Impact of obesity after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for rare peritoneal malignancies: Paradox of obesity or poor prognostic factor?

BACKGROUND: Obesity is a public health concern with an increasing occurrence worldwide. Literature regarding impact of obesity on results after management of peritoneal carcinomatosis is poor. Our aim was to compare postoperative and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies according to the body mass index. METHODS: All the patients managed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies (including mainly pseudomyxoma peritonei and peritoneal mesothelioma), between 1995 and 2020, were retrospectively included from the French national registry of rare peritoneal tumors. RESULTS: 1450 patients were retrospectively included (63.5 % female, mean age 54 ± 13 years). Patients were divided into two groups according to their body mass index: non-obese (n = 1248, 86 %) and obese (n = 202, 14 %). Overall morbidity was significantly lower in non-obese patients in comparison with obese patients (n = 532/1248, 43 % vs n = 106/202, 53 %, p = 0.009). Medical and surgical morbidities were significantly lower in non-obese patients in comparison with obese patients (423/1258, 34 % vs n = 86/202, 43 %, p = 0.02 and n = 321/1248, 26 % vs n = 67/202, 33 %, p = 0.003, respectively). One-, 5- and 10-year overall survivals were similar between non-obese and obese patients (95 %, 82 % and 70 % vs 94 %, 76 % and 63 %; p = 0.1). One-, 5- and 10-year disease free survivals were similar between non-obese and obese patients (84 %, 67 % and 61 % vs 79 %, 62 % and 56 %, p = 0.1). CONCLUSION: Obese patients have to be carefully managed after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies. Some perioperative prophylactic treatments could be specifically implemented to reduce thromboembolic events, metabolic and wound complications.

Social inequalities in health: How do they influence the natural history of colorectal cancer?

As regards colorectal cancer (CRC) in France, social inequalities in health (SIH) exist. Underprivileged patients are characterized by reduced incidence of CRC and, conversely, by excess mortality. The explanatory mechanisms of the SIHs influencing survival are complex, multidimensional and variable according to healthcare system. Among the most deprived compared to the least deprived patients, SIHs are reflected by lower participation in screening campaigns, and CRC diagnosis is more frequently given at a later stage in an emergency context. During treatment, disadvantaged patients are more at risk of having to undergo open surgery and of enduring severe postoperative complications and belated chemotherapy (when recommended). Study of SIHs poses unusual challenges, as it is necessary not only to pinpoint social deprivation, but also to locate the different treatment facilities existing in a given territorial expanse. In the absence of individualized socioeconomic information, research in France on the social determinants of health is based on duly constituted cancer registries, in which an ecological index of social deprivation, the European Deprivation Index (EDI), provides an aggregate measure of the socioeconomic environment of a given individual in a given geographical setting at a given point in time. All in all, studies on SIHs are justified as means of identification and comprehension of the mechanisms underlying social deprivation, the objective being to more precisely orient programs and practices aimed at combating SIH.

Management of postoperative pancreatic fistula after pancreaticoduodenectomy.

A postoperative pancreatic fistula (POPF) is the main complication after cephalic pancreaticoduodenectomy (CPD). Unlike its prevention, the curative management of POPFs has long been poorly codified. This review seeks best practices for managing POPFs after CPD. The diagnosis of a POPF is based on two signs: (i) an amylase level in drained fluid more than 3 times the upper limit of the blood amylase level; and (ii) an abnormal clinical course. In the standardised definition of the International Study Group of Pancreatic Surgery, a purely biochemical fistula is no longer counted as a POPF and is treated by gradual withdrawal of the drain over at most 3 weeks. POPF risk can be scored using pre- and intraoperative clinical criteria, many of which are related to the quality of the pancreatic parenchyma and are common to several scoring systems. The prognostic value of these scores can be improved as early as Day 1 by amylase assays in blood and drained fluid. Recent literature, including in particular the Dutch randomised trial PORSCH, argues for early systematic detection of a POPF (periodic assays, CT-scan with injection indicated on standardised clinical and biological criteria plus an opinion from a pancreatic surgeon), for rapid minimally invasive treatment of collections (percutaneous drainage, antibiotic therapy indicated on standardised criteria) to forestall severe septic and/or haemorrhagic forms, and for the swift withdrawal of abdominal drains when the risk of a POPF is theoretically low and evolution is favourable. A haemorrhage occurring after Day 1 always requires CT angiography with arterial time and monitoring in intensive care. Minimally invasive treatment of a POPF (radiologically-guided percutaneous drainage or, more rarely, endoscopic drainage, arterial embolisation) should be preferred as first-line treatment. The addition of artificial nutrition (enteral via a nasogastric or nasojejunal tube, or parenteral) is most often useful. If minimally invasive treatment fails, then reintervention is indicated, preserving the remaining pancreas if possible, but the expected mortality is higher.

PIPAC nebulizer: How to test the new devices in the market, expert recommendations.

Pressurized intraperitoneal aerosol chemotherapy, named PIPAC, is now used in many centers around the world and as an intraperitoneal drug delivery system for treatment of peritoneal carcinomatosis. Recently, many of us have encountered problems during PIPAC procedures due to changes in material and production features of the original PIPAC nebulizer. Concomitantly, new PIPAC nebulizers proposed by other manufacturers are being launched on the market; which claim that they are the same as the original device in delivering PIPAC. However, these new devices are all different in terms of materials, technical characteristics and costs. We have considered that, to maintain the acquired results of PIPAC, we must ensure that the new systems are equivalent. The characteristics deemed essential by the expert group are as follows: 1: The nebulizer must be able to create droplets through an injector pressure between 10 and 20 bars, 2: The mean droplet size must be 3 micrometers, with 95% of the droplets between 0 and 10 micrometers, 3: The diffusion angle must be 70 degrees, which is the minimum.

Prevention of radiation enteritis by interposition of an intra-abdominal spacer before irradiation of an appendiceal tumour abscess drainage route.

The initial presentation of a mucinous adenocarcinoma of the appendix can be a peri-appendicular abscess. The abdominal wall muscles can be invaded during radiological or surgical drainage. The management of such a tumour is complex. The resection of a drainage route can be uncertain and R1. In this case, further treatment with adjuvant radiotherapy may be necessary. One possible deleterious side effect of radiotherapy on the abdominal wall is radiation injury to the bowel. As a preventive measure, a spacer (here a breast prosthesis) can be interposed.

Peritoneal recurrence of colorectal cancer with microsatellite instability: Is immunotherapy alone more effective than surgery?

A 67-year-old man was treated with systemic chemotherapy and cytoreductive surgery for microsatellite instable (MSI), deficient mismatch repair (dMMR) right colonic cancer with peritoneal metastases. Disease was controlled only when anti-PD1 and anti-CTLA4 immune checkpoint inhibitors were introduced. The patient is in complete remission after five years of follow-up. First-line immunotherapy could have a central role in the management of patients with peritoneal recurrence from MSI/dMMR colorectal cancer even though amenable to surgical treatment.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

Social deprivation aggravates post-operative morbidity in carcinologic colorectal surgery: Results of the COINCIDE multicenter study.

AIM OF THE STUDY: Evaluate the impact of social deprivation on morbidity and mortality in surgery for colorectal cancer. METHODS: The COINCIDE prospective cohort included nearly 2,000 consecutive patients operated on for colorectal cancer at the Assistance Publique-Hospitals of Paris (AP-HP) from 2008 to 2010. The data on these patients were crossed with the PMSI administrative database. The European Social Deprivation Index (EDI) was calculated for each patient and classified into five quintiles (quintiles 4 and 5 being the most disadvantaged patients). Thirty-day post-operative morbidity was determined according to the Dindo-Clavien classification, with a Had®Hoc re-analysis of each file. Statistical analysis was performed using the proprietary Q-finder® algorithm. RESULTS: One thousand two hundred and fifty nine curative colorectal resections were analyzed. Mortality was 2.7% and severe morbidity (Dindo-Clavien≥3) occurred in 16.4%. Mortality was not statistically significantly increased among the most disadvantaged who made up almost two thirds of the population (64.2%). Patients in quintiles 4 and 5 had a statistically significant increase in severe morbidity. The relative risk remained 1.5 even after adjustment for the known risk factors found in the analysis: age>70 years, ASA score, urgency, and laparotomy. CONCLUSIONS: The EDI represents an independent risk factor for severe morbidity after carcinologic colorectal resection. This study suggests that the determinants of health are multidimensional and do not depend solely on the quality and performance of the care system. The inclusion of this index in our surgical databases is therefore necessary, as is its use in health policy for the distribution of resources.

Restricted access to innovative surgical technique related to a specific training, is it ethical? Example of the PIPAC procedure. A systematic review and an experts survey.

OBJECTIVE: Using the example of Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), we analyse the development model of this procedure and provide an ethical analysis of the involvement of the industry in a new development. SUMMARY BACKGROUND DATA: In the case of breakthrough innovation, medical training is essential for safe use of the new procedure. In some cases, pharmaceutical companies decide to organise this training. But when it becomes the only training opportunity to use the device, scientists and clinicians could be exposed to a conflict of interest? METHODS: We performed a literature review of PIPAC publications using the STROBE criteria. Then, we conducted interviews with an expert panel to analyse the ethical impact of involvement of the industry in the development of the PIPAC procedure. RESULTS: The number of publications has increased every year since the first publication in Germany, where the technology was developed in 2013. The scientific production was of good quality, with a mean STROBE score of 18.2 ± 2.4 out of 22 points. Ten of the 33 included studies declared a conflict of interest. From the interviews, the main axe concerning the implication of the industry was the training model. The company had decided that only trained and approval surgeon could perform the PIPAC procedure. All four interviewed practitioners agreed that it was initially a good way to implement the procedure safely, but later they felt uncomfortable about the control and validation by the industry. CONCLUSION: Based on the growing number of published papers from a growing number of international centres, the controlled training model is not limiting. However, the different levels of conflict of interest complicate transparency, and we postulated that this development model is limited to the beginning of the procedure diffusion. CLINICALTRIAL. GOV REGISTRATION: NCT04341337.

[Strategy for the practice of digestive and oncologic surgery in COVID-19 epidemic situation]. / Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d'épidémie de COVID-19.

The COVID-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery - go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer - colon, pancreas, oesogastric, hepatocellular carcinoma - morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and /or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality - oesogastric, hepatic or pancreatic - is most often best deferred.

Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic.

The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery-go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer-colon, pancreas, oesogastric, hepatocellular carcinoma-morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality-oesogastric, hepatic or pancreatic-is most often best deferred.