Robotic Dual-Console Distal Pancreatectomy: Could it be Considered a Safe Approach and Surgical Teaching even in Pancreatic Surgery? A Retrospective Observational Study Cohort.

BACKGROUND: The study aims to assess the safety and feasibility of the robotic dual-console during a robotic distal pancreatectomy METHODS: The data of the consecutive patients submitted to RDP from 2012 to 2019 at the Verona University were retrieved from a prospectively maintained database. The patients submitted to RDP were divided into the dual-console platform group (DG) and compared to the standard robotic procedure group (SG). RESULTS: In the study period, 102 robotic distal pancreatectomies were performed, of whom 42 patients (41%) belonged to the DG and 60 patients (59%) to the SG. Higher operation time was recorded in the DG compared to the SG (410 vs. 265 min, p < 0.001). The overall conversion rate of the series was 7% (n 7 patients). All the conversions were observed in the SG (p = 0.021). No differences in morbidity or pancreatic fistula rate were recorded (p > 0.05). No mortality events in the 90th postoperative days were reported in this series. CONCLUSIONS: The robotic dual-console approach for distal pancreatectomy is safe, feasible, and reproducible. The postoperative surgical outcomes are comparable to the standard RDP with the single-console da Vinci Surgical System®. This surgical technique can widely and safely improve the robotic surgical training program.

Robotic spleen-preserving distal pancreatectomy: the Verona experience.

BACKGROUND: The minimally invasive approach in spleen-preserving distal pancreatectomy has currently been emphasized in benign and pre-malignant pancreatic diseases. The study aims to demonstrate the safety and feasibility of our technique of robotic spleen-preserving distal pancreatectomy (RSPDP) by a stepwise approach. METHODS: The data of consecutive patients presented for RSPDP from 2014 to 2019 at Verona University were retrieved from a prospectively maintained database. The patients were divided into two groups based on the surgical procedure performed, such as Kimura's (KG) or Warshaw's (WG) technique, and then compared. RESULTS: In the study period, 32 patients underwent RSPDP. Twenty-three patients presented for the Kimura procedure (72%), while nine patients underwent the Warshaw procedure (28%). A higher body mass index was found in the KG (26 ± 4 vs. 22 ± 3, p = 0.037). Regarding the pathological data, the WG group differed in the tumor dimension, and the lymph nodes harvested (30 ± 2 vs. 17 ± 10, 9 ± 5 vs. 3 ± 4, p = 0.0028, and p = 0.005, respectively). Notably, no conversions and mortality were recorded. The overall morbidity was 25% ( eight patients) with no difference between the groups (p = 0.820). The mean length of stay was 8 days, and was similar between the groups (p = 0.350). CONCLUSIONS: The present study suggests that RSPDP is a valid option for the treatment of benign or pre-malignant pancreatic diseases of the distal pancreas, with comparable morbidity with the standard treatment and no mortality. Further research is needed to standardize the technique and to assess the immunological, surgical, and financial benefits of the procedure.

Use of an intraoperative wound protector to prevent surgical-site infection after pancreatoduodenectomy: randomized clinical trial.

BACKGROUND: Surgical-site infection (SSI) increases treatment costs, duration of hospital stay and readmission rate after pancreatic surgery. This study aimed to assess whether a wound protector could reduce the risk of superficial incisional SSI after pancreatoduodenectomy. METHODS: This RCT included patients undergoing pancreatoduodenectomy at Verona University Hospital, between 2017 and 2018. The experimental group had a dual-ring wound protector, whereas the control group had standard surgical drapes. The groups were stratified by preoperative biliary stent placement. The primary outcome was the overall rate of superficial SSI. RESULTS: An interim analysis was conducted after 212 patients had been enrolled; 22 patients (10·4 per cent) were excluded owing to inability to complete the pancreatoduodenectomy, or the need for postoperative reintervention. Some 94 patients (49·5 per cent) had a wound protector and 96 (50·5 per cent) had standard drapes. There were no differences between groups in demographics, or in intraoperative findings, pathological data or surgical outcomes. The overall superficial SSI rate was 7·4 per cent, which did not differ between groups (7 per cent in each group; P = 0·585). Subanalysis of patients with a preoperative biliary stent showed a similar outcome (superficial SSI rate 9 versus 8 per cent with wound protector versus surgical drapes respectively; P = 0·536). The trial was stopped prematurely on the grounds of futility. CONCLUSION: Use of a wound protector did not reduce the rate of superficial SSI after pancreatoduodenectomy. Registration number: NCT03820648 (http://www.clinicaltrials.gov).

ANTECEDENTES: La infección de la herida quirúrgica (surgical-site infection, SSI), especialmente de la incisión, aumenta sobremanera los costes del tratamiento, la duración de la estancia y la tasa de reingresos en la cirugía de páncreas. En los últimos años se han introducido los protectores de las heridas (wound protectors, WP) con la intención de reducir la tasa de SSI. Este estudio tuvo como objetivo evaluar si un WP podría reducir la incidencia de la SSI superficial de la incisión (superficial incisional surgical-site infection, SI-SSI) en pacientes sometidos a duodenopancreatectomía cefálica (pancreaticoduodenectomy, PD). MÉTODOS: Ensayo aleatorizado controlado en el que se incluyeron los pacientes a los que se realizó una PD en la Universidad de Verona entre 2017 y 2018. En el grupo experimental se utilizó un WP de doble anillo, mientras que el grupo control se utilizaron tallas quirúrgicas convencionales (standard drape, SD). Los grupos se estratificaron también según la colocación preoperatoria de una prótesis biliar. RESULTADOS: Se incluyeron 212 pacientes, de los que 22 (10%) abandonaron el estudio debido a la imposibilidad de realizar la DP o a la necesidad de una reintervención durante el curso postoperatorio. Los pacientes se dividieron en 94 (49%) en el grupo WP y 96 (51%) en el grupo SD. No se detectaron diferencias entre grupos en cuanto a las variables demográficas y a los resultados intraoperatorios, patológicos o quirúrgicos. La tasa global de SI-SSI fue del 7,4%, que no difirió entre los grupos (WP 7,5% versus SD 7,3%, P = 0,585). Teniendo en cuenta los resultados descritos, se cumplieron los criterios de futilidad del análisis y el ensayo se interrumpió prematuramente. CONCLUSIÓN: En el entorno de un centro de alto volumen, la WP por si sola no redujo la tasa de SI-SSI. Cabría plantear su utilización dentro de un programa multimodal, que debería incluir un replanteamiento interno de la institución encaminado a la reducción de complicaciones infecciosas.

Viability and stress protection of chronic lymphoid leukemia cells involves overactivation of mitochondrial phosphoSTAT3Ser727.

Chronic lymphoid leukemia (CLL) is characterized by the accumulation of functionally defective CD5-positive B lymphocytes. The clinical course of CLL is highly variable, ranging from a long-lasting indolent disease to an unpredictable and rapidly progressing leukemia requiring treatment. It is thus important to identify novel factors that reflect disease progression or contribute to its assessment. Here, we report on a novel STAT3-mediated pathway that characterizes CLL B cells-extended viability and oxidative stress control. We observed that leukemic but not normal B cells from CLL patients exhibit constitutive activation of an atypical form of the STAT3 signaling factor, phosphorylated on serine 727 (Ser(727)) in the absence of detectable canonical tyrosine 705 (Tyr705)-dependent activation in vivo. The Ser(727)-phosphorylated STAT3 molecule (pSTAT3Ser(727)) is localized to the mitochondria and associates with complex I of the respiratory chain. This pSer(727) modification is further controlled by glutathione-dependent antioxidant pathway(s) that mediate stromal protection of the leukemic B cells and regulate their viability. Importantly, pSTAT3Ser(727), but neither Tyr705-phosphorylated STAT3 nor total STAT3, levels correlate with prolonged in vivo CLL B cells survival. Furthermore, STAT3 activity contributes to the resistance to apoptosis of CLL, but not normal B cells, in vitro. These data reveal that mitochondrial (Mt) pSTAT3Ser(727) overactivity is part of the antioxidant defense pathway of CLL B cells that regulates their viability. Mt pSTAT3Ser(727) appears to be a newly identified cell-protective signal involved in CLL cells survival. Targeting pSTAT3Ser(727) could be a promising new therapeutic approach.

Vibrational entropy and the structural organization of proteins.

In this paper we analyze the vibrational spectra of a large ensemble of non-homologous protein structures by means of a novel tool, that we coin Hierarchical Network Model (HNM). Our coarse-grained scheme accounts for the intrinsic heterogeneity of force constants displayed by protein arrangements and also incorporates side chain degrees of freedom. Our analysis shows that vibrational entropy per unit residue correlates with the content of secondary structure. Furthermore, we assess the individual contribution to vibrational entropy of the novel features of our scheme as compared with the predictions of state-of-the-art network models. This analysis highlights the importance of properly accounting for the intrinsic hierarchy in force strengths typical of the different atomic bonds that build up and stabilize protein scaffolds. Finally, we discuss possible implications of our findings in the context of protein aggregation phenomena.

"Paraduodenal" pancreatitis: results of surgery on 58 consecutives patients from a single institution.

BACKGROUND: Cystic dystrophy of heterotopic pancreas, groove pancreatitis, pancreatic hamartoma of the duodenum, paraduodenal wall cyst, and myoadenomatosis are all terms grouped together, from a pathological viewpoint, as definitions of paraduodenal pancreatitis (PP). The objective of the present study was to investigate the clinical characteristics, therapeutic strategies, and results in 58 patients undergoing pancreatic resection for PP. METHODS: From January 1990 to December 2006 data were prospectively collected on 58 patients who were diagnosed with PP who then underwent pancreaticoduodenectomy. RESULTS: In this patient cohort the median age was 44.7 years; only 4 patients were women, and only 3 had non-drinker and/or non smoker habits. The overall morbidity was 18.9%, and the median hospitalization was 11 days. There were no postoperative deaths. In a median follow-up of 96.3 months, all patients noted a decrease in the pain associated with PP; 35 patients (76%) had complete disappearance of pain, whereas occasional relapsing pain occurred in the remaining 11 (24%). CONCLUSIONS: Patients with PP have clinical characteristics similar to those of chronic pancreatitis. The diagnostic imaging modalities of choice are ultrasonographic endoscopy and magnetic resonance cholangiopancreaticography. Based on our surgical experience, pancreaticoduodenectomy seems to be a reasonable choice of treatment in patients with PP.

Model for the hydration of nonpolar compounds and polymers.

We introduce an exactly solvable statistical-mechanical model of the hydration of nonpolar compounds, based on grouping water molecules in clusters where hydrogen bonds and isotropic interactions occur; interactions between clusters are neglected. Analytical results show that an effective strengthening of hydrogen bonds in the presence of the solute, together with a geometric reorganization of water molecules, are enough to yield hydrophobic behavior. We extend our model to describe a nonpolar homopolymer in aqueous solution, obtaining a clear evidence of both "cold" and "warm" swelling transitions. This suggests that our model could be relevant to describe some features of protein folding.

Previous cholecystectomy, gastrectomy, and diabetes mellitus are not crucial risk factors for pancreatic cancer in patients with chronic pancreatitis.

INTRODUCTION: In the general population, cholecystectomy, diabetes, and chronic pancreatitis seem to be associated with an increased risk of developing pancreatic cancer. AIMS: We assessed whether previous cholecystectomy, gastrectomy, or diabetes mellitus may be risk factors for pancreatic cancer in patients with chronic pancreatitis. METHODOLOGY: We analyzed 853 patients with chronic pancreatitis (110 women, 743 men) with a median follow-up period of 14 years with particular reference to establishing which patients had previously undergone cholecystectomy or distal gastric resection (Billroth II anastomosis) or had diabetes or gallstone disease and the respective time scales involved. RESULTS: Pancreatic cancer developed in 17 patients with chronic pancreatitis after a median period of 8 years from onset of pancreatitis symptoms (range, 3-38 years). Excluding two cholecystectomies performed 1 year before diagnosis of cancer, cholecystectomy was performed in 7/17 (41%) patients with pancreatic cancer and in 381/836 (46%) of the other patients with chronic pancreatitis. Forty-nine (10%) patients with chronic pancreatitis and no pancreatic cancer had undergone cholecystectomy during the years before the onset of chronic pancreatitis, whereas none of the patients in whom a pancreatic malignancy developed had undergone cholecystectomy before the onset of chronic pancreatitis symptoms. Gastrectomies were performed in 116 patients (14%), 47 before the onset of chronic pancreatitis. Only 2/17 patients with pancreatic cancer had undergone previous gastrectomy, though in both cases only shortly before diagnosis of the cancer. Diabetes was diagnosed in 353 patients, but only in 30 (4%) before onset of chronic pancreatitis. Only 1/17 patients (6%) with pancreatic cancer had long-standing diabetes, whereas diabetes developed in 3/17 shortly before diagnosis of pancreatic cancer. CONCLUSIONS: Cholecystectomy, gastrectomy, and diabetes are not major risk factors for the development of pancreatic cancer in patients with chronic pancreatitis.

Modeling hydration water and its role in polymer folding.

The hydrophobic effect is the dominant force which drives a proteintowards its native state, but its physics has not been thoroughlyunderstood yet. We introduce an exactly solvable model of the solvation ofnon-polar molecules in water, which shows that the reduced number ofallowed configurations of water molecules when the solute is present isenough to give rise to hydrophobic behaviour. We apply our model to anon-polar homopolymer in aqueous solution, obtaining a clear evidence ofboth `cold' and `warm' collapse transitions that recall those of proteins.Finally we show how the model can be adapted to describe the solvation ofaromatic and polar molecules.

[Clinical evolution of chronic pancreatitis and quality of life]. / Evoluzione clinica della pancreatite cronica e qualità della vita.

Nowadays the availability of reliable, efficacious methods of assessing the outcome of chronic pancreatitis is mandatory, especially in view of the several new procedures developed to relieve the symptoms of the disease. Together with the traditional evaluation of postoperative morbidity and mortality and the assessment of exo/endocrine function in patient follow-up, we currently consider the patient's perception of his or her health status as a priority. This information is obtained by administering quality of life questionnaires along with reliable physical and psychometric evaluation.

Assessment and treatment of severe pancreatitis. Protease inhibitor.

From the theoretical point of view, antiproteolytic therapy would seem to be the rationale for acute pancreatitis management. Unfortunately, clinical human trials studying the role of antiproteases in the treatment of acute pancreatitis differ in several respects in terms of their basic design. As a consequence, any form of homogeneous analysis of the reported data as a whole is impossible. Considering the data emerging from a meta-analysis of five trials a rational use of antiproteases may result in a reduction of complications requiring surgery and of patient management costs only in selected cases, meaning by that severe and necrotic forms. As regards presumptive applications, over 400 patients were prospectively tested versus placebo in a double-blind trial with the aim of preventing acute pancreatitis after ERCP. The complication incidence was significantly lower among the pretreated patients; anyway, also in this field of protease inhibitor clinical application it is necessary to identify the patients with the greatest risk to develop post-ERCP acute pancreatitis. In conclusion, antiproteases can still play a role when given prophylactically or when used in the very early phases of the disease; moreover a 'multiple drugs approach' (including, for example, suitable antibiotics) seems to represent nowadays the most modern and rational treatment of acute pancreatitis.

Topological aspects of geometrical signatures of phase transitions.

Certain geometric properties of submanifolds of configuration space are numerically investigated for classical phi(4) models in one and two dimensions. Peculiar behaviors of the computed geometric quantities are found only in the two-dimensional case, when a phase transition is present. The observed phenomenology strongly supports, though in an indirect way, a recently proposed topological conjecture about a topology change of the configuration space submanifolds as counterpart to a phase transition.

To what extent is surgery superior to endoscopic therapy in the management of chronic pancreatitis?

The surgeon was the only figure involved in the management of chronic pancreatitis patients unresponsive to medical treatment, until a few years ago. Nowadays, because of less invasive, endoscopy offers a seductive alternative to surgery. Up to now no clinical prospective and randomized data comparing the results of the two different approaches are available. Surgery seems to be the only solution for chronic pancreatitis with duodenal stenosis and the last chance of eliminating diagnostic uncertainty. Also in the case of biliary tract involvement surgery should be regarded as the procedure of choice, inasmuch as the stenosis is benign and generally long-lasting, and endoscopic treatment would have to be repeated several times; endoscopy, in this indication, should be reserved only for patients who present contraindicating surgery conditions (such as severe jaundice, colangitis etc.); the endoscopist should assess whether to insert a stent or a naso-biliary drainage tube referring the patient back to the surgeon once good clinical conditions have been restored. Endoscopy and surgery should be regarded not as adversaries in the management of chronic pancreatitis and its complications, but as complementary procedures in an integrated approach. The maximum degree of complementarity should be achieved in the management of pseudocysts and in cases presenting severe, incapacitating pain. In selected cases endoscopy can play a definitive role. The generally good surgical outcomes, moreover, should convince endoscopists not to insist with repeated, hazardous manoeuvres in cases of failure. Particularly interesting is the possibility of performing endoscopic sphincterotomy combined with extracorporeal shock-wave lithotripsy prior to surgical treatment in cases of chronic calcifying calcific pancreatitis. The crushing of the calculi and partial clearance of the duct have simplified surgery and complete clearance of the duct in those patients receiving such treatment in our experience.