A prospective study on radiofrequency ablation locally advanced pancreatic cancer

BACKGROUND:Radiofrequency ablation(RFA)has been suggested as a new treatment option for patients with locally advanced cancer.This study aimed to prospectively evaluate the efficacy and safety of intraoperative RFA in patients with unresectable,locally advanced,non-metastatic carcinoma of the pancreatic head.METHODS:RFA was the first step of the surgical procedure and was carried out on the mobilized pancreatic head followed by biliary by-pass and gastrojejunal-anastomosis.Intra-and post-operative morbidity and mortality,performance status, pain control,quality of life,and survival at 24 months were evaluated.RESULTS:Seven patients(3 men and 4 women;median age 66 years,range 47-80 years)were studied and 4 were eligible for treatment.The RFA procedure was carried out in 3 of the 4 patients;in one patient it was not carried out because of the upstaging of the neoplasm.In all 3 patients RFA achieved complete necrosis of the lesion.A biliary fistula developed 7 days after the procedure in one patient;all 3 patients developed ascites 8.6 days(range 7-9 days)on average after RFA.All patients died respectively,at 3,4,and 5 months after the treatment.CONCLUSIONS:In our experience,RFA is a feasible procedure, but it presents a very high rate of postoperative complications.Moreover,pain control,life quality and survival rate are poor.The few data suggest no impact on survival.

State of the art biological therapies in pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC) is one of the most lethal malignancies with a five-year survival rate of approximately 5%. Several target agents have been tested in PDAC, but almost all have failed to demonstrate efficacy in late phase clinical trials, despite the better understanding of PDAC molecular biology generated by large cancer sequencing initiatives in the past decade. Eroltinib(a small-molecule tyrosine-kinase inhibitor of epidermal growth factor receptor) plus gemcitabine is the only schedule with a biological agent approved for advanced pancreatic cancer, but it has resulted in a very modest survival benefit in unselected patients. In our work, we report a summary of the main clinical trials(closed and ongoing) that refer to biological therapy evaluation in pancreatic cancer treatment.

Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases

Synchronous colorectal carcinoma(SCRC) indicates more than one primary colorectal carcinoma(CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases(CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown goodresults, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases:Between conventional and mini-invasive approaches

The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate.Staged approach,with initial colorectal resection followed by liver resection(LR),or even the reverse,liver-first approach in specific situations,is traditionally preferred.Simultaneous resections,however,represent an appealing strategy,because may have perioperative risks comparable to staged resections in appropriately selected patients,while avoiding a second surgical procedure.In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases,simultaneous major hepatectomies may determine worse perioperative outcomes,so that parenchymal-sparing LR should represent the most appropriate option whenever feasible.Mini-invasive colorectal surgery has experienced rapid spread in the last decades,while laparoscopic LR has progressed much slower,and is usually reserved for limited tumours in favourable locations.Moreover,mini-invasive parenchymal-sparing LR is more complex,especially for larger or multiple tumours in difficult locations.It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise,at least for more complex procedures.This review aims to critically analyze the current status and future perspectives of simultaneous resections,and the present role of the available miniinvasive techniques.

Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis

Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas.Ger-man authors have defined this area as a"groove".We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space.A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 paperswere considered for the present study;there were 19 cohort studies and 40 case reports.The majority of patients having groove pancreatitis were middle aged.Mean age was significantly higher in patients having groove carcinoma.The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multi-detector computer tomography,magnetic resonance imaging and endoscopic ultrasonography.These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating"groove pancreatitis"from "groove adenocarcinoma".In conclusion,chronic pan-creatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and,in the majority of them,the pan-creatitis had calcifications.

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.

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

BACKGROUND The therapeutic approach of metastatic renal cell carcinoma(RCC)represents a real challenge for clinicians,because of the variable clinical course;the recent availability of numerous targeted therapies that have significantly improved overall oncological results,but still with a low percentage of complete responses;and the increasing role of metastasectomy(MSX)as an effective strategy to achieve a durable cure,or at least defer initiation of systemic therapies,in selected patients and in the context of multimodality treatment strategies.CA^E SUMMARY We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC;he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy,with subsequent systemic therapy with Fluorouracil,Interferon-alpha and Interleukin 2.The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences,successfully treated with multiple systemic treatments,repeated local treatments,including two pancreatic resections,conservative resection and ablation of multiple bilobar liver metastases,resection and stereotactic body radiotherapy of multiple lung metastases.He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites,including resection of more than 38 metastases,and 5 years after his last MSX.CONCLUSION This case highlights that effective multimodality therapeutic strategies,including multiple systemic treatments and iterative aggressive surgical resection,can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.

A bizarre foreign body in the appendix:A case report

Foreign bodies are rare causes of appendicitis and,in most cases,ingested foreign bodies pass through the alimentary tract asymptomatically.However,ingested foreign bodies may sometimes remain silent within the appendix for many years without an inflammatory response.Despite the fact that cases of foreign-bodyinduced appendicitis have been documented,sharp and pointed objects are more likely to cause perforations and abscesses,and present more rapidly after ingestion.Various materials,such as needles and drill bits,as well as organic matter,such as seeds,have been implicated as causes of acute appendicitis.Clinical presentation can vary from hours to years.Blunt foreign bodies are more likely to remain dormant for longer periods and cause appendicitis through obstruction of the appendiceal lumen.We herein describe a patient presenting with a foreign body in his appendix which had been swallowed 15 years previously.The contrast between the large size of the foreign body,the long clinical history without symptoms and the total absence of any histological inflammation was notable.We suggest that an elective laparoscopic appendectomy should be offered to such patients as a possible management 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.

Pancreatic mucinous cystadenocarcinoma in a patient harbouring BRCA1 germline mutation effectively treated with olaparib: A case report

BACKGROUND Pancreatic mucinous cystadenocarcinoma(MCAC)is a rare malignancy with a poor prognosis when it presents metastases at diagnosis.Due to its very low incidence,there are no clear recommendations for the treatment of advanced disease.Olaparib(an oral PARP inhibitor)has been approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma harbouring germline BRCA1/2 mutations.Herein,we report the first case of a germline BRCA1 mutated unresectable MCAC which was effectively treated with olaparib.CASE SUMMARY A 41-year-old woman,without personal or family history of cancer,was diagnosed with ovarian and peritoneal metastases of MCAC.She underwent 12 cycles of gemcitabine plus oxaliplatin(GEMOX)obtaining a partial response and allowing radical surgery.One year later,local recurrence was documented,and other 12 cycles of GEMOX were administered obtaining a complete response.Seven years later,another local recurrence,not amenable to surgical resection,was diagnosed.She started FOLFIRINOX(oxaliplatin,irinotecan,leucovorin and fluorouracil),obtaining a partial response after 8 cycles.Given the excellent response to platinum-based chemotherapy,BRCA testing was performed,and a BRCA1 germline mutation was detected.She was switched to maintenance olaparib due to chemotherapy-related toxicities and achieved an almost complete metabolic response,with a reduction in the diameter of the lesion,after three months of therapy.CONCLUSION The current case suggests the beneficial effect of olaparib in BRCA mutated MCAC.However,further studies are required.

Laparoscopic distal pancreatectomy in Italy:a systematic review and meta-analysis

BACKGROUND： The use of laparoscopic distal pancreatectomy（LDP） increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers（high or low volume） in which this procedure is more frequently performed.DATA SOURCE： A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers（HVCs） and in low volume centers（LVCs）.RESULTS： From 95 potentially relevant citations identified, only5 studies were included. A total of 125 subjects were analyzed, of whom 95（76.0%） were from HVCs and 30（24.0%） from LVCs.The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8in HVCs and 3.0 in LVCs（P0.001）. The most frequent lesions operated on in HVCs were cystic tumors（62.1%, P0.001） while,in LVCs, solid neoplasms（76.7%, P0.001）. In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs（17.9% vs 50.0%, P〈0.001）. Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs（70.2%vs 25.0%, P0.004）. The length of stay was shorter in HVCs than in LVCs（7.5 vs 11.3, P0.001）. No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula,reoperation and margin status.CONCLUSIONS： LDPs were frequently performed in Italy.The ＂HVC approach＂ is characterized by a careful selection of patients undergoing LDP. The ＂LVC approach＂ is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy.