Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy. The study of the early stages of carcinogenesis provides the opportunity for the identification of actionable pathways that underpin therapeutic resistance. METHODS: We analyzed 43 Intraductal papillary mucinous neoplasms (IPMN) (12 Low-grade and 31 High-grade) by Spatial Transcriptomics. Mouse and human pancreatic cancer organoids and T cells interaction platforms were established to test the role of mucins expression on T cells activity. Syngeneic mouse model of PDAC was used to explore the impact of mucins downregulation on standard therapy efficacy. RESULTS: Spatial transcriptomics showed that mucin O-glycosylation pathway is increased in the progression from low-grade to high-grade IPMN. We identified GCNT3, a master regulator of mucins expression, as an actionable target of this pathway by talniflumate. We showed that talniflumate impaired mucins expression increasing T cell activation and recognition using both mouse and human organoid interaction platforms. In vivo experiments showed that talniflumate was able to increase the efficacy of the chemotherapy by boosting immune infiltration. CONCLUSIONS: Finally, we demonstrated that combination of talniflumate, an anti-inflammatory drug, with chemotherapy effectively improves anti-tumor effect in PDAC.

External validation of scores predicting postoperative fistula after pancreatogastrostomy for pancreatoduodenectomy reconstruction. A single center experience.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most frequent complication of pancreatic surgery and can be fatal. Selection and stratification of patients according to the risk of POPF are important for the perioperative management. Predictive metrics have been developed and validated in pancreatojejunostomy. Aim of this study is to assess whether the most used prognostic scores can be predictive of fistula following Wirsung-pancreaticogastrostomy (WPG) for pancreatoduodenectomy (PD)reconstruction. METHOD: This single-center prospective observational study included 212 PDs between January 2008 and October 2022 with a standardized WPG. All component variables of the six scores were separately validated in our cohort. The overall predictive ability of the six fistula scores was measured and compared with the receiver operating characteristics curves (ROC) method and expressed by the area under the ROC-curve (AUC). Univariate and multivariate logistic regression analyses were performed considering all risk factors in the scores in order to identify variables independently correlated with POPF in the WPG. RESULTS: CR-POPF occurred in 36 of 212 (17 %) patients. All scores showed poor prognostic stratification for the development of CR-POPF. The occurrence of CR-POPF was associated with nine factors: male gender (p = 0.003); BMI (kg/m2) (p = 0.005); ASA (%) (p = 0.003); Soft pancreatic texture (%) (p = 0.003), Pathology (p = 0.008); MPD (p = 0.011); EBL (mL) (p = 0.021); Preop. Bilirubin (mg/dl) (p = 0.038); Preop. Glucose (mg/dl) (p = 0.0369). Male gender (OR: 5.54, CI 1.41-21.3) and soft consistency of the remnant pancreas (OR: 3.83, CI 1.14-12.8) were the only independent prognostic factors on multivariate analysis. CONCLUSIONS: Our study including exclusively pancreatogastrostomies failed to validate the most used predictive scores for POPF. We found that only male gender and soft pancreatic texture are associated with POPF. Specific predictive scores following pancreatogasgtrostomy are needed.

Chronic Exposure to Chlorpyrifos Damages Thyroid Activity and Imbalances Hepatic Thyroid Hormones Signaling and Glucose Metabolism: Dependency of T3-FOXO1 Axis by Hyperglycemia.

Early life exposure to Endocrine Disruptor Chemicals (EDCs), such as the organophosphate pesticide Chlorpyrifos (CPF), affects the thyroid activity and dependent process, including the glucose metabolism. The damage of thyroid hormones (THs) as a mechanism of action of CPF is underestimated because the studies rarely consider that TH levels and signaling are customized peripherally. Here, we investigated the impairment of metabolism/signaling of THs and lipid/glucose metabolism in the livers of 6-month-old mice, developmentally and lifelong exposed to 0.1, 1, and 10 mg/kg/die CPF (F1) and their offspring similarly exposed (F2), analyzing the levels of transcripts of the enzymes involved in the metabolism of T3 (Dio1), lipids (Fasn, Acc1), and glucose (G6pase, Pck1). Both processes were altered only in F2 males, affected by hypothyroidism and by a systemic hyperglycemia linked to the activation of gluconeogenesis in mice exposed to 1 and 10 mg/kg/die CPF. Interestingly, we observed an increase in active FOXO1 protein due to a decrease in AKT phosphorylation, despite insulin signaling activation. Experiments in vitro revealed that chronic exposure to CPF affected glucose metabolism via the direct modulation of FOXO1 activity and T3 levels in hepatic cells. In conclusion, we described different sex and intergenerational effects of CPF exposure on the hepatic homeostasis of THs, their signaling, and, finally, glucose metabolism. The data points to FOXO1-T3-glucose signaling as a target of CPF in liver.

A Cross-Species Analysis Reveals Dysthyroidism of the Ovaries as a Common Trait of Premature Ovarian Aging.

Although the imbalance of circulating levels of Thyroid Hormones (THs) affects female fertility in vertebrates, its involvement in the promotion of Premature Ovarian Aging (POA) is debated. Therefore, altered synthesis of THs in both thyroid and ovary can be a trait of POA. We investigated the relationship between abnormal TH signaling, dysthyroidism, and POA in evolutionary distant vertebrates: from zebrafish to humans. Ovarian T3 signaling/metabolism was evaluated by measuring T3 levels, T3 responsive transcript, and protein levels along with transcripts governing T3 availability (deiodinases) and signaling (TH receptors) in distinct models of POA depending on genetic background and environmental exposures (e.g., diets, pesticides). Expression levels of well-known (Amh, Gdf9, and Inhibins) and novel (miR143/145 and Gas5) biomarkers of POA were assessed. Ovarian dysthyroidism was slightly influenced by genetics since very few differences were found between C57BL/6J and FVB/NJ females. However, diets exacerbated it in a strain-dependent manner. Similar findings were observed in zebrafish and mouse models of POA induced by developmental and long-life exposure to low-dose chlorpyrifos (CPF). Lastly, the T3 decrease in follicular fluids from women affected by diminished ovarian reserve, as well as of the transcripts modulating T3 signaling/availability in the cumulus cells, confirmed ovarian dysthyroidism as a common and evolutionary conserved trait of POA.

Laparoscopic Left Hepatectomy for Hepatocellular Carcinoma Recurrence Following Liver Transplantation.

BACKGROUND: Despite the successful oncological results of liver transplantation, patients with hepatocellular carcinoma (HCC) can develop tumor recurrence. When technically feasible, liver resection represents the preferred treatment for recurrent HCC, even in the setting of transplanted patients. Recent progresses in minimally invasive liver resections have pushed the surgical community to attempt more challenging cases. We report a full laparoscopic left hepatectomy for HCC recurrence on transplanted liver. METHODS: A routine follow-up computed tomography (CT) scan of a 53-year-old male who previously underwent an orthotopic liver transplantation for alcoholic-related liver disease showed a 3 cm HCC in segment 4 in close relationship with the peripheral portion of the left portal pedicle. A full laparoscopic left hepatectomy was performed using an extrahepatic intraglissonean approach. RESULTS: Operative time was 332 min and blood loss was 100 mL. The patient had an uneventful postoperative recovery and was discharged home after 3 days. CONCLUSIONS: Laparoscopic liver resection on transplanted patients is feasible. Challenging clinical scenarios should only be attempted in referral centers and after an appropriate learning curve.1-8.

FUS driven circCNOT6L biogenesis in mouse and human spermatozoa supports zygote development.

Circular RNA (circRNA) biogenesis requires a backsplicing reaction, promoted by inverted repeats in cis-flanking sequences and trans factors, such as RNA-binding proteins (RBPs). Among these, FUS plays a key role. During spermatogenesis and sperm maturation along the epididymis such a molecular mechanism has been poorly explored. With this in mind, we chose circCNOT6L as a study case and wild-type (WT) as well as cannabinoid receptor type-1 knock-out (Cb1-/-) male mice as animal models to analyze backsplicing mechanisms. Our results suggest that spermatozoa (SPZ) have an endogenous skill to circularize mRNAs, choosing FUS as modulator of backsplicing and under CB1 stimulation. A physical interaction between FUS and CNOT6L as well as a cooperation among FUS, RNA Polymerase II (RNApol2) and Quaking (QKI) take place in SPZ. Finally, to gain insight into FUS involvement in circCNOT6L biogenesis, FUS expression was reduced through RNA interference approach. Paternal transmission of FUS and CNOT6L to oocytes during fertilization was then assessed by using murine unfertilized oocytes (NF), one-cell zygotes (F) and murine oocytes undergoing parthenogenetic activation (PA) to exclude a maternal contribution. The role of circCNOT6L as an active regulator of zygote transition toward the 2-cell-like state was suggested using the Embryonic Stem Cell (ESC) system. Intriguingly, human SPZ exactly mirror murine SPZ.

ZFP36L2 Role in Thyroid Functionality.

Thyroid hormone levels are usually genetically determined. Thyrocytes produce a unique set of enzymes that are dedicated to thyroid hormone synthesis. While thyroid transcriptional regulation is well-characterized, post-transcriptional mechanisms have been less investigated. Here, we describe the involvement of ZFP36L2, a protein that stimulates degradation of target mRNAs, in thyroid development and function, by in vivo and in vitro gene targeting in thyrocytes. Thyroid-specific Zfp36l2-/- females were hypothyroid, with reduced levels of circulating free Thyroxine (cfT4) and Triiodothyronine (cfT3). Their hypothyroidism was due to dyshormonogenesis, already evident one week after weaning, while thyroid development appeared normal. We observed decreases in several thyroid-specific transcripts and proteins, such as Nis and its transcriptional regulators (Pax8 and Nkx2.1), and increased apoptosis in Zfp36l2-/- thyroids. Nis, Pax8, and Nkx2.1 mRNAs were also reduced in Zfp36l2 knock-out thyrocytes in vitro (L2KO), in which we confirmed the increased apoptosis. Finally, in L2KO cells, we showed an altered response to TSH stimulation regarding both thyroid-specific gene expression and cell proliferation and survival. This result was supported by increases in P21/WAF1 and p-P38MAPK levels. Mechanistically, we confirmed Notch1 as a target of ZFP36L2 in the thyroid since its levels were increased in both in vitro and in vivo models. In both models, the levels of Id4 mRNA, a potential inhibitor of Pax8 activity, were increased. Overall, the data indicate that the regulation of mRNA stability by ZFP36L2 is a mechanism that controls the function and survival of thyrocytes.

CircNAPEPLD is expressed in human and murine spermatozoa and physically interacts with oocyte miRNAs.

Circular RNAs (circRNAs) have a critical role in the control of gene expression. Their function in spermatozoa (SPZ) is unknown to date. Twenty-eight genes, involved in SPZ/testicular and epididymal physiology, were given in circBase database to find which of them may generate circular transcripts. We focused on circNAPEPLDiso1, one of the circular RNA isoforms of NAPEPLD transcript, because expressed in human and murine SPZ. In order to functionally characterize circNAPEPLDiso1 as potential microRNA (miRNA) sponge, we performed circNAPEPLDiso1-miR-CATCH and then profiled the expression of 754 miRNAs, by using TaqMan® Low Density Arrays. Among them, miRNAs 146a-5p, 203a-3p, 302c-3p, 766-3p and 1260a (some of them previously shown to be expressed in the oocyte), resulted enriched in circNAPEPLDiso1-miR-CATCHed cell lysate: the network of interactions generated from their validated targets was centred on a core of genes involved in the control of cell cycle. Moreover, computational analysis of circNAPEPLDiso1 sequence also showed its potential translation in a short form of NAPEPLD protein. Interestingly, the expression analysis in murine-unfertilized oocytes revealed low and high levels of circNAPEPLDiso1 and circNAPEPLDiso2, respectively. After fertilization, circNAPEPLDiso1 expression significantly increased, instead circNAPEPLDiso2 expression appeared constant. Based on these data, we suggest that SPZ-derived circNAPEPLDiso1 physically interacts with miRNAs primarily involved in the control of cell cycle; we hypothesize that it may represent a paternal cytoplasmic contribution to the zygote and function as a miRNA decoy inside the fertilized oocytes to regulate the first stages of embryo development. This role is proposed here for the first time.

Severe chest allodynia as an unusual first presentation of hydatid disease: a case report.

BACKGROUND: Cystic echinococcosis (CE) is a worldwide zoonosis and the liver is the most commonly affected organ. Clinical manifestations range from completely asymptomatic cysts to a potential lethal cyst rupture and anaphylaxis. CASE PRESENTATION: Severe chest allodynia was an unusual clinical presentation of hepatic cyst rupture in the retroperitoneal space, without any other specific symptoms. CE diagnosis was confirmed by computed tomography scan and magnetic resonance. The patient underwent hepatectomy with complete resolution of the neuropathic pain. CONCLUSIONS: Retroperitoneal hydatid cyst rupture is a rare event and its clinical manifestation may mimic other chest neuropathies.

Pancreatic fistula following laparoscopic distal pancreatectomy is probably unrelated to the stapler size but to the drainage modality and significantly decreased with a small suction drain.

INTRODUCTION: Risk factors of postoperative pancreatic fistula (POPF) after laparoscopic distal pancreatectomy (LDP) are not well known and were studied, including the stapler cartridge size and drainage modality. METHODS: Between January 2008 and December 2016, 181 LDP were performed and the pancreas was sectioned by stapler in 130 patients (72%). Patients received white (2.5 mm), blue (3.5 mm), or green (4.1 mm) staplers and the size was not based on any pre or peroperative randomization. As primary analysis of the first 84 patients (28 in each group) showed no effect of stapler size on POPF, we decided to use the white (total = 47) or blue and finally the blue (total = 55) of medium size for standardization. Drainage was obtained by multi-tubular drain (first, 79) and a small suction drain (last, 102). Risk factors of POPF were studied and grades B and C were compared to grade A or no POPF. RESULTS: POPF (n = 66; 36%) was of grade A (n = 25, 14%), grade B (n = 32, 18%), and grade C (n = 9, 5%). The comparison of the three groups of staplers showed that the blue stapler was used more with a small suction drain (85 vs 23%, p < 0.0001), had lower rate of grade B POPF (p = 0.028), and a shorter hospital stay (p = 0.004). On multivariate analysis, only the use of a small suction drain was associated with significant decrease in grades B and C POPF (6 vs 44%, odds ratio 7.385 (1.919-28.418); p = 0.004). CONCLUSION: The occurrence of POPF following LDP is influenced by the type of drainage alone and is significantly decreased with a small suction drain.

Insight into Nephrocan Function in Mouse Endoderm Patterning.

Endoderm-derived organs as liver and pancreas are potential targets for regenerative therapies, and thus, there is great interest in understanding the pathways that regulate the induction and specification of this germ layer. Currently, the knowledge of molecular mechanisms that guide the in vivo endoderm specification is restricted by the lack of early endoderm specific markers. Nephrocan (Nepn) is a gene whose expression characterizes the early stages of murine endoderm specification (E7.5-11.5) and encodes a secreted N-glycosylated protein. In the present study, we report the identification of a new transcript variant that is generated through alternative splicing. The new variant was found to have differential and tissue specific expression in the adult mouse. In order to better understand Nepn role during endoderm specification, we generated Nepn knock-out (KO) mice. Nepn-/- mice were born at Mendelian ratios and displayed no evident phenotype compared to WT mice. In addition, we produced nullizygous mouse embryonic stem cell (mESC) line lacking Nepn by applying (CRISPR)/CRISPR-associated systems 9 (Cas9) and employed a differentiation protocol toward endoderm lineage. Our in vitro results revealed that Nepn loss affects the endoderm differentiation impairing the expression of posterior foregut-associated markers.

Exploring the Molecular Crosstalk between Pancreatic Bud and Mesenchyme in Embryogenesis: Novel Signals Involved.

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development; nevertheless, the precise space-temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium-mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.

NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function.

The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful downstaging was observed, and in 100 % of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9 months. From LT, overall mean survival was 30.2 months with a free survival of 29.6 months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p = 0.113). Free survival analysis was not significant (p = 0.897) between the two populations. CONCLUSIONS: We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Intrathoracic gastric volvulus as a severe, delayed surgical complication after left subphrenic peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian cancer.

Patients with extensive peritoneal spread from advanced ovarian cancer often undergo several upper abdominal surgical procedures including subphrenic peritonectomy to obtain optimal cytoreduction. The most common complications are pleural effusions, pancreatic leakage and endoabdominal collections. This case report describes an unusual complication, a diaphragmatic hernia with an intrathoracic gastric volvulus developing four months after the patient underwent left subphrenic peritonectomy during interval debulking surgery and hyperthermic intraperitoneal chemotherapy for advanced ovarian cancer.

The state of general surgery residents in Italy after COVID-19 outbreak: a nationwide cross-sectional study.

INTRODUCTION: A significant reorganization of working activities including those of teaching hospitals occurred after COVID-19 outbreak, leading to the need to re-assess the current status of training after the pandemic. This study aimed to investigate the state of general surgery (GS) residency in Italy. The impact of COVID-19 on GS residents was also assessed. METHODS: Between October and November 2020, an anonymous online survey was distributed to GS residents across Italy. Email addresses were provided by the Regional Committees of the Italian Polyspecialistic Society of Young Surgeons. The residents completed a set of questions regarding their training schedule and three standardized questionnaires to measure burnout and psychological distress. RESULTS: Overall, 1709 residents were contacted and 648 completed the survey. Almost two-thirds of the residents (68.4%, n = 443) reported to not reach the minimum annual operative case volume. According to ordinal logistic regression analysis, two of the most perceived effects of COVID-19 by trainees on training were reduction of surgical activities (OR = 2.21, p < 0.001) and increased concerns about future employment (OR = 1.14, p = 0.025). Loss of training opportunities was also associated with a significant increase of distress (OR = 1.26, p = 0.003) but not with burnout. CONCLUSIONS: This study provided a snapshot of the situation of GS residents in Italy after COVID-19 outbreak. Reduction of activities due to pandemic highlighted the need to improve the level of surgical education in our country by implementing all the new available tools for training and ensuring at the same time the well-being of the residents.

Minimally Invasive Surgery for Perihilar Cholangiocarcinoma: A Systematic Review of the Short- and Long-Term Results.

Surgery and postoperative systemic chemotherapy represent the standard treatment for patients with perihilar cholangiocarcinoma (PHC). Minimally Invasive Surgery (MIS) for hepatobiliary procedures has spread worldwide in the last two decades. Since resections for PHC are technically demanding, the role of MIS in this field is yet to be established. This study aimed to systematically review the existing literature on MIS for PHC, to evaluate its safety and its surgical and oncological outcomes. A systematic literature review on PubMed and SCOPUS was performed according to the PRISMA guidelines. Overall, a total of 18 studies reporting 372 MIS procedures for PHC were included in our analysis. A progressive increase in the available literature was observed over the years. A total of 310 laparoscopic and 62 robotic resections were performed. A pooled analysis showed an operative time ranging from 205.3 ± 23.9 and 840 (770-890) minutes, and intraoperative bleeding between 101.1 ± 13.6 and 1360 ± 809 mL. Minor and major morbidity rates were 43.9% and 12.7%, respectively, with a 5.6% mortality rate. R0 resections were achieved in 80.6% of patients and the number of retrieved lymph nodes ranged between 4 (3-12) and 12 (8-16). This systematic review shows that MIS for PHC is feasible, with safe postoperative and oncological outcomes. Recent data has shown encouraging results and more reports are being published. Future studies should address differences between robotic and laparoscopic approaches. Given the management and technical challenges, MIS for PHC should be performed by experienced surgeons, in high-volume centers, on selected patients.

Challenging Scenarios and Debated Indications for Laparoscopic Liver Resections for Hepatocellular Carcinoma.

Laparoscopic liver resections (LLRs) have been increasingly adopted for the treatment of hepatocellular carcinoma (HCC), with safe short- and long-term outcomes reported worldwide. Despite this, lesions in the posterosuperior segments, large and recurrent tumors, portal hypertension, and advanced cirrhosis currently represent challenging scenarios in which the safety and efficacy of the laparoscopic approach are still controversial. In this systematic review, we pooled the available evidence on the short-term outcomes of LLRs for HCC in challenging clinical scenarios. All randomized and non-randomized studies reporting LLRs for HCC in the above-mentioned settings were included. The literature search was run in the Scopus, WoS, and Pubmed databases. Case reports, reviews, meta-analyses, studies including fewer than 10 patients, non-English language studies, and studies analyzing histology other than HCC were excluded. From 566 articles, 36 studies dated between 2006 and 2022 fulfilled the selection criteria and were included in the analysis. A total of 1859 patients were included, of whom 156 had advanced cirrhosis, 194 had portal hypertension, 436 had large HCCs, 477 had lesions located in the posterosuperior segments, and 596 had recurrent HCCs. Overall, the conversion rate ranged between 4.6% and 15.5%. Mortality and morbidity ranged between 0.0% and 5.1%, and 18.6% and 34.6%, respectively. Full results according to subgroups are described in the study. Advanced cirrhosis and portal hypertension, large and recurrent tumors, and lesions located in the posterosuperior segments are challenging clinical scenarios that should be carefully approached by laparoscopy. Safe short-term outcomes can be achieved provided experienced surgeons and high-volume centers.

Double inferior vena cava does not complicate para-aortic nodal dissection for the treatment of pancreatic carcinoma.

Duplication of the inferior vena cava (IVC) involves large veins on both sides of the aorta that join anteriorly at the level of the renal arteries to become the suprarenal IVC. We report CT scan and intraoperative images of a patient with duplication of the IVC who underwent pancreaticoduodenectomy with para-aortic lymphadenectomy for carcinoma of the pancreatic head: nodal dissection along the left caval vein was not carried out. The anatomical background of the lymphatic flow to the para-aortic lymph nodes and the theoretic basis for lymph node dissection of the para-aortic area in cases of double IVC are highlighted. Lymphadenectomy along the left caval vein is not necessary in patients with double IVC who undergo pancreaticoduodenectomy with extended lymphadenectomy for carcinoma of the pancreatic head in the absence of preoperative appearance of para-aortic disease.