The importance of integrating diagnostic modalities in patient selection for CRS-HIPEC in colorectal peritoneal metastases.

BACKGROUND: Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS. PURPOSE: To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting. MATERIAL AND METHODS: All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC). RESULTS: The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%-86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan. CONCLUSIONS: A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.

Teres ligamentum wrap covering the pancreaticojejunostomy following pancreatoduodenectomy is associated with a lower rate of postoperative pancreas fistula: a prospective cohort study.

BACKGROUND: Post-operative pancreas fistula (POPF) is a common complication after pancreatoduodenectomy (PD). A Teres Ligamentum (TL)-wrap covering the pancreaticojejunostomy (PJ) is suggested as a potential solution to reduce POPF. The aim of this study was to compare POPF incidence (grade B/C) in patients with or without a TL-wrap. METHODS: A prospective cohort study was performed between January 2019-December 2021. All consecutive patients were included. Patient, tumor and surgical characteristics and postoperative complications were compared in both open and robot-assisted surgery. RESULTS: A total of 118 consecutive patients were included. The first 57 patients were treated without and the following 61 patients with a TL-wrap. There were no statistically significant differences between both groups regarding patient, pre-operative treatment and surgical characteristics. The occurrence of POPF was strongly reduced in the TL-wrap group compared to patients without a TL-wrap (3.3% vs 28.1%, P < 0.001). Also mean length of hospital stay was reduced (11.5 vs 18.8 days, P = 0.030). CONCLUSION: The use of a TL-wrap covering the PJ as addition to the modified Blumgart anastomosis technique is associated with a significantly reduced POPF rate and a reduced length of hospital stay. A TL-wrap is a simple addition to a PJ that may be considered to improve postoperative outcome. This association must be studied more definitively in a randomized controlled trial.

The strengths and limitations of routine staging before treatment with abdominal CT in colorectal cancer.

BACKGROUND: Advanced colorectal cancer (CRC), either locally advanced, metastasized (mCRC) or both, is present in a relevant proportion of patients. The chances on curation of advanced CRC are continuously improving with modern multi-modality treatment options. For incurable CRC the focus lies on palliation of symptoms, which is not necessarily a resection of the primary tumor. Both situations motivate adequate staging before treatment in CRC. This prospective observational study evaluates the outcomes after the introduction of routine staging with abdominal CT before treatment. METHODS: In a prospective observational study of 612 consecutive patients (2007-2009), the ability of abdominal CT to find liver metastases (LM), peritoneal carcinomatosis (PC) and T4 stage in colon cancer (CC) was analysed. RESULTS: Advanced CRC was present in 58% of patients, mCRC in 31%. The ability to find LM was excellent (99%), cT4 stage CC good (86%) and PC poor (33%). In the group of surgical patients with emergency presentations, the incidences of both mCRC (51%) and locally advanced colon cancer (LACC) (69%) were higher than in the elective group (20% and 26% respectively). Staging tended to be omitted more often in the emergency group (35% versus 12% in elective surgery). CONCLUSIONS: The strengths of staging with abdominal CT are to find LM and LACC, however it fails in diagnosing PC. On grounds of the incidence of advanced CRC, staging is warranted in patients with emergency presentations as well.

Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid.

Tumor-derived cell-free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC-LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC-PM). This study evaluated the presence of tumor-derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC-PM and in the plasma of 100 patients with isolated CRC-LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor-derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC-LM and 20% of CRC-PM patients and in peritoneal fluid in all CRC-PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC-PM plasma than in CRC-LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC-PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor-derived cfDNA in plasma is a poor biomarker to monitor CRC-PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC-PM treatment decisions.

Palliative chemotherapy for patients with synchronous metastases of small-bowel adenocarcinoma: A reflection of daily practice.

Background: As small-bowel adenocarcinoma (SBA) is scarce, no standard systemic regimen in metastatic disease has been defined. Objective: To obtain insights into the use and effects of palliative chemotherapy in patients with metastatic SBA in a population-based setting. Methods: Data from the Netherlands Cancer Registry of patients with metastatic SBA between 2007 and 2016 were used (n = 522). For patients treated with palliative chemotherapy, differences in treatment regimens and survival were evaluated. Results: Palliative chemotherapy was received by 38% of patients (n = 199). First-line combination chemotherapy was administered to 80% of patients, mainly CAPOX/FOLFOX. Single-agent chemotherapy mostly consisted of capecitabine. Second-line treatment, mostly irinotecan-based (58%), was prescribed to 27% of patients. Age 70 years or older was an adverse predictive factor for receiving first-line combination chemotherapy (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.08-0.62) and second-line therapy (OR 0.3, 95% CI 0.10-0.72). Median overall survival with palliative chemotherapy was 9.3 months, compared with 3.0 months without. In subanalyses, patients who received only first-line treatment had a median overall survival of 5.6 and 7.0 months after single-agent and combination chemotherapy, respectively. Conclusion: A minority of patients were treated with palliative chemotherapy. First-line treatment consisted predominantly of oxaliplatin-based combination chemotherapy, whereas second-line treatment was mainly irinotecan-based. Population-based median overall survival for selected patients treated with chemotherapy amounted to nine months.

Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC).

INTRODUCTION: Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy. METHODS AND ANALYSIS: This multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body surface area (BSA)) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response. ETHICS AND DISSEMINATION: This study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders. TRIAL REGISTRATION NUMBER: NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.

Massive surgical emphysema following transanal endoscopic microsurgery.

We describe an impressive and rare case of surgical emphysema after minimally invasive rectal surgery. This case reports on a patient who developed massive retroperitoneal, intraperitoneal and subcutaneous emphysema directly following a transanal endoscopic microsurgery (TEM) procedure for a rectal intramucosal carcinoma. Free intra-abdominal air after gastro-intestinal surgery can be a sign of a bowel perforation or anastomotic leakage. This is a serious complication often requiring immediate surgery. In our patient an abdominal computed tomography-scan with rectal contrast showed no signs of a rectal perforation. Therefore this emphysema was caused by the insufflation of CO2 gas in the rectum during the TEM-procedure. Conservative treatment resulted in an uneventful recovery. With the increasing usage of TEM for rectal lesions we expect this complication to occur more often. After ruling out a full thickness rectal wall perforation in patients with surgical emphysema following TEM, conservative treatment is the treatment of choice.

Challenges in diagnosing adhesive small bowel obstruction.

Adhesive small bowel obstruction (ASBO) is the most frequently encountered surgical disorder of the small intestine. Up to 80% of ASBO cases resolve spontaneously and do not require invasive treatment. It is important to identify such patients that will benefit from conservative treatment in order to prevent unnecessarily exposing them to the risks associated with surgical intervention, such as morbidity and further adhesion formation. For the remaining ASBO patients, timely surgical intervention is necessary to prevent small bowel strangulation, which may cause intestinal ischemia and bowel necrosis. While early identification of these patients is key to decreasing ASBO-related morbidity and mortality, the non-specific signs and laboratory findings upon clinic presentation limit timely diagnosis and implementation of appropriate clinical management. Combining the clinical presentation findings with those from other diagnostic imaging modalities, such as abdominal X-ray, computed tomography-scan and water-soluble contrast studies, will improve diagnosis of ASBO and help clinicians to better evaluate the potential of conservative management as a safe strategy for a particular patient. Nonetheless, patients who present with moderate findings by all these approaches continue to represent a challenge. A new diagnostic strategy is urgently needed to further improve our ability to identify early signs of strangulated bowel, and this diagnostic modality should be able to indicate when surgical management is required. A number of potential serum markers have been proposed for this purpose, including intestinal fatty acid binding protein and α-glutathione S transferase. On-going research is attempting to clearly define their diagnostic utility and to optimize their potential role in determining which patients should be managed surgically.