Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome. The research involved a transcriptome-wide analysis, comparing profiles of splicing profiles in PDAC primary cells with normal ductal cells. This revealed more than 400 significant differential splicing events in genes involved in regulation of gene expression, primarily related to mRNA splicing, and metabolism of nucleic acids. PDAC cultures were highly sensitive to the SF3B1 modulators, E7107 and Pladienolide-B, showing IC50s in the low nanomolar range. These compounds induced apoptosis, associated to induction of the MCL-1/S splice variant. and reduced cell migration, associated to RON mis-splicing. In an orthotopic mouse model, E7107 showed promising results. Furthermore, we evaluated SF3B1 expression in specimens from 87 patients and found a significant association of SF3B1 expression with progression-free and overall survival. In conclusion, SF3B1 emerges as both a potential prognostic factor and therapeutic target in PDAC, impacting cell proliferation, migration, and apoptosis. These findings warrant future studies on this new therapeutic strategy against PDAC.

Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.

Delayed gastric emptying after pylorus-preserving pancreatoduodenectomy: Comparison between traditional open surgery and full-robotic approach with da Vinci Xi.

INTRODUCTION: Delayed gastric emptying (DGE) is a frequent complication after pancreatoduodenectomy, especially after pylorus preservation (Pp). We evaluated the effect of a fully robotic approach with da Vinci Xi on DGE after PpPD. METHODS: Open and robotic PDs were performed in 353 and 50 cases, respectively, from January 2009 to March 2022. We compared the clinical outcomes and incidence of clinically relevant DGE between robotic PpPD (R-PpPD) and open PpPD after one-to-one case-control matching. RESULTS: Each group consisted of 30 patients. Clinically relevant DGE was less common after R-PpPD (3/30 [10%] vs. 10/30 cases [33.3%], p = 0.028). The median length of hospital stay (LoS) was significantly lower in the R-PpPD group (10 vs. 15 days, p = 0.013). CONCLUSION: The reduced tissue trauma by the minimally invasive robotic approach is associated with a lower incidence of DGE, reducing the LoS and encouraging PpPD performed using the fully robotic approach.

Prediction Model for Early-Stage Pancreatic Cancer Using Routinely Measured Blood Biomarkers.

Importance: Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could facilitate early detection of pancreatic cancer and prevent potentially unnecessary diagnostic tests for patients at low risk. An externally validated model using CA19-9 and bilirubin serum levels in a larger cohort of patients with pancreatic cancer or benign periampullary diseases is needed. Objective: To assess the discrimination, calibration, and clinical utility of a prediction model using readily available blood biomarkers (carbohydrate antigen 19-9 [CA19-9] and bilirubin) to distinguish early-stage pancreatic cancer from benign periampullary diseases. Design, Setting, and Participants: This diagnostic study used data from 4 academic hospitals in Italy, the Netherlands, and the UK on adult patients with pancreatic cancer or benign periampullary disease treated from 2014 to 2022. Analyses were conducted from September 2022 to February 2023. Exposures: Serum levels of CA19-9 and bilirubin from samples collected at diagnosis and before start of any medical intervention. Main Outcomes and Measures: Discrimination (measured by the area under the curve [AUC]), calibration, and clinical utility of the prediction model and the biomarkers, separately. Results: The study sample comprised 249 patients in the development cohort (mean [SD] age at diagnosis, 67 [11] years; 112 [45%] female individuals), and 296 patients in the validation cohort (mean [SD] age at diagnosis, 68 [12] years; 157 [53%] female individuals). At external validation, the prediction model showed an AUC of 0.89 (95% CI, 0.84-0.93) for early-stage pancreatic cancer vs benign periampullary diseases, and outperformed CA19-9 (difference in AUC [ΔAUC], 0.10; 95% CI, 0.06-0.14; P < .001) and bilirubin (∆AUC, 0.07; 95% CI, 0.02-0.12; P = .004). In the subset of patients without elevated tumor marker levels (CA19-9 <37 U/mL), the model showed an AUC of 0.84 (95% CI, 0.77-0.92). At a risk threshold of 30%, decision curve analysis indicated that performing biopsies based on the prediction model was equivalent to reducing the biopsy procedure rate by 6% (95% CI, 1%-11%), without missing early-stage pancreatic cancer in patients. Conclusions and Relevance: In this diagnostic study of patients with pancreatic cancer or benign periampullary diseases, an easily applicable risk score showed high accuracy for distinguishing early-stage pancreatic cancer from benign periampullary diseases. This model could be used to assess the added diagnostic and clinical value of novel biomarkers and prevent potentially unnecessary invasive diagnostic procedures for patients at low risk.

Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism.

Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.

Prognostic Significance of Integrin Subunit Alpha 2 (ITGA2) and Role of Mechanical Cues in Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma (PDAC).

INTRODUCTION: PDAC is an extremely aggressive tumor with a poor prognosis and remarkable therapeutic resistance. The dense extracellular matrix (ECM) which characterizes PDAC progression is considered a fundamental determinant of chemoresistance, with major contributions from mechanical factors. This study combined biomechanical and pharmacological approaches to evaluate the role of the cell-adhesion molecule ITGA2, a key regulator of ECM, in PDAC resistance to gemcitabine. METHODS: The prognostic value of ITGA2 was analysed in publicly available databases and tissue-microarrays of two cohorts of radically resected and metastatic patients treated with gemcitabine. PANC-1 and its gemcitabine-resistant clone (PANC-1R) were analysed by RNA-sequencing and label-free proteomics. The role of ITGA2 in migration, proliferation, and apoptosis was investigated using hydrogel-coated wells, siRNA-mediated knockdown and overexpression, while collagen-embedded spheroids assessed invasion and ECM remodeling. RESULTS: High ITGA2 expression correlated with shorter progression-free and overall survival, supporting its impact on prognosis and the lack of efficacy of gemcitabine treatment. These findings were corroborated by transcriptomic and proteomic analyses showing that ITGA2 was upregulated in the PANC-1R clone. The aggressive behavior of these cells was significantly reduced by ITGA2 silencing both in vitro and in vivo, while PANC-1 cells growing under conditions resembling PDAC stiffness acquired resistance to gemcitabine, associated to increased ITGA2 expression. Collagen-embedded spheroids of PANC-1R showed a significant matrix remodeling and spreading potential via increased expression of CXCR4 and MMP2. Additionally, overexpression of ITGA2 in MiaPaCa-2 cells triggered gemcitabine resistance and increased proliferation, both in vitro and in vivo, associated to upregulation of phospho-AKT. CONCLUSIONS: ITGA2 emerged as a new prognostic factor, highlighting the relevance of stroma mechanical properties as potential therapeutic targets to counteract gemcitabine resistance in PDAC.

Surgical treatment of recurrent retroperitoneal sarcoma in its different patterns: A 15-years' two-centers experience.

INTRODUCTION: There is limited data available regarding the role of surgery in the treatment of retroperitoneal sarcoma (RPS) recurrences. We herein report the short- and mid-term outcomes of patients who underwent surgical treatment of RPS recurrences at two Italian centers over a 15-years' experience. MATERIALS AND METHODS: From January 2005 to January 2020, 33 patients underwent surgical treatment of isolated locally recurrent RPS (LR group), locally recurrent RPS associated with the presence of distant recurrence (LR + DM group), and distant-only recurrent RPS (DM group). Only procedures performed to obtain a macroscopically radical treatment with curative intent were included. Data regarding pre-, intra-, post-operative course, and follow-up, collected in an Institutional database, were retrospectively analyzed, and compared. RESULTS: LR-group was composed of 15 patients, LR + DM group of 9 patients, and DM group of 9 patients. During the follow-up, 78.5% of the LR group, 77.8% of the DM group and 100% of the LR + DM group (p = 0.244) experienced a second recurrence. 7/11 (63.6%) patients in the LR group, 2/7 (28.5%) patients in the DM-group, and 0/9 (0.0%) patients in the LR + DM group underwent to almost one further local treatments of their recurrences (p = 0.010). No differences in the mean disease-free survival (p = 0.127), overall survival (OS) (p = 0.165) was reported among the three groups. Repeated surgery was an independent factor affecting survival in multivariate analysis (p = 0.01). CONCLUSIONS: A surgical treatment of RPS recurrences should always be taken into consideration, also in metastatic patients and/or in those who have already undergone surgery for previous RPS recurrence, because this approach may offer survival benefits.

Initial 50 consecutive full-robotic pancreatoduodenectomies without conversion by a single surgeon: a learning curve analysis from a tertiary referral high-volume center.

BACKGROUND: Several studies report on a learning curve for robotic pancreatoduodenectomy (R-PD) ranging between 20 and 80 operations, with conversion rates varying between 1.1 and 35%. However, as these publications mostly refer to initial robotic experiences and do not take into account the previous surgical background in pancreatic surgery (PS) and in robotic-assisted surgery (RAS), the center's volume, as well as the platform used, we aimed to perform a surgical outcomes analysis with a particular view to these aspects. METHODS: Intraoperative and perioperative outcomes of the first 50 consecutive R-PD performed with the da Vinci Xi by the same surgeon, within a tertiary referral high-volume center, between January 2018 and March 2022, were analyzed. The surgeon was previously experienced in both PS and RAS. Shewhart control chart and cumulative sum (CUSUM) analysis were used to evaluate the learning curve of R-PD. RESULTS: All the operations were performed with a full-robotic technique, without any conversion to open surgery. Twenty of 50 patients (40%) had a BMI ≥ 25 kg/m2, while 24/50 (48%) had undergone previous abdominal surgery. Mean console time was 276.30 ± 31.16 min. The median post-operative length of hospital stay was 10 days, while 20/50 (40%) patients were discharged within post-operative day 8. Six patients (12%) had major complications (Clavien-Dindo grade 3 or above). There was no 30-day mortality. Shewhart control chart and CUSUM analysis did not show a significant learning curve during the study period. CONCLUSIONS: An extensive prior experience in both PS and RAS, within a tertiary referral high-volume center with availability of the da Vinci Xi platform, can significantly flatten the learning curve and, therefore, enable safe performance of challenging operations, i.e., pancreatoduodenectomies with a minimally invasive approach, with very low risk of conversion to open surgery, even in the first 50 operations.

Comparison of different pancreatic stump management strategies during robot-assisted distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) represents the most feared complication after distal pancreatectomy, and the possible role of robotic assistance in this setting is poorly investigated so far. METHODS: We analysed short-term outcomes of 88 patients who had undergone robot-assisted distal pancreatectomy (RDP), dividing them according to pancreatic stump management: selective Wirsung duct ligation/hand sewn suture (WirsLIG group), use of robotic EndoWrist staplers (RobSTAP group), and use of laparoscopic staplers (LapSTAP group). RESULTS: Mean operative time resulted significantly longer in WirsLIG group (291.1 ± 77.21 min vs. 245 ± 56.22 min in RobSTAP group vs. 221.77 ± 64.64 min in LapSTAP group). No significant differences were found in median hospital stay and in POPF occurrence. CONCLUSIONS: No strategy for pancreatic stump management during RDP has proven superior to the others in reducing POPF rates. The hand-sewn technique resulted more time consuming, nevertheless it remains essential where there is not enough space to insert the stapler.

Robotic Hepatectomy plus Biliary Reconstruction for Bismuth Type III and Type IV Hilar Cholangiocarcinoma: State of the Art and Literature Review.

BACKGROUND: In Bismuth type III and IV Hilar Cholangiocarcinoma (III-IV HC), surgical resection is the only chance for long-term survival. As the surgical procedure is complex and Robotic-Assisted Surgery (RAS) may be particularly suitable in this setting, the aim of this study is to evaluate the potential benefits of RAS in III-IV HC in terms of post-operative outcomes. METHODS: We conducted a systematic review using the PRISMA checklist for article selection. We searched the PubMed database and included only studies with clinical data about the treatment of III-IV HC using RAS. RESULTS: A total of 12 papers involving 50 patients were included. All cases were Bismuth IIIa (n = 18), IIIb (n = 27) or IV type (n = 5) and underwent hepatectomy with biliary confluence resection and reconstruction. The mean operative time was 500 minutes with a conversion rate of 4%. The mean hospital stay was 12.2 days, and the morbidity and 30-day mortality rate were 61.9% and 2%, respectively. Over a mean follow up period of 10.1 months, 9/18 cases experienced recurrence (50%). CONCLUSIONS: RAS for III-IV HC is safe and feasible, at least if performed by experienced surgeons on selected cases. The oncological outcomes appear acceptable, given the aggressiveness of this pathology, but further studies are needed to fully elucidate the exact role of robotics in this setting.

Surgery combined with intra-operative microwaves ablation for the management of colorectal cancer liver metastasis: A case-matched analysis and evaluation of recurrences.

Background: Hepatic resection is the only chance of cure for a subgroup of patients with colorectal cancer liver metastasis. As the oncologic outcomes of intra-operative microwaves ablation combined with hepatic resection still remain uncertain in this setting, we aimed to compare this approach with surgery alone in patient's candidate to metastases resection with radical intent. Methods: Using a case-matched methodology based on age, gender, American Society of Anesthesiology score, Body Mass Index, and burden that take in consideration the number and maximum size of lesions, 20 patients undergoing hepatic resection plus intra-operative microwaves (SURG + IMW group) and 20 patients undergoing hepatic resection alone (SURG group), were included. Relapse-free Survival and post-resection Overall Survival were compared between patients of two groups. Results: At the median follow up of 22.4 ± 17.8, 12/20 patients (60%) in SURG +IMW group and 13/20 patients (65%) in the SURG group experienced liver metastasis recurrence (p=0.774). None of them had recurrence at the same surgical or ablation site of the first hepatic treatment. 7/12 patients in the SURG+IMW group and 7/13 patients in the SURG group underwent at least one further surgical treatment after relapse (p = 1.000). No difference was reported between the two groups in terms of Relapse-free Survival (p = 0.685) and post-resection Overall Survival (p = 0.151). The use of intra-operative microwaves was not an independent factor affecting Relapse-free Survival and post-resection Overall Survival at univariate and multivariate analysis. Conclusions: Patients with colorectal cancer liver metastasis undergoing surgery plus intra-operative microwaves have similar post-operative results compared with surgery alone group. The choice between the two approaches could be only technical, depending on the site, number, and volume of the metastases. This approach could also be used in patients with liver metastasis relapse who have already undergone hepatic surgery.

Lactate Dehydrogenase and its clinical significance in pancreatic and thoracic cancers.

The energy metabolism of tumor cells is considered one of the hallmarks of cancer because it is different from normal cells and mainly consists of aerobic glycolysis, fatty acid oxidation, and glutaminolysis. It is about one hundred years ago since Warburg observed that cancer cells prefer aerobic glycolysis even in normoxic conditions, favoring their high proliferation rate. A pivotal enzyme driving this phenomenon is lactate dehydrogenase (LDH), and this review describes prognostic and therapeutic opportunities associated with this enzyme, focussing on tumors with limited therapeutic strategies and life expectancy (i.e., pancreatic and thoracic cancers). Expression levels of LDH-A in pancreatic cancer tissues correlate with clinicopathological features: LDH-A is overexpressed during pancreatic carcinogenesis and showed significantly higher expression in more aggressive tumors. Similarly, LDH levels are a marker of negative prognosis in patients with both adenocarcinoma or squamous cell lung carcinoma, as well as in malignant pleural mesothelioma. Additionally, serum LDH levels may play a key role in the clinical management of these diseases because they are associated with tissue damage induced by tumor burden. Lastly, we discuss the promising results of strategies targeting LDH as a treatment strategy, reporting recent preclinical and translational studies supporting the use of LDH-inhibitors in combinations with current/novel chemotherapeutics that can synergistically target the oxygenated cells present in the tumor.

Transforming Growth Factor-Beta Signaling in Cancer-Induced Cachexia: From Molecular Pathways to the Clinics.

Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-ß). Besides its double-edged role as a tumor suppressor and activator, TGF-ß causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation. Additionally, TGF-ß induces inhibin and activin, causing weight loss and muscle depletion, while MIC-1/GDF15, a member of the TGF-ß superfamily, leads to anorexia and so, indirectly, to muscle wasting, acting on the hypothalamus center. Against this background, the blockade of TGF-ß is tested as a potential mechanism to revert cachexia, and antibodies against TGF-ß reduced weight and muscle loss in murine models of pancreatic cancer. This article reviews the role of the TGF-ß pathway and to a minor extent of other molecules including microRNA in cancer onset and progression with a special focus on their involvement in cachexia, to enlighten whether TGF-ß and such other players could be potential targets for therapy.

Pattern of recurrence and survival after D2 right colectomy for cancer: is there place for a routine more extended lymphadenectomy?

BACKGROUND: Conventional Right Colectomy with D2 lymphadenectomy (RC-D2) currently represent the most common surgical treatment of right-sided colon cancer (RCC). However, whether it should be still considered a standard of care, or replaced by a routine more extended D3 lymphadenectomy remains unclear. In the present study, we aim to critically review the patterns of relapse and the survival outcomes obtained from our 11-year experience of RC-D2. METHODS: Clinical data of 489 patients who underwent RC-D2 for RCC at two centres, from January 2009 to January 2020, were retrospectively reviewed. Patients with synchronous distant metastases and/or widespread nodal involvement at diagnosis were excluded. Post-operative clinical-pathological characteristics and survival outcomes were evaluated including the pattern of disease relapse. RESULTS: We enrolled a total of 400 patients with information follow-up. Postoperative morbidity was 14%. The median follow-up was 62 months. Cancer recurrence was observed in 55 patients (13.8%). Among them, 40 patients (72.7%) developed systemic metastases, and lymph-node involvement was found in 7 cases (12.8%). None developed isolated central lymph-node metastasis (CLM), in the D3 site. The estimated 3- and 5-year relapse-free survival were 86.1% and 84.4%, respectively. The estimated 3- and 5-year cancer-specific OS were 94.5% and 92.2%, respectively. CONCLUSIONS: The absence of isolated CLM, as well as the cancer-specific OS reported in our series, support the routine use of RC-D2 for RCC. However, D3 lymphadenectomy may be recommended in selected patients, such as those with pre-operatively known CLM, or with lymph-node metastases close to the origin of the ileocolic vessels.

"Depart from evil, and do good": Turning Axl from uncontrolled tumorigenic gene to biomarker for early detection of pancreatic cancer.

Attempts to achieve early diagnosis are crucial to improve the outcome of patients with pancreatic ductal adenocarcinoma (PDAC). Here we present a critical evaluation of a recent study unraveling the potential of circulating AXL as a novel blood marker for early detection of PDAC and differential diagnosis from chronic pancreatitis (CP).

Potential Role of Exosomes in the Chemoresistance to Gemcitabine and Nab-Paclitaxel in Pancreatic Cancer.

In recent years, a growing number of studies have evaluated the role of exosomes in pancreatic ductal adenocarcinoma cancer (PDAC) demonstrating their involvement in a multitude of pathways, including the induction of chemoresistance. The aim of this review is to present an overview of the current knowledge on the role of exosomes in the resistance to gemcitabine and nab-paclitaxel, which are two of the most commonly used drugs for the treatment of PDAC patients. Exosomes are vesicular cargos that transport multiple miRNAs, mRNAs and proteins from one cell to another cell and some of these factors can influence specific determinants of gemcitabine activity, such as the nucleoside transporter hENT1, or multidrug resistance proteins involved in the resistance to paclitaxel. Additional mechanisms underlying exosome-mediated resistance include the modulation of apoptotic pathways, cellular metabolism, or the modulation of oncogenic miRNA, such as miR-21 and miR-155. The current status of studies on circulating exosomal miRNA and their possible role as biomarkers are also discussed. Finally, we integrated the preclinical data with emerging clinical evidence, showing how the study of exosomes could help to predict the resistance of individual tumors, and guide the clinicians in the selection of innovative therapeutic strategies to overcome drug resistance.

Perioperative Nutritional Aspects in Total Pancreatectomy: A Comprehensive Review of the Literature.

Total pancreatectomy (TP) is a highly invasive procedure often performed in patients affected by anorexia, malabsorption, cachexia, and malnutrition, which are risk factors for bad surgical outcome and even may cause enhanced toxicity to chemo-radiotherapy. The role of nutritional therapies and the association between nutritional aspects and the outcome of patients who have undergone TP is described in some studies. The aim of this comprehensive review is to summarize the available recent evidence about the influence of nutritional factors in TP. Preoperative nutritional and metabolic assessment, but also intra-operative and post-operative nutritional therapies and their consequences, are analyzed in order to identify the aspects that can influence the outcome of patients undergoing TP. The results of this review show that preoperative nutritional status, sarcopenia, BMI and serum albumin are prognostic factors both in TP for pancreatic cancer to support chemotherapy, prevent recurrence and prolong survival, and in TP with islet auto-transplantation for chronic pancreatitis to improve postoperative glycemic control and obtain better outcomes. When it is possible, enteral nutrition is always preferable to parenteral nutrition, with the aim to prevent or reduce cachexia. Nowadays, the nutritional consequences of TP, including diabetes control, are improved and become more manageable.