Modest agreement between magnetic resonance and pathological tumor regression after neoadjuvant therapy for rectal cancer in the real world.

Magnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high-volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0-3 vs pTRG 4; mrTRG 2-5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73-0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that "T3 greater than 5 mm extent" was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15-0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI.

Acetone compression improves lymph node yield and metastasis detection in colorectal cancer.

Lymph node status is one of the most important prognostic factors in colorectal cancer, and accurate pathological nodal staging and detection of lymph node metastases is crucial for determination of post-operative management. Current guidelines, including the TNM staging system and European Society for Medical Oncology (ESMO) guidelines, recommend examination of at least 12 lymph nodes. However, identification of an adequate number of lymph nodes can be challenging, especially in the setting of neoadjuvant treatment, which may reduce nodal size. In this study, we investigated 384 colorectal cancer resections that were processed at our department of pathology between January 2012 and December 2022, in which the number of detected lymph nodes was less than 12 subsequent to conventional preparation of mesocolic fat tissue. By means of acetone compression, lymph node harvest increased significantly (p < 0.0001), and the intended number of ≥ 12 lymph nodes was achieved in 98% of resection specimens. The number of nodal positive cases increased significantly from n = 95 (24.7%) before versus n = 131 (34.1%) after acetone compression due to additionally identified lymph node metastases (p < 0.001). In 36 patients (9.4%) initially considered as nodal negative, acetone compression led to a staging adjustment to a nodal positive category and thereby drove a recommendation to offer post-operative therapy. In conclusion, acetone compression is a reliable and useful method implementable in routine surgical pathology for the retrieval of lymph nodes in colorectal cancer specimen, allowing for an adequate lymph node sampling and an increase in nodal staging reliability.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO guidelines.

The impact of bariatric and metabolic surgery on cancer development.

Obesity (BMI ≥ 30 kg/m2) with related comorbidities such as type 2 diabetes mellitus, cardiovascular disease, sleep apnea syndrome, and fatty liver disease is one of the most common preventable risk factors for cancer development worldwide. They are responsible for at least 40% of all newly diagnosed cancers, including colon, ovarian, uterine, breast, pancreatic, and esophageal cancer. Although various efforts are being made to reduce the incidence of obesity, its prevalence continues to spread in the Western world. Weight loss therapies such as lifestyle change, diets, drug therapies (GLP-1-receptor agonists) as well as bariatric and metabolic surgery are associated with an overall risk reduction of cancer. Therefore, these strategies should always be essential in therapeutical concepts in obese patients. This review discusses pre- and post-interventional aspects of bariatric and metabolic surgery and its potential benefit on cancer development in obese patients.

Necrosis and angioinvasion predict adverse outcome in pancreatic neuroendocrine tumors after curative surgical resection: results of a single-center series.

BACKGROUND: The prediction of outcome in pancreatic neuroendocrine tumors (P-NETs) still represents a challenge. Several clinicopathologic parameters have been proposed to predict adverse outcome. The aim of this study was to evaluate the impact of tumor necrosis and angioinvasion on the outcome after curative R0 resection of P-NETs. METHODS: We reviewed our institutional experience over the last 30 years. A total of 82 patients with a mean age of 54 years (range 17-83 years) underwent surgical resection of P-NETs during the period from 1964 to 2006. There were 41 men and 41 women. The patients' outcomes after R0 surgical treatment were analyzed in relation to the presence or absence of tumor cell necrosis and angioinvasion as judged by histologic methods. RESULTS: The overall (n = 82) 5-year survival was 52.4% (± 6.0%). Forty-eight of the patients underwent a R0 resection successfully. These patients showed a 5-year survival of 59.04% (± 7.8%); the median survival was 101 ± 36 months. Necrosis status was documented on 47 of the R0 resected patients (97.9%). The survival median of patients with tumor cell necrosis was significantly shorter than those without necrosis (41 ± 25 vs. 173 ± 69 months, respectively, P = 0.006). The patients' mean 5-year survival was also significantly decreased (28.9 ± 15.0% vs. 68.5.6 ± 8.9%). Angioinvasion status was documented on 43 of the R0 resected patients (90.0%). The median survival of these patients was decreased from 173 ± 51 to 54 ± 18 months when angioinvasion was observed in the histological sections (P = 0.104). The patients' mean 5-year survival was also decreased from 69.2 ± 9.3% to 35.9 ± 14.0%. CONCLUSIONS: Long-term survival of patients with P-NETs is influenced by various pathologic factors. Among our patients, there was not a significant difference in overall survival based on the diameter of the primary tumor or the lymph node status after R0 surgical resection. The presence of necrosis in the TNM and World Health Organization classification for pancreatic endocrine tumor was associated with significant poor overall survival in each classification category. Hence, necrosis represents an independent variable for poor prognosis.

Potential benefit in information providing and influence on patient anxiety and satisfaction by means of preoperative explanatory videos in total extraperitoneal inguinal hernioplasty: study protocol of a multicentre, double-blinded, randomised parallel-group controlled trial.

INTRODUCTION: The use of electronic media in informed consent giving has become increasingly important in recent years. Due to the easy access to information via electronical media, patients are primed in a heterogeneous manner concerning expectations and wishes regarding surgical interventions. Inherent to its nature elective interventions are critically questioned as there is time for information gathering and reflection. In this study, we set out to investigate the effect of an educational video as a supporting element in the process of informed consent giving for one the most frequently performed interventions in general surgery, namely inguinal hernia repair. METHODS AND ANALYSIS: In a multicentre setup, eligible patients for primary inguinal hernia repair will be randomly assigned to one of three groups. All three groups will have a preoperative informed consent discussion with a physician in which they will eventually sign the informed consent sheet if participation is desired. Eventually, all three groups will get an online link. For two groups, the link will lead to a video with audiovisual information (an inguinal hernia video for the intervention group and a mock video for the control group). The intervention video provides basic principles of endoscopic extraperitoneal hernia repair. The second video is similar in length and design and displays general aspects of day surgery in the two study centres. All the three study groups will be provided with a copy of the informed consent form as it is standard by now. The third group's link will lead to the digital version of the informed consent brochure. Primary outcomes will consist of (1) score in a multiple choice test assessing gain of knowledge regarding hernia repair, (2) difference in the State-Trait Anxiety Inventory and (3) patient satisfaction questionnaire Individual Clinician Feedback (ICF, Picker Institute, Germany) as assessed 1-2 days after the first consultation. The study design guarantees double blinding, there will be no unblinding at any point. All patients will receive the same, quality and number of medical consultations as well as in the same surgical treatment. (Minor differences in the total extraperitoneal technique of the surgical treatment due to anatomical or pathophysiological differences are independent of the group allocation). Except for the additional videos, there will be no difference in in the information provided and the treatment prior, during or after the hernia repair. ETHICS AND DISSEMINATION: We plan to publish the study in a peer-reviewed journal. The proposed research project has been reviewed by the Cantonal Ethics Committee (BASEC-No 2020-01548). In accordance with national legal regulations in Switzerland stated by the Human Research Act, the proposed project was declared exempt from approval requirement. TRIAL REGISTRATION NUMBER: NCT04494087; Pre-results.

ECCO Topical Review Optimising Reporting in Surgery, Endoscopy, and Histopathology.

BACKGROUND AND AIMS: Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach. The quality of medical reporting is crucial in this context. The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. METHODS: A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohn's and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥ 80% of participants agreed on a recommendation. RESULTS: Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. CONCLUSIONS: Interdisciplinary high-quality care requires thorough and standardised reporting across specialties. This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.

Organizing a COVID-19 triage unit: a Swiss perspective.

Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p < 0.001). Conclusion: Our triage unit was set-up as part of a large-scale restructuring process. Current challenges include low sensitivity for test results as well as limited staff and resources. We hope that our experience will help other health care institutions develop similar triage systems.

Novel germline mutations of the MEN1 gene in Greek families with multiple endocrine neoplasia type 1.

INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder associated with mutations of the MEN1 gene and characterized by the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells and the anterior pituitary. AIM: To identify MEN1 gene mutations and characterize clinical manifestations in Greek patients with MEN1. PATIENTS AND METHODS: We studied four unrelated index patients with MEN1, 17 relatives and 100 control subjects. Among the relatives, seven were clinically and/or biochemically affected, while 10 were unaffected. DNA extraction, polymerase chain reaction (PCR) and direct sequencing of the MEN1 exons 2-10 and exon/intron boundaries were performed according to standard procedures. RESULTS: We identified novel MEN1 gene mutations in three out of four index patients (75%) and in all affected (100%) relatives. Novel mutations included: a frameshift mutation in exon 4 (c.684_685insG) at codon 229 (index patient A); a frameshift mutation in exon 8 (c.1160_1170dupAGGAGCGGCCG) involving codons 387-390 (index patient B); and a missense mutation in exon 4 (c.776T > C), which substitutes leucine with proline at codon 259 (L259P) (index patient C). In the fourth index patient, a common polymorphism (D418D) was detected. CONCLUSIONS: This is the first report to reveal a high prevalence of novel MEN1 gene mutations among Greek MEN1 patients with apparent absence of genotype-phenotype correlation. Because of the small number of patients examined, the high prevalence detected might be a chance phenomenon.

Immunohistochemical expression of bcl-2 in Dukes' stage B and C colorectal carcinoma patients: correlation with p53 and ki-67 in evaluating prognostic significance.

The objective of this study was to evaluate the expression of bcl-2 in Dukes' stage B and stage C (AJCC/UICC stage I and III) colorectal adenocarcinomas and to examine its association with clinicopathological features, p53, ki-67 and long term outcome. Paraffin embedded specimens from 61 patients with Dukes' stage B (AJCC/UICC stage I) and 39 patients with Dukes' stage C (AJCC/UICC stage III) colorectal adenocarcinoma who were treated with surgery were assessed. We used immunohistochemistry to determine the expression of bcl-2, p53 and ki-67 with a five-year follow-up. Positive bcl-2 expression was seen in 27 cases (27%). Expression of bcl-2 protein was related to tumor stage (p=0.0117). There was very strong evidence of an association between bcl-2 staining and ki-67 score (p<0.001). There was a trend towards increased survival in patients whose tumors expressed bcl-2 protein (p=0.001). When entered into a multivariate analysis model, which also included p53 and stage, bcl-2 staining emerged as a prognostic indicator variable. Expression of bcl-2 appears to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Definition of the "Drug-Angiogenic-Activity-Index" that allows the quantification of the positive and negative angiogenic active drugs: a study based on the chorioallantoic membrane model.

Since the introduction of the angiogenic therapy by Folkman et al. in the 1970'ies many antiangiogenic drugs were identified. Only few of them are still now in clinical use. Also the Vascular Endothelial Growth Factor (VEGF), the cytokine with the highest angiogenic activity, has been identified. Its antagonist, Bevacizumab, is produced and admitted for the angiogenic therapy in first line for metastatic colorectal cancer. When we look at preclinical studies, they fail of in vivo models that define the "Drug-Angiogenic-Activity-Index" of angiogenic or antiangiogenic drugs. This work proposes a possible standardized procedure to define the "Drug Angiogenic Activity Index" by counting the vascular intersections (VIS) on the Chorioallantoic Membrane after drug application. The equation was defined as follows: {ΔVIS[Drug]-ΔVIS[Control]} / Δ VIS[Control]. For VEGF a Drug-Angiogenic-Activity-Index of 0.92 was found and for Bevacizumab a -1. This means almost that double of the naturally angiogenic activity was achieved by VEGF on the Chorioallantoic membrane. A complete blocking of naturally angiogenic activity was observed after Bevacizumabs application. Establishing the "Drug-Angiogenic-Activity-Index" in the preclinical phase will give us an impact of effectiveness for the new constructed antiangiogenic drugs like the impact of effectiveness in the cortisone family.

Large adrenal oncocytoma with uncertain malignant potential: case report and review of literature.

OBJECTIVE: To report a case of oncocytoma, a relatively rare adrenal tumor, which most commonly is detected as an adrenal incidentaloma. METHODS: We present a case report, including laboratory, imaging, and pathologic findings, of a 47-year-old obese woman who had hypertension and an incidentally found large, left adrenal mass. RESULTS: On the basis of the hormonal evaluation, this mass was a nonsecreting adrenal tumor, which histologically proved to be an oncocytoma with borderline malignant characteristics. A collective analysis of the few cases of adrenal oncocytoma published in the medical literature showed that our case corresponded to the previously published cases in preponderant location (left side) as well as the general size (11.4 cm in the largest dimension) and weight (372 g). CONCLUSION: Adrenal oncocytoma should be included in the differential diagnosis of adrenal incidentalomas, especially if large tumors are detected. In addition, a longterm follow-up is suggested because there are no certain clues about the true potential of this tumor.

Metastatic melanoma of the gallbladder: an unusual clinical presentation of acute cholecystitis.

Metastatic disease from cutaneous melanoma can affect all organs of the body, and varies in its biological behavior and clinical presentation. We present the case of a 58-year-old man who arrived at our clinic with acute abdominal pain, which, after investigation, was diagnosed as acute cholecystitis. The patient underwent laparotomy and cholecystectomy. Two years ago, he underwent surgical removal of a primary cutaneous melanoma on his right upper back. Pathological examination revealed the presence of malignant melanoma with a metastatic lesion of the gallbladder.

A new approach to accurate diagnosis of acute appendicitis.

This study aimed (1) to develop a simple scoring system incorporating ultrasound (US) examination and clinical or laboratory predictors for increasing diagnostic accuracy in acute appendicitis (AA), and (2) to evaluate the performance of the scoring system as compared to that of previous models. Fifteen variables including US assessment for patients admitted with suspected AA were considered in multivariate analysis using the finding of AA at operation as the end point (internal study). The new score, together with 11 previous ones, was applied to a prospective independent population of subjects with suspected AA, and the respective performances were compared (external validation study). Among 303 patients (170 males, mean age 28.3 +/- 13.3 years) of the internal study, 161 went on to surgery, and 130 had AA at operation. Four independent correlates of AA were identified and used for the derivation of the following integer-based scoring system: number of points = 6 for US demonstrating AA + 4 for tenderness in the right lower quadrant + 3 for rebound tenderness + 2 for leukocyte count >12,000/microl. In the external study (201 subjects, 105 males, mean age 28.7 +/- 11.9 years, 109 operated, 87 with AA), when the cut-off of >/or = 8 points for AA was used, sensitivity, specificity, accuracy, and area under the curve of the proposed score were 95.4%, 97.4%, 96.5%, and 93%, respectively, exceeding noticeably the previous models. The proposed scoring system introduces a quantitative combination of the clinical evaluation with US imaging and a marker of inflammatory response, which may enhance the diagnostic accuracy for subjects with suspected AA especially in geographical areas where CT scanning is not readily available on a 24-hour basis.

Prognostic impact of DNA ploidy pattern, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma.

BACKGROUND: DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. METHODS: In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. RESULTS: Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. CONCLUSIONS: These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas.