Indocyanine Green Angiography for Quality Assessment of Renal Graft Before Transplantation: A Pilot Study.

OBJECTIVES: Criteria for donation have been expanded to meet the great demand for organ transplant, resulting in different tools and classifications to help physicians to better assess the quality of the transplanted kidney. In this study, we evaluated the use of indocyanine green angiography as an additional tool to evaluate the renal microcirculation and the quality of the potential kidney graft. MATERIALS AND METHODS: All kidneys from extended criteria donors or donors after cardiac death available for transplant underwent indocyanine green angiog-raphy before implantation and after reconditioning, when hypothermic perfusion was required. We performed fluorescent angiography with a 10-mm-view laparoscope connected to a high-definition camera system while a solution of indocyanine green and Celsior was injected into the renal artery. We compared fluorescence intensities with postoperative graft function and then analyzed increases in fluorescence intensity before and after hypothermic machine perfusion treatment. RESULTS: In transplanted kidneys preserved in traditional cold storage, we found a statistically significant difference in fluorescence intensity values between groups with early graft function and delayed graft function. Fluorescence intensity increased significantly in all perfused kidneys after hypothermic machine perfusion treatment, indicating that intensity was directly proportional to improved renal microcirculation. Among 21 kidneys retrieved for transplant that adhered to the inclusion criteria, 11 were examined histopathologically, with a Karpinski score ranging from 2 to 7. The kidney that scored 7 was immediately discarded. Five underwent hypothermic pulsatile perfusion since they came from donors after cardiac death. Fluorescence intensity increased significantly in all perfused kidneys (4/5 were closest to doubling). Histopathological evaluations and Karpinski scores of the grafts indicated that all 5 were considered suitable for transplant. CONCLUSIONS: Indocyanine green angiography can be used in the future as an additional useful tool to help physicians to assess graft quality before implantation.

Dental Prosthesis in Esophagus: A Right Cervicotomic Approach.

Foreign body ingestion in the upper digestive tract is a relatively common emergency. Less than 1% have to be treated surgically. We report the case of a 68-year-old man who ingested a dental prosthesis, probably during a seizure, and thus unknowingly, and presented two days later to the emergency department complaining of a mild dysphagia. A chest radiograph showed the presence of a removable dental prosthesis in the upper esophageal tract. The patient was brought to the operating room where a multidisciplinary equipe was assembled. Two attempts of retrieval with a flexible and a rigid endoscope failed because the removable dental prosthesis was stuck in the right pyriform sinus. Therefore, the surgeon performed an uncommon right cervicotomy and retrieved the foreign body through a right-side esophagotomy. The surgical approach depends on the nature and location of the foreign body. Urgent treatment is required whenever the patient develops dyspnea or dysphagia because of the high risk of inhalation and asphyxia. Removal of any esophageal foreign body has to be performed within 12-24 h. Repeated attempts to retrieve large dental prosthesis using an endoscope may result in esophageal perforation therefore when such risk of complication is too high, a surgical approach becomes inevitable. In our opinion, surgery remains the extrema ratio after a failed endoscopic retrieval attempt but can be lifesaving despite high risk of complications.

Liver Trauma: Until When We Have to Delay Surgery? A Review.

Liver involvement after abdominal blunt trauma must be expected, and in up to 30% of cases, spleen, kidney, and pancreas injuries may coexist. Whenever hemodynamics conditions do not contraindicate the overcoming of the ancient dogma according to which exploratory laparotomy should be performed after every major abdominal trauma, a CT scan has to clarify the liver lesions so as to determine the optimal management strategy. Except for complete vascular avulsion, no liver trauma grade precludes nonoperative management. Every attempt to treat the injured liver by avoiding a strong surgical approach may be considered. Each time, a nonoperative management (NOM) consisting of a basic "wait and see" attitude combined with systemic support and blood replacement are inadequate. Embolization should be considered to stop the bleeding. Percutaneous drainage of collections, endoscopic retrograde cholangiopancreatography (ERCP) with papilla sphincterotomy or stent placement and percutaneous transhepatic biliary drainage (PTBD) may avoid, or at least delay, surgical reconstruction or resection until systemic and hepatic inflammatory remodeling are resolved. The pathophysiological principle sustaining these leanings is based on the opportunity to limit the further release of cell debris fragments acting as damage-associated molecular patterns (DAMPs) and the following stress response associated with the consequent immune suppression after trauma. The main goal will be a faster recovery combined with limited cell death of the liver through the ischemic events that may directly follow the trauma, exacerbated by hemostatic procedures and surgery, in order to reduce the gross distortion of a regenerated liver.

Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study.

BACKGROUND: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the "bystander effect" and "trained immunity." The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. OBJECTIVE: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. METHODS: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients' vaccination history; and (3) a clinical analysis to detect the immunological profile. RESULTS: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022. CONCLUSIONS: We will recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factor serum levels, and immune cell activity. Anamnestic data, such as preceding vaccinations and comorbidities, biochemical findings like lymphocyte immunophenotyping, and pre-existing persistent cytomegalovirus infection, allow depicting the risk profile of severe COVID-19. Proof of the roles of these immunological phenomena in the development of COVID-19 can be the basis for the implementation of therapeutic immunomodulatory treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04375176; https://clinicaltrials.gov/ct2/show/NCT04375176. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29892.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients.

BACKGROUND: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2. METHODS: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively. FINDINGS: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva. INTERPRETATION: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

Predictive Models for the Functional Recovery of Transplanted Kidney.

BACKGROUND: Renal transplantation is the gold standard treatment for end-stage renal disease, however, in 20% of cases, the graft develops a delayed graft function (DGF) that is associated with both early and late worsening of the outcome. The aim of this study was to examine and validate in a population of transplanted patients the appropriateness of the predictive score systems of DGF available to identify patients who might take advantage of a tailored immunosuppressive therapy. MATERIALS AND METHODS: We conducted a systematic review of the literature to identify articles concerning scoring systems predicting DGF to identify those applicable to the study population and subsequently comparing their appropriateness for defining the most accurate one. RESULTS: From an analysis of the scientific literature, we found 7 scoring systems predicting DGF. Of these, 3 can be calculated for the study population. We enrolled 247 renal transplants in the study. DGF was recorded in 41 cases (15.95%). The Irish score recognized 25 of 41 cases (60.98%), the Jeldres score 41 of 41 cases (100%), and the Chapal score only 7 of 41 (17.07%). Although the Irish score did not identify all cases of DGF, the analysis of data revealed that it is the most accurate, with area under the receiver operating characteristic almost overlapping. CONCLUSIONS: The study resulted in some interesting and promising conclusions about the predictability of DGF, defining the Irish score as the most reliable. This result can be considered the fundamental requirement to develop a custom therapeutic algorithm to be applied to all recipients with higher probability of developing DGF.

Indocyanine Green Angiography for Quality Assessment of the Kidney During Transplantation: An Outcome Predictor Prospective Study.

BACKGROUND: Microvascular damage is the main cause of delayed graft function (DGF) after kidney transplant. Assessing its extent may be helpful in predicting DGF to achieve better postoperative management, especially in terms of an immunosuppressive regimen. Our aim was to explore the capability of intraoperative indocyanine green (ICG) angiography to examine the microvasculature of the kidney. METHODS: We conducted a prospective cohort study on 37 kidney transplant recipients in a high-volume kidney transplant center. During surgery, after graft implant, an ICG angiography was performed through a high-definition Storz camera system (Karl Storz GmbH, Tuttlingen, Germany) with successive quantitative assessment of fluorescence using Icy bioimage analysis. RESULTS: All transplanted kidneys that showed immediate recovery of their function had a fluorescent intensity ≥49.953 with a mean of 96.930 ± 21. The fluorescence intensity for kidneys that showed a delayed recovery of their function never exceeded 55.648, and the mean was 37.718 ± 13. The difference between the 2 groups was statistically significant with a P value < .001. The only kidney that never recovered showed a fluorescence intensity consistently <25.220, the lowest detected. CONCLUSIONS: This study demonstrates that intraoperative ICG angiography may be used to assess the microvasculature of the graft. A statistically significant difference in terms of fluorescent intensity can be highlighted between kidneys that immediately recover their function and those with delayed recovery. Further larger studies are needed to confirm the capability of the technique to predict DGF to optimize the transplanted patients' management.

Plasmablastic lymphoma presenting as a brachial artery aneurysm associated with haemodialysis arteriovenous access ligation in a renal transplant patient.

INTRODUCTION: Plasmablastic lymphoma is a rare and aggressive neoplasm, generally associated with immunodeficiencies and related to latent Epstein-Barr virus infection. This case is the first reported case of plasmablastic lymphoma relapse in aneurysmatic brachial artery wall. CASE DESCRIPTION: We describe the case of male patient who underwent cadaveric donor kidney transplant when he was 61 years old and radio-cephalic distal arteriovenous fistula ligation 8 months later. After 8 years, he developed gingival plasmablastic lymphoma treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone regimen with subsequent remission. During follow-up, a mid-forearm vascular access was created because of the worsening of renal function. Twenty-two months later, the patient showed a symptomatic 20 mm brachial artery aneurysm with radiological signs of imminent rupture, for which he was surgically treated. The histological evaluation of the brachial artery specimen revealed a relapse of plasmablastic lymphoma in the arterial wall and in an adjacent lymph node. CONCLUSION: Brachial artery aneurysms are a rare complication in kidney transplant recipients after ligation of arteriovenous access for haemodialysis. Here, we report a case in which this condition is associated with an even rarer plasmablastic lymphoma. A common aetiology, due to immunosuppressive therapy, is postulated for the two coexisting diseases.

Retrograde Intrarenal Surgery Through an Incision of the Ureter as a Good Treatment Option for Large Ureteropelvic Impacted Stones in Transplanted Kidneys.

Urolithiasis is a rare complication after kidney transplant. Over the years, treatment of kidney stones has evolved radically, but a standard approach for transplanted kidneys has not yet been defined. Here, we present a 69-year-old male patient who received successful treatment of nephrolithiasis of the transplanted kidney. The patient, who had received a kidney from a deceased donor, was admitted to our department following a posttransplant Doppler ultrasonography showing severe hydronephrosis of the transplanted kidney associated with acute renal function decay. Computed tomography scan confirmed the hydronephrosis of the transplanted kidney, showing a large, impacted, ureteropelvic 3-cm-diameter stone and other concretions around the ureteral stent. The patient was then treated with retrograde intrarenal surgery during an open ureterotomy. His postoperative course was uneventful, and he showed good functional reprise and a rapid decrease of serum creatinine levels. Intraoperative retrograde intrarenal surgery could be a valid option for treatment of kidney stones of the transplanted kidney during open surgery of the ureter or during ureterovesical anastomosis.

Feasibility of en bloc thulium laser enucleation of the prostate in a large case series. Are results enhanced by experience?

OBJECTIVE: To provide the first large single-operator case series of patients who undergo "en bloc" thulium laser enucleation of the prostate (ThuLEP) and to demonstrate an improvement in enucleation efficacy with experience. METHODS: We prospectively evaluated a cohort of patients with symptomatic benign prostatic hyperplasia (BPH) who underwent "en bloc" ThuLEP between May 2015 and November 2017. Association between dependent variables (delivered energy and operating time) and independent variables (adenoma volume and experience) were estimated with regression analysis. The experience was calculated as the time interval between the date of the first operation of the series and the date of the operation being considered. RESULTS: A total of 100 patients were registered for the study. Median operative time was 56.5 min (interquartile range [IQR]: 40-85 min). Median enucleation time was 17.4 min (IQR: 15-21.5 min). Median enucleation index (enucleation time per adenoma gram) was 0.3 min/g (0.2-0.3 min/g). The overall operative time is not influenced by experience, but we registered a significant trend towards a reduction in the total amount of energy delivered energy normalized per adenoma gram (p = 0.0148). CONCLUSION: We believe that further attention is needed for these new "en bloc" prostatic enucleation techniques, which can facilitate some surgical steps, leading to a widespread use of laser technology for BPH surgical treatment.

Pretransplant Nephrectomy for Large Polycystic Kidneys in ADPKD (Autosomal Dominant Polycystic Kidney Disease) Patients: Is Peritoneal Dialysis Recovery Possible after Surgery?

The choice of modality for renal replacement therapy in patients with ADPKD varies, often based on patient choice, physician-related factors, and resource availability. For a long time peritoneal dialysis (PD) was considered as relative contraindication due to the possible limited intraperitoneal space. In recent years, some studies suggested it is a valid option also in patients with ADPKD to be considered as a first line treatment in potentially fit patients. Diuresis volume lowering and potential permanent damage of peritoneal integrity, both leading to a necessary switch to haemodialysis, are the two most important dangers after nephrectomy, especially if bilateral, in PD patients. We performed a retrospective analysis of patient underwent native polycystic kidney nephrectomy in order to state the possibility to recover peritoneal dialysis after surgery.

Right-Sided versus Left-Sided Colectomies for Cancer: Surgical Outcomes and Novel Considerations.

INTRODUCTION: The aim of this study is to compare short-term outcomes of right versus left colectomies performed as a form of cancer treatment. MATERIALS AND METHODS: This study includes 305 consecutive patients with adenocarcinoma treated by laparoscopic or open colectomy. Right colectomy has been compared with left colectomy. The study endpoints were the first flatus day, the first evacuation day, the first day of postoperative solid oral diet intake, and the postoperative hospital stay length. RESULTS: There were 140 (45.9%) right colectomies and 165 (54.1%) left colectomies performed. The cut-off values for the considered (median) endpoints were three, five, four, and eight days, respectively. The first day of postoperative solid oral diet intake and the length of postoperative hospital stay are significantly associated with the type of resection. CONCLUSIONS: The colon cancer patients treated by right-sided colectomy assumed a solid oral diet and presented a longer postoperative hospital stay compared with the patients treated by left-sided colectomy.

Multimodal treatment of gastric cancer.

Gastric cancer is the second leading cause of death from malignant disease worldwide. Although complete surgical resection remains the only curative modality for early stage gastric cancer, surgery alone only provides long-term survival in 20% of patients with advanced-stage disease. To improve current results, it is necessary to consider multimodality treatment, including chemotherapy, radiotherapy and surgery. Recent clinical trials have shown survival benefit of combining different neoadjuvant or adjuvant protocols compared with surgery with curative intent. Furthermore, the implementation of chemotherapy with novel targeted agents could play an important role in the multimodal management of advanced gastric cancer. In this paper, we focus on a multidisciplinary approach in the treatment of gastric cancer and discuss future strategies to improve the outcome for these patients.

Impact of lymph node ratio on survival of colorectal cancer patients.

BACKGROUND AND PURPOSE: This study analyzed the prognostic significance of the staging system based on the metastatic Node Ratio (NR) compared with the TNM staging system in patients with colorectal cancer. METHODS: We reviewed the data of 444 patients who underwent colorectal resection for cancer between January 2005 and December 2011. NR categories NR0 (0%), NR1 (1-19%) and NR2 (≥ 20%) were determined by the best cut-off approach at log-rank test. To compare the prognostic power of the NR versus pN, we plotted these different factors against the mortality estimates. Additionally, we evaluated the relationship between these variables and the extent of lymphadenectomy. RESULTS: Both the NR and the pN classification significantly stratified patient outcomes (p < 0.0001), but the NR system seems to better discriminate prognostic subgroups than the pN. Furthermore, NR is less dependent on the extent of lymphadenectomy than pN. CONCLUSIONS: NR is a simple and reliable tool to stratify survival of colorectal cancer patients and it seems to have a higher prognostic power than the current pN system, because it is less dependent on the extent of lymphadenectomy.