Colorectal cancer with microsatellite instability: Right-sided location and signet ring cell histology are associated with nodal metastases, and extranodal extension influences disease-free survival.

Colorectal cancer (CRC) with microsatellite instability (MSI) accounts for 15-18 % of all CRCs and represents the category with the best prognosis. This study aimed at determining any possible clinical/pathological features associated with a higher risk of nodal metastasization in MSI-CRC, and at defining any possible prognostic moderators in this setting. All surgically resected CRCs of the last 20 years (mono-institutional series) with a PCR-based diagnosis of MSI, with and without nodal metastasis, have been retrieved for histological review, which was performed following WHO guidelines. Furthermore, the most important prognostic moderators have been investigated with a survival analysis. The study of 33 cases of MSI-CRCs with nodal metastasis highlighted a high fidelity of histology maintenance between primary tumors and matched nodal metastases. At survival analysis, the strongest prognostic variable in MSI-CRCs with nodal metastasis was the extranodal extension (multivariate analysis, HR: 14.4, 95 %CI: 1.46-140.9, p = 0.022). Furthermore, through a comparison between nodal positive (33 cases) and nodal negative (71 cases) MSI-CRCs, right-sided location (p < 0.0001), pT4 stage (p = 0.0004) and signet-ring histology (p = 0.0089) emerged as parameters more commonly associated with nodal metastasization. These findings shed new light on the biology of MSI-CRC and can be of help for the prognostic stratification of MSI-CRC patients.

Rapid screening for malignancy in organ donors: 15-year experience with the Verona "Alert" protocol and review of the literature.

BACKGROUND: Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines. METHODS: A two-step ALERT process was used: ALERT1 consisting of clinical, radiological, and laboratory tests; ALERT2, consisting of intraoperative assessment in suspicious lesions. RESULTS: Four hundred of 506 potential deceased donors entered the ALERT system. Forty-one of 400 (10%) donors were excluded due to unacceptable risk of transmission. Of the remaining 359 193 required histopathology, which excluded malignancy or determined acceptable risk in 161/193 (83%). Thirty-five malignancies were identified: 19 (54%) at ALERT1, four (11%) at ALERT2, nine (26%) picked up at ALERT1 and confirmed by ALERT2. Three (9%) were missed by ALERT and diagnosed at postmortem examination. Prostate (n=12%, 34%) and renal cell (n=7%, 20%) were the most frequent carcinomas. The majority (92%) of prostate adenocarcinomas were of low risk and donation proceeded compared to 43% of renal carcinomas. Four renal carcinomas, two breast carcinomas, and a single case of nine different malignancies excluded donation. Positive ALERT donors had statistically more malignant reports than negative ALERT donors (P=<.05). CONCLUSION: Histopathology is an essential component of the multidisciplinary assessment of donors.

De Novo Renal Neoplasia After Kidney Transplantation According to New 2016 WHO Classification of Renal Tumors.

BACKGROUND De novo renal neoplasia developing after kidney transplantation at Verona Kidney Transplant Center were reviewed according to new 2016 WHO Renal Tumor Classification. MATERIAL AND METHODS Primary renal tumors developed in native or transplanted kidneys de novo following renal transplantation were retrieved and histologically reviewed by three expert uropathologists. Immunoexpression of the diagnostic antigens CD13, CD10, CK7, CK34bE12, AMACR, CAIX, AE1/AE3, CK14, GATA-3, HMB-45, cathepsin-k, S100A1, and parvalbumin was assessed. Predictive antigens ph-mTOR and ph-p70S6k were also tested. RESULTS Two thousands and sixteen kidney transplantations have been carried out from 1968-2015. Follow-up was available per 1,646 patients (mean 8.4 years). We observed 16 cases of de novo renal neoplasia arising in patients 16 to 286 months post-transplantation. Nine clear cell, two papillary RCCs and a single case of the new WHO entity denominated "acquired cystic disease-associated RCC" were identified in native kidneys. Another new WHO tumor entity called "clear cell papillary RCC" was diagnosed and a new variant of papillary RCC with diffuse clear cytoplasm was also identified. The majority of tumors were low stage and low grade according to the new ISUP grading system. Seven patients were additionally treated with mTOR inhibitors. Post-cancer follow-up ranged from 62 to 281 months. One patient showed a recurrence (a lung metastases) and died. Of the remaining patients, three died of non-cancer-related causes. CONCLUSIONS The application of the new WHO 2016 classification has importance as it identifies new (18% of tumors) morphotypes that are likely to behave in a less aggressive fashion.

Direct Revascularization with Autotransplant Technique for a True Aneurysm of the Renal Artery 20 Years after Kidney Transplantation.

BACKGROUND: True degenerative aneurysm of renal artery represents a very rare evolution in kidney transplantation. The cases presented in the literature are usually perianastomotic or mycotic pseudoaneurysm related to surgical technical defects or local infections. CASE REPORT: Herewith, we present the case of a voluminous true aneurysm developed in a young patient transplanted at our hospital 20 years before. All follow-up ultrasounds were always normal until the last disclosing a voluminous aneurysm of the transplanted renal artery. The subsequent angio-CT-scan confirmed the presence of a 52-mm saccular dilatation of the renal artery. For the complex anatomy, the endovascular approach was excluded, and a surgical revascularization was staged. We treated this lesion with the autotransplant technique, preserving the transplanted kidney, resecting the aneurysm, and performing a direct anastomosis after cold perfusion of the kidney. CONCLUSIONS: The autotransplant technique demonstrated to be a safe and effective approach in this challenging and very unusual situation.

Donor kidneys with miliary papillary renal cell neoplasia: the role of the pathologist in determining suitability for transplantation.

BACKGROUND: Kidneys with single or multiple tumors, provided that they have histological features recognized as being associated with low risk of recurrence, are considered suitable for transplantation. It is known that kidneys with multiple primary renal tumors show poor renal function and that function dramatically declines when tumors have a miliary configuration. Despite this, no guidelines are in place to differentiate between multifocal tumors and those that are miliary in nature. CASE REPORT: We report a case in which initial examination revealed papillary renal cell neoplasia in deceased donor kidneys, which were later confirmed on histological and genetic testing to be multiple and miliary in distribution. Gross examination showed closely opposed neoplasms, and on histological examination these were found to be papillary renal cell carcinomas and renal papillary adenomas. This ultimately led to the decision that both kidneys were unsuitable for transplantation. CONCLUSIONS: At present there are no recommendations as to how tumor-bearing donor kidneys should be handled in order to determine if miliary neoplasia is present. From our case it is apparent that, in addition to obvious tumor nodules, at least 3 samples of cortex should be examined. This case highlights the important role of the pathologist in assessing donor kidneys with evidence of neoplasia.

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

OBJECTIVE: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. DESIGN: Partially retrospective cohort study. SETTING: Two Italian transplantation centers. PATIENTS: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. MAIN OUTCOME MEASURES: Cumulative incidences and risk factors of the first and subsequent NMSCs. RESULTS: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. CONCLUSIONS: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Transhepatic fibrinolysis of mesenteric and portal vein thrombosis in a patient with ulcerative colitis: a case report.

AIM: To present a case of acute mesenteric and portal vein thrombosis treated with thrombolytic therapy in a patient with ulcerative colitis in acute phase and to review the literature on thrombolytic therapy of mesenteric-portal system. Treatment of acute portal vein thrombosis has ranged from conservative treatment with thrombolysis and anticoagulation therapy to surgical treatment with thrombectomy and/or intestinal resection. METHODS: We treated our patient with intraportal infusion of plasminogen activator and then heparin through a percutaneous transhepatic catheter. RESULTS: Thrombus resolved despite premature interruption of the thrombolytic treatment for neurological complications, which subsequently resolved. CONCLUSION: Conservative management with plasminogen activator, could be considered as a good treatment for patients with acute porto-mesenteric thrombosis.

Using the angio-seal to achieve hemostasis in prosthetic endovascular surgery: report of three cases.

At least 10% of patients who undergo bilateral aortofemoral bypass are at risk of needing a reoperation for late prosthetic thrombosis because of reduced outflow as the disease progresses. To prevent occlusion of the prostheses, we performed endovascular surgery with transprosthetic access for distal stenosis. We report our experience of using the Angio-Seal with transprosthetic access after angioplasty in three patients who had undergone bilateral aortofemoral bypass. Hemostasis was achieved in all three patients. There were no complications, such as hemorrhage, hematoma, or prosthetic infection, and all three patients were discharged within 24 h. At the 12-, 15-, and 24-month follow-up, none of the patients had any sign of recurrent claudication. Using the Angio-Seal in bilateral aortofemoral bypass provided the means of treating distal stenosis by endovascular surgery with transprosthetic access. This method is both rapid and safe, and may broaden the indications for the endovascular treatment of distal arteriopathies in patients with vascular prostheses.