreduction (CC) score was used to assess residual tumor after surgery and defined as follows: CC0 score no visible peritoneal carinomatosis; CC1 less than 2,5 mm tumor nodules persisting; CC2 tumor nodules between 2,5 mm and 2,5 cm after surgery [10]. The chemotherapeutic agent was selected based on type of primary tumour as well as patient’s previous response to systemic chemotherapy. Cisplatin and doxorubicin was used in most cases, excluding colon and appendiceal cases in which mitomycin was used.

Adequate exposure of the diaphragm was obtained with liver mobilization. The final decision on the type of DS was based on the direct inspection, palpation and dissection of the lesions at the time of surgery. According to this, the procedures were divided into stripping peritonectomy (SP) and full-thickness resection (FTR) (Fig. 1). No ablation procedures were included in this study. SP was defined as the dissection of the peritoneum from the underlying muscle, according to the extension of the disease. The specimen was removed en bloc, but a segmental resection was helpful in cases with partial tumour involvement. If no cleavage plane was found or if the peritonectomy left tumor behind, a FTR was performed using electrosurgery dissection and ipsilateral stripping was associated. A primary continuous absorbable 0–1 running suture under a water seal was used to close the diaphragm avoiding tension, while a mesh was used only to close large defects. At the end of the procedure, a “bubble test” was performed to identify possible small pleural openings. In order to decrease the risk of pneumothorax, the anesthetist manually ventilated the patient and air was removed by suction through a Foley catheter placed in the pleura, which was removed at the time of suture’s end. One chest drain was electively placed in all patients, whereas two drains were placed following FTR, before the start of HIPEC. This allowed accurate monitoring in case of perfusate moving into the thoracic cavity. If the amount drained from the drains was significant, probably due to a missed defect in the diaphragm, the perfusion was temporarily stopped and surgical closure performed. Postoperatively all patients had serial chest x-ray to verify the absence of pneumothorax. Tubes removal occurred when the amount of drained fluid was less than 100 ml in 24 h, usually after approximately 5–7 postoperative days.

Anesthesia followed the use of restrictive fluid therapy combined with goal-directed therapy guided by hemodynamic monitoring according to a previously reported protocol [11]. At the end of the surgical procedures, all patients were admitted in the Intensive Care Unit (ICU) for an average time of 48 h and the mean duration of intubation was approximately 12 h. All patients received adequate pain control, venous thromboembolism (VTE) prophilaxis with low molecular weight heparin and early postoperative mobilization with the implementation of breathing exercises and physiotherapy. The program included early postoperative chest-expanding exercises twice a day and use of respiratory stimulators three times a day, for at least 15 days after surgery. A standardized protocol for the prevention, monitoring and treatment of infections was also used, as previously reported [12].

Postoperative results were categorized according to the 90-day morbidity and mortality National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 [13]. Specific DS-related respiratory complications included respiratory failure, pneumothorax, pneumonia and pleural effusion. Pulmonary embolism (PE) was not included since it was not considered a complication specific of DS. A five-point scale to grade the severity of post-procedural adverse events was used. Clinical observation was the only required treatment in minor complications (grade I). Moderate complications required only minimal medical intervention (grade II). Severe complications required imaging-guided percutaneous or surgical drainage (including chest tube or therapeutic endoscopy) (grade III). Life-threatening complications requiring urgent intervention or intubation were graded IV. Deaths related to complications were graded V. Incidence of postoperative bleeding due to the diaphragmatic procedures was also evaluated.

First, patients and tumours characteristics together with the incidence of postoperative complications were recorded and categorized. A comparison with a second group of patients submitted to CRS with HIPEC without DS during the same period was then performed.

Written informed consent was obtained from all patients. The study was performed in accordance with the precepts established by the Declaration of Helsinki.

The continuous data as mean and standard deviation was reported. Categorical data were reported as frequency and percentage values. The association between variables was tested by Pearson’s Chi-square test or Fisher’s exact test, when appropriate. Student’s t-test was used to compare mean values. A p-value ≤ 0.05 was considered statistically significant.

Multivariate logistic regression model was developed using stepwise regression (forward selection) to identify variables independently associated with DS. Enter limit and remove limit were p = 0.10 and p = 0.15, respectively.

Statistical evaluations were performed by use of the SPSS (v. 21.0, SPSS Inc. Chicago, IL, USA).

Section snippets

Results

Three hundred and thirty patients were submitted to CRS with HIPEC for PC in the period of study. Among these, 222 (67.3%) underwent diaphragmatic procedures and were included in the analysis. Fig. 2 depicts the type of procedures. The vast majority involved the right hemidiaphragm, with only 1 left FTR. Primary closure of the diaphragm was possible in all but one patient who had reconstruction with polytetrafluoroethylene mesh.

Baseline characteristics of patients are described in Table 1. Mean

Discussion

The present study reported diaphragmatic interventions in two-thirds of cases submitted to CRS with HIPEC. Three (1.3%) patients died postoperatively and specific DS-related complications occurred in 21 (9.4%) patients. Chest drains were routinely placed and the incidence of plural effusions and pnemothorax was nihil. Grade 4 complications occurred in 14 (6.3%) cases, most being represented by bleedings requiring reoperation.

Although the exact mechanisms are not cleary defined, diaphragmatic

CRediT authorship contribution statement

Fabio Carboni: Conceptualization, Methodology, Validation, Investigation, Data curation, Writing - original draft, Writing - review & editing. Orietta Federici: Resources. Settimio Zazza: Resources. Isabella Sperduti: Methodology, Software, Formal analysis, Data curation. Mario Valle: Conceptualization, Methodology, Validation, Investigation, Data curation, Writing - review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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