Abstract Rationale: Metastatic neuroendocrine neoplasms (NENs) to the breast are very rare entities comprising only 1% to 2% of all metastatic breast tumors. In this article, we describe a case of a neuroendocrine ileal neoplasm metastatic to breast and liver, with breast metastatic tumor to be the initial manifestation of the disease. Patient concerns: We herein report a rare case of a female patient admitted to our department with a palpable painful mass on her left breast. Diagnosis: The surgical and histological investigation revealed a metastatic neuroendocrine neoplasm to the breast originated from terminal ileum. Interventions: A left lumpectomy, right hemicolectomy, cholecystectomy, left hepatectomy along with liver metastasectomies (V, VI, VIII) plus radiofrequency ablation of lesions to the right liver lobe plus standard lymphadenectomy was performed. Outcomes: Considering the advanced stage of the disease, the patient received an adjuvant therapy of somatostatin analog plus everolimus. Under the guidance of oncological consultation, patients follow-up with CT and MRI scan and clinical re-evaluations in the first 3 and 6 months, substantiates no evidence of recurrence and she presents herself asymptomatic. Lessons: An appropriate level of suspicion and selective immunohistochemistry in these cases, particularly where no prior history of a known primary neuroendocrine neoplasm occurs, may help to diagnose a previously undetected neuroendocrine tumor elsewhere in the body and provide guidance for the appropriate treatment selection.
PDAC is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) is routinely used for PDAC patients. Based on the combinatorial therapy approach to treating highly malignant and refractory cancers such as PDAC, we hypothesized that LMWHs could augment the effectiveness of immune checkpoint inhibitors and induce an efficient antitumoral activity.1
Methods
BxPC-3, PANC-1, and MIA-PaCa2 were incubated alone or in combination with Tinzaparin (T) and/or Nab-Paclitaxel (A) and/or Gemcitabine (G) and/or Nivolumab (NI), Pembrolizumab (PE) and/or Ipilimumab (IPI). The effect of these regimes on various signaling pathways controlling proliferation and apoptosis was identified in vitro through Western blot. Cell viability was measured with MTT assay. NOD/SCID mice will be used to generate xenografts with the PANC-1 cell line. Human peripheral blood mononuclear cells (PBMCs) from healthy donors will be injected to give mice a human-like immune system.2
Results
In a triple combinatorial scheme, NI/PE+IPI+T, the protein levels of VEGFR2 were decreased (0.1 to 0.7 folds) in a dose-dependent way in mtKRAS PC cell lines (PANC1 and MIAPACA2). The number of PANC-1 cells was decreased around 40% in a triple combinatorial scheme of T+IPI+(NI or PE) after 48 hours. The triple combination of Gemcitabine + Nab-paclitaxel + Tinzaparin leads to a decrease in tumor size relative to control by 51% and relative to Nab-P + G by 15%. The combination of chemotherapy, immunotherapy, and Tinzaparin leads to a reduction in tumor size compared to control by up to 60%. Tinzaparin contributes an additional 20% Preliminary data show that the quadruple therapeutic regimen increases the percentage of CD8+ cells from 5% to 27% and decreases Tregs' percentage from 9.5% to 4% (in TILs).
Conclusions
In vitro experiments show a decrease in the cell viability of PC cell lines and a reduction in the protein levels of VEGFR2 in mtKRAS cell lines. In vivo experiments with NOD/SCID mice and humanized NOD/SCID mice show a significant reduction in tumor volume in the combination therapy regimens with Tinzaparin. Possible mechanisms for these effects include an increase in CD8+ cells, a decrease in Tregs cells, a reduction in VEGFR-2 expression, and an increase in cancer cell apoptosis. This synergistic strategy can create new avenues for the treatment of patients with pancreatic cancer, achieving a better clinical outcome and greater survival.
References
Bokas A, Papakotoulas P, Sarantis P, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. Mechanisms of the Antitumor Activity of Low Molecular Weight Heparins in Pancreatic Adenocarcinomas. Cancers (Basel). 2020;12(2):432. Published 2020 Feb 13. doi:10.3390/cancers12020432. Chen Q, Wang J, Liu WN, Zhao Y. Cancer Immunotherapies and Humanized Mouse Drug Testing Platforms. Transl Oncol. 2019;12(7):987–995. doi:10.1016/j.tranon.2019.04.020.
