Deep endometriosis with pericolic lymph node involvement: A case report and literature review

Deep infiltrating endometriosis is an often-painful disorder affecting women during their reproductive years that usually involves the structures of the pelvis and frequently the gastrointestinal tract.We present the case of a 37-year-old female patient with an endometrial growth on the sigmoid colon wall causing pain,diarrhea and the presence of blood in the feces.The histology of the removed specimen also revealed the involvement of the utero-vesical fold,the recto-vaginal septum and a pericolic lymph node,which are all quite uncommon findings.To identify the endometrial cells,we performed immunohistochemical staining for CD10and the estrogen and progesterone receptors.

Role of abdominal ultrasound for the surveillance follow-up of pancreatic cystic neoplasms: a cost-effective safe alternative to the routine use of magnetic resonance imaging

BACKGROUND Patients with pancreatic cystic neoplasms(PCN), without surgical indication at the time of diagnosis according to current guidelines, require lifetime imagebased surveillance follow-up. In these patients, the current European evidencedbased guidelines advise magnetic resonance imaging(MRI) scanning every 6 mo in the first year, then annually for the next five years, without reference to any role for trans-abdominal ultrasound(US). In this study, we report on our clinical experience of a follow-up strategy of image-based surveillance with US, and restricted use of MRI every two years and for urgent evaluation whenever suspicious changes are detected by US.AIM To report the results and cost-efficacy of a US-based surveillance follow-up for known PCNs, with restricted use of MRI.METHODS We retrospectively evaluated the records of all the patients treated in our institution with non-surgical PCN who received follow-up abdominal US and restricted MRI from the time of diagnosis, between January 2012 and January 2017. After US diagnosis and MRI confirmation, all patients underwent US surveillance every 6 mo for the first year, and then annually. A MRI scan was routinely performed every 2 years, or at any stage for all suspicious US findings.In this communication, we reported the clinical results of this alternative followup, and the results of a comparative cost-analysis between our surveillance protocol(abdominal US and restricted MRI) and the same patient cohort that has been followed-up in strict accordance with the European guidelines recommended for an exclusive MRI-based surveillance protocol.RESULTS In the 5-year period, 200 patients entered the prescribed US-restricted MRI surveillance follow-up. Mean follow-up period was 25.1 ± 18.2 mo. Surgery was required in two patients(1%) because of the appearance of suspicious features at imaging(with complete concordance between the US scan and the on-demand MRI). During the follow-up, US revealed changes in PCN appearance in 28 patients(14%). These comprised main pancreatic duct dilatation(n = 1), increased size of the main cyst(n = 14) and increased number of PNC(n = 13). In all of these patients, MRI confirmed US findings, without adding more information.The bi-annual MRI identified evolution of the lesions not identified by US in only11 patients with intraductal papillary mucinous neoplasms(5.5%), largely consisting of an increased number of very small PCN(P = 0.14). The overall mean cost of surveillance, based on a theoretical use of the European evidenced-based exclusive MRI surveillance in the same group of patients, would have been 1158.9± 798.6 € per patient, in contrast with a significantly lower cost of 366.4 ± 348.7 €(P < 0.0001) incurred by the US-restricted MRI surveillance used at our institution.CONCLUSION In patients with non-surgical PCN at the time of diagnosis, US surveillance could be a safe complementary approach to MRI, delaying and reducing the numbers of second level examinations and therefore reducing the costs.

Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology

BACKGROUND Ampullary adenocarcinomas(AACs)are heterogeneous tumors currently classified into three important sub-classes(SC):Intestinal(INT),Pancreato-Biliary(PB)and Mixed-Type(MT).The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent.However,they respond differently to chemotherapy and have different prognostic outcomes.The SC are often difficult to identify with conventional histology alone.The clinical outcome of all three remains unclear,particularly for MT.AIM To identify two main subtypes of AACs,using an immunohistochemical(IHC)score based on CDX2,CK7 and CK20.METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2,CK7 and CK 20.An IHC score was obtained for each marker by counting the number of positive cells(0=no stained cells;1<25%;2<50%and 3>50%)and their intensity(1=weak;2=moderate and 3=strong).A global score(GS)was then obtained by summation of the IHC scores of each marker.The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype,obtaining only two AACs subtypes.The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.RESULTS Histological parameters defined the AACs subtypes as follows:15%INT,45%PB and 40%MT.Using IHC expression and the GS,75%and 25%of MT samples were assigned to either the INT or the PB group.The mean value of the GS was 9.5(range 4-16).All INT samples had a GS above the average,distinct from the PB samples which had a GS score significantly below the average(P=0.0011).The INT samples were identified by high expression of CDX2 and CK20,whereas PB samples exhibited high expression of CK7 and no expression of CK20(P=0.0008).The INT group had a statistically significant higher overall survival than in the PB group(85.7 mo vs 20.3 mo,HR:8.39;95%CI:1.38 to 18.90;P=0.0152).CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes,which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.

