Regional Therapy Approaches for Gastric Cancer with Limited Peritoneal Disease.

PURPOSE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

Adoption of cytoreductive surgery in the management of peritoneal malignancies-Global trends.

Cytoreductive surgery (CRS) has now been accepted as an integral component in the management of gastrointestinal and gynecological cancers with peritoneal metastases. Since the adoption of CRS is influenced by access to advanced medical facilities, trained multidisciplinary teams, and funding, there is wide variability in incorporation of CRS into routine clinical practice between high- versus low- and middle-income countries. This review highlights the global trends in the adoption of CRS for peritoneal malignancies with a specific focus on the establishment of CRS programs and barriers to incorporate CRS into routine clinical care in low- and middle-income countries.

Utilization of parenteral nutrition in major gastrointestinal surgery: An opportunity for quality improvement.

BACKGROUND & AIMS: Parenteral nutrition (PN) is commonly utilized to support patients in the perioperative period of major gastrointestinal (GI) surgeries. This study sought to evaluate PN utilization based on malnutrition status and duration of PN use in a single academic institution to evaluate baseline ASPEN recommendation concordance and identify opportunities for quality improvement. METHODS: Patients who had undergone major GI surgical oncology operations and received PN were identified over six months. The medical charts were reviewed for clinicopathologic variables, nutrition status, and the initiation and duration of PN. The cohort was stratified by PN recommendation concordance, and intergroup comparisons were made to identify factors associated with non-concordant utilization of PN. RESULTS: Eighty-one patients were identified, 38.3% of patients were initiated on PN due to dysmotility. Other indications were: intra-abdominal leak (27.2%), mechanical obstruction (18.5%), and failure to thrive (16.0%). Non-concordant PN utilization was identified in 67.9% (55/81) of patients. The most frequent reason for non-concordance was initiation outside the recommended time frame due to severity of malnutrition; well-nourished patients started "too soon" accounted for 29.0% (16/55), and 61.8% started "too late," most of whom were moderately or severely malnourished (34/55). In 16.0% (13/81) of the overall cohort, PN was administered for fewer than five days. CONCLUSIONS: PN use during the perioperative period surrounding major GI oncologic operations is clinically nuanced and frequently not concordant with established ASPEN recommendations. Quality improvement efforts should focus on reducing delayed PN initiation for nutritionally at-risk patients without increasing premature PN use in well-nourished patients.

Determinants, Costs, and Consequences of Common Bile Duct Injury Requiring Operative Repair Among Privately Insured Individuals in the United States, 2003-2020.

Objective: Characterize the determinants, all-cause mortality risk, and healthcare costs associated with common bile duct injury (CBDI) following cholecystectomy in a contemporary patient population. Background: Retrospective cohort study using nationwide patient-level commercial and Medicare Advantage claims data, 2003-2019. Beneficiaries ≥18 years who underwent cholecystectomy were identified using Current Procedure Terminology (CPT) codes. CBDI was defined by a second surgical procedure for repair within one year of cholecystectomy. Methods: We estimated the association of common surgical indications and comorbidities with risk of CBDI using logistic regression; the association between CBDI and all-cause mortality using Cox proportional hazards regression; and calculated average healthcare costs associated with CBDI repair. Results: Among 769,782 individuals with cholecystectomy, we identified 894 with CBDI (0.1%). CBDI was inversely associated with biliary colic (odds ratio [OR] = 0.82; 95% confidence interval [CI]: 0.71-0.94) and obesity (OR = 0.70, 95% CI: 0.59-0.84), but positively associated with pancreas disease (OR = 2.16, 95% CI: 1.92-2.43) and chronic liver disease (OR = 1.25, 95% CI: 1.05-1.49). In fully adjusted Cox models, CBDI was associated with increased all-cause mortality risk (hazard ratio = 1.57, 95% CI: 1.38-1.79). The same-day CBDI repair was associated with the lowest mean overall costs, with the highest mean overall costs for repair within 1 to 3 months. Conclusions: In this retrospective cohort study, calculated rates of CBDI are substantially lower than in prior large studies, perhaps reflecting quality-improvement initiatives over the past two decades. Yet, CBDI remains associated with increased all-cause mortality risks and significant healthcare costs. Patient-level characteristics may be important determinants of CBDI and warrant ongoing examination in future research.

Performance of multiparametric prostate magnetic resonance imaging validated by targeted and systematic transperineal biopsies.

Objective: To measure the performance of multiparametric (mp) magnetic resonance imaging (MRI) to identify intraprostatic tumour deposits using a systematic and targeted MR-guided transperineal prostate biopsy technique. Materials and Methods: Patients underwent a combined systematic and targeted MR-guided transperineal biopsy procedure in the dorsal lithotomy position under general anaesthesia. Systematic biopsies were spaced 10 mm or less apart and additional biopsies targeted any Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4 or 5 lesions identified on mpMRI. Cancer detection rates were calculated on a per patient and per lesion basis. Results: A total of 125 patients underwent the biopsy procedure. The positive predictive value (PPV) of mpMRI per patient was 59% for any cancer and 49% for Gleason score (GS) ≥ 7 cancer. The negative predictive value (NPV) of mpMRI per patient was 67% for any cancer and 88% for GS ≥ 7 cancer. On a per lesion basis, the PPV of PI-RADS 3 lesions for any and GS ≥ 7 cancer was 24% and 10%. For PI-RADS 4 lesions it was 42% and 32%. For PI-RADS 5 lesions, it was 76% and 70%. MpMRI failed to identify GS ≥ 7 cancer found on systematic biopsy in 22% of patients. Conclusion: Based on a combination of systematic and targeted transperineal prostate biopsies, mpMRI showed a high NPV and low PPV for GS ≥ 7 cancer on a per patient basis. The PPV of mpMRI on a per lesion basis increased with increasing PI-RADS score. However, there were a significant number of both false positive as well as false negative (mpMRI invisible) areas within the prostate that contained GS ≥ 7 cancer. Therefore, pathologic confirmation using both targeted and systematic mapping biopsy is necessary to accurately identify all intraprostatic tumour deposits.

Characterizing gastrointestinal dysfunction after pancreatic resection: a single-center retrospective study.

BACKGROUND: There are many well-described potential gastrointestinal (GI) side effects of pancreatic resection that can cause patients to suffer from chronic malabsorption, diarrhea, and persistent nausea. These GI symptoms can affect postoperative recovery, initiation of adjuvant therapy, and overall quality of life (QOL). The purpose of this study is to quantify the incidence of post-procedural complications and identify patients at higher risk for experiencing GI dysfunction after pancreatectomy. METHODS: A retrospective review of patients who underwent pancreatic resection at a single institution between January 2014 and December 2019 was performed. Demographics, operative factors, and postoperative gastrointestinal symptomatology and treatments were obtained by chart review. Significance tests were performed to compare GI dysfunction between patient subgroups. RESULTS: A total of 545 patients underwent pancreatic resection; within the cohort 451 patients (83%) underwent a pancreaticoduodenectomy (PD) and the most common indication was pancreatic adenocarcinoma. Two-thirds of patients (67%) reported gastrointestinal symptoms persisting beyond hospitalization. Only 105 patients (20%) were referred to gastroenterology for evaluation with 30 patients (5.5%) receiving a formal diagnosis. Patients who underwent PD were more likely to report GI symptoms and patients who identified as Caucasian were more likely to be referred to gastroenterology for evaluation. CONCLUSIONS: Gastrointestinal dysfunction after pancreatic resection occurs frequently yet only a small percentage of patients are referred for formal testing and diagnosis. There also appears to be a racial difference in referral patterns. Patients would benefit if earlier attention was dedicated to the diagnosis and corresponding treatment for postoperative digestive health disorders to optimize treatment planning and QOL.

Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation.

Fecal microbiota transplantation (FMT) has shown promising results in animal models of obesity, while results in human studies are inconsistent. We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome. The mucosal microbiome, fecal microbiome, and fecal metabolome showed individual clustering in each subject after FMT. The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome, characterized by an increased relative abundance of Bacteroides. Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal, colonic mucosal, and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid (EPA), compared with those without weight loss. Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B. bifidum, and fatty acid metabolism-associated metabolites showed positive correlations with A. onderdonkii. We report for the first time the individualized response of fecal and mucosa microbiome to FMT in obese subjects and highlight that FMT is less capable of shaping the small intestine microbiota. These findings contribute to personalized microbe-based therapies for obesity.

Surgical Indications and Outcomes of Resection for Pancreatic Neuroendocrine Tumors with Vascular Involvement.

Complete surgical resection of pancreatic neuroendocrine tumors (pNETs) has been suggested as the only potentially curative treatment. A proportion of these tumors will present late during disease progression, and invade or encase surrounding vasculature; therefore, surgical treatment of locally advanced disease remains controversial. The role of surgery with vascular reconstruction in pNETs is not well defined, and there is considerable variability in the use of aggressive surgery for these tumors. Accurate preoperative assessment is critical to evaluate individual considerations, such as anatomical variants, areas and lengths of vessel involvement, proximal and distal targets, and collateralization secondary to the degree of occlusion. Surgical approaches to address pNETs with venous involvement may include thrombectomy, traditional vein reconstruction, a reconstruction-first approach, or mesocaval shunting. Although the amount of literature on pNETs with vascular reconstruction is limited to case reports and small institutional series, the last two decades of studies have demonstrated that aggressive resection of these tumors can be performed safely and with acceptable long-term survival.

Clinical features and postoperative survival in patients with sporadic versus multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: An international cohort study.

BACKGROUND: The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic characteristics and outcomes of multiple endocrine neoplasia type 1-associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database. METHODS: A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias. RESULTS: Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded. CONCLUSION: Multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1-associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.

Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome.

BACKGROUND: Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear. OBJECTIVE: To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus. METHODS: We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months. RESULTS: At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months. CONCLUSION: These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.

Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2-infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution. METHODS: We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non-COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites. RESULTS: Compared with non-COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05). CONCLUSIONS: Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome.

More Than an ERAS Pathway is Needed to Meet Target Length of Stay After Pancreaticoduodenectomy.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols have been successfully instituted for pancreaticoduodenectomy (PD). This study evaluates reasons patients fail to meet length of stay (LOS) and areas for pathway improvement. MATERIALS AND METHODS: A multidisciplinary team developed and implemented an ERAS protocol for open PD in 2017. The study includes a medical record review of all patients who were perioperatively managed with the ERAS protocol and failed to meet LOS after PD procedures. Target LOS was defined as 7 d. RESULTS: From 2017 to 2020, 44% (93 of 213) of patients using ERAS protocol after PD procedures failed to meet target LOS. The most common reason to fail target LOS was ileus or delayed gastric emptying (47 of 93, LOS 11). Additional reasons included work-up of leukocytosis or pancreatic leak (17 of 93, LOS 14), additional "night" of observation (14 of 93, LOS 8), and orthostatic hypotension (3 of 93, LOS 10). Of these additional 46 patients, 19 patients underwent computed tomography (on or after POD 7) and only four patients received additional inpatient intervention. CONCLUSIONS: The most common reason for PD pathway failure included slow return of gastrointestinal function, a known complication after PD. The remaining patients were often kept for observation without additional intervention. This group represents an actionable cohort to target for improving LOS through surgeon awareness rather than protocol modification.

Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: a 24-week, double-blind, randomised controlled trial.

OBJECTIVE: The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM). DESIGN: In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24. RESULTS: Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05). CONCLUSION: Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness. TRIAL REGISTRATION NUMBER: NCT03127696.

Fluorescence lifetime predicts performance of voltage sensitive fluorophores in cardiomyocytes and neurons.

Voltage imaging with fluorescent indicators offers a powerful complement to traditional electrode or Ca2+-imaging approaches for monitoring electrical activity. Small molecule fluorescent indicators present the unique opportunity for exquisite control over molecular structure, enabling detailed investigations of structure/function relationships. In this paper, we tune the conjugation between aniline donors and aromatic π systems within the context of photoinduced electron transfer (PeT) based voltage indicators. We describe the design and synthesis of four new voltage-sensitive fluorophores (VoltageFluors, or VFs). Three of these dyes have higher relative voltage sensitivities (ΔF/F) than the previously-reported indicator, VF2.1.Cl. We pair these new indicators with existing VFs to construct a library of voltage indicators with varying degrees of conjugation between the aniline nitrogen lone pair and the aromatic π system. Using a combination of steady-state and time-resolved fluorescence spectroscopy, cellular electrophysiology, fluorescence lifetime imaging microscopy (FLIM), and functional imaging in mammalian neurons and human cardiomyocytes, we establish a detailed link between the photophysical properties of VF dyes and their ability to report on membrane potential dynamics with high signal-to-noise. Anilines with intermediate degrees of conjugation to the aromatic π system experience intermediate rates of PeT and possess the highest absolute voltage sensitivities. Measured using FLIM in patch-clamped HEK cells, we find that the absolute voltage sensitivity of fluorescence lifetime (Δτfl per mV), coupled with traditional fluorescence intensity-based metrics like ΔF/F and signal-to-noise ratio (SNR), provides a powerful method to both predict and understand indicator performance in cellular systems.

Temporal landscape of human gut RNA and DNA virome in SARS-CoV-2 infection and severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the enveloped RNA virus SARS-CoV-2 primarily affects the respiratory and gastrointestinal tracts. SARS-CoV-2 was isolated from fecal samples, and active viral replication was reported in human intestinal cells. The human gut also harbors an enormous amount of resident viruses (collectively known as the virome) that play a role in regulating host immunity and disease pathophysiology. Understanding gut virome perturbation that underlies SARS-CoV-2 infection and severity is an unmet need. METHODS: We enrolled 98 COVID-19 patients with varying disease severity (3 asymptomatic, 53 mild, 34 moderate, 5 severe, 3 critical) and 78 non-COVID-19 controls matched for gender and co-morbidities. All subjects had fecal specimens sampled at inclusion. Blood specimens were collected for COVID-19 patients at admission to test for inflammatory markers and white cell counts. Among COVID-19 cases, 37 (38%) patients had serial fecal samples collected 2 to 3 times per week from time of hospitalization until after discharge. Using shotgun metagenomics sequencing, we sequenced and profiled the fecal RNA and DNA virome. We investigated alterations and longitudinal dynamics of the gut virome in association with disease severity and blood parameters. RESULTS: Patients with COVID-19 showed underrepresentation of Pepper mild mottle virus (RNA virus) and multiple bacteriophage lineages (DNA viruses) and enrichment of environment-derived eukaryotic DNA viruses in fecal samples, compared to non-COVID-19 subjects. Such gut virome alterations persisted up to 30 days after disease resolution. Fecal virome in SARS-CoV-2 infection harbored more stress-, inflammation-, and virulence-associated gene encoding capacities including those pertaining to bacteriophage integration, DNA repair, and metabolism and virulence associated with their bacterial host. Baseline fecal abundance of 10 virus species (1 RNA virus, pepper chlorotic spot virus, and 9 DNA virus species) inversely correlated with disease COVID-19 severity. These viruses inversely correlated with blood levels of pro-inflammatory proteins, white cells, and neutrophils. Among the 10 COVID-19 severity-associated DNA virus species, 4 showed inverse correlation with age; 5 showed persistent lower abundance both during disease course and after disease resolution relative to non-COVID-19 subjects. CONCLUSIONS: Both enteric RNA and DNA virome in COVID-19 patients were different from non-COVID-19 subjects, which persisted after disease resolution of COVID-19. Gut virome may calibrate host immunity and regulate severity to SARS-CoV-2 infection. Our observation that gut viruses inversely correlated with both severity of COVID-19 and host age may partly explain that older subjects are prone to severe and worse COVID-19 outcomes. Altogether, our data highlight the importance of human gut virome in severity and potentially therapeutics of COVID-19. Video Abstract.

Regional lymph node sampling in hepatoma resection: insight into prognosis.

BACKGROUND: The importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis. METHODS: Patients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003-2015). Cohort-based clinicopathologic comparisons were made based on completion of regional LNS. Propensity-score matching reduced bias. Overall and disease-specific survival (OS/DSS) were analyzed. RESULTS: Among 5395 patients, 835 (15.4%) underwent regional LNS. Patients undergoing LNS had larger tumors (7.0vs4.8 cm) and higher T-stage (30.9 vs. 17.6% T3+, both p < 0.001). Node-positive rate was 12.0%. Median OS (50 months for both) and DSS (28 vs. 29 months) were similar between cohorts, but node-positive patients had decreased OS/DSS (20/16 months, p < 0.01). Matched patients undergoing LNS had equivalent OS (46 vs. 43 months, p = 0.869) and DSS (27 vs. 29 months, p = 0.306) to non-LNS patients. The prognostic impact of node positivity persisted after matching (OS/DSS 24/19 months, p < 0.01). Overall disease-specific mortality were both independently elevated (overall HR 1.71-unmatched, 1.56-matched, p < 0.01; disease-specific HR 1.40-unmatched, p < 0.01, 1.25-matched, p = 0.09). CONCLUSION: Regional LNS is seldom performed during resection for HCC, but it provides useful prognostic information. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional LNS to facilitate optimal multidisciplinary management.

Laparoscopic hepatic lobectomy for symptomatic polycystic liver disease.

BACKGROUND: Laparoscopic fenestration has largely replaced open fenestration of liver cysts. However, most hepatectomies for polycystic liver disease (PCLD) are performed open. Outcomes data on laparoscopic hepatectomy for PCLD are lacking. METHODS: Patients who underwent surgery for PCLD at a single institution between 2010 and 2019 were reviewed and grouped by operative approach. Pre- and post-operative volumes were calculated for patients who underwent resection. Primary outcomes were: volume reduction, re-admission and postoperative complications. RESULTS: Twenty-six patients were treated for PCLD: 13 laparoscopic fenestration, nine laparoscopic hepatectomy, three open hepatectomy and one liver transplantation. Median length of stay for patients after laparoscopic resection was 3 days (IQR 2-3). The only complication was post-operative atrial fibrillation in one patient. There were no readmissions. Overall volume reduction was 51% (range 22-69) for all resections, 32% (range 22-46) after open resection and 56% (range 39-69) after laparoscopic resection. CONCLUSION: Volume reduction achieved through laparoscopic approach exceeded open volume reduction at this institution and is comparable to volume reduction in previously published open resection series. Adequate volume reduction can be accomplished by laparoscopic means with acceptable postoperative morbidity.

Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization.

BACKGROUND & AIMS: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gastrointestinal tissues, little is known about the roles of gut commensal microbes in susceptibility to and severity of infection. We investigated changes in fecal microbiomes of patients with SARS-CoV-2 infection during hospitalization and associations with severity and fecal shedding of virus. METHODS: We performed shotgun metagenomic sequencing analyses of fecal samples from 15 patients with Coronavirus Disease 2019 (COVID-19) in Hong Kong, from February 5 through March 17, 2020. Fecal samples were collected 2 or 3 times per week from time of hospitalization until discharge; disease was categorized as mild (no radiographic evidence of pneumonia), moderate (pneumonia was present), severe (respiratory rate ≥30/min, or oxygen saturation ≤93% when breathing ambient air), or critical (respiratory failure requiring mechanical ventilation, shock, or organ failure requiring intensive care). We compared microbiome data with those from 6 subjects with community-acquired pneumonia and 15 healthy individuals (controls). We assessed gut microbiome profiles in association with disease severity and changes in fecal shedding of SARS-CoV-2. RESULTS: Patients with COVID-19 had significant alterations in fecal microbiomes compared with controls, characterized by enrichment of opportunistic pathogens and depletion of beneficial commensals, at time of hospitalization and at all timepoints during hospitalization. Depleted symbionts and gut dysbiosis persisted even after clearance of SARS-CoV-2 (determined from throat swabs) and resolution of respiratory symptoms. The baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity; there was an inverse correlation between abundance of Faecalibacterium prausnitzii (an anti-inflammatory bacterium) and disease severity. Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of angiotensin-converting enzyme 2 (ACE2) in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients. CONCLUSIONS: In a pilot study of 15 patients with COVID-19, we found persistent alterations in the fecal microbiome during the time of hospitalization, compared with controls. Fecal microbiota alterations were associated with fecal levels of SARS-CoV-2 and COVID-19 severity. Strategies to alter the intestinal microbiota might reduce disease severity.