Acute cholecystitis: Which flow-chart for the most appropriate management?

Acute cholecystitis (AC) is a very common disease in clinical practice. Laparoscopic cholecystectomy remains the gold standard treatment for AC, however due to aging population, the increased prevalence of multiple comorbidities and the extensive use of anticoagulants, surgical procedures may be too risky when dealing with patients in emergency settings. In these subsets of patients, a mini-invasive management may be an effective option, both as a definitive treatment or as bridge-to-surgery. In this paper, several non-operative treatments are described and their benefits and drawbacks are highlighted. Percutaneous gallbladder drainage (PT-GBD) is one of the most common and widespread techniques. It is easy to perform and has a good cost/benefit ratio. Endoscopic transpapillary gallbladder drainage (ETGBD) is a challenging procedure that is usually performed in high volume centers by expert endoscopists, and it has a specific indication for selected cases. EUS-guided drainage (EUS-GBD) is still not widely available, but it is an effective procedure that could have several advantages, especially in rate of reinterventions. All these treatment options should be considered together in a stepwise approach and addressed to patients after an accurate case-by-case evaluation in a multidisciplinary discussion. In this review, we provide a possible flowchart in order to optimize treatments, resource and provide to patients a tailored approach.

Intrahepatic CD69+Vδ1 T cells re-circulate in the blood of patients with metastatic colorectal cancer and limit tumor progression.

BACKGROUND: More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack of reliable prognostic markers. Vδ1 cells are a subset of tissue-resident gamma delta (γδ) T lymphocytes endowed with a broad array of antitumor functions and showing a natural high tropism for the liver. However, little is known about their impact in the clinical outcomes of CLM. METHODS: We isolated human γδ T cells from peripheral blood (PB) and peritumoral (PT) tissue of 93 patients undergone surgical procedures to remove CLM. The phenotype of freshly purified γδ T cells was assessed by multiparametric flow cytometry, the transcriptional profiles by single cell RNA-sequencing, the functional annotations by Gene Ontology enrichment analyses and the clonotype by γδ T cell receptor (TCR)-sequencing. RESULTS: The microenvironment of CLM is characterized by a heterogeneous immune infiltrate comprising different subsets of γδ tumor-infiltrating lymphocytes (TILs) able to egress the liver and re-circulate in PB. Vδ1 T cells represent the largest population of γδ TILs within the PT compartment of CLM that is greatly enriched in Vδ1 T effector (TEF) cells expressing constitutive high levels of CD69. These Vδ1 CD69+ TILs express a distinct phenotype and transcriptional signature, show high antitumor potential and correlate with better patient clinical outcomes in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, intrahepatic CD69+ Vδ1 TILs can egress CLM tissue to re-circulate in PB, where they retain a phenotype, transcriptional signature and TCR clonal repertoires resembling their liver origin. Importantly, even the increased frequencies of the CD69+ terminally differentiated (TEMRA) Vδ1 cells in PB of patients with CLM significantly correlate with longer OS. The positive prognostic score of high frequencies of CD69+ TEMRA Vδ1 cells in PB is independent from the neoadjuvant chemotherapy and immunotherapy regimens administered to patients with CLM prior surgery. CONCLUSIONS: The enrichment of tissue-resident CD69+ Vδ1 TEMRA cells re-circulating at high frequencies in PB of patients with CLM limits tumor progression and represents a new important clinical tool to either predict the natural history of CLM or develop alternative therapeutic protocols of cellular therapies.

Stent-free duct-to-duct biliary reconstruction after hepatectomy for liver tumors involving biliary confluence at the hepatic hilum: a monocentric experience.

Roux-en-Y hepaticojejunostomy (HJ) is the standard of care for biliary reconstruction. Its weaknesses are the loss of the sphincter functionality, which could lead to repeated cholangitis, and the reduced endoscopic accessibility to the biliary tree. In the context of liver transplantation it has been shown that duct-to-duct biliary anastomosis may be suitable as an alternative to HJ, significantly reducing the risk of cholangitis. Here we present our experience on stent-free duct-to-duct reconstruction, performed in six patients receiving hepatectomy with resection of the biliary confluence. Operative mortality was nil. Anastomotic leak occurred in four patients and resolved spontaneously in all cases. One patient developed anastomotic stricture 17 months after surgery and only one patient developed tumor recurrence at the anastomotic site; in both cases the endoscopic stenting succeeded in restoring the ducts patency. With a median follow-up of 24 months (range 19-28 months), no cholangitis or other biliary-related complications were observed. Our experience, although limited, shows satisfactory oncological and functional outcomes, confirming all previously published results.

Inpatient Care during the COVID-19 Pandemic: A Survey of Italian Physicians.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern. OBJECTIVE: We explored the clinical management of inpatients with COVID-19 in Italy. METHODS: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed. RESULTS: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%. CONCLUSIONS: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available.

Peri-tumoural CD3+ Inflammation and Neutrophil-to-Lymphocyte Ratio Predict Overall Survival in Patients Affected by Colorectal Liver Metastases Treated with Surgery.

BACKGROUND: Systemic and local inflammation plays an important role in many cancers and colorectal liver metastases (CRLM). While the role of local immune response mediated by CD3+ tumour-infiltrating lymphocytes is well-established, new evidence on systemic inflammation and cancer, such as neutrophil-lymphocyte ratio (NLR), is emerging. The aim of this study is to seek an association between the CD3+ lymphocytes and NLR with patients' prognosis and possibly stratifying it accordingly. METHODS: From January 2005 to January 2013, 128 consecutive patients affected by CRLM and treated with chemotherapy and surgery were included in the study. Different cutoff levels were calculated with ROC curves for each of the biomarkers, and their relative outcome in terms of overall survival (OS) and recurrence-free survival (RFS) was determined. Associating the two biomarkers, three risk groups were determined: low risk (two protective biomarkers), intermediate risk (one protective biomarker) and high risk (no protective biomarker). RESULTS: After a median follow-up of 45 months, median OS and RFS were 44 and 9 months, respectively. For OS, 29 (22.66%), 59 (46.09%) and 40 (31.25%) patients were in the low, intermediate and high-risk groups, respectively. Adjusted Cox regression analysis showed an increased risk of death in the intermediate group (HR 2.67 p = 0.007 95% CI 1.31-5.42) and high-risk group (HR 2.86 p = 0.005 95% CI 1.37-5.99) compared to the low-risk group (reference). CONCLUSION: Systemic and local immune response index allows stratification of patients in different OS and RFS risk groups.

R1 Resection for Colorectal Liver Metastases: a Survey Questioning Surgeons about Its Incidence, Clinical Impact, and Management.

BACKGROUND: A ≥ 1-mm margin is standard for resection of colorectal liver metastases (CLM). However, R1 resection is not rare (10-30%), and chemotherapy could mitigate its impact. The possibility of detaching CLM from vessels (R1 vascular margin) has been described. A reappraisal of R1 resection is needed. METHODS: A 19-question survey regarding R1 resection for CLM was sent to hepatobiliary surgeons worldwide. Seven clinical cases were included. RESULTS: In total, 276 surgeons from 52 countries completed the survey. Ninety percent reported a negative impact of R1 resection (74% local recurrence, 31% hepatic recurrence, and 36% survival), but 50% considered it sometimes required for resectability. Ninety-one percent of responders suggested that the impact of R1 resection is modulated by the response to chemotherapy and/or CLM characteristics. Half considered the risk of R1 resection to be an indication for preoperative chemotherapy in patients who otherwise underwent upfront resection, and 40% modified the chemotherapy regimen when the tumor response did not guarantee R0 resection. Nevertheless, 80% scheduled R1 resection for multiple bilobar CLM that responded to chemotherapy. Forty-five percent considered the vascular margin equivalent to R0 resection. However, for lesions in contact with the right hepatic vein, right hepatectomy remained the standard. Detachment from the vein was rarely considered (10%), but 27% considered detachment in the presence of multiple bilobar CLM. CONCLUSIONS: A negative margin is still standard for CLM, but R1 resection is no longer just a technical error. R1 resection should be part of the modern multidisciplinary, aggressive approach to CLM.

Is Tumor Detachment from Vascular Structures Equivalent to R0 Resection in Surgery for Colorectal Liver Metastases? An Observational Cohort.

BACKGROUND: R0 resection is the standard for colorectal liver metastases (CLMs). Adequacy of R1 resections is debated. Detachment of CLMs from vessels has been proposed to prioritize parenchyma sparing and increase resectability, but outcomes are still to be elucidated. The present study aimed to clarify the outcomes of R1 surgery (margin <1 mm) in patients with CLMs, distinguishing standard R1 resection (parenchymal margin, R1Par) and R1 resection with detachment of CLMs from major intrahepatic vessels (R1Vasc). METHODS: All patients undergoing first resection between 2004 and June 2013 were prospectively considered. R0, R1Par, and R1Vasc were compared in per-patient and per-resection area analyses. RESULTS: The study included 627 resection areas in 226 consecutive patients. Fifty-one (8.1 %) resections in 46 (20.4 %) patients were R1Vasc, and 177 (28.2 %) resections in 107 (47.3 %) patients were R1Par. Thirty-two (5.1 %) surgical margin recurrences occurred in 28 (12.4 %) patients. Local recurrence risk was similar between the R0 and R1Vasc groups (per-patient analysis 5.3 vs. 4.3 %; per-resection area analysis 1.5 vs. 3.9 %, p = n.s.) but increased in the R1Par group (19.6 and 13.6 %, p < 0.05 for both). The R1Par group had a higher rate of hepatic-only recurrences (49.5 vs. 36.1 %, p = 0.042). On multivariate analysis, R1Par was an independent negative prognostic factor of overall survival (p = 0.034, median follow-up 33 months); conversely R1Vasc versus R0 had no significant differences. CONCLUSIONS: R1Par resection is not adequate for CLMs. R1Vasc surgery achieves outcomes equivalent to R0 resection. CLM detachment from intrahepatic vessels can be pursued to increase patient resectability and resection safety (parenchymal sparing).