Three distinct outcomes in patients with colorectal adenocarcinoma and lymphovascular invasion: the good, the bad, and the ugly.

PURPOSE: In colorectal cancer (CRC), lymphovascular invasion (LVI) is a predictor of poor outcome and its analysis is nowadays recommended. Literature is still extremely heterogeneous, and we hypothesize that, within such a group of patients, there are any further predictors of survival. METHODS: A total of 2652 patients with I-III-stage CRC undergoing resection between 2002 and 2018 were included in a retrospective analysis of demographic, clinical, and histology with the aim of defining the impact of LVI on overall survival (OS) and its relationship with other prognostic factors. RESULTS: Overall, 5-year-OS was 62.6% (77-month-median survival). LVI was found in 558 (21%) specimens and resulted associated with 44.9%-5-year-OS (44 months) vs. 64.1% (104 months) of LVI cases. At multivariate analysis, LVI (p = 0.009), T3-4 (p < 0.001), and N ≠ 0 (p < 0.001) resulted independent predictors of outcome. LVI resulted as being associated with older age (p < 0.013), T3-4 (p < 0.001), lower grading (p < 0.001), N ≠ 0 (p < 0.001), mucinous histology (p < 0.001), budding (p < 0.001), and PNI (p < 0.001). Within the LVI + patients, T3-4 (p = 0.009) and N ≠ 0 (p < 0.001) resulted as independent predictors of shortened OS. In particular, N-status impacted the prognosis of patients with T3-4 tumors (p = 0.020), whereas it did not impact the prognosis of patients with T1-2 tumors (p = 0.393). Three groups (T1-2anyN, T3-4N0, T3-4 N ≠ 0), with distinct outcome (approximately 70%-, 52%-, and 35%-5-year-OS, respectively), were identified. CONCLUSIONS: LVI is associated with more aggressive/more advanced CRC and is confirmed as predictor of poor outcome. By using T- and N-stage, a simple algorithm may easily allow re-assessing the expected survival of patients with LVI + tumors.

Fighting cancer in coronavirus disease era: organization of work in medical oncology departments in Emilia Romagna region of Italy.

Aim: To assess the measures applied to reduce the spread of coronavirus disease (COVID-19) and the timing of their application in medical oncology departments. Materials & methods: We surveyed all medical oncology departments from the Italian Emilia Romagna region via a multidomain questionnaire. The questions covered items on patients, healthcare workers, risk reduction measure and clinical trials. Results: A total of 12 centers involving 861 healthcare members joined the survey. The measures applied to patients and health workers partially converged in all the departments while major divergences were found in the clinical trials domain. High rate of COVID-19 infection occurred among medical doctors (21/208, 10.1%) and social care workers (13/110, 11.8%). Rate of infection among nurses was 5.7% (24/418). Conclusion: All measures able to reduce risk of COVID-19 infection must be applied in medical oncology departments. Early introduction of risk reduction measures may be a critical issue.

Impact of Metformin Use and Diabetic Status During Adjuvant Fluoropyrimidine-Oxaliplatin Chemotherapy on the Outcome of Patients with Resected Colon Cancer: A TOSCA Study Subanalysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain. MATERIALS AND METHODS: This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes. RESULTS: Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48-4.77; p = .4781) nor with RFS (HR, 1.56; 95% CI, 0.69-3.54; p = .2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS. CONCLUSIONS: Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC. IMPLICATIONS FOR PRACTICE: The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival.

Snacking in nutrition and health.

Many studies suggest that distributing energy and nutrient intake across 4-5 eating occasions/day (rather than across three standard meals) could favourably affect human health. The inclusion of 1-2 snacks in the daily pattern alleviates the potential digestive and metabolic overload caused by fewer heavier meals and might contribute to meet recommendations for food groups (e.g. fruits, dairy) and nutrients like fibre and vitamins. The snack composition should be evaluated taking into account the whole day's diet. In early and late ages, and for specific population groups, snacking may need to follow particular characteristics in order to be optimal, both in terms of composition and timing. This document, which is the result of a collaboration of experts across several fields of research, intends to provide a review of the current scientific literature on meal frequency and health, highlighting the beneficial effects of correct snack consumption across the human lifespan.

Primary Retroperitoneal Cystoadenocarcinoma: A Systematic Review.

BACKGROUND/AIMS: The aim of this study was to perform a systematic review on primary retroperitoneal cystoadenocarcinoma (PRC), which is an extremely rare disease. METHODS: According to PRISMA guidelines, all the literature about PRC from 1977 to 2015 was reviewed. Thirty articles were selected; characteristics of the patients were collected and described; time to recurrence and overall survival (OS) were investigated when available. RESULTS: Thirty seven patients were included of whom 33 were females; the median age at presentation was 43. PRC was more common in postmenopausal women. Surgery was the standard therapy; the role of chemotherapy and/or radiotherapy was uncertain. Thirty percent of the patients relapsed after 58 months from the surgery; the rupture of the cyst occurred in 13% of the cases and it was associated with poor prognosis as well as premenopausal status. At 125 months from the diagnosis, 72% of the patients were alive and the median OS was not reached. CONCLUSIONS: The present systematic review about PRC is the first performed until the date of drafting this paper. We described some clinical features of PRC and their possible prognostic value. No conclusive data can be presented due to the small population analyzed and to publication bias.

Surgical management of irreparable rotator cuff tears.

PURPOSE: In this prospective case control study, the effectiveness of surgical management of irreparable rotator cuff tears in terms of patient's status and quality of life was evaluated in two groups of patients: one group receiving arthroscopic debridement associated with acromioplasty and bursectomy and the other receiving an arthroscopic partial repair of the rotator cuff tear. METHODS: Sixty-eight patients (47 males and 21 females) undergoing arthroscopic shoulder surgery for massive irreparable rotator cuff tear were enrolled in our study. Patients were divided into two groups: Group AP (debridement associated with acromioplasty and bursectomy) and Group PR (partial repair). Pre- and post-operative range of motion (ROM), modified-UCLA shoulder score and strength measurement were performed. The RC-QOL was used at the time of the last follow-up to assess patients' perception of their quality of life. RESULTS: The final follow-up was 7.8 (±2.3, range 5-9) years. ROM measures were significantly increased from pre- to post-operative evaluations, with significant intergroup differences (P < 0.001). The overall modified-UCLA shoulder score showed a mean pre-operative value of 7.6 ± 2.6 (95 % CI 6.7-8.5) for Group AP and 8.6 ± 4.1 (95 % CI 7.0-9.9) (n.s.) for Group PR. The post-operative values at the latest follow-up showed a statistically significant improvement in both groups [21.4 ± 3.7 (95 % CI 20.1-22.7) for Group AP and 28.8 ± 4.2 (95 % CI 27.3-30.2) for Group PR] (P < 0.0001), with a significant intergroup difference (P < 0.0001). The RC-QOL demonstrated a statistically significant difference between the groups [Group AP: 61.8 ± 6.1(95 % CI 59.6-63.9); Group PR: 71.2 ± 9.8 (95 % CI 67.7-74.6)] (P < 0.0002). CONCLUSION: Both techniques are effective in reducing patients' symptoms, with higher functional outcomes for partial repair. However, the choice of which technique to undertake should take into account the patients' features concerning the acromio-humeral interval and levels of daily activities. LEVEL OF EVIDENCE: Therapeutic case-control study, Level III.

Bilateral double osteotomy in severe torsional malalignment syndrome: 16 years follow-up.

BACKGROUND: Torsional malalignment syndrome (TMS) is a well defined condition consisting of a combination of femoral antetorsion and tibial lateral torsion. The axis of knee motion is medially rotated. This may lead to patellofemoral malalignment with an increased Q angle and chondromalacia, patellar subluxation and dislocation. Conservative management is recommended in all but the most rare and severest cases. In these cases deformity correction requires osteotomies at two levels per limb. MATERIALS AND METHODS: From 1987 to 2002 in our institution three patients underwent double femoral and tibial osteotomy for TMS bilateral correction (12 osteotomies). All patients were reviewed at mean follow-up of 16 years. RESULTS: At final follow-up no patients reported persistence of knee or hip pain. At clinical examination both lower limbs showed a normal axis and a normal patella anterior position. Pre-operative femoral version measurement showed an average hip internal rotation of 81.5° (range 80°-85°) and average hip external rotation of 27.2° (10°-40°). Thigh-foot angle measurement showed an average value of 38.6° (32°-45°). At final follow-up femoral version measurement showed an average hip internal rotation of 49° (range 45°-55°) and average hip internal rotation of 44.3° (20°-48°) (Figs. 1, 2, 3, 4, 5, 6). Thigh-foot angles measurement showed an average value of 21.6° (18°-24°) outward. CONCLUSION: We recommend a clinical, radiographical and CT scan evaluation of all torsional deformity. In cases of significant deformity, internally rotating the tibia alone is not sufficient. Ipsilateral outward femoral and inward tibial osteotomies are our current recommendation for TMS, both performed at the same surgical setting.

Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells.

Pancreatic ductal adenocarcinoma is one of the most lethal solid malignancies, characterized by its aggressiveness and metastatic potential, with a 5-year survival rate of only 13%. Progress in the management of metastatic disease has been modest. A robust connection between nervous system and tumor progression exists, with prominent neural alterations having been observed during pancreatic cancer's progression, including neural hypertrophy, neural density, and neural remodeling. The pancreatic tumor microenvironment includes s set of cells and structures that constantly dialogue with cancer cells, influencing its growth and behavior. The microglia is key cellular components of the tumor microenvironment, and Schwann cells are the principal glial cells in the peripheral neural system. Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting a variety of factors and can support a tumor's invasion of nerves and distant metastasis, with further pain exacerbation. Schwann cells secrete various pain-related molecules, such as the neural growth factor, to mediate the activation of primary sensory neurons, leading to pain induction. The binding of the neural growth factor to tropomyosin receptor kinase A is an important signaling mechanism for pain perception in humans. Consequently, directing efforts towards targeting neural invasion may provide an alternative strategy to improve the prognosis of and alleviate pain in patients with pancreatic cancer.

A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists.

Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.

Bone Metastases from Intrahepatic Cholangiocarcinoma Confer Worse Prognosis.

BACKGROUND: Metastatic intrahepatic cholangiocarcinoma still has a dismal prognosis. The aim of our study was to investigate the prognostic role of bone metastases in patients affected by intrahepatic cholangiocarcinoma. METHODS: A total of 186 metastatic intrahepatic cholangiocarcinoma patients were retrospectively reviewed. Clinicopathologic and survival data were collected and reviewed, in particular overall survival, progression-free survival after first-line treatment and time from end of first-line therapy to cancer death. RESULTS: Around 11% of intrahepatic cholangiocarcinoma patients developed bone metastases. This subgroup of patients showed no differences in progression-free survival to first-line chemotherapy but had a shorter median overall survival of 4 months compared to the group with liver involvement only (p = 0.03). If treated, the outcome for ECOG PS 2 patients with bone metastases was worse in comparison to patients with liver involvement only with poor performance status (p = 0.003). The presence of bone metastases, poor performance status and no subsequent second-line treatment was associated with a worse outcome in multivariate analysis. CONCLUSIONS: Patients with intrahepatic carcinoma and bone metastases with poor ECOG performance status might be treated with best supportive care and not active chemotherapy treatment, the decisions which have to be shared with patients.

Second-Line Chemotherapy for Intrahepatic Cholangiocarcinomas: What Is the Real Gain?

