Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions.

BACKGROUND AND AIMS: Differentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs. METHODS: We retrospectively analyzed 110 consecutive patients with PCLs from 2 Italian Hospitals who underwent EUS with H-Flow and EUS fine needle aspiration to obtain cystic fluid. The accuracy of fluid biomarkers was evaluated against morphological features on radiology and EUS. Gold standard for diagnosis was surgical resection. A clinical and radiological follow up was applied in those patients who were not resected because not surgical indication and no signs of malignancy were shown. RESULTS: Of 110 patients, 65 were diagnosed with a mucinous cyst, 41 with a non-mucinous cyst, and 4 with an undetermined cyst. Fluid analysis alone yielded 76.7% sensitivity, 56.7% specificity, 77.8 positive predictive value (PPV), 55.3 negative predictive value (NPV) and 56% accuracy in diagnosing pancreatic cysts alone. Our composite method yielded 97.3% sensitivity, 77.1% specificity, 90.1% PPV, 93.1% NPV, 73.2% accuracy. CONCLUSIONS: This new composite could be applied to the holistic approach of combining cyst morphology, vascularity, and fluid analysis alongside endoscopist expertise.

Mutational Mosaics of Cell-Free DNA from Pancreatic Cyst Fluids.

BACKGROUND: Pancreatic cyst fluids (PCFs) enriched in tumor-derived DNA are a potential source of new biomarkers. The study aimed to analyze germinal variants and mutational profiles of cell-free (cf)DNA shed into the cavity of pancreatic cysts. METHODS: The study cohort consisted of 71 patients who underwent endoscopic ultrasound fine-needle aspiration of PCF. Five malignant cysts, 19 intraductal papillary mucinous neoplasms (IPMNs), 11 mucinous cystic neoplasms (MCNs), eight serous cystic neoplasms (SCNs), and 28 pseudocysts were identified. The sequencing of 409 genes included in Comprehensive Cancer Panel was performed using Ion Proton System. The mutation rate of the KRAS and GNAS canonical loci was additionally determined using digital PCR. RESULTS: The number of mutations detected with NGS varied from 0 to 22 per gene, and genes with the most mutations were: TP53, KRAS, PIK3CA, GNAS, ADGRA2, and APC. The frequencies of the majority of mutations did not differ between non-malignant cystic neoplasms and pseudocysts. NGS detected KRAS mutations in malignant cysts (60%), IPMNs (32%), MCNs (64%), SCNs (13%), and pseudocysts (14%), with GNAS mutations in 20%, 26%, 27%, 13%, and 21% of samples, respectively. Digital PCR-based testing increased KRAS (68%) and GNAS (52%) mutations detection level in IPMNs, but not other cyst types. CONCLUSIONS: We demonstrate relatively high rates of somatic mutations of cancer-related genes, including KRAS and GNAS, in cfDNA isolated from PCFs irrespectively of the pancreatic cyst type. Further studies on molecular mechanisms of pancreatic cysts malignant transformation in relation to their mutational profiles are required.

Psychological distress in patients under surveillance for intraductal papillary mucinous neoplasms of the pancreas: The "Sword of Damocles" effect calls for an integrated medical and psychological approach a prospective analysis.

INTRODUCTION: Most intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can be safely surveilled. Their psychological impact is not known. The aim of this study is to obtain a psychological profile of patients under surveillance and compare the results to patients undergoing surgery. METHODS: Patients under surveillance for IPMNs evaluated between 2017 and 2019 at the pancreatic cysts clinic of The Pancreas Institute of Verona were compared to patients undergoing surgery for the same disease. Patients with high-risk stigmata were excluded in both groups. Patients were profiled with the Barratt Simplified Measure of Socio-Economic Status (BSMSS), the Brief Coping Orientation to Problems Experienced (Brief-COPE), the Perceived Stress Scale (PSS), the Symptom Checklist-90 and the Short Form Health Survey (SF-36). Age, sex, BSMSS and Brief-COPE were used to match patients with the propensity score as potential sources of bias. RESULTS: Two hundred patients were profiled. After the matching, 74 patients under surveillance were compared to 74 patients who underwent surgery. Patients under surveillance reported significantly increased scores for symptoms such as somatization (0.71 vs. 0.54, p = 0.032), depression (0.45 vs 0.31, p = 0.047) and anxiety (0.45 vs. 0.27, p = 0.002). They also reported a reduced health perception in the domain of physical role functioning (54 vs. 68, p = 0.046). CONCLUSION: Patients under surveillance for a presumed IPMN experience anxiety and stress and feel less healthy than do patients undergoing surgery. This reduction in quality of life should always be taken into account and warrants an integrated medical-psychological approach in selected cases.

Evaluating the ability to detect pancreatic lesions using a special ultrasonography examination focusing on the pancreas.

PURPOSE: The ability to detect pancreatic cysts was compared between special ultrasonography (US) examination focusing on the pancreas (special pancreatic US) and routine upper abdominal ultrasonography to objectively assess the ability of the former to detect cysts. SUBJECTS AND METHODS: Of 3704 patients who underwent special pancreatic US at our hospital, 186 underwent routine upper abdominal US within six months, had pancreatic cysts, and underwent magnetic resonance imaging (MRI). In these patients, 447 cysts measuring ≥5mm were detected via MRI, which was used as the gold standard. The ability and sensitivity of the US modalities to detect each cyst was determined. RESULTS: The sensitivity of special pancreatic US was 92.2% (95% confidence interval [CI], 89.7%-94.7%) and that of routine upper abdominal US was 70.2% (95% CI, 66.0%-74.5%). McNemar test (Stata Version 13.1) revealed a significant difference in the cyst (≥5mm) detection sensitivity between the two modalities (p<0.001). An analysis stratified by patients similarly revealed a significant difference between the two modalities (p<0.001). The cyst detection sensitivity was also analyzed in various parts of the pancreas. The sensitivity of special pancreatic US was 88.7% for the uncinate process and inferior head, 97.5% for the head, 97.1% for the body, 89.0% for the body-tail, and 66.7% for the tail, whereas that of routine upper abdominal US was 74.2% for the uncinate process, 69.5% for the head, 81.0% for the body, 67.0% for the body-tail, and 26.7% for the tail. The McNemar test revealed significant differences in the sensitivity of the two modalities for all pancreatic parts (p<0.001-0.016). CONCLUSION: Compared with routine upper abdominal US, special pancreatic US had higher sensitivity in detecting pancreatic cysts.

Cyst fluid carcinoembryonic antigen level is not predictive of invasive cancer in patients with intraductal papillary mucinous neoplasm of the pancreas.

CONTEXT: Cyst fluid CEA concentration>192 ng/mL has proven accurate to differentiate mucinous from non-mucinous pancreatic cystic neoplasms. It is unclear whether the degree of cyst fluid CEA elevation is predictive of malignant behavior in IPMNs. OBJECTIVES: To determine whether elevated cyst fluid CEA concentrations were predictive of invasive cancer. DESIGN: Cross sectional study. SETTING: Single National Cancer Institute comprehensive cancer care center experience. PATIENTS: 47 patients underwent preoperative EUS-FNA with cyst fluid analysis and surgical resection of an IPMN over a 9 year period. MAIN OUTCOME MEASUREMENTS: Cyst fluid CEA concentrations among the four grades associated with IPMN (low grade dysplasia, moderate dysplasia, high grade dysplasia, and invasive cancer). RESULTS: The mean±standard deviation cyst fluid CEA concentration increased as the pathology progressed from low grade dysplasia (1,261±1,679 ng/mL) to moderate dysplasia (7,171±22,210 ng/mL) to high grade dysplasia (10,807±36,203 ng/mL). However, the mean CEA level decreased (462±631 ng/mL) once invasive cancer developed (P=0.869). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a cyst fluid CEA concentration greater than 200 ng/mL for the diagnosis of malignant IPMN (cases of high grade dysplasia and invasive IPMN) was 52.4%, 42.3%, 42.3%, 52.4% and 46.8%, respectively. LIMITATIONS: Single center experience, small patient numbers, retrospective data collection. CONCLUSION: The degree of cyst fluid CEA elevation is a poor predictor of malignant degeneration within IPMNs. Clinical management decisions regarding surgical resection should not be based upon degree of cyst fluid CEA elevation.

[Pancreatic tumors]. / Tumores pancreáticos.

The management of pancreatic cancer is complex and prognosis is poor. The etiopathogenesis of pancreatic cancer has been related to several factors, such as diabetes mellitus, smoking and alcohol use, the presence of pancreatic cystic lesions and distinct genetic syndromes. Among the diagnostic options, endoscopic ultrasound (EUS) continues to be developed, with the use of elastography, contrast agents and EUS-guided aspiration and the application of technical improvements that increase diagnostic efficacy (such as the use of specific stains, new aspiration needles, etc.). New biomarkers are also being sought that would help in differential diagnosis, such as M2PK, adiponectin, and Reg4. Among prognostic factors, the importance of nodal involvement and study of surgical resection margins has been confirmed. The role of individual predisposition in determining response to specific treatments continues to be investigated. Research also continues into the development of EUS-guided injection of therapeutic substances and the role of oncological treatment, with new data on the utility of gemcitabine and of statins as mediators of angiogenic suppression or of high-dose vitamin C with cytotoxic effects. Notable in the field of palliative treatment is the development of new biliary stents that aim to reduce obstruction rates. The development of EUS and EUS-guided fine-needle aspiration has been crucial in cystic pancreatic tumors, especially in distinguishing benign from malignant lesions or those with potential for malignant transformation (presence of mural modules, dilatation of the main pancreatic duct, the presence of masses, CEA levels, etc.). The characteristics of these tumors must be determined to evaluate whether surgery or conservative management is the best therapeutic option.

Therapeutic fistuloscopy: an alternative approach in the management of postoperative fistulas.

BACKGROUND/AIM: Since the treatment of postoperative fistulas remains a difficult problem, we applied endoscopic treatment in such 14 persistent fistulas. METHODS: Fourteen patients presented with postoperative fistulas: 7 patients (low-output group) due to residual cavity after liver hydatid disease surgery and 7 patients (high-output group) after small-bowel resection (n = 3), diverted duodenostomy (n = 1), vertical gastroplasty (n = 1), external pancreatic cyst drainage (n = 1), and transduodenal sphincteroplasty (n = 1). The therapeutic procedures included mechanical removal of silk sutures, necrotic material, and hydatid membranes in the low-output group and fibrin sealing in the high-output group. RESULTS: Fistuloscopy was performed 170-278 days (mean +/- SD 198.7 +/- 36.7 days) and 18-51 days (mean +/- SD 34.0 +/- 11.3 days) postoperatively in low- and high-output fistula patients, respectively, when the average daily output was 20-50 (32.8 +/- 12.5) ml and 200-1,000 (563.1 +/- 319.4) ml, respectively. The low-output group needed only one fistuloscopy session, while the other group required a median number of three sessions plus fibrin sealing, the total amount of fibrin glue used per patient being 2-14 (6.5 +/- 4.4) ml. No procedure-related complication occurred. All fistulas except one healed within 10-33 (21.8 +/- 7.9) days and 2-17 (9.2 +/- 5.1) days in low- and high-output groups, respectively. CONCLUSIONS: We believe fistuloscopy to be a useful tool in the management of gastrointestinal fistulas, but more experience should be gained in using this technique.

[Efficacy of the impulse magnetic field therapy in patients after the outer drainage of abdominal cysts diagnosed with the use of isotopic and ultrasound techniques]. / Skutecznosc terapii impulsowym polem magnetycznym po drenazu zewnetrznym zmian torbielowatych jamy brzusznej diagnozowanych ultrasonograficznie i izotopowo.

154 patients with pancreatic, renal or hepatic cysts have been treated with the outer drainage under USG monitoring. Because of cysts' contact with tracts penetrating to an organ or its lack, the patients have been divided into two groups. Directly after the puncture all the patients have undergone the high frequency impulse magnetic field therapy. A distinct, positive treatment effect has been found in patients who have gone through not only drainage, but also magnetic field.

Aspecoto quirúrgico en el manejo de los pseudoquistes pancoreáticoos / Surgical aspects in the management of pancreatic pseudocysts

Durante los años de 1969 hasta 1979 fueron operados 35 pacientes por 36 ocasiones de pseudoquistes pancreáticos en el Departamento de Cirugía del Hospital Universitarios de Göettingen, República Federal de Alemania. Se utilizaron como medios de diagnóstico los exámenes de laboratorio, en especial amilasa sérica y urinaria seriada, al igual que creatinina así como también ecografía abdominal, estudio contrastado del tracto gastrointestinal superior, standard de tórax, enema baritado de colon y radiografía de vías biliares. A pesar del alto número de accidentes de tránsito, los pseudoquistes pancreáticos de origen traumático fueron bastante escasos y la mayoría de ellos fueron operados como resultado de una pacreatitis crónica. Lo contrario sucedió en los pseudoquistes pancreáticos que resultaron de una pancreatitis aguda así como también en la aguda recidivante, en las que se encontró un número bastante escaso. Los pseudoquistes pancreáticos por pancreatitis aguda de origen biliar solo fueron observados exclusivamente en dos casos. Se realizó una sola intervención quirúrgica en 31 casos mientras que en una resección pancreática, de las cuatro existentes, fué la única ocasión en la que tuvo que recurrirse a una segunda y tercera intervención. El drenaje externo fué realizado exclusivamente en tres casos mientras que 28 veces se realizó drenaje interno. La técnica que se utilizó con mayor frecuencia como drenaje interno fué la Cistoyeyunostomía en Y de Roux en 21 pacientes. Este método nos demostró ser el más apropiado tanto por razones morfológicas como funcionales. Nosotros observamos que no tuvimos ninguna mortalidad en nuestros operados así como también la morbilidad post-operatoria fué mínima, es así que, tres pacientes tuvieron un curso post-operatorio complicado. El tiempo de hospitalización promedio fué de 25 días. Creemos que la Cystoyeyunostomía en Y de Roux debe ser utilizada como tratamiento quirúrgico de preferencia para el drenaje del pseudoquiste pancreático

Aspecoto quirúrgico en el manejo de los pseudoquistes pancoreáticoos / Surgical aspects in the management of pancreatic pseudocysts

Durante los años de 1969 hasta 1979 fueron operados 35 pacientes por 36 ocasiones de pseudoquistes pancreáticos en el Departamento de Cirugía del Hospital Universitarios de G÷ettingen, República Federal de Alemania. Se utilizaron como medios de diagnóstico los exámenes de laboratorio, en especial amilasa sérica y urinaria seriada, al igual que creatinina así como también ecografía abdominal, estudio contrastado del tracto gastrointestinal superior, standard de tórax, enema baritado de colon y radiografía de vías biliares. A pesar del alto número de accidentes de tránsito, los pseudoquistes pancreáticos de origen traumático fueron bastante escasos y la mayoría de ellos fueron operados como resultado de una pacreatitis crónica. Lo contrario sucedió en los pseudoquistes pancreáticos que resultaron de una pancreatitis aguda así como también en la aguda recidivante, en las que se encontró un número bastante escaso. Los pseudoquistes pancreáticos por pancreatitis aguda de origen biliar solo fueron observados exclusivamente en dos casos. Se realizó una sola intervención quirúrgica en 31 casos mientras que en una resección pancreática, de las cuatro existentes, fué la única ocasión en la que tuvo que recurrirse a una segunda y tercera intervención. El drenaje externo fué realizado exclusivamente en tres casos mientras que 28 veces se realizó drenaje interno. La técnica que se utilizó con mayor frecuencia como drenaje interno fué la Cistoyeyunostomía en Y de Roux en 21 pacientes. Este método nos demostró ser el más apropiado tanto por razones morfológicas como funcionales. Nosotros observamos que no tuvimos ninguna mortalidad en nuestros operados así como también la morbilidad post-operatoria fué mínima, es así que, tres pacientes tuvieron un curso post-operatorio complicado. El tiempo de hospitalización promedio fué de 25 días. Creemos que la Cystoyeyunostomía en Y de Roux debe ser utilizada como tratamiento quirúrgico de preferencia para el drenaje del pseudoquiste pancreático (AU)

[Pancreatoscanography with 75Se-methionine following glucose loading]. / Pankreatoskanografiia s 75Se-metioninom posle sakharnoi nagruzki.

Altogether 110 patients with different pancreatic diseases were examined on the Picker magna-scanner 500 I (USA) with 75Se-methionine (9.2 MBq). Glucose load at a dose of 0.33 g/kg is recommended 50 min before examination increasing RP accumulation in the pancreas parenchyma and improving scanographic image. It is pointed out that the coincidence of scanographic and pathohistological diagnoses in pancreas cancer is noted in 62.5%, in cystic formations in 89%, and in chronic pancreatitis in 93% cases.

[Surgical aspect in the management of pancreatic pseudocyst]. / Aspecto quirúrgico en el manejo de los pseudoquistes pancreáticos.

During the years from 1969 to 1979, 35 patients were operated 36 occasioned by pancreatic pseudocysts in the Department of Surgery of the University Hospital of Göettingen, West Germany. They were utilized as diagnostic methods laboratory exams, especially serial seric and urinary amylase as creatinine and at the same time abdominal echography, upper gastrointestinal tract X-rays, thorax X-rays, Barium Enema and Biliary tract X-rays. Although the great number of transit accidents, the traumatic pancreatic pseudocysts were seldom found and most of them were operated as a result of a chronic pancreatitis. Contrarily the pancreatic pseudocysts as result of an acute pancreatitis and recurrent acute pancreatitis were in a limited number. We observed only 2 cases of acute pancreatitis with biliary etiology. We realized one operation in 31 cases and in one resection, four of the series, was the only occasion that we recurred for a second and a third operation. The external drainage was realized exclusively in 3 cases while internal drainage was performed 28 times. The surgical technic frequently used as internal drainage was the Roux en-Y Cystojejunostomy and was perfomed in 21 patients. This method demonstrated to be the most fit by morphologic as functional reasons. We observed that our mortality was null and our post-operative morbility was minimal, so, we have only 3 patients with complicated post-operative course. The mean hospitalization time was 25 days. We surgical treatment of choice for the drainage of the pancreatic pseudocysts.

[Exogenous zinc deficiency syndrome]. / Das exogen bedingte Zinkmangelsyndrom.

Two cases of acquired zinc deficiency after excessive bowel resection and total pancreatectomy and after total parenteral nutrition are reported. Skin lesions include diffuse hair loss and a psoriasis like dermatitis localized mainly at acral areas and around body orifices, which disappeared rapidly after oral supplementation of zinc sulfate. Clinical symptoms, etiological factors, differential diagnosis and therapy are discussed.

Pancreatography with contrast medium containing polyethylene hydrogenated castor oil.

A new contrast medium has been used for endoscopic pancreatography. Good visualization of the pancreas was obtained by this method. No side-effects of this method were observed by clinical and histologic examination, either in clinical or experimental studies. Clinically, the new method provided more detailed information regarding pancreatic changes in chronic pancreatitis. It is suggested that this method may make detection of a small tumor of the pancreas in the parenchyma and permit earlier diagnosis of carcinoma of the pancreas.

Normal and abnormal motility of the stomach.

The analysis of gastric motility makes possible the distinction between purely anatomic changes and those of a functional nature with or without associated morphologic alterations. Hence, through evaluation of gastric and duodenal motor function contributes significantly to the radiographic examination of the upper gastrointestinal tract.

[Pleuresies in chronic pancreatitis and in pancreatic pseudocysts. A study apropos of 20 cases]. / Les pleurésies des pancréatites chroniques et des pseudo-kystes du pancréas. Etude à propos de 20 observations

The pleurisies rich in amylase of the chronic pancreatitis and of pancreatic pseudo-cysts, studied in 20 cases, are quite unfrequent (0.5% of pleurisies of all kinds in the medical milieu). A pseudo-cyst was found 12 times out of 20 and a chronic pancreatitis without pseudocyst was found 8 times out of 20. Pleural effusion has a definite diagnostic valve, because in 70% of cases pancreatopathy cannot be recognized before it happens. The pleural liquid is rich in proteins and haemorrhagic in 2/3 of cases and its amylasic activity is either high or very high. Amylase level in pleural liquid is usually superior to amylasemia. The injection of lipiodol in the pleural cavity enables the visualization of a transdiaphragmatic fistula but this examination is not always well tolerated. The preoperatory cystography can opacify the pleura. In the absence of pseudo-cyst, medical treatment can dry the pleurisy in 70% of cases but does not modify the evolution of the pancreatic affection which will require surgery. Where a pseudo-cyst is concerned, surgery will often and quickly be the remedy.

[Haustral changes in the colon due to diseases of the pancreas and stomach (author's transl)]. / Haustren-Veränderungen am Kolon durch Nachbarschafts-Prozesse besonders seitens des Pankreas und des Magens

The radiological anatomy of the colon, as shown by double contrast enema, is described. Changes in the haustral pattern may often be due to lesions outside the colon.