Report of consensus panel 5 from the 11th international workshop on Waldenstrom's macroglobulinemia on COVID-19 prophylaxis and management.

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae.

Report of consensus panel 7 from the 11th international workshop on Waldenström macroglobulinemia on priorities for novel clinical trials.

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have impacted the development of effective novel agents and improved our knowledge of how the genomic background of WM may influence selection of therapy. Consensus Panel 7 (CP7) of the 11th International Workshop on WM was convened to examine the current generation of completed and ongoing clinical trials involving novel agents, consider updated data on WM genomics, and make recommendations on the design and prioritization of future clinical trials. CP7 considers limited duration and novel-novel agent combinations to be the priority for the next generation of clinical trials. Evaluation of MYD88, CXCR4 and TP53 at baseline in the context of clinical trials is crucial. The common chemoimmunotherapy backbones, bendamustine-rituximab (BR) and dexamethasone, rituximab and cyclophosphamide (DRC), may be considered standard-of-care for the frontline comparative studies. Key unanswered questions include the definition of frailty in WM; the importance of attaining a very good partial response or better (≥VGPR), within stipulated time frame, in determining survival outcomes; and the optimal treatment of WM populations with special needs.

Iatrogenic ureteral injuries and their prevention in colorectal surgery: results from a nationwide survey.

AIM: Iatrogenic ureteral injury (IUI) occurs rarely during colorectal surgery but is associated with significant mortality, morbidity and medicolegal issues. Few cases are reported, and recommendations regarding prevention are lacking. The aim of this study is to describe the current state of practice regarding IUI and its prevention among general surgeons in Switzerland. METHOD: All Swiss general surgeons who are members of either the Swiss Association of Laparoscopic and Thoracoscopic Surgery or the Swiss Surgical Society were invited to participate in an anonymous online survey. Demographics, surgical practice, rate of IUI and methods used to prevent IUI were investigated. RESULTS: All participants were board-certified general surgeons, 63.4% were certified visceral surgeons and 17.9% were certified colorectal surgeons. The mean level of experience in colorectal surgery was 15.6 ± 9.2 years. Formal ureter identification was considered mandatory during sigmoid or rectal surgery by 83.7% of participants, and 31.7% considered identification of the right ureter during right colectomy to be mandatory. In total, 61.8% of the participants and 78.4% of surgeons with more than 20 years of experience had encountered at least one IUI. Prophylactic ureteral stenting was considered useful in complex procedures by 93.5% of participants, and 56.9% had used stents at least once in the past 12 months. Noninvasive techniques for identifying ureters would be considered in regular daily practice by 54.5% of the participants. CONCLUSION: Most general surgeons experience IUI. Ureter identification is widely integrated in colorectal procedures. Prophylactic stenting is widely used for difficult cases. Noninvasive methods to improve ureter identification are now needed.

In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial.

Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3.106, 8.106 and 12.106 NK cells/kg) following by a high-dose interleukin-2 (IL-2). Cetuximab was administered intravenously every week for 7 weeks. Nine patients with liver metastases of colorectal or pancreatic cancers were included, three per dose level. Hepatic artery injection was successfully performed in all patients with no report of dose-limiting toxicity. Two patients had febrile aplasia requiring a short-term antibiotherapy. Grade 3/4 anemia and thrombopenia were also observed related to the chemotherapy. Objective clinical responses were documented in 3 patients and among them 2 occurred in patients injected with cell products harboring two KIR ligand mismatches and one in a patient with one KIR ligand mismatch. Immune monitoring revealed that most patients presented an increase but transient of IL-15 and IL-7 cytokines levels one week after chemotherapy. Furthermore, a high expansion of FoxP3+regulatory T cells and PD-1+ T cells was observed in all patients, related to IL-2 administration. Our results demonstrated that combining allogeneic NK cells transfer via intra-hepatic artery, cetuximab and a high-dose IL-2 is feasible, well tolerated and may result in clinical responses.

Multicentre phase II trial of near-infrared imaging in elective colorectal surgery.

BACKGROUND: Decreasing anastomotic leak rates remain a major goal in colorectal surgery. Assessing intraoperative perfusion by indocyanine green (ICG) with near-infrared (NIR) visualization may assist in selection of intestinal transection level and subsequent anastomotic vascular sufficiency. This study examined the use of NIR-ICG imaging in colorectal surgery. METHODS: This was a prospective phase II study (NCT02459405) of non-selected patients undergoing any elective colorectal operation with anastomosis over a 3-year interval in three tertiary hospitals. A standard protocol was followed to assess NIR-ICG perfusion before and after anastomosis construction in comparison with standard operator visual assessment alone. RESULTS: Five hundred and four patients (median age 64 years, 279 men) having surgery for neoplastic (330) and benign (174) pathology were studied. Some 425 operations (85·3 per cent) were started laparoscopically, with a conversion rate of 5·9 per cent. In all, 220 patients (43·7 per cent) underwent high anterior resection or reversal of Hartmann's operation, and 90 (17·9 per cent) low anterior resection. ICG angiography was achieved in every patient, with a median interval of 29 s to visualization of the signal after injection. NIR-ICG assessment resulted in a change in the site of bowel division in 29 patients (5·8 per cent) with no subsequent leaks in these patients. Leak rates were 2·4 per cent overall (12 of 504), 2·6 per cent for colorectal anastomoses and 3 per cent for low anterior resection. When NIR-ICG imaging was used, the anastomotic leak rates were lower than those in the participating centres from over 1000 similar operations performed with identical technique but without NIR-ICG technology. CONCLUSION: Routine NIR-ICG assessment in patients undergoing elective colorectal surgery is feasible. NIR-ICG use may change intraoperative decisions, which may lead to a reduction in anastomotic leak rates.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries.

Incisional hernia after robotic single-site cholecystectomy: a pilot study.

PURPOSE: Robotic LaparoEndoscopic Single-Site Surgery Cholecystectomy has been performed for 5 years using a dedicated platform (da Vinci® Single-Site®) with the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). While short-term feasibility has been described, long-term assessment of this method is currently outstanding. The aim of this study was to assess long-term parietal complications of this technique. METHODS: In this retrospective study, patients operated between 2011 and 2013 were evaluated. Parietal incision was assessed with ultrasonography and patients screened for residual pain from scar tissue. Demographic and perioperative data were also collected. RESULTS: We evaluated 48 patients [38 female, 79.2%; median age 49 years (range: 24-81 years)]; mean BMI 25.9 kg/m2 [±SD 4.1 kg/m2]. After a median follow-up of 39 months (range: 25-46 months), six incisional hernias (two patients had a positive echography but a negative clinical examination) were found (12.5%, 95% CI 7.5-30.2), and two patients had a surgical repair. The overall rate of incisional hernia was 16.7% (95% CI 7.5-30.2). Residual pain was observed in 5 of 48 patients. CONCLUSION: This preliminary study suggests that a clinically significant rate of incisional hernias can occur after R-LESS-C. Larger studies comparing R-LESS-C to alternative methods with long-term follow-up are necessary.

Prognostic Factors for Enteroatmospheric Fistula in Open Abdomen Treated with Negative Pressure Wound Therapy: a Multicentre Experience.

BACKGROUND: Reductions in mortality were reported with negative pressure wound therapy for laparostomy. However, some authors have voiced concern over an increased risk of enteroatmospheric fistulae. In this retrospective study, we hypothesized that surgical and metabolic derangements could increase the incidence of enteroatmospheric fistulae. We aimed to assess our experience and report long-term outcomes. METHODS: A multicentre review of all patients with a laparostomy managed with negative pressure wound therapy between 2005 and 2015 was undertaken. Features associated with enteroatmospheric fistulae were included in multivariate logistic regression. RESULTS: Fifty-seven patients were treated according to uniform protocol. Fourteen per cent (8/57) presented enteroatmospheric fistulae. Mesenteric ischaemia and preoperative arterial serum lactate >3.5 mmol/L were associated with a significantly increased risk of enteroatmospheric fistulae. Preoperative arterial serum lactate >3.5 mmol/L was an independent predictor of enteroatmospheric fistulae with an odds ratio of 12.41 (95% CI 1.54-99.99). All mesenteric ischaemia patients with anastomosis (5/15) presented enteroatmospheric fistulae. In-hospital mortality was 26.3% (15/57). One-year mortality was 33.3% (19/57). Incisional hernia rate was 5.2% (2/38) after 14.2 (2.4-56.3) months of follow-up. DISCUSSION: Mesenteric ischaemia increases the risk of enteroatmospheric fistulae. Anastomosis should only be created in revascularized patients. When mesenteric vascularization is not restored, diversion is advised.

Effect of ischaemic preconditioning on recurrence of hepatocellular carcinoma in an experimental model of liver steatosis.

BACKGROUND: Livers with parenchymal abnormalities tolerate ischaemia-reperfusion (IR) injury poorly. IR injury is a risk factor for hepatocellular carcinoma (HCC) recurrence. This study assessed the link between liver parenchymal abnormalities and HCC recurrence, and evaluated the protective effect of ischaemic preconditioning. METHODS: C57BL/6 mice were fed a choline-deficient diet for 6 and 12 weeks, or standard chow. Hepatic IR and ischaemic preconditioning were achieved by clamping liver blood inflow. Hepa 1-6 HCC cells were inoculated through the spleen. Thereafter, tumour burden, serum α-fetoprotein and cancer cell aggressiveness were compared among groups. RESULTS: Hepatocellular damage and expression of inflammatory genes (encoding interleukin 6, tumour necrosis factor α, hypoxia inducible factor 1α and E-selectin) were exacerbated after IR injury in mice with severe steatosis. Compared with control livers or those with minimal steatosis, livers exposed to a prolonged choline-deficient diet developed larger tumour nodules and had higher serum α-fetoprotein levels. Non-ischaemic liver lobes from mice with steatosis were not protected from accelerated tumour growth mediated by IR injury. This remote effect was linked to promotion of the aggressiveness of HCC cells. Ischaemic preconditioning before IR injury reduced the tumour burden to the level of that in non-ischaemic steatotic controls. This protective effect was associated with decreased cancer cell motility. CONCLUSION: Livers with steatosis tolerated IR poorly, contributing to more severe HCC recurrence patterns in mice with increasingly severe steatosis. IR injury also had a remote effect on cancer cell aggressiveness. Ischaemic preconditioning before IR injury reduced tumour load and serum α-fetoprotein levels. SURGICAL RELEVANCE: Liver ischaemia-reperfusion (IR) injury is associated with organ dysfunction and surgical morbidity. Livers with steatosis tolerate IR injury poorly in the setting of both liver resection and liver transplantation. Ischaemic preconditioning is a simple method to mitigate IR injury. This study shows that ischaemic preconditioning of mouse livers with steatosis reduces ischaemia-mediated tumour growth acceleration. Liver parenchymal abnormalities such as warm IR injury and liver steatosis should be taken into account to predict accurately the risk of liver cancer recurrence after surgical management. Ischaemic preconditioning strategies may hold therapeutic potential not only to mitigate surgical morbidity but also to reduce postoperative recurrence of liver cancer.

Discriminatory influence of Pinpoint perfusion imaging on diversion ileostomy after laparoscopic low anterior resection.

While still debated, it was advised to perform a protective temporary ileostomy after a low anterior resection (LAR). This might help to decrease the leak rate and therefore offers the patient better outcomes. Anastomotic leak can occur in many situations after a LAR and the control of the risk factors helps to adapt the need of an ileostomy. Near infrared technology allows assessing the microvascularisation of the anastomosis at the time of surgery and therefore might be an important tool to avoid a stoma in given situation. This article reviews the evidences with the use of this technology.

Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation.

BACKGROUND: To date, studies assessing the risk of post-transplant hepatocellular carcinoma (HCC) recurrence have focused on tumour characteristics. This study investigated the impact of donor characteristics and graft quality on post-transplant HCC recurrence. METHODS: Using the Scientific Registry of Transplant Recipients patients with HCC who received a liver transplant between 2004 and 2011 were included, and post-transplant HCC recurrence was assessed. A multivariable competing risk regression model was fitted, adjusting for confounders such as recipient sex, age, tumour volume, α-fetoprotein, time on the waiting list and transplant centre. RESULTS: A total of 9724 liver transplant recipients were included. Patients receiving a graft procured from a donor older than 60 years (adjusted hazard ratio (HR) 1.38, 95 per cent c.i. 1.10 to 1.73; P = 0.006), a donor with a history of diabetes (adjusted HR 1.43, 1.11 to 1.83; P = 0.006) and a donor with a body mass index of 35 kg/m(2) or more (adjusted HR 1.36, 1.04 to 1.77; P = 0.023) had an increased rate of post-transplant HCC recurrence. In 3007 patients with documented steatosis, severe graft steatosis (more than 60 per cent) was also linked to an increased risk of recurrence (adjusted HR 1.65, 1.03 to 2.64; P = 0.037). Recipients of organs from donation after cardiac death donors with prolonged warm ischaemia had higher recurrence rates (adjusted HR 4.26, 1.20 to 15.1; P = 0.025). CONCLUSION: Donor-related factors such as donor age, body mass index, diabetes and steatosis are associated with an increased rate of HCC recurrence after liver transplantation.

Robotic general surgery: current practice, evidence, and perspective.

BACKGROUND: Robotic technology commenced to be adopted for the field of general surgery in the 1990s. Since then, the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, CA, USA) has remained by far the most commonly used system in this domain. The da Vinci surgical system is a master-slave machine that offers three-dimensional vision, articulated instruments with seven degrees of freedom, and additional software features such as motion scaling and tremor filtration. The specific design allows hand-eye alignment with intuitive control of the minimally invasive instruments. As such, robotic surgery appears technologically superior when compared with laparoscopy by overcoming some of the technical limitations that are imposed on the surgeon by the conventional approach. PURPOSE: This article reviews the current literature and the perspective of robotic general surgery. CONCLUSIONS: While robotics has been applied to a wide range of general surgery procedures, its precise role in this field remains a subject of further research. Until now, only limited clinical evidence that could establish the use of robotics as the gold standard for procedures of general surgery has been created. While surgical robotics is still in its infancy with multiple novel systems currently under development and clinical trials in progress, the opportunities for this technology appear endless, and robotics should have a lasting impact to the field of general surgery.

[Right-sided colonic diverticular disease: quo vadis?]. / Maladie diverticulaire du côlon droit: quo vadis?

Symptomatic diverticular disease of the right colon is a rare entity in our latitudes, where it represents only 1.5% of all diverticulitis. In contrary, this disease is endemic in Asian countries. Besides, it has several differences with its left counterpart. Indeed, a right-sided diverticular disease is more often symptomatic, while the risk of complicated episodes seems lower. Right-sided diverticular disease usually manifests as right iliac fossa pain or low gastrointestinal bleeding. First described on 1912, there are no clear guidelines. The approach is usually conservative in Asia; when surgery cannot be avoided, a limited resection is performed. In Western countries, a surgical approach is more often considered. We reviewed the current literature and propose a way to manage right diverticulitis.

[Cell transplantation: current treatments and future prospects]. / Transplantation cellulaire: traitements actuels et perspectives d'avenir.

Regenerative medicine aims to replace a body function or specific cell loss. It includes therapies at the forefront of modem medicine, issuing from translational biomedical research. Transplantation of organs and cells has revolutionized the management of patients for whom medical treatment is a failure. Unfortunately, organ shortage is limiting treatment possibility. As an example, among the 15,000 patients with type I diabetes in Switzerland, only approximately 30 can receive a pancreas or an islet transplant per year. Second example, 500 patients die each year in Switzerland from alcoholic cirrhosis because no treatment is available. Transplantation of islet cells, hepatocytes, mesenchymal stem cells or dopaminergic neurons represents hope fora therapy available for large populations of patients.

[Robotic-assisted organ transplantation]. / Transplantation d'organes avec assistance robotique.

Advanced surgical procedures have traditionally been a domain of open surgery. However, minimally invasive approaches are evolving with the development of robotic technology which appears capable to overcome technical limitations of conventional laparoscopy. While traditionally perceived as impossible indications for minimally invasive surgery, reports on robotic organ transplantations have surfaced with promising results.

Systematic review and meta-analysis of percutaneous subclavian vein puncture versus surgical venous cutdown for the insertion of a totally implantable venous access device.

BACKGROUND: Totally implantable venous access devices (TIVADs) are commonly used in patients with cancer. Although several methods of implantation have been described, there is not enough evidence to support the use of a specific technique on a daily basis. The objective of this study was systematically to assess the literature comparing percutaneous subclavian vein puncture with surgical venous cutdown. METHODS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched by two independent authors. No time limits were applied. A systematic review and meta-analysis was carried out according to the recommendations of the Cochrane Collaboration, including randomized clinical trials comparing primary percutaneous subclavian vein puncture with surgical venous cutdown. RESULTS: Six trials were included, with 772 patients overall. The primary implantation failure rate was significantly lower for the percutaneous approach compared with surgical cutdown (odds ratio (OR) 0.26, 95 per cent confidence interval (c.i.) 0.07 to 0.94; P = 0.039). There was no evidence supporting a significant difference in terms of risk of pneumothorax, haematoma, venous thrombosis, infectious events or catheter migration. After taking between-study heterogeneity into account by using a random-effects model, procedure duration was not significantly longer for surgical cutdown: weighted mean difference +4 (95 per cent c.i. -12 to 20) min (P = 0.625). CONCLUSION: Percutaneous subclavian vein puncture is associated with a higher TIVAD implantation success rate and a procedure duration similar to that of surgical cutdown. Pneumothorax develops exclusively after percutaneous puncture and requires special attention from clinicians dealing with TIVAD insertion.

Robotic distal pancreatectomy: a valid option?

Although reported in the literature, conventional laparoscopic approach for distal pancreatectomy is still lacking widespread acceptance. This might be due to two-dimensional vision and decreased range of motion to reach and safely dissect this highly vascularized retroperitoneal organ by laparoscopy. However, interest in minimally invasive access is growing ever since and the robotic system could certainly help overcome limitations of the laparoscopic approach in the challenging domain of pancreatic resection, notably in distal pancreatectomy. Robotic distal pancreatectomy with and without spleen preservation has been reported with encouraging outcomes for benign and borderline malignant disease. As a result of upgraded endowristed manipulation and three-dimensional visualization, improved outcome might be expected with the launch of the robotic system in the procedure of distal pancreatectomy. Our aim was thus to extensively review the current literature of robot-assisted surgery for distal pancreatectomy and to evaluate advantages and possible limitations of the robotic approach.

[Prevention of bacterial risk: pathogen inactivation/detection of bacteria]. / Prévention du risque bactérien: inactivation des pathogènes/détection des bactéries.

Bacterial contamination of blood products remains the most important infectious risk of blood transfusion in 2013. Platelet concentrates (PC) are in cause in the majority of the transfusion reaction due to bacterial contaminations. A lot of prevention methods have been developed over the last 10 years (pre-donation interview, skin decontamination, diversion of the first 30 mL of the donation, leuko-reduction...), they have focused on limiting the contamination of the donations and prevent the bacterial growth in donations and/or in the blood products. These measures were effective and led to significantly reducing the risk of adverse effects associated with bacterial growth. However, every year there are about six accidents (with a high level of imputability) and one death. The reduction of the bacterial risk remains a priority for the French Blood Establishment (EFS). The procedure for skin disinfection is going to be improved in order to further strengthen this crucial step to avoid the contamination of donation. Methods of pathogen inactivation applied to plasma and PC are available in France and their effectiveness is demonstrated on the bacterial risk. Methods for bacterial detection of PC are used in many countries now. Automated culture is the most common. Alternatives are now available in the form of rapid tests able to analyze the PC just before the delivery and avoid false negatives observed with automated culture. Assessments are under way to confirm these benefits in 2013.