When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.

BACKGROUND: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. METHODS: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. RESULTS: A total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006). CONCLUSIONS: Neoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Outcomes of graciloplasty in the treatment of fecal incontinence: a systematic review and meta-analysis of the literature.

BACKGROUND: Patients with refractory fecal incontinence symptoms can be treated with several surgical procedures including graciloplasty. Reported outcomes and morbidity rates of this procedure are highly variable. The aim of this study was to assess continence rate and safety of dynamic and adynamic graciloplasty. METHODS: PubMed and Google Scholar databases were systematically searched from inception until January 2022 according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Reviews, animal studies, studies with patients < 18 years or < 10 patients, with no success rate reported or non-English text, were excluded. Main outcome measures were overall continence and morbidity rates of each technique. RESULTS: Fourteen studies were identified, incorporating a total of 450 patients (337 females), published between 1980 and 2021. Most common etiology of incontinence (35.5%-n = 160) was obstetric trauma followed by anorectal trauma (20%-n = 90). The weighted mean rate of continence after dynamic graciloplasty was 69.1% (95% CI 0.53-0.84%, I2 = 90%) compared to 71% (95% CI 0.54-0.87, I2 = 82.5%) after adynamic. Although the weighted mean short-term complication rate was lower in the dynamic group (26% versus 40%), when focusing on complications requiring intervention under general anesthesia, there was a much higher incidence (43.4% versus 10.5%) in the dynamic group. The weighted mean rate of long-term complications was 59.4% (95% CI 0.13-1.04%, I2 = 97.7%) in the dynamic group, almost twice higher than in the adynamic group [30% (95% CI - 0.03 to 0.63), I2 = 95.8%]. Median follow-up ranged from 1 to 13 years. CONCLUSIONS: Our data suggest that graciloplasty may be considered for incontinent patients. Dynamic graciloplasty may harbor higher risk for reoperation and complications compared to adynamic. The fact that the functional results between adynamic and dynamic graciloplasty are equivalent and the morbidity rate of adynamic graciloplasty is significantly lower reinforce the graciloplasty as an option to treat appropriately selected patients with fecal incontinence.

Biological therapy prior to repeat ileocolic resection in Crohn's disease can reduce the postoperative complication rate.

BACKGROUND: The aim of this study was to assess the effect of preoperative biologic therapy on the surgical outcome of Crohn's disease (CD) patients undergoing repeat ileocolic resection. METHODS: This was a retrospective analysis of all CD patients who underwent repeat ileocolic resection at Cleveland Clinic