Robot-assisted trans-gastric drainage and debridement of walled-off pancreatic necrosis using the EndoWrist stapler for the da Vinci Xi:A case report

BACKGROUND Walled-off pancreatic necrosis (WOPN) is a late complication of acute pancreatitis. The management of a WOPN depends on its location and on patient's symptoms. Trans-gastric drainage and debridement of WOPN represents an important surgical treatment option for selected patients. The da Vinci surgical System has been developed to allow an easy, minimally invasive and fast surgery, also in challenging abdominal procedures. We present here a case of a WOPN treated with a robotic trans-gastric drainage using the da Vinci Xi. CASE SUMMARY A 63-year-old man with an episode of acute necrotizing pancreatitis was referred to our center. Six wk after the acute episode the patient developed a walled massive fluid collection, with an extensive pancreatic necrosis, causing obstruction of the gastrointestinal tract. The patient underwent a robotic transgastric drainage and debridement of the WOPN performed with the da Vinci Xi platform. Firstly, an anterior ideal gastrotomy was carried out, guided by intraoperative ultrasound (US)-scan using the TilePro? function. Then, through the gastrotomy, the best location for drainage on the posterior gastric wall was again US-guided identified. The anastomosis between the posterior gastric wall and the walled-off necrosis wall was carried out with the new EndoWrist stapler with vascular cartridge. Debridement and washing of the cavity through the anastomosis were performed. Finally, the anterior gastrotomy was closed and the cholecystectomy was performed. The postoperative course was uneventful and a post-operative computed tomography-scan showed the collapse of the fluid collection. CONCLUSION In selected cases of WOPN the da Vinci Surgical System can be safely used as a valid surgical treatment option.

Detailing the ultrastructure’s increase of prion protein in pancreatic adenocarcinoma

BACKGROUND Recent evidences have shown a relationship between prion protein(PrPc)expression and pancreatic ductal adenocarcinoma(PDAC).Indeed,PrPc could be one of the markers explaining the aggressiveness of this tumor.However,studies investigating the specific compartmentalization of increased PrPc expression within PDAC cells are lacking,as well as a correlation between ultrastructural evidence,ultrastructural morphometry of PrPc protein and clinical data.These data,as well as the quantitative stoichiometry of this protein detected by immuno-gold,provide a significant advancement in understanding the biology of disease and the outcome of surgical resection.AIM To analyze quantitative stoichiometry and compartmentalization of PrPc in PDAC cells and to correlate its presence with prognostic data METHODS Between June 2018 and December 2020,samples from pancreatic tissues of 45 patients treated with pancreatic resection for a preoperative suspicion of PDAC at our Institution were collected.When the frozen section excluded a PDAC diagnosis,or the nodules were too small for adequate sampling,patients were ruled out from the present study.Western blotting was used to detect,quantify and compare the expression of PrPc in PDAC and control tissues,such as those of non-affected neighboring pancreatic tissue of the same patient.To quantify the increase of PrPc and to detect the subcellular compartmentalization of PrPc within PDAC cells,immuno-gold stoichiometry within specific cell compartments was analyzed with electron microscopy.Finally,an analysis of quantitative PrPc expression according to prognostic data,such as cancer stage,recurrence of the disease at 12 mo after surgery and recurrence during adjuvant chemotherapy was made.RESULTS The amount of PrPc within specimen from 38 out of 45 patients was determined by semi-quantitative analysis by using Western blotting,which indicates that PrPc increases almost three-fold in tumor pancreatic tissue compared with healthy pancreatic regions[242.41±28.36 optical density(OD)vs 95±17.40 OD,P<0.0001].Quantitative morphometry carried out by using immuno-gold detection at transmission electron microscopy confirms an increased PrPc expression in PDAC ductal cells of all patients and allows to detect a specific compartmentalization of PrPc within tumor cells.In particular,the number of immuno-gold particles of PrPc was significantly higher in PDAC cells respect to controls,when considering the whole cell(19.8±0.79 particles vs 9.44±0.45,P<0.0001).Remarkably,considering PDAC cells,the increase of PrPc was higher in the nucleus than cytosol of tumor cells,which indicates a shift in PrPc compartmentalization within tumor cells.In fact,the increase of immuno-gold within nuclear compartment exceeds at large the augment of PrPc which was detected in the cytosol(nucleus:12.88±0.59 particles vs 5.12±0.32,P<0.0001;cytosol:7.74.±0.44 particles vs 4.3±0.24,P<0.0001).RESULTS In order to analyze the prognostic impact of PrPc,we found a correlation between PrPc expression and cancer stage according to pathology results,with a significantly higher expression of PrPc for advanced stages.Moreover,24 patients with a mean follow-up of 16.8 mo were considered.Immuno-blot analysis revealed a significantly higher expression of PrPc in patients with disease recurrence at 12 mo after radical surgery(360.71±69.01 OD vs 170.23±23.06 OD,P=0.023),also in the subgroup of patients treated with adjuvant CT(368.36±79.26 OD in the recurrence group vs 162.86±24.16 OD,P=0.028),which indicates a correlation with a higher chemo-resistance.CONCLUSION Expression of PrPc is significantly higher in PDAC cells compared with control,with the protein mainly placed in the nucleus.Preliminary clinical data confirm the correlation with a poorer prognosis.

