Timeline of Development of Pancreatic Cancer and Implications for Successful Early Detection in High-Risk Individuals.

BACKGROUND & AIMS: To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals and identify factors associated with successful early detection. METHODS: We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC or underwent pancreatic surgery, or both, in 16 international surveillance programs. RESULTS: Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during a median follow-up of 29 months after baseline (interquartile range [IQR], 40 months). Of these, 13 of 28 (46%) presented with a new lesion (median size, 15 mm; range 7-57 mm), a median of 11 months (IQR, 8; range 3-17 months) after a prior examination, by which time 10 of 13 (77%) had progressed beyond the pancreas. The remaining 15 of 28 (54%) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid), and 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been monitored for 21 months (IQR, 15 months) and had a median growth of 5 mm/y (IQR, 8 mm/y). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (vs solid or indeterminate lesions (odds ratio, 5.388; 95% confidence interval, 1.525-19.029) and small lesions (odds ratio, 0.890/mm; 95% confidence interval 0.812-0.976/mm). CONCLUSIONS: In nearly half of high-risk individuals developing high-grade dysplasia or PC, no prior lesions are detected by imaging, yet they present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly growing cysts are needed.

Detection of elusive polyps using a large-scale artificial intelligence system (with videos).

BACKGROUND AND AIMS: Colorectal cancer is a leading cause of death. Colonoscopy is the criterion standard for detection and removal of precancerous lesions and has been shown to reduce mortality. The polyp miss rate during colonoscopies is 22% to 28%. DEEP DEtection of Elusive Polyps (DEEP2) is a new polyp detection system based on deep learning that alerts the operator in real time to the presence and location of polyps. The primary outcome was the performance of DEEP2 on the detection of elusive polyps. METHODS: The DEEP2 system was trained on 3611 hours of colonoscopy videos derived from 2 sources and was validated on a set comprising 1393 hours from a third unrelated source. Ground truth labeling was provided by offline gastroenterologist annotators who were able to watch the video in slow motion and pause and rewind as required. To assess applicability, stability, and user experience and to obtain some preliminary data on performance in a real-life scenario, a preliminary prospective clinical validation study was performed comprising 100 procedures. RESULTS: DEEP2 achieved a sensitivity of 97.1% at 4.6 false alarms per video for all polyps and of 88.5% and 84.9% for polyps in the field of view for less than 5 and 2 seconds, respectively. DEEP2 was able to detect polyps not seen by live real-time endoscopists or offline annotators in an average of .22 polyps per sequence. In the clinical validation study, the system detected an average of .89 additional polyps per procedure. No adverse events occurred. CONCLUSIONS: DEEP2 has a high sensitivity for polyp detection and was effective in increasing the detection of polyps both in colonoscopy videos and in real procedures with a low number of false alarms. (Clinical trial registration number: NCT04693078.).

[COMPARISON OF QUALITY OF COLONOSCOPY IN AN ACADEMIC HOSPITAL VS. A COMMUNITY HOSPITAL OUTPATIENT SERVICE].

BACKGROUND: Extensive use of colonoscopy in hospitals and community clinics has highlighted the need to assess the quality of the procedures in order to reduce costs and increase their efficiency. OBJECTIVES: This institutional review board (IRB)-approved study aimed to compare the quality of colonoscopies performed in a teaching hospital to those performed at a community health service. METHODS: Demographic information, time of procedure, indications, quality of bowel preparation, premedication, depth of examination, polyp detection, biopsies and followup recommendations were retrospectively obtained from 700 colonoscopy reports from the Rambam Healthcare Campus and 824 colonoscopy reports from Elisha. This data was compared to relevant literature benchmarks. RESULTS: There was no statistically significant difference between the hospital vs. community endoscopy services in the patients' demographics, depth of examination (92.4% vs. 94.1% complete), polyp detection rate (29.1% vs. 26.8%) and biopsies in patients with diarrhea (75% vs. 67%). Indications for colonoscopy differed: gastrointestinal bleeding was more common at the hospital, while screening was more common in the community. Premedication varied: more fentanyl and dormicum and less propofol were used in the community. Good bowel preparation was more frequent in the community (68.8% vs. 47.2% in hospital, p<0.0001). Follow-up recommendations were documented more often in the community (74% vs. 53% in hospital, p<0.0001). The range for many quality indicators (QIs) varied greatly amongst physicians. CONCLUSIONS: Remediation of weaker areas seems feasible through upgrading electronic medical records and increasing awareness of quality indicators (Qis). Colonoscopies performed in both hospital and community services were of good quality compared to the relevant literature, with significant variations in some QIs.

Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model.

INTRODUCTION: Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. AIM: This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects. METHODS AND RESULTS: In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline (p < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes (p < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection (p = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups (p = 0.007). CONCLUSIONS: Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.

The impact of preoperative stoma site marking on the incidence of complications, quality of life, and patient's independence.

BACKGROUND: Preoperative stoma site marking and counseling aim to improve patients' rehabilitation and adaptation to a new medical condition. Objective studies are needed to provide evidence of the impact of care by stoma therapists. Key quality indicators include patients' quality of life, independence, and complication rates as affected by the variable modes of stoma site marking and planning. OBJECTIVE: The aim of this study was to evaluate the impact of preoperative stoma site marking on patients' quality of life, independence, and complication rates. DESIGN: : A validated stoma quality-of-life questionnaire was used as the main assessment tool. Complications were noted on regular postoperative visits. SETTING: This is a single-center, clinical study. The study was conducted at the Rambam Health Care Campus in Haifa, Israel. Rambam Health Care Campus is a tertiary university hospital. PATIENTS: All patients who underwent an elective stoma creation between 2006 and 2008 were included. MAIN OUTCOME MEASURES: Evaluated parameters included demographics, stoma type, marking status, complication rates, quality of life, and independence parameters. RESULTS: : One hundred five patients (60 men and 45 women) were included, of whom 52 (49.5%) were preoperatively marked and 53 (50.5%) were not marked. Sixty stomas (57%) were permanent, and 45 (43%) stomas were temporary. The quality of life of patients whose stoma sites were preoperatively marked was significantly better than that of the unmarked patients (p < 0.05 in 18 of 20 items), their independence parameters were significantly better, and their complication rates significantly lower. All of these results were significant irrespective of the stoma type. CONCLUSIONS: Preoperative stoma site marking is crucial for improving patients' postoperative quality of life, promoting their independence, and reducing the rates of postoperative complications. The role of the enterostomal therapist is very important in the ostomates' pre- and postoperative care.

Yellow brain culinary-medicinal mushroom, Tremella mesenterica Ritz.:Fr. (higher Basidiomycetes), is subjectively but not objectively effective for eradication of Helicobacter pylori: a prospective controlled trial.

Inhibitory effects of the higher Basidiomycetes mushrooms, including species of genus Tremella, on the growth of Helicobacter pyroli (Hp) have been described. This study aimed to test T. mesenterica (Tm) efficacy in vivo on eradication of Hp. This IRB-approved study included 52 consenting patients diagnosed with Hp infections. The patients were selected for 10-day treatments with one of the three arms of the protocol, namely, (i) Tm 2 g, (ii) Tm given with omeprazole 20 mg, or (iii) omeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1000 mg (all regimens given twice daily). The Tm submerged cultivated mycelium in the form of tablets (1 g) was supplied free of charge to patients. Three weeks after completing the therapy, breath testing was assessed for Hp eradication. The patients who took the standard triple therapy had a 70% (n = 14) eradication rate of Hp. Of the patients taking Tm, with and without omeprazole, only one had a breath test indicative of eradication of Hp, p < 0.000. Tm-treated patients had fewer adverse events and equivalent symptomatic relief. Limitations of this study include the brief duration of Tm therapy. Longer treatment might achieve better results, but was judged to be not warranted, so as to not excessively further delay accepted therapy. Ten-day Tm was not found to be effective in vivo in eradicating Hp, whether if given with or without omeprazole. Significant symptomatic relief found among Tm-treated patients suggests that further study of Tm is well justified.

Optimizing your reception area.

Through the optimization of reception areas (waiting rooms), physicians can improve the medical experiences of their patients. A qualitative investigation identified issues relevant to improving the quality of the reception area and was used to develop a thorough questionnaire. Most patients were satisfied with accessibility, reception area conditions, and performance of doctors and nurses. The main reasons for dissatisfaction were due to remediable points. No correlations were found between patient satisfaction and age, sex, or religion. A 36-item checklist for satisfaction with reception areas is offered as a useful tool for health quality self-assessment.

A multidisciplinary survey on controversies in the use of EUS-guided FNA: assessing perspectives of surgeons, oncologists and gastroenterologists.

BACKGROUND: EUS-guided FNA can help diagnose and differentiate between various pancreatic and other lesions.The aim of this study was to compare approaches among involved/relevant physicians to the controversies surrounding the use of FNA in EUS. METHODS: A five-case survey was developed, piloted, and validated. It was collected from a total of 101 physicians, who were all either gastroenterologists (GIs), surgeons or oncologists. The survey compared the management strategies chosen by members of these relevant disciplines regarding EUS-guided FNA. RESULTS: For CT operable T2NOM0 pancreatic tumors the research demonstrated variance as to whether to undertake EUS-guided FNA, at p < 0.05. For inoperable pancreatic tumors 66.7% of oncologists, 62.2% of surgeons and 79.1% of GIs opted for FNA (p < 0.05). For cystic pancreatic lesions, oncologists were more likely to send patients to surgery without FNA. For stable simple pancreatic cysts (23 mm), most physicians (66.67%) did not recommend FNA. For a submucosal gastric 19 mm lesion, 63.2% of surgeons recommended FNA, vs. 90.0% of oncologists (p < 0.05). CONCLUSIONS: Controversies as to ideal application of EUS-FNA persist. Optimal guidelines should reflect the needs and concerns of the multidisciplinary team who treat patients who need EUS-FNA. Multi-specialty meetings assembled to manage patients with these disorders may be enlightening and may help develop consensus.

Exposure during pancreatic surgery. Do we have to examine the falciform and round ligaments for pancreatic cancer metastasis?

CONTEXT: Metastatic and locally advanced disease is unfortunately a common clinical occurrence in patients affected by pancreatic cancer. The most frequent sites of metastasis are the liver and the peritoneal lining. The falciform and round ligaments are routinely resected and sent for pathology, but no metastases have ever been reported. OBJECTIVE: In this study, we assess whether the falciform and round ligaments are possible sites for metastases and if routine pathology examination of these structures is justified. DESIGN: Retrospective, single institution study. PATIENTS: The charts of all patients who underwent pancreatic resection from June 2005 through January 2011 were reviewed retrospectively. Data on age, gender, type of operation performed, preoperative CA 19-9 levels, vascular and perineural invasion, tumor differentiation and pathological staging were retrieved from the hospital electronic data base. Only patients with malignant lesions of the pancreas were included in the study. MAIN OUTCOME MEASURES: Presence of pancreatic metastasis in the falciform and round ligaments. RESULTS: Fifty-seven patients were included in the study. Forty patients had undergone pancreaticoduodenectomies, 10 subtotal pancreatectomies, 2 total pancreatectomies, and 1 distal pancreatectomy. Four patients had exploratory laparotomy but exploration revealed stage III or IV disease, thus the planned resection was not carried out. The falciform and round ligaments were all negative for metastasis in all patients. DISCUSSION: Metastatic progression of pancreatic cancer is poorly understood. Theoretically, metastases to the falciform and round ligaments could occur by either contiguous, hematogenic or lymphatic spread. In our study, none of the patients had metastases to the falciform and round ligaments, regardless of the pathological staging. CONCLUSION: We concluded that routine pathological examination of the falciform and round ligaments is not justified if the surgeon elects to remove the structures for ease of exploration and retraction during surgery. This may lighten the workload and reduce costs in a busy pathology laboratory.

Optimizing management of pancreatic cysts--prospective re-assessment for 157 cases.

BACKGROUND/AIMS: Ongoing debate continues regarding the appropriate management of pancreatic cysts (PCs). Disagreement prevails regarding frequency of needed follow-up, if and when to perform any PC needle biopsy and indications for surgical resection. EUS is increasingly used to help determine management of PCs. METHODOLOGY: One hundred and fifty seven consecutive patients with PCs were identified out of 5000 patients who underwent EUS between 1995-2007. In 2008, these patients were then prospectively provided clinical follow-up, and CEA, CA19-9 and CRP. RESULTS: No symptoms could be definitively related to the PCs. Twenty four of 157 patients with suspected malignant cysts, mucinous cysts or IPMN had undergone surgical treatment. Whipple's operation was performed in 14 patients and distal pancreatectomy in 10 patients. Fifty PCs were located in the head of pancreas. In 89 patients prospective blood tests were performed; in 6 of them elevated levels of CA-19-9 were detected, 3 of these also had elevated serum CEA. Twelve patients had increased CRP values. No complication (requiring hospitalization) and no mortality related to EUS had occurred. CONCLUSIONS: Elements identified as important for assessment of PCs included: size, serum and fluid markers, imaging characteristics and clinical follow-up. These factors should be included in the recommended guidelines.

[Quality indicators in colonoscopy].

BACKGROUND: Extensive use of colonoscopy has highlighted the need to assess the quality of the procedures in order to reduce costs and increase efficiency. AIMS: (1) To assess quality indicators of colonoscopies performed by specialist physicians in Rambam HeaLth Care Campus; (2) To improve the quality of colonoscopies using the data collected. METHODS: Data was collected retrospectively from reports of 700 colonoscopies performed by 7 gastroenterology specialists in Rambam Health Care Campus. The data collected was compared to relevant Literature benchmarks for accepted quality indicators. RESULTS: A total of 95.3% of procedures had appropriate indications. Good or excellent bowel preparation was documented for 57.4% of procedures with a range for individual physicians from 18.2%-84%. Completion rate was 92.4% (range 89.9%-97%). Overall polyp detection rate was 29.1% (range 17%-45%). Polyp detection rate in screening colonoscopies was 13.2% for women and 26.1% for men. Biopsies were taken in 90.3% of colonoscopies performed for inflammatory bowel disease (IBD) follow-up and in 75% of colonoscopies performed in patients with chronic diarrhea. Follow-up recommendations were noted in 82.6% of procedures with any indication for follow-up (range 70%-92.5%). CONCLUSIONS: Colonoscopies are performed in Rambam Health Care Campus in an effective manner with regard to completion rate and polyp detection. High rates of intermediate or poor bowel preparation, suboptimal rates of taking biopsies and making follow-up recommendations were noted. Significant variations among participating physicians were noted. Conclusions led to operative changes in practice, including improving computerized reports, standardizing assessments of preparation and initiating a continuous quality improvement program.

Pancreatic cancer in Israel: the epidemiology, possibilities of prevention, early detection and screening.

Pancreatic cancer is not a common malignancy in Israel, but it is the third most common cause of cancer mortality, attributable to a lack of screening tests, inaccessibility of the pancreas, and late cancer stage at diagnosis. We reviewed the epidemiology, known risk factors and screening methods available in Israel and describe the Israeli national consortium that was established to identify persons at risk and decide on screening methods to detect and treat their early-stage pancreatic cancer. In collaboration with the Israel National Cancer Registry, we evaluated the incidence and trends of the disease in the Jewish and non-Jewish populations. The consortium reviewed known lifestyle risk habits, genetic causes, and screening methodologies used and available in Israel. Overall, there are about 600 new patients per year, with the highest incidence occurring in Jewish men of European birth (age-standardized rate 8.11/10(5) for 2003-06). The 5 year survival is about 5%. The consortium concluded that screening will be based on endoscopic ultrasonography. Pancreatic cancer patients and families at risk will be enrolled, demographic and lifestyle data collected and a cancer pedigree generated. Risk factors will be identified and genetic tests performed as required. This concerted national program to identify persons at risk, recommend which environmental risk factors to avoid and treat, and perform endoscopic ultrasound and genetic screening where appropriate, might reduce the incidence of invasive pancreatic cancer and/or improve its prognosis.

EUS clarifies the natural history and ideal management of GISTs.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are mesenchymal gastrointestinal tumors expressing C-kit (CD117). Endoscopic ultrasonography (EUS) evaluations of GISTs can help determine optimal therapy and follow-up care. The current study assesses the natural history of 100 GISTs evaluated by EUS, and the impact of EUS on their management. METHODOLOGY: Retrospective review of 2600 EUS files performed over 11 years identified 100 patients with GISTs. Relevant data from all appropriate files and interviews with patients or family of deceased patients were tabulated regarding the GISTs. RESULTS: Every GIST had definitive cytology (n=43) or histology. Seventy of the 100 patients underwent more than one evaluation. Size of the GISTs at initial diagnosis averaged 20.5 mm and at follow-up examination 23.2 mm. Fourteen of 70 GISTs showed significant enlargement (> 1 mm/month). Enlargement during follow-up of GISTs was significantly more common with GISTs over 17 mm at initial diagnosis (p<0.018). Thirty-four were excised (7 endoscopically). Clinically asymptomatic GISTs tended to be smaller. Thirteen percent of GIST patients had second primary malignancy. CONCLUSIONS: EUS elucidates GIST natural history and can help guide management. GISTs larger than 17 mm should be monitored by EUS and considered for more aggressive treatment. Searching for synchronous tumors in patients with GISTs should be considered.

Overcoming barriers to colorectal cancer screening tests.

BACKGROUND: The frequency of colorectal cancer screening tests in Israel is poor, and is much lower than in the United States. This low rate has been attributed to health system failures as well as to barriers on the part of both physicians and patients. OBJECTIVES: To further identify particular health system failures, physician and patient-based barriers, and the effectiveness of public lectures in improving the frequency of performance of CRC screening tests. METHODS: Public lectures on colorectal cancer prevention were held. A gastroenterologist presented the lectures, which were followed immediately by a questionnaire and 4 months later by a telephone call. RESULTS: Of the 80% of attendees who had never undergone any CRC screening test, only 18% reported family physician recommendations for such tests. Eighty-four percent reported willingness to undergo fecal occult blood testing and 52% to undergo colonoscopy; 62% replied that they should undergo some CRC screening test and 90% believed that these tests save lives. Of the women, 47% expressed preference for a female gastroenterologist. Follow-up showed that 34% proceeded to undergo some CRC screening test: 60% chose colonoscopy and 40% FOBT. CONCLUSIONS: Public lectures are effective in improving compliance with the CRC screening test. Physicians should recommend these tests to appropriate individuals. Same-gender gastroenterologists should be considered for individuals uneasy about someone from the opposite gender performing the test. Assessing the various health-promotion efforts can direct us in implementing finite resources to greatest effect. Local cancer institutes and societies may be supportive in disseminating screening information in this way.