ERAS, length of stay and private insurance: a retrospective study.

PURPOSE: Hospital discharge after colorectal resection within an Enhanced Recovery After Surgery (ERAS) program occurs earlier compared to standard-care postoperative pathways but often later than what objective criteria of "readiness for discharge" could allow. The aim of this study was to analyse reasons and risk factors of such discharge delay. METHODS: All elective patients admitted for colorectal resection at the regional Hospital of Lugano in 2014 and 2015 were included. The postoperative day on which patients fulfilled consensus agreed criteria (according to Fiore) for readiness for discharge (POD-F) and the effective day of discharge (POD-D) were determined. We analysed the reasons for discharge delay (POD-D>POD-F) and performed univariate and multivariate analysis to determine risk factors. RESULTS: One hundred thirty-eight patients were included in the study. Median POD-F was 5 (2-48) days, POD-D was 6 (3-50) days. In 94 patients, POD-D occurred later than POD-F with a median delay of 1 (1-11) days. Reasons for discharge delay were insufficient social support in 13 (14%), patient's preference in 39 (41%) and medical team preference in 41 (44%). Private insurance (OR 2.61, 95%CI 1.08-6.34, p = 0.034) and patient discharged on a day other than Monday (OR 2.94, 95%CI 1.16-7.14, p = 0.023) were independent predictors for discharge delay. CONCLUSION: Even when objective criteria for readiness for discharge have been fulfilled, patients and/or doctors often do not feel comfortable with hospital discharge at this time point. Length of stay, even within an ERAS program, is still influenced by several non-medical factors and is therefore not a precise surrogate marker of outcomes.

Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor-Based 3D Culture System.

Colorectal cancer (CRC) is a leading cause of cancer-related death. Conventional chemotherapeutic regimens have limited success rates, and a major challenge for the development of novel therapies is the lack of adequate in vitro models. Nonmalignant mesenchymal and immune cells of the tumor microenvironment (TME) are known to critically affect CRC progression and drug responsiveness. However, tumor drug sensitivity is still evaluated on systems, such as cell monolayers, spheroids, or tumor xenografts, which typically neglect the original TME. Here, it is investigated whether a bioreactor-based 3D culture system can preserve the main TME cellular components in primary CRC samples. Freshly excised CRC fragments are inserted between two collagen scaffolds in a "sandwich-like" format and cultured under static or perfused conditions up to 3 d. Perfused cultures maintain tumor tissue architecture and densities of proliferating tumor cells to significantly higher extents than static cultures. Stromal and immune cells are also preserved and fully viable, as indicated by their responsiveness to microenvironmental stimuli. Importantly, perfusion-based cultures prove suitable for testing the sensitivity of primary tumor cells to chemotherapies currently in use for CRC. Perfusion-based culture of primary CRC specimens recapitulates TME key features and may allow assessment of tumor drug response in a patient-specific context.

Medullary-like hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent primary hepatic cancer. Pathological features can define the biological behavior and prognosis. Medullary-like HCC is a very rare variant that has been described only twice in literature. In the present study, we report the case of a non-cirrhotic 72-year-old man, who presented two HCC lesions on routine screening for hepatitis C virus liver disease. Radiological imaging and biopsy showed two different subtypes: one classic HCC, which was treated with chemoembolization, and a second PET/CT-positive carcinoma with a PET/CT-positive metastatic coeliac lymph node, which was resected laparoscopically with a left lateral sectionectomy and extended lymphadenectomy. Histopathology revealed a medullary-like HCC; lymph node analysis confirmed the metastatic nature of the PET/CT-positive coeliac node and showed an incidental B-cell lymphoma in the hepatic pedicle lymph nodes. To the best of our knowledge this is the third case of medullary-like HCC described in the literature, and the first associated to a concomitant typical HCC.

Gut microbiota modulate T cell trafficking into human colorectal cancer.

OBJECTIVE: Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. DESIGN: Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. RESULTS: CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. CONCLUSIONS: Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues.

Are Antiplatelet and Anticoagulants Drugs A Risk Factor for Bleeding in Mild Traumatic Brain Injury?

OBJECTIVE: Facing mild traumatic brain injury, clinicians must decide whether to perform a computed tomography (CT) scan to detect a potential intracranial hemorrhage. Many useful guidelines have been developed for the general population, but there is no general consensus about the best practice to adopt when dealing with patients on antiplatelet or anticoagulation drugs. The relatively recent introduction of new anticoagulants and second-generation antiplatelet drugs poses new challenges in this field. There are no data in the literature about the relative risk of intracranial bleeding in such categories. METHODS: We enrolled 2773 consecutive patients presenting at our emergency department with mild traumatic brain injury as chief complaint and evaluated the results of their head CT scans, stratifying their anticoagulation and/or antiplatelet drug regime. RESULTS: Of these patients, 1608 matched the criteria for head CT scan and had a Glasgow Coma Scale (GCS) score of 15; 517 were on antiplatelet drugs, whereas 213 were on anticoagulants. The risk of developing intracranial bleeding was significantly higher for patients on antiplatelet drugs, whereas the risk of anticoagulated patients overlapped with that of the general population. The trend for second-generation drugs was of higher risk of bleeding only for antiplatelets. CONCLUSIONS: Patients with a GCS score of 15 on long-term anticoagulation therapy seem to be at no higher risk for intracranial hemorrhage than are nonanticoagulated patients. On the contrary, patients with a GCS score of 15 on antiplatelet therapy seem to be more prone to developing intracranial bleeding than are the general population, with a trend to be more at risk when it comes to second-generation drugs.

Ultrasound screening for abdominal aortic aneurysms.

QUESTIONS UNDER STUDY: This pilot study aimed to assess the feasibility, acceptance and costs of an ultrasound scan screening programme for abdominal aortic aneurysms (AAA) in the elderly male population resident in Canton Ticino, Switzerland. METHODS: The target population were male patients aged 65-80 years who attended the outpatient clinics of the Lugano Regional Hospital in 2013. The patients showing interest were contacted by phone to verify their eligibility and fix the appointment for the ultrasound scan of the abdominal aorta. Patients with recent examinations suitable for AAA detection were excluded. Aneurysm was defined as an abdominal aorta with sagittal and/or axial diameter  30 mm. Patients' characteristics and study results were presented as descriptive statistics. The chi-squared test was used to compare categorical variables with p <0.05 as a statistical significance threshold. RESULTS: 1634 patients received the screening information leaflet and 745 (45.6%) underwent the ultrasound scan. Among the 1091 eligible patients, the acceptance rate was 68.3%. A previously unknown AAA was diagnosed in 31 patients (4.2%, 95% confidence interval 2.8-5.9%). Age and area of residence had a statistically significant impact on patient's acceptance rate (p <0.05). The mean cost per screened patient was CHF 88. CONCLUSIONS: AAA screening of male patients aged 65-80 years is feasible with limited financial and organisational effort. Adherence might be improved by a larger community-based programme and involvement of general practitioners.

The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer.

Purpose: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer. Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes, and functional features of colorectal cancer-infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells.Experimental Design: CD66b+ and CD8+ cell infiltration was analyzed by IHC on a tissue microarray including >650 evaluable colorectal cancer samples. Phenotypic profiles of tissue-infiltrating and peripheral blood CD66b+ cells were evaluated by flow cytometry. CD66b+/CD8+ cells crosstalk was investigated by in vitro experiments.Results: CD66b+ cell infiltration in colorectal cancer is significantly associated with increased survival. Interestingly, neutrophils frequently colocalize with CD8+ T cells in colorectal cancer. Functional studies indicate that although neutrophils are devoid of direct antitumor potential, coculture with peripheral blood or tumor-associated neutrophils (TAN) enhances CD8+ T-cell activation, proliferation, and cytokine release induced by suboptimal concentrations of anti-CD3 mAb. Moreover, under optimal activation conditions, CD8+ cell stimulation in the presence of CD66b+ cells results in increasing numbers of cells expressing CD45RO/CD62L "central memory" phenotype. Importantly, combined tumor infiltration by CD66b+ and CD8+ T lymphocytes is associated with significantly better prognosis, as compared with CD8+ T-cell infiltration alone.Conclusions: Neutrophils enhance the responsiveness of CD8+ T cells to T-cell receptor triggering. Accordingly, infiltration by neutrophils enhances the prognostic significance of colorectal cancer infiltration by CD8+ T cells, suggesting that they might effectively promote antitumor immunity. Clin Cancer Res; 23(14); 3847-58. ©2017 AACR.

Successful Endovascular Repair of a Penetrating Aortic Ulcer in Bacterial Aortitis.

Infective aortitis (IA) and penetrating aortic ulcer (PAU) impending for rupture represent 2 hostile life-threatening conditions. Simultaneous presentations of these rare entities can be considered an exception. The pleomorphic clinical presentation and the multifactorial etiology require a multidisciplinary approach to reach a correct diagnosis and an urgent treatment. We report the case of a 65-year-old patient presented with acute abdominal pain and septic shock secondary to a bacterial aortitis and penetrating ulcer of abdominal aorta. Unfit for surgery due to severe comorbidities, he was treated by means of a tubular endograft and long-term antibiotic therapy. A rapid improvement of clinical conditions was observed during the subsequent hospital stay. Complete regression of aortic involvement was demonstrated after 1 year. In conclusion, for selected patients affected by IA and PAU an endovascular approach associated to long-term antibiotic therapy may be safe and effective.

The management of bilateral myelolipoma: Case report and review of the literature.

INTRODUCTION: Bilateral adrenal myelolipoma is a rare benign neoplasm. We presented the case of a young man affected by a bilateral myelolipoma and the analysis of the literature of bilateral cases of myelolipoma. Our purpose is to give a suggestion of clear terms of reference regarding the management of this kind of bilateral neoplasm. PRESENTATION OF CASE: We reported the case of a 41-year-old healthy man complained of abdominal pain in the upper quadrants. No significant alterations were found in routine blood and endocrinological tests. The imaging (CT and MRI) showed a huge right adrenal mass and a smaller lesion at the left adrenal gland. The preoperative pathological characterization was suggestive for a myelolipoma. A right open adrenalectomy was performed, and a radiological surveillance was planned for the left tumor. The pathological exam confirmed the diagnosis. DISCUSSION: In literature, there are 36 cases described. The clinical presentation consisted of symptomatic tumors, incidentally diagnosed lesions or myelolipomas in patients with an associated endocrinal disorder. Symptomatic tumors or those bigger than 7cm, because of the potential risk of rupture, are usually treated surgically. In smaller (<7cm) and asymptomatic ones the surgical treatment is not univocal. CONCLUSION: In the setting of the surgical treatment, it is important to preserve in some way the hormonal function. For that reason, the bilateral adrenalectomy has to be reserved for symptomatic or sizeable (>7cm) cases. As far as we know, this is the first review on bilateral myelolipomas.

In-stent restenosis: mid-term results of debulking using excimer laser and drug-eluting balloons: sustained benefit?

BACKGROUND: In-stent restenosis (ISR) after endovascular treatment of stenotic and occlusive disease of the infrainguinal arteries is still a clinical challenge. The purpose of this study is to evaluate the mid-term follow-up of a combination therapy using laser debulking and drug-eluting balloons for ISR. METHODS: A prospective cohort of 14 patients (10 female, 4 male) with clinically relevant (Rutherford 3-6) ISR who were treated with excimer-laser angioplasty and drug-eluting balloons and a clinical follow-up of at least 9 months was evaluated. RESULTS: Mean age was 78 ± 6.5 years (range, 67-88 years). The mean lesion length treated was 133.2 ± 107.2 mm (range, 10-380 mm). The mean time to occurrence of restenosis after initial treatment was 8.6 ± 4.7 months (range, 2-18 months). Technical success was 100%. Distal embolization occurred in 2 cases, and was treated successfully by endovascular means. No other periprocedural major adverse events occurred. All patients were available for clinical follow-up and 12 patients were available with Duplex follow-up. At a mean clinical follow-up of 19.1 ± 8.7 months (range, 9-38 months), 1 target lesion revascularization was seen (at 3 years after the ISR treatment). In the patients with critical limb ischemia (n = 7), no major amputations were needed. Twelve patients had Duplex control (mean follow-up, 19.4 ± 9.4 months; range, 9-38 months). Binary restenosis (>50%) was seen in 1 case at 36 months; it was the same patient who had TLR. A 25%-50% stenosis was seen in 4 patients (mean follow-up, 25 months; range, 19-38 months). No sign of neointimal hyperplasia was demonstrated in 7 patients (mean follow-up, 14.3 months; range, 9-19 months). CONCLUSION: These mid- to long-term data compare favorably with results obtained with standard balloon angioplasty, cutting-balloon angioplasty, and balloon angioplasty using drug-eluting balloon. Longer follow-up and randomized trials are necessary to further define the role of combined excimer-laser debulking and drug-eluting balloon angioplasty in the treatment of ISR.

A huge mucinous cystadenoma of ovarian: a rare case report and review of the literature.

We report a case of a 63-years-old woman with a ten years history of increasing abdominal girth with associated abdominal pain. Abdomino-pelvic ultrasound and computed tomography scan revealed a large left ovarian cyst. The patient underwent laparotomy, resection of ovarian cyst and hysterectomy with bilateral ovarian resection. The removed huge mucinous cystadenoma, weighed 27 kg. Her post-operative course was unremarkable.

GM-CSF Production by Tumor Cells Is Associated with Improved Survival in Colorectal Cancer.

PURPOSE: Colorectal cancer infiltration by CD16(+) myeloid cells correlates with improved prognosis. We addressed mechanistic clues and gene and protein expression of cytokines potentially associated with macrophage polarization. EXPERIMENTAL DESIGN: GM-CSF or M-CSF-stimulated peripheral blood CD14(+) cells from healthy donors were cocultured with colorectal cancer cells. Tumor cell proliferation was assessed by (3)H-thymidine incorporation. Expression of cytokine genes in colorectal cancer and autologous healthy mucosa was tested by quantitative, real-time PCR. A tumor microarray (TMA) including >1,200 colorectal cancer specimens was stained with GM-CSF- and M-CSF-specific antibodies. Clinicopathological features and overall survival were analyzed. RESULTS: GM-CSF induced CD16 expression in 66% ± 8% of monocytes, as compared with 28% ± 1% in cells stimulated by M-CSF (P = 0.011). GM-CSF but not M-CSF-stimulated macrophages significantly (P < 0.02) inhibited colorectal cancer cell proliferation. GM-CSF gene was expressed to significantly (n = 45, P < 0.0001) higher extents in colorectal cancer than in healthy mucosa, whereas M-CSF gene expression was similar in healthy mucosa and colorectal cancer. Accordingly, IL1ß and IL23 genes, typically expressed by M1 macrophages, were expressed to significantly (P < 0.001) higher extents in colorectal cancer than in healthy mucosa. TMA staining revealed that GM-CSF production by tumor cells is associated with lower T stage (P = 0.02), "pushing" growth pattern (P = 0.004) and significantly (P = 0.0002) longer survival in mismatch-repair proficient colorectal cancer. Favorable prognostic effect of GM-CSF production by colorectal cancer cells was confirmed by multivariate analysis and was independent from CD16(+) and CD8(+) cell colorectal cancer infiltration. M-CSF expression had no significant prognostic relevance. CONCLUSIONS: GM-CSF production by tumor cells is an independent favorable prognostic factor in colorectal cancer.

High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor.

BACKGROUND: Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). METHODS: A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. RESULTS: MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO-. CONCLUSIONS: High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC.

Clinical impact of programmed cell death ligand 1 expression in colorectal cancer.

BACKGROUND: Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed. MATERIALS AND METHODS: A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression. RESULTS: Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P = 0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P = 0.0001) and validation (P = 0.03) sets. A similar trend (P = 0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n = 42) were found to be significantly associated (r = 0.33, P = 0.03). CONCLUSION: PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.

The challenge of posttraumatic thrombus embolization from abdominal aortic aneurysm causing acute limb ischemia.

We report the first documented case of distal thromboembolism originating from an abdominal aortic aneurysm (AAA) after a blunt trauma. A 72-year-old man with a known 6.2 cm AAA was brought to our emergency department with signs of bilateral acute limb ischemia developing immediately after an accidental fall. The occlusion was confirmed at computed tomographic angiography, and the aneurysm showed a fragmentated/ulcerated mural thrombus, morphologically different as compared to the previous computed tomography (CT). A thromboembolectomy was performed and, after treatment of the ischemic complications, the aneurysm was repaired by open surgery. Embolization from aneurysms in the setting of a trauma is a challenge for the vascular surgeon, also because of its rare occurrence. We describe the management and discuss the operative strategy we opted for in this patient.