Use of zebrafish embryos as avatar of patients with pancreatic cancer:A new xenotransplantation model towards personalized medicine

BACKGROUND The response to chemotherapy treatment of patients with pancreatic ductal adenocarcinoma(PDAC)is difficult to predict and the identification of patients who most likely will benefit from aggressive chemotherapy approaches is crucial.The concept of personalized medicine has emerged in the last years with the objective to tailor the medical treatment to the individual characteristics of each patient,and particularly to the tumor biology of each patient.The need for invivo xenotransplantation models for cancer patients has increased exponentially,and for this reason zebrafish avatars have gained popularity.Preliminary studies were conducted also with PDAC tissue.AIM To develop a simple,not expensive,diffusible zebrafish embryo model as avatar for patients affected by PDAC.METHODS Tumor tissue was taken from the surgical specimen by the histopathologist.After its fragmentation into small pieces,they are stained with CM-Dil.Small pieces of stained tissue were transplanted into the yolk of wt AB zebrafish embryos with a glass capillary needle.Embryos were incubated at 35°C in E3 medium supplemented with 1%Pen/Strep in the presence or absence of drugs for the following days in respect of the treatment plan(Gemcitabine;Gemcitabine and Oxaliplatin;Gemcitabine and nab-Paclitaxel;5-Fluorouracil and Folinic acid and Oxaliplatin and Irinotecan).The response of zebrafish xenografts to the chemotherapy options has been analyzed by monitoring the fluorescent stained area at 2 h post injection(hpi),1 d and 2 d post injection(dpi).In each time point,the mean size of the stained area was measured by ImageJ and it was normalized with respect to the 1 dpi time point mean relative tumor area(RTA).We evaluated the effect of the chemotherapy exposition comparing the mean RTA of each treated subgroup and the control group and evaluating the percentage reduction of the mean RTA by comparing each treated subgroup with the control group.RESULTS Between July 2018 and October 2019,a total of 15 patients with pancreatic cancer were prospectively enrolled.In all cases,it was possible to take a fragment of the tumor from the surgical specimen for the xenotransplantation in the zebrafish embryos.The histological examination confirmed the presence of a PDAC in all cases.In absence of chemotherapy(control group),over time the Dil-stained area showed a statistically significant increase in all cases.A statistically significant reduction of the mean RTA in the treated subgroups for at least one chemotherapy scheme was reported in 6/15(40%)cases.The analysis of the percentage reduction of the RTA in treated subgroups in comparison to the control group revealed the presence of a linear relationship in each subgroup between the percentage reduction of the RTA and the number of cases reporting each percentage threshold considered for the analysis.CONCLUSION Our model seems to be effective for the xenotransplantation of PDAC tissue and evaluation of the effect of each chemotherapy scheme on the xenotransplanted tumor tissue.

Open avenues for carotenoid biofortification of plant tissues

Plant carotenoids are plastidial isoprenoids that function as photoprotectants,pigments,and precursors of apocarotenoids such as the hormones abscisic acid and strigolactones.Humans do not produce carotenoids but need to obtain them from their diet as precursors of retinoids,including vitamin A.Carotenoids also provide numerous other health benefits.Multiple attempts to improve the carotenoid profile of different crops have been carried out by manipulating carotenoid biosynthesis,degradation,and/or storage.Here,we will focus on open questions and emerging subjects related to the use of biotechnology for carotenoid biofortification.After impressive achievements,new efforts should be directed to extend the use of genome-editing technologies to overcome regulatory constraints and improve consumer acceptance of the carotenoid-enriched products.Another challenge is to prevent off-target effects like those resulting from altered hormone levels and metabolic homeostasis.Research on biofortification of green tissues should also look for new ways to deal with the negative impact that altered carotenoid contents may have on photosynthesis.Once a carotenoid-enriched product has been obtained,additional effort should be devoted to confirming that carotenoid intake from the engineered food is also improved.Thiswork involves ensuring post-harvest stability and assessing bioaccessibility of the biofortified product to confirm that release of carotenoids from the food matrix has not been negatively affected.Successfully addressing these challenges will ensure new milestones in carotenoid biotechnology and biofortification.