Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.

Quantitative PCR Is Faster, More Objective, and More Reliable Than Immunohistochemistry for the Diagnosis of Cytomegalovirus Gastrointestinal Disease in Allogeneic Stem Cell Transplantation.

Diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease relies on the presence of GI symptoms and detection of CMV, mainly by immunohistochemistry (IHC), in GI biopsy specimens. Thus, in a symptomatic patient, a positive CMV-IHC result is accepted as a diagnosis of CMV disease. However, a positive CMV-PCR in GI tissue is considered "possible" CMV disease. Therefore, it would be very useful if, in practice, both techniques showed equal sensitivity and reliability. This is because PCR has many practical advantages over IHC for detecting CMV. The aim of this study was to compare quantitative PCR with IHC for the diagnosis of GI CMV disease. A total of 186 endoscopic GI biopsy specimens from 123 patients with GI symptoms after an allogeneic stem cell transplantation (allo-SCT; 2004-2017) were analyzed by IHC and PCR on 113 paraffin-embedded and 73 fresh samples. The results were then compared. Of the patients with macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, "proven" CMV disease, n = 28), all but 1 were CMV-PCR positive. Of the patients without macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, probable CMV disease, n = 4), only 1 was CMV-PCR positive. Eight patients had CMV-IHC-negative/CMV-PCR-positive gut biopsy specimens. These cases fall within the current definition of possible CMV disease. In 6 of these 8 cases (75%), the viral load in GI tissue was very high (>10,000 copies/µg). Taken together, the results from the proven and probable cases revealed that CMV-PCR shows the same sensitivity (100%), specificity (98%), and positive (93%) and negative predictive value (100%) as CMV-IHC. Detection of CMV in fresh GI mucosa by quantitative PCR is as useful as IHC for the diagnosis of GI CMV disease. The results show that quantitative PCR has the same sensitivity, specificity, and positive/negative predictive value as IHC.

Lymph node pooling: a feasible and efficient method of lymph node molecular staging in colorectal carcinoma.

BACKGROUND: Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP). RESULTS: Molecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort). A median of 13 LNs (IQR 10-18) per patient were harvested in the individual cohort, and 18 LNs (IQR 13-25) per patient in the pooling cohort (p ≤ 0.001). The median of molecular assays performed in the pooling cohort was 2 per patient (IQR 1-3), saving a median of 16 assays/patient. The number of molecular assays performed in the individual cohort was 13 (IQR 10-18), corresponding to the number of LNs to be analyzed. The sensitivity and specificity of the pooling method for LN involvement (assessed by hematoxylin and eosin) were 88.9% (95% CI 56.5-98.0) and 79.2% (95% CI 68.9-86.8), respectively; concordance, 80.2%; PPV, 33.3%; NPV, 98.4%. The individual method had 100% sensitivity (95% CI 72.2-100), 44.6% specificity (95% CI 34.8-54.7), 50% concordance, 16.4% PPV, and 100% NPV. The amount of tumor burden detected in all LNs of a case, or total tumor load (TTL) was similar in both cohorts (p = 0.228). CONCLUSIONS: LN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.

Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden.

BACKGROUND: Colorectal cancer (CRC) screening programs result in the detection of early-stage asymptomatic carcinomas suitable to be surgically cured. Lymph nodes (LN) from early CRC are usually small and may be difficult to collect. Still, at least 12 LNs should be analyzed from colectomies, to ensure a reliable pN0 stage. Presurgical endoscopic tattooing improves LN procurement. In addition, molecular detection of occult LN tumor burden in histologically pN0 CRC patients is associated with a decreased survival rate. We aimed to study the impact of presurgical endoscopic tattooing on the molecular detection of LN tumor burden in early colon neoplasms. METHODS: A prospective cohort study from a CRC screening-based population was performed at a tertiary academic hospital. LNs from colectomies with and without preoperative endoscopic tattooing were assessed by two methods, hematoxylin and eosin (HE), and RT-LAMP, to detect tumor cytokeratin 19 (CK19) mRNA. We compared the amount of tumor burden and LN yields from tattooed and non-tattooed specimens. RESULTS: HE and RT-LAMP analyses of 936 LNs were performed from 71 colectomies containing early carcinomas and endoscopically unresectable adenomas (8 pT0, 17 pTis, 27 pT1, 19 pT2); 47 out of 71 (66.2 %) were tattooed. Molecular positivity correlated with the presence of tattoo in LN [p < 0.001; OR 3.1 (95 % CI 1.7-5.5)]. A significantly higher number of LNs were obtained in tattooed specimens (median 17 LN vs. 14.5 LN; p = 0.019). CONCLUSIONS: Endoscopic tattooing enables the analysis of those LNs most prone to harbor tumor cells and improves the number of LN harvested.

Budget Impact Analysis of Molecular Lymph Node Staging Versus Conventional Histopathology Staging in Colorectal Carcinoma.

BACKGROUND: The presence of lymph node (LN) metastasis is a critical prognostic factor in colorectal cancer (CRC) patients and is also an indicator for adjuvant chemotherapy. The gold standard (GS) technique for LN diagnosis and staging is based on the analysis of haematoxylin and eosin (H&E)-stained slides, but its sensitivity is low. As a result, patients may not be properly diagnosed and some may have local recurrence or distant metastases after curative-intent surgery. Many of these diagnostic and treatment problems could be avoided if the one-step nucleic acid amplification assay (OSNA) was used rather than the GS technique. OSNA is a fast, automated, standardised, highly sensitive, quantitative technique for detecting LN metastases. OBJECTIVES: The aim of this study was to assess the budget impact of introducing OSNA LN analysis in early-stage CRC patients in the Spanish National Health System (NHS). METHODS: A budget impact analysis comparing two scenarios (GS vs. OSNA) was developed within the Spanish NHS framework over a 3-year time frame (2017-2019). The patient population consisted of newly diagnosed CRC patients undergoing surgical treatment, and the following costs were included: initial surgery, pathological diagnosis, staging, follow-up expenses, systemic treatment and surgery after recurrence. One- and two-way sensitivity analyses were performed. RESULTS: Using OSNA instead of the GS would have saved €1,509,182, €6,854,501 and €10,814,082 during the first, second and third years of the analysis, respectively, because patients incur additional costs in later years, leading to savings of more than €19 million for the NHS over the 3-year time horizon. CONCLUSIONS: Introducing OSNA in CRC LN analysis may represent not only an economic benefit for the NHS but also a clinical benefit for CRC patients since a more accurate staging could be performed, thus avoiding unnecessary treatments.

Outcomes after neoadjuvant treatment with gemcitabine and erlotinib followed by gemcitabine-erlotinib and radiotherapy for resectable pancreatic cancer (GEMCAD 10-03 trial).

BACKGROUND: Neoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients. METHODS: Patients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000 mg/m2/week) plus daily erlotinib (ERL) (100 mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300 mg/m2/week), ERL 100 mg/day and concomitant radiotherapy (45 Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R0 < 40% and useful if the R0 > 70% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440. RESULTS: Twenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p = 0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p = 0.009). CONCLUSION: The results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings.

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.

Virtual microscopy in the undergraduate teaching of pathology.

BACKGROUND: Little evidence is available concerning the impact of virtual microscopy (VM) in the undergraduate teaching of pathology. We aimed: (1) to determine the impact in student scores when moving from conventional microscopy (CM) to VM; (2) to assess the students' impressions and changes in study habits regarding the impact of this tool. METHODS: We evaluated two groups taking the discipline of pathology in the same course, one using CM and the other VM. The same set of slides used in the CM classes was digitized in a VENTANA iScan HT (Roche Diagnostics, Sant Cugat, Spain) at ×20 and observed by the students using the Virtuoso viewer (Roche Diagnostics). We evaluated the skill level reached by the students with an online test. A voluntary survey was undertaken by the VM group to assess the students' impressions regarding the resource. The day and time of any accession to the viewer were registered. RESULTS: There were no differences between the two groups in their marks in the online test (mean marks for the CM and the VM groups: 9.87 ± 0.34 and 9.86 ± 0.53, respectively; P = 0.880). 86.6% of the students found the software friendly, easy-to-use and effective. 71.6% of the students considered navigation easier with VM than with CM. The most appreciated feature of VM was the possibility to access the images anywhere and at any time (93.3%). 57.5% of the accesses were made on holidays and 41.9% later than 6:00 pm. CONCLUSIONS: Virtual microscopy can effectively replace the traditional methods of learning pathology, providing mobility and convenience to medical students.

Clinical and autopsy correlation evaluated in a university hospital in Spain (1991-2000).

The authors present a 10-year retrospective study (1991-2000) of all autopsies performed at the Hospital Clinic, Barcelona (Catalonia, Spain) studied by a multidisciplinary committee. The clinicopathologic correlation of the primary underlying disease with the immediate cause of death was reviewed. Between 1991 and 2000, 2,495 autopsies were performed, 1933 of which were evaluated by the committee. The autopsy rate fell from 20% in 1993 to 9.1% in 2000. The clinicopathologic correlation in underlying primary disease was correct in 92.67% of the cases; there was a major discrepancy in 3.51% and a minor discrepancy in 3.82%. As regards the immediate cause of death, major errors were found in 5.89% of cases and minor errors in 6.17%. Despite the scientific and technologic advances in medicine, we have seen that there are still clinicopathologic discrepancies. The postmortem examination continues to play an important role in auditing clinical practice and diagnostic performance, and also for educational purposes. Evaluation by a multidisciplinary committee is the more reliable system for the study of the clinicopathologic correlation.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation.

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.

[Pseudopapillary solid tumor of the pancreas: report of 6 cases]. / Neoplasia sólida seudopapilar de páncreas. Estudio de 6 casos.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasms (SPNs) are rare tumours of the exocrine pancreas. Although they can develop metastasis, the prognosis is good. The aim of this study was to describe the characteristics of these tumours attended in our hospital. PATIENTS AND METHOD: All cases of SPN in the database of the Pathology Department between 1991 and 2010 were included. Age, sex, symptoms, type of surgery, pathologic and immunohistochemical characteristics, and clinical evolution were analyzed. RESULTS: Six cases were identified; all of them were women with a median age of 27.5 years. One patient presented haemoperitoneum, 2 abdominal pain and 3 were diagnosed incidentally. The most frequent localization was the pancreatic tail (n=4) and the median size was 7.7 cm. Four tumours were benign and 2 carcinomas. One of them had liver and lymph node metastases. Ki-67 proliferation index was low (1-3%). After a median follow-up of 33.5 months, all patients were alive and without evidence of relapse. CONCLUSION: SPNs occur in young women. In most cases surgical resection is curative. A low mitotic index confers a good prognosis and a long survival.

[Malignancy predictive factors in pancreatic intraductal papillary mucinous neoplasm]. / Factores predictivos de malignidad en la neoplasia mucinosa papilar intraductal de páncreas.

BACKGROUND AND OBJECTIVE: Intraductal papillary mucinous neoplasm (IPMN) is a premalignant lesion of the pancreas. Its natural history is not well known. We evaluated the characteristics and predictor factors of malignancy of IPMN. PATIENTS AND METHOD: A retrospective analysis was performed in 88 patients diagnosed with IPMN between January 1997 and December 2008. The diagnosis was done by abdominal computed tomography (CT), pancreatic-magnetic resonance imaging (MRI) and/or endoscopic ultrasound (EUS). Gender, age, symptoms, origin, location, CA 19.9 serum levels, size of tumours and nodules by imaging techniques, type of surgery, malignancy and survival were evaluated. Nine pre-surgical variables were selected, and univariate and multivariate analysis to identify independent prognostic factors of malignancy were performed. RESULTS: The mean age was 64 years and 53% were men. 39% of tumours were incidental. 50% had their origin on the main pancreatic duct, 37% on collateral branchs and 13% were multifocal. 68% patients were operated: 42% had malignant neoplasms (32% carcinoma in situ and 68% invasive). Twelve patients died (1 benign, 1 in situ and 10 invasive). Univariate and multivariate analysis identified the symptoms and the tumour size (≥ 22 mm [median of our serie] and ≥ 30 mm [size accepted in literature]) as independent predictor factors of malignancy. CONCLUSIONS: Many IPMN are incidental findings. The presence of symptoms and size of the tumour are independent prognostic factors of malignancy and they should be considered to decide therapeutic actions.

Teaching in Spanish medical schools.

The study reported here assessed the current situation of the teaching of medicine, the healthcare facilities available and the teaching staff employed at Spanish medical schools, on the basis of a national survey devised by the Conferencia Nacional de Decanos de Facultades de Medicina. There was a 100% response rate from the 27 medical schools. Twenty-three of these schools introduced new study plans between 1993 and 2000. In all cases these plans are basically discipline oriented, with different levels of integration between the subjects offered. The study also analysed teaching in bioethics, healthcare management, experience in primary care and alternative or complementary medicine. In the 2000-01 academic year there were 4471 first-year students; as for the healthcare facilities available, there were 67,331 hospital beds in 112 hospitals and 234 Primary Care Centres. There was an average of 4.49 teaching beds per student. There were 3081 full and associate professors, roughly half of whom were teaching in the preclinical cycle and roughly half in the clinical cycle, and 4492 clinical assistant professors. The average student-professor ratio at Spanish medical schools is currently 3.02: 1.0, with variations of between 6.22 and 1.04.

Defining the learning outcomes of graduates from the medical school at the University of Barcelona (Catalonia, Spain).

It is generally accepted that medical schools must clearly define learning outcomes for their students. During the process of curriculum change initiated in 1990, Spanish medical schools introduced a range of general objectives but no specific outcomes were defined. In 2001, in an effort to improve its curriculum, the Medical School at the University of Barcelona decided to define the specific learning outcomes for its graduates. The process was carried out by a teachers' group, comprising individuals from different branches of medicine, drawing largely on the Outcome-based Education in Medicine model introduced by the Scottish Deans' Medical Curriculum Group (2000). Other different stakeholders were asked to give any suggestions for modifications in order to prepare a definitive document to be approved by the medical school. The whole process took two years to complete. The authors discuss the advantages of such a process for students, teachers and the institution.