BACKGROUND: The presence of actionable alterations in advanced biliary tract cancer patients opened new therapeutic possibilities for second-line treatments. However, for around 60% of the patients, chemotherapy remains the only therapeutic option. The aim of our study was to evaluate outcomes and prognostic parameters in patients with intrahepatic cholangiocarcinomas treated with second-line chemotherapy. METHODS: A total of 255 consecutive metastatic intrahepatic cholangiocarcinoma (ICC) patients were retrospectively reviewed and clinicopathologic and survival data were collected. RESULTS: Fourty-four percent of ICC patients underwent second-line chemotherapy. In particular, younger ICC patients with better ECOG PS status, and with disease control after first-line chemotherapy were those who were treated with second-line treatments. Median progression-free survival in the patients treated with second-line chemotherapy was 3 months. Finally, the patients affected by intrahepatic cholangiocarcinoma with better ECOG PS, with prior surgical resection of the primary tumor, who responded to first-line chemotherapy, and had better progression-free survival with second-line chemotherapy, were associated with better outcomes in multivariate analysis. CONCLUSIONS: Not all patients seem to benefit from second-line chemotherapy. To improve therapeutic decisions, performance status and disease control with first-line chemotherapy should lead to the decision on the usefulness of second-line treatments in advanced ICC patients.

Influence of Trabecular Geometry on Scaffold Mechanical Behavior and MG-63 Cell Viability.

In a scaffold-based approach for bone tissue regeneration, the control over morphometry allows for balancing scaffold biomechanical performances. In this experimental work, trabecular geometry was obtained by a generative design process, and scaffolds were manufactured by vat photopolymerization with 60% (P60), 70% (P70) and 80% (P80) total porosity. The mechanical and biological performances of the produced scaffolds were investigated, and the results were correlated with morphometric parameters, aiming to investigate the influence of trabecular geometry on the elastic modulus, the ultimate compressive strength of scaffolds and MG-63 human osteosarcoma cell viability. The results showed that P60 trabecular geometry allows for matching the mechanical requirements of human mandibular trabecular bone. From the statistical analysis, a general trend can be inferred, suggesting strut thickness, the degree of anisotropy, connectivity density and specific surface as the main morphometric parameters influencing the biomechanical behavior of trabecular scaffolds, in the perspective of tissue engineering applications.

Revealing invisible cell phenotypes with conditional generative modeling.

Biological sciences, drug discovery and medicine rely heavily on cell phenotype perturbation and microscope observation. However, most cellular phenotypic changes are subtle and thus hidden from us by natural cell variability: two cells in the same condition already look different. In this study, we show that conditional generative models can be used to transform an image of cells from any one condition to another, thus canceling cell variability. We visually and quantitatively validate that the principle of synthetic cell perturbation works on discernible cases. We then illustrate its effectiveness in displaying otherwise invisible cell phenotypes triggered by blood cells under parasite infection, or by the presence of a disease-causing pathological mutation in differentiated neurons derived from iPSCs, or by low concentration drug treatments. The proposed approach, easy to use and robust, opens the door to more accessible discovery of biological and disease biomarkers.

Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.

Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study.

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0-56.7), and the 18-month overall survival was 73.1% (95%CI:61.6-81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.

Olaparib as a single agent treatment in pre-treated metastatic pancreatic cancer patient harboring BRCA2 mutation: What could we expect?

BACKGROUND: Despite ongoing developments, pancreatic cancer remains one of the most difficult tumors to treat. Even the most effective chemotherapy regimens, only marginally improve the outcome of Pancreatic cancer patients, which rarely exceeds one year. A small subset of Pancreatic cancer patients, carriers of germline variants of BRCA1/2, are clinically relevant as therapeutic targets in pancreatic cancer, both for the first-line and maintenance therapy, as they are more responsive to platinum-based chemotherapy agents and PARP inhibitors. Though, a little is known about the efficacy of olaparib monotherapy in later lines, or in poor responders to platinum-based regimens. METHODS: We describe a case of a patient with pancreatic cancer harboring BRCA2 mutation, treated with radical surgery, adjuvant treatment and three different palliative chemotherapy regimens at disease recurrence (FOLFOX in first line with progression-free survival of five months, gemcitabine and nab-paclitaxel in the second line with progression-free survival of six months and FOLFIRI in the third line with progression-free survival of three months) before olaparib off-label treatment. RESULTS: Interestingly, the patient remained 10 months on olaparib treatment, without disease progression, and without any side effects from the treatment. CONCLUSION: In conclusion, this case highlights the clinically relevant progression-free survival with olaparib treatment in later line and the potential of better health-related quality of life in this small subset of Pancreatic cancer patients.

It Takes Two to Tango: Potential Prognostic Impact of Circulating TGF-Beta and PD-L1 in Pancreatic Cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechanisms underlying PDAC aggressiveness and immune evasion, soluble TGF-beta (sTGF-beta) and sPD-L1, in both metastatic and radically-resected PDAC. To this aim we prospectively enrolled 38 PDAC patients and performed appropriate statistical analyses in order to evaluate their correlation, and role in the prediction of disease relapse/progression, and patients' outcome. Results: Metastatic patients showed lower levels of circulating sTGF-beta and higher levels of sPD-L1 compared to radically-resected patients. Moreover, a decrease in sTGF-beta levels (but not sPD-L1) was significantly associated with disease relapse in radically-resected patients. We also observed lower sTGF-beta at disease progression after first-line chemotherapy in metastatic patients, though this change was not statistically significant. We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. Conclusions: These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers.

Should patients on levothyroxine therapy be screened for pancreatic cancer?

BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive disease with increasing incidence. Thyroid hormones play different roles in development and physiological processes of the entire digestive system, including pancreas. Therefore, many have hypothesized that thyroid hormone supplementation for hypothyroidism disorders might increase the risk of malignancy. PATIENTS AND METHODS: We conducted retrospective observational mono-centre study. The aim was to examine the prevalence of thyroid disorders among patients with pancreatic cancer. Moreover, we investigated the impact of thyroid hormone supplementation in pancreatic cancer patients' outcome and the correlation with various clinicopathologic parameters. RESULTS: A total of 92 consecutive pancreatic cancer patients were retrospectively reviewed: 18.5% patients had a history of hypothyroidism and all received a replacement hormone therapy with levothyroxine, in particular 20% in metastatic group and 11% in radically resected PDAC patients' group. Nor in radically resected neither in metastatic group, we did not observe any statistically significant difference in outcome between the group with or without thyroid disorders. On multivariate analyses, cox proportional hazards model analysis showed that only the presence of perineural invasion was associated with a significantly higher hazard ratio for overall survival in metastatic PDAC patients (HR=2.7; 95%CI=1.029-6.925; p=0.009). CONCLUSIONS: We observed higher prevalence of thyroid disorders in PDAC patients. Further studies are warranted to explore the impact of levothyroxine therapy on outcome in PDAC patients.

Surgery for ACL deficiency in patients over 50.

PURPOSE: To compare the outcomes of arthroscopic ACL reconstruction procedure in 20 middle-aged patients (12 men and 8 women) and 20 subjects younger than 30 years (control group) at a minimum post-operative follow-up of 24 months. METHODS: Pre- and post-operative anterior-posterior laxity was assessed by Lachman test, pivot shift test and KT1000 arthrometer at manual maximum stress. Clinical functional evaluation was assessed according to IKDC Committee (IKDC) subjective knee form, IKDC ligament standard evaluation and Lysholm score. RESULTS: At 2 years, all variables significantly improved in both groups compared to pre-operative values (P < 0.05), with non-significant intergroup difference. CONCLUSIONS: When faced with ACL deficiency, physiological age, condition of the knee at the time of examination, life expectancy and activity level are probably more important than chronologic age. In the present study, arthroscopic surgery for the management of ACL tear and secondary lesions provides comparable clinical outcomes in middle-aged patients and in patients aged below 30.