Current Management of Pancreatic Neuroendocrine Tumors: From Demolitive Surgery to Observation

Incidental diagnosis of pancreatic neuroendocrine tumors (PanNETs) greatly increased in the last years. In particular, more frequent diagnosis of small PanNETs leads to many challenging clinical decisions. These tumors are mostly indolent, although a percentage (up to 39%) may reveal an aggressive behaviour despite the small size. Therefore, there is still no unanimity about the best management of tumor smaller than 2 cm. The risks of under/overtreatment should be carefully evaluated with the patient and balanced with the potential morbidities related to surgery. The importance of the Ki-67 index as a prognostic factor is still debated as well. Whenever technically feasible, parenchyma-sparing surgeries lead to the best chance of organ preservation. Lymphadenectomy seems to be another important prognostic issue and, according to recent findings, should be performed in noninsulinoma patients. In the case of enucleation of the lesion, a lymph nodal sampling should always be considered. The relatively recent introduction of minimally invasive techniques (robotic) is a valuable option to deal with these tumors. The current management of PanNETs is analysed throughout the many available published guidelines and evidences with the aim of helping clinicians in the difficult decision-making process

The S0_0(0) structure in highly compressed hydrogen and the orientational transition

A calculation of the rotational S$_0$(0) frequencies in high pressure solid para-hydrogen is performed. Convergence of the perturbative series at high density is demonstrated by the calculation of second and third order terms. The results of the theory are compared with the available experimental data to derive the density behaviour of structural parameters. In particular, a strong increase of the value of the lattice constant ratio $c/a$ and of the internuclear distance is determined. Also a decrease of the anisotropic intermolecular potential is observed which is attributed to charge transfer effects. The structural parameters determined at the phase transition may be used to calculate quantum properties of the rotationally ordered phase.Comment: accepted Europhysics Letter

Oesophagus Cancer : wich treatment ? Personal experience using a Multidisciplinary Therapeutic Approach.

BachGround :Actually the oesophageal and cardias carcinoma is a high morbility and mortality disease too.The main reason is a underestimated disphagic disease with a delayed clinical evaluation. The result is a very low quality of life and severe mortality. The purpose of this study was to reduce the high grade of the disphagia and improve the quality of life in patients affected by oesophagus cancer stenosis using a MultiDisciplinary Therapeutic Approach. Materials & Methods :In our last Universitary Endoscopic Ambulatory,during 10 years, we observed 135 patients affected by oesophageus disease .The grave or severe disphagia was the more frequent symptom.Sometime,there were other symptoms linked to disphagia (tab.1). The 89% cases arrived to our evaluation without an adeguate clinical-endoscopic-radiological documentation.All had previously been treated with anti H2 and pro-kinetic drugs for several months.We observed 1)Primitive Neoplasm (78/120 p.=65%) 2)Secondary Neoplasm(12/120 p.= 10%) 3)Neoplastic Recurrences (17/120 p.=14.5%) 4)Flogistic Disease (5/120p.=4.16%) 5)Achalasia (5/120p.=4.16) 6)Barrett’s Disease (3/120p.=2.5%) (tab.2-3).Male/female ratio was 2.5/1.Various risk factors were classified (smoke=60%,Alchohol intake over 1000cc/die=60%,Obesity=25%,Barrett =2.5%)(tab.4) All the patients were valued with accurate clinical evaluation using a Multianalises Score System (tab.5-6-7-8-) In evaluating operability,we considered several parameters concerning the General Clinical Status and the Neoplasm Stage (TNM) (tab.9-10-11) Surgical treatment was established for only a few patients (15/135) which might gain advantages one-step open-surgical oesophagectomy,alone or combined to chemo-radio therapy,in according to international leterature. The others 120 patients with disphagia (III°rd level=80 p., IV°th level = 40 p.) were valued no-responders to classic open-VLS Surgery (tab.12-13).They were treated with ELS (Endoscopic Laser Surgery) alone or combined to others treatments (EGDS Savary Dilatation,Endoprosthesis, X-Rays Therapy). Flexible fibre CO2 Laser and single-use pinches were employed to perform this kind of treatment.The Endoscopic Laser Energy was administered with a continuous power flow (20-40 Watts) and mixed Technique.We used a specific treatment to single patient and disease.The single dose ranged 800-2000 Joules.The procedure was cyclically repeated every 15-60 days.The Total Dose ranged 2000-6000 Joules.In general ,we prefered the EGDS Savary Dilatation before the LES and positionating self expanding covered or non-covered stents (102)after ELS according Radiologist collegues. If necessary ,RadioTherapy (mean dose 39 Gy) was associated too. Results : we obtained a total recanalisation in flogistic disphagia disease.We obtained an important recanalisation in the first 12 months in the 85% of the neoplastic stenosis and an enough recanalisation in the 60% of the cases between 12-24 months from the first treatment.After 24 months ,we obtained an useful canalisation only in the 30% of the cases(tab.14).We registered some complications link to the treatment.(tab.15).The only one intra-operative death was in a 78 y.old patient affected by cardiomegaly.Probably ,the cause was an arrest hearth because of the fatality laser energy propagation.So,the mortality for this laser-surgery treatment was lower than 1% and also the morbidity was reduced when compared to the other centers ‘dates.We registered oesophagus Iatrogenous perforations (3) too.These healed spontaneously after specific therapy (2) using thoracic drainage,antibiotic drugs,total parenteral nutrition).It has been necessary to place only one covered endoprosthesis. Our protocol provided a 3-years follow-up with long term survival ranging 30-900 days. Conclusions :ELS could be considered the main treatment to inoperable oesophageal cancer.According our dates we think that the Treatment don’t influence the survival ,reduces absolutely the disphagic symptoms and improve the quality of life. The Cost/Benefit is profitable too.(tab.16) Tab.1 Symptom % Dysphagia 78 Epigastric pain 6 Heatburn 3 Weight loss only 3 Odinophagia 2 Vomiting/Regurgitation 2 Fatigue 2 GastroIntestinal bleeding 1 Nausea 1 Indigestion 1 Sore throat 1 Tab.2 Patology Diagnosis n.patients % Primitive Cancer 78 65 Secondary Cancer 12 10 K. Recurrences 17 14.5 Flogistic disease 5 4.16 Achalasia 5 4.16 Barrett’esophagus 3 2.5 Tab.3 Primitive Cancer n.patients % Cervical esoph. 10/78 12.8 Thoracic 17/78 21.7 Cardias 51/78 66.5 Tab.3 Secondary Cancer n.patients % Cervical esoph. (from laringeal K.) 7/12 58.2 Cardias (from lung-mediastinic K.) 5/12 39.7 Tab.4 Risk Factors Smoke 70 % Alcohol 60 % Obesity 30 % Barrett’s esophagus 2.5 % Tab.5 Clinical Evaluation General Status Pulmonary Function Cardio-Vascular Function Hepatic Function Renal Function Neurological Function Diabetes Tumor Stage Tab.6 Clinical Evaluation - General Status Sex Age Karnofsky Index Alcohol Abuse Tobacco Abuse Weight loss Dispepsia Mental Cooperation Blood examination Tab.7 Clinical Evaluation - Pulmonary/Renal Function Vital Capacity V.C Focal Expiratory Volume FEV 1 Peak Flow PaO2 mm/Hg PaCO2 mm/Hg Creatinine Clearance mg/ml Tab.8 Clinical Evaluation - Cardiac/Hepatic Function ECG X-rays Chest Cardiologist Visit Serum Albumin Bilirubin P.T- P.T.T Aminopyrine Breath Test Cirrhosis Tab.9 Clinical Evaluation - Mental cooperation / Risk Karnofsky Index > 80 & good cooperation / Normal Karnofsky Index < 80 & good cooperation/ Compromised Karnofsky Index < 80 & bad cooperation/Severely impaired Tab.10 Clinical Evaluation - Cardiac Function / Risk Normal Normal Compromised Increased Severely impaired Highest Tab.10 Clinical Evaluation -Pulmonary Function / Risk VC > 90% PaO2 >70 mm/Hg Normal VC < 90% PaO2< 70 mm/Hg Compromised Tab.11 Clinical Evaluation –Hepatic Function / Risk ABT > 0.4 Normal ABT < 0.4 no Cirrhosis Compromised Cirrhosis Severely Impaired Tab.12 Conditions for inoperable patients III th Stage Neoplasm T3 N2 M0-1 Age over 75 Cardio-Vascular disease Coagulopaties Weight loss Immuno Compromised Tab.13 Pre-Operative Disphagia Patients III grade IV grade 120 80 40 Tab.14 Post-Operative Disphagia grade % n.patients Follow-up/months I 85 102/120 <12 I 60 72/120 >12 <24 II 30 36/120 >24 Tab.15 Intra-Peri Operative Complications n.patient % Exitus 1/120 0.83 Iatrogenous perforation 3/120 2.5 Re – Stricture (after RadioTherapy) 2/120 1.66 Tab.16 Cost effectiveness in the management of oesophageal K. Surgery RadioTherapy Laser Stents No Treatm. Median Cost $ 8070 4720 3520 2450 1390 Range 2540-39780 3364- 6687 2530- 6340 1647- 5550 1132- 2348 Cost /month Survival 457 364 342 / / References : 1. Palliative therapy for patients with unresecable esophageal. Freeman R.K.,Ascioti A.J.,Muhidara R.J. Surg Clin North Am 2012 Oct;92(5):1337-51 2. The use of self-expandable metallic stents for palliative treatment of inoperable esophageal cancer. Eroghu A.,Turkylmaz A.,Subasi M.,Kareoglanoghu N Dis Esophagus 2010 Jan;23(1):64-90 3. Advanced esophageal carcinoma recanalization. Molna’rova’ A Klin Onkol 2008;21(5):309-312 4. Inoperable esophageal cancer and out come of palliative care. Besharat S.,Jabbari A.,Semnani S.,Keshtkar A.,Marjanis World J GastroEnterol 2008 June 21;14(23):3725-8 5. Causes and treatment of recurrence dysphagia after self-expanding metallic stent placement for palliation of esophageal carcinoma. Homs MY.,Steyerberg E.W.,Knipers E.J.,Van der Goost A.,Haringsma J.,Van Blankenstein M.,Siersema P.D. Endoscopy 2004 Oct;36(10):880-6 6. Endoscopic Laser Surgery in Flogistic Disease and non operable cancer of oesophagus. Fiorito R.,Bellanova G.,Milito G.,Filingeri V.,Venditti D.,Casciani C.U. Atti 7mo Congresso Nazionale della Societa’ Italiana di Chirurgia Endoscopica;Urbino 9-11 Sett/2001 7. Neoplasie inoperabili del cardias : degenerazione e dislocamento di self expanding covered stents dopo RadioTerapia. Fiorito R. , Moraldi A. , Pocek M.,Sergiacomi G.L.,Bellanova G.,Filingeri V.,Casciani C.U. Atti 101°Congresso Societa’ Italiana di Chirurgia; Catania 10-13 Ott./1999 Abstrac book p.129-130 8. Palliation of inoperable oesophageal carcinoma treated by self expanding stents. Guemes A.,De Gregorio M.A., Salinas J.C., Torcal J.,Sousa R.,Burdio F.,Fernandez J.and Lozano R. Br J Surg 1998;85,supp.2:182-184 9. Restenting malignant oesophageal strictures LaGattolla N.R.F., Rowe H., Anderson H.,Dunk A.A Br J Surg 1998;85:261-263 10. Management of malignant oesophageal obstruction with self-expanding metallic stents. Cowling M.G., Hale A., Grundy A. Br J Surg 1998;85:264-266 11. Advances in the surgical treatment of oesophageal cancer. Sugimachi K. Br J Surg 1998;85:289-290 12. Palliative treatment of neoplastic oesophageal strictures by self-expanding metallic stents. Pocek M., Iascone C., Fiorito R. Atti 6 th World Congress of the International Society for Disease of the oesophagus; Milan Aug.23-29/1995:vol.I ,pag.501-504 13. Esophageal cancer and palliation of dysphagia. Massey S. Clin J Oncol Nurs 2011 June:15(3):327-

Robot-assisted versus laparoscopic pancreatoduodenectomy: a pan-European multicenter propensity-matched study

Background: The use of robot -assisted and laparoscopic pancreatoduodenectomy is increasing, yet large adjusted analyses that can be generalized internationally are lacking. This study aimed to compare outcomes after robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy in a pan-European cohort. Methods: An international multicenter retrospective study including patients after robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy from 50 centers in 12 European countries (2009-2020). Propensity score matching was performed in a 1:1 ratio. The primary outcome was major morbidity (Clavien-Dindo >= III). Results: Among 2,082 patients undergoing minimally invasive pancreatoduodenectomy, 1,006 underwent robot -assisted pancreatoduodenectomy and 1,076 laparoscopic pancreatoduodenectomy. After matching 812 versus 812 patients, the rates of major morbidity (31.9% vs 29.6%; P = .347) and 30-day/inhospital mortality (4.3% vs 4.6%; P = .904) did not differ significantly between robot -assisted pancreatoduodenectomy and laparoscopic pancreatoduodenectomy, respectively. Robot -assisted pancreatoduodenectomy was associated with a lower conversion rate (6.7% vs 18.0%; P < .001) and higher lymph node retrieval (16 vs 14; P = .003). Laparoscopic pancreatoduodenectomy was associated with shorter operation time (446 minutes versus 400 minutes; P < .001), and lower rates of postoperative pancreatic fistula grade B/C (19.0% vs 11.7%; P < .001), delayed gastric emptying grade B/C (21.4% vs 7.4%; P < .001), and a higher R0 -resection rate (73.2% vs 84.4%; P < .001). Conclusion: This European multicenter study found no differences in overall major morbidity and 30day/in-hospital mortality after robot -assisted pancreatoduodenectomy compared with laparoscopic pancreatoduodenectomy. Further, laparoscopic pancreatoduodenectomy was associated with a lower rate of postoperative pancreatic fistula, delayed gastric emptying, wound infection, shorter length of stay, and a higher R0 resection rate than robot -assisted pancreatoduodenectomy. In contrast, robot -assisted pancreatoduodenectomy was associated with a lower conversion rate and a higher number of retrieved lymph nodes as compared with laparoscopic pancreatoduodenectomy. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Oesophagus Cancer : wich treatment ? Personal experience using a Multidisciplinary Therapeutic Approach.

BachGround :Actually the oesophageal and cardias carcinoma is a high morbility and mortality disease too.The main reason is a underestimated disphagic disease with a delayed clinical evaluation. The result is a very low quality of life and severe mortality. The purpose of this study was to reduce the high grade of the disphagia and improve the quality of life in patients affected by oesophagus cancer stenosis using a MultiDisciplinary Therapeutic Approach. Materials &amp; Methods :In our last Universitary Endoscopic Ambulatory,during 10 years, we observed 135 patients affected by oesophageus disease .The grave or severe disphagia was the more frequent symptom.Sometime,there were other symptoms linked to disphagia (tab.1). The 89% cases arrived to our evaluation without an adeguate clinical-endoscopic-radiological documentation.All had previously been treated with anti H2 and pro-kinetic drugs for several months.We observed 1)Primitive Neoplasm (78/120 p.=65%) 2)Secondary Neoplasm(12/120 p.= 10%) 3)Neoplastic Recurrences (17/120 p.=14.5%) 4)Flogistic Disease (5/120p.=4.16%) 5)Achalasia (5/120p.=4.16) 6)Barrett’s Disease (3/120p.=2.5%) (tab.2-3).Male/female ratio was 2.5/1.Various risk factors were classified (smoke=60%,Alchohol intake over 1000cc/die=60%,Obesity=25%,Barrett =2.5%)(tab.4) All the patients were valued with accurate clinical evaluation using a Multianalises Score System (tab.5-6-7-8-) In evaluating operability,we considered several parameters concerning the General Clinical Status and the Neoplasm Stage (TNM) (tab.9-10-11) Surgical treatment was established for only a few patients (15/135) which might gain advantages one-step open-surgical oesophagectomy,alone or combined to chemo-radio therapy,in according to international leterature. The others 120 patients with disphagia (III°rd level=80 p., IV°th level = 40 p.) were valued no-responders to classic open-VLS Surgery (tab.12-13).They were treated with ELS (Endoscopic Laser Surgery) alone or combined to others treatments (EGDS Savary Dilatation,Endoprosthesis, X-Rays Therapy). Flexible fibre CO2 Laser and single-use pinches were employed to perform this kind of treatment.The Endoscopic Laser Energy was administered with a continuous power flow (20-40 Watts) and mixed Technique.We used a specific treatment to single patient and disease.The single dose ranged 800-2000 Joules.The procedure was cyclically repeated every 15-60 days.The Total Dose ranged 2000-6000 Joules.In general ,we prefered the EGDS Savary Dilatation before the LES and positionating self expanding covered or non-covered stents (102)after ELS according Radiologist collegues. If necessary ,RadioTherapy (mean dose 39 Gy) was associated too. Results : we obtained a total recanalisation in flogistic disphagia disease.We obtained an important recanalisation in the first 12 months in the 85% of the neoplastic stenosis and an enough recanalisation in the 60% of the cases between 12-24 months from the first treatment.After 24 months ,we obtained an useful canalisation only in the 30% of the cases(tab.14).We registered some complications link to the treatment.(tab.15).The only one intra-operative death was in a 78 y.old patient affected by cardiomegaly.Probably ,the cause was an arrest hearth because of the fatality laser energy propagation.So,the mortality for this laser-surgery treatment was lower than 1% and also the morbidity was reduced when compared to the other centers ‘dates.We registered oesophagus Iatrogenous perforations (3) too.These healed spontaneously after specific therapy (2) using thoracic drainage,antibiotic drugs,total parenteral nutrition).It has been necessary to place only one covered endoprosthesis. Our protocol provided a 3-years follow-up with long term survival ranging 30-900 days. Conclusions :ELS could be considered the main treatment to inoperable oesophageal cancer.According our dates we think that the Treatment don’t influence the survival ,reduces absolutely the disphagic symptoms and improve the quality of life. The Cost/Benefit is profitable too.(tab.16) Tab.1 Symptom % Dysphagia 78 Epigastric pain 6 Heatburn 3 Weight loss only 3 Odinophagia 2 Vomiting/Regurgitation 2 Fatigue 2 GastroIntestinal bleeding 1 Nausea 1 Indigestion 1 Sore throat 1 Tab.2 Patology Diagnosis n.patients % Primitive Cancer 78 65 Secondary Cancer 12 10 K. Recurrences 17 14.5 Flogistic disease 5 4.16 Achalasia 5 4.16 Barrett’esophagus 3 2.5 Tab.3 Primitive Cancer n.patients % Cervical esoph. 10/78 12.8 Thoracic 17/78 21.7 Cardias 51/78 66.5 Tab.3 Secondary Cancer n.patients % Cervical esoph. (from laringeal K.) 7/12 58.2 Cardias (from lung-mediastinic K.) 5/12 39.7 Tab.4 Risk Factors Smoke 70 % Alcohol 60 % Obesity 30 % Barrett’s esophagus 2.5 % Tab.5 Clinical Evaluation General Status Pulmonary Function Cardio-Vascular Function Hepatic Function Renal Function Neurological Function Diabetes Tumor Stage Tab.6 Clinical Evaluation - General Status Sex Age Karnofsky Index Alcohol Abuse Tobacco Abuse Weight loss Dispepsia Mental Cooperation Blood examination Tab.7 Clinical Evaluation - Pulmonary/Renal Function Vital Capacity V.C Focal Expiratory Volume FEV 1 Peak Flow PaO2 mm/Hg PaCO2 mm/Hg Creatinine Clearance mg/ml Tab.8 Clinical Evaluation - Cardiac/Hepatic Function ECG X-rays Chest Cardiologist Visit Serum Albumin Bilirubin P.T- P.T.T Aminopyrine Breath Test Cirrhosis Tab.9 Clinical Evaluation - Mental cooperation / Risk Karnofsky Index &gt; 80 &amp; good cooperation / Normal Karnofsky Index &lt; 80 &amp; good cooperation/ Compromised Karnofsky Index &lt; 80 &amp; bad cooperation/Severely impaired Tab.10 Clinical Evaluation - Cardiac Function / Risk Normal Normal Compromised Increased Severely impaired Highest Tab.10 Clinical Evaluation -Pulmonary Function / Risk VC &gt; 90% PaO2 &gt;70 mm/Hg Normal VC &lt; 90% PaO2&lt; 70 mm/Hg Compromised Tab.11 Clinical Evaluation –Hepatic Function / Risk ABT &gt; 0.4 Normal ABT &lt; 0.4 no Cirrhosis Compromised Cirrhosis Severely Impaired Tab.12 Conditions for inoperable patients III th Stage Neoplasm T3 N2 M0-1 Age over 75 Cardio-Vascular disease Coagulopaties Weight loss Immuno Compromised Tab.13 Pre-Operative Disphagia Patients III grade IV grade 120 80 40 Tab.14 Post-Operative Disphagia grade % n.patients Follow-up/months I 85 102/120 &lt;12 I 60 72/120 &gt;12 &lt;24 II 30 36/120 &gt;24 Tab.15 Intra-Peri Operative Complications n.patient % Exitus 1/120 0.83 Iatrogenous perforation 3/120 2.5 Re – Stricture (after RadioTherapy) 2/120 1.66 Tab.16 Cost effectiveness in the management of oesophageal K. Surgery RadioTherapy Laser Stents No Treatm. Median Cost $ 8070 4720 3520 2450 1390 Range 2540-39780 3364- 6687 2530- 6340 1647- 5550 1132- 2348 Cost /month Survival 457 364 342 / / References : 1. Palliative therapy for patients with unresecable esophageal. Freeman R.K.,Ascioti A.J.,Muhidara R.J. Surg Clin North Am 2012 Oct;92(5):1337-51 2. The use of self-expandable metallic stents for palliative treatment of inoperable esophageal cancer. Eroghu A.,Turkylmaz A.,Subasi M.,Kareoglanoghu N Dis Esophagus 2010 Jan;23(1):64-90 3. Advanced esophageal carcinoma recanalization. Molna’rova’ A Klin Onkol 2008;21(5):309-312 4. Inoperable esophageal cancer and out come of palliative care. Besharat S.,Jabbari A.,Semnani S.,Keshtkar A.,Marjanis World J GastroEnterol 2008 June 21;14(23):3725-8 5. Causes and treatment of recurrence dysphagia after self-expanding metallic stent placement for palliation of esophageal carcinoma. Homs MY.,Steyerberg E.W.,Knipers E.J.,Van der Goost A.,Haringsma J.,Van Blankenstein M.,Siersema P.D. Endoscopy 2004 Oct;36(10):880-6 6. Endoscopic Laser Surgery in Flogistic Disease and non operable cancer of oesophagus. Fiorito R.,Bellanova G.,Milito G.,Filingeri V.,Venditti D.,Casciani C.U. Atti 7mo Congresso Nazionale della Societa’ Italiana di Chirurgia Endoscopica;Urbino 9-11 Sett/2001 7. Neoplasie inoperabili del cardias : degenerazione e dislocamento di self expanding covered stents dopo RadioTerapia. Fiorito R. , Moraldi A. , Pocek M.,Sergiacomi G.L.,Bellanova G.,Filingeri V.,Casciani C.U. Atti 101°Congresso Societa’ Italiana di Chirurgia; Catania 10-13 Ott./1999 Abstrac book p.129-130 8. Palliation of inoperable oesophageal carcinoma treated by self expanding stents. Guemes A.,De Gregorio M.A., Salinas J.C., Torcal J.,Sousa R.,Burdio F.,Fernandez J.and Lozano R. Br J Surg 1998;85,supp.2:182-184 9. Restenting malignant oesophageal strictures LaGattolla N.R.F., Rowe H., Anderson H.,Dunk A.A Br J Surg 1998;85:261-263 10. Management of malignant oesophageal obstruction with self-expanding metallic stents. Cowling M.G., Hale A., Grundy A. Br J Surg 1998;85:264-266 11. Advances in the surgical treatment of oesophageal cancer. Sugimachi K. Br J Surg 1998;85:289-290 12. Palliative treatment of neoplastic oesophageal strictures by self-expanding metallic stents. Pocek M., Iascone C., Fiorito R. Atti 6 th World Congress of the International Society for Disease of the oesophagus; Milan Aug.23-29/1995:vol.I ,pag.501-504 13. Esophageal cancer and palliation of dysphagia. Massey S. Clin J Oncol Nurs 2011 June:15(3):327-