Despite recent advances in multimodality and multidisciplinary treatment of colorectal liver metastases, many patients suffer from extensive bilobar disease, which prevents the performance of a single procedure due to an insufficient future liver remnant (FLR). We present a novel indication for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) as a “liver-first” approach when inadequate FLR was faced preoperatively, in a patient with extensive bilobar liver metastatic disease of colon cancer origin. A 51-year-old lady was referred to our center due to a stage IV colon cancer with extensive bilobar liver disease and synchronous colon obstruction. During the multidisciplinary tumor board, it was recommended to proceed first in a palliative loop colostomy (at the level of transverse colon) operation and afterwards to offer her palliative chemotherapy. After seven cycles of chemotherapy, the patient was re-evaluated by CT scans that revealed an excellent response (>30 %), but the metastatic liver disease was still considered inoperable. Moreover, with the completion of 12 cycles, the indicated restaging process showed further response. Subsequent to a thorough review by the multidisciplinary team, it was decided to proceed to the ALPPS procedure as a feasible means to perform extensive or bilobar liver resections, combined with a decreased risk of tumor progression in the interim. All in all, ALPPS can offer a feasible but surgically demanding liver-first approach with satisfactory short-term results in selected patients. Larger studies are mandatory to evaluate short- and long-term results of the procedure on survival, morbidity, and mortality.
Abstract Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context.
Takotsubo cardiomyopathy, also known as "broken heart syndrome," "apical ballooning syndrome," and "stress-induced cardiomyopathy," was first des cribed in Japanese patients in 1990 by Sato and colleagues. Takotsubo cardiomyopathy is an increasingly recognized syndrome characterized by transient and reversible systolic dysfunction of the apical and middle segments of the left ventricle. This syndrome resembles acute myocardial infarction in the absence of evident coronary artery occlusion. Although the precise pathophysiology of takotsubo cardiomyopathy is still unknown, it seems that it is associated with excessive sympathetic stimulation, microvascular dysfunction, coronary artery vasospasm, and abnormal myocardial tissue metabolism.Herein, we sought to recognize and summarize the available literature data on Takotsubo cardiomyopathy regarding solid-organ transplant, in an attempt to provide the demographic and morphologic functional characteristics of patients with Takotsubo cardiomyopathy and related clinical implications.Transplant surgeons should maintain a high index of clinical suspicion and never underestimate takotsubo cardiomyopathy as a potential cause of heart failure following solid-organ transplant.
Pancreatic surgery is still thought as a challenging field even for experienced hepatobilliary (HPB) surgeons and high volume tertiary centers. The purpose of this study was to present the results (mortality and morbidity) of pancreatic surgery in a high volume center, in operations performed solely by inexperienced surgeons (two 6th year residents and a HPB fellow) under the supervision of expert surgeons on the field.Forty-one consecutive patients who underwent curative-intent pancreatic resection with a modified pancreaticojejunostomy between January 2010 and December 2014 at Asklepios Hospital Barmbek, Germany, were identified from our institutional computer-based database. Two 6th year residents and an HPB-fellow performed all pancreatic anastomoses under the instructions of an experienced surgeon. Perioperative outcomes were recorded and analyzed.Median postoperative length of stay for all patients was 15 days (IQR:7-31). In the first 90 postoperative days, the postoperative mortality rate was 0% and morbidity rate reached 39%. Reoperation was required in 1 patient (2.44%). However, no reoperation was performed for pancreatic anastomotic failure. No postoperative hemorrhage requiring interventional procedure or reoperation occurred in any patient.The outcomes of pancreatic surgery performed by less experienced surgeons are satisfactory. The instructions of an expert surgeon in a high volume hospital definitely secures a favorable outcome after pancreatic surgery with lower mortality and morbidity rates compared with current literature trends.
Pancreatic injury is uncommon, accounting for less than 7% of penetrating and 5% of blunt abdominal trauma. Blunt isolated pancreatic trauma in football has been rarely described in the literature and its diagnosis, detection and treatment still remains a challenge. We report a case of a young adult with an isolated complete rupture of the pancreatic body due to a blunt abdominal trauma during a football game. In order to preserve the pancreas and therefore retain function, we performed a terminolateral pancreaticojejunostomy. The postoperative course of the patient was uneventful. The diagnosis of isolated injuries of the pancreas in blunt abdominal trauma can be difficult and challenging and due to the nature of the game physicians should be highly alerted when dealing with football players sustaining abdominal trauma.
Background/Aim: Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. Patients and Methods: Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. Results: Our study included 108 cases of sarcoma resection (60 first-time, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Five- and 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). Conclusion: Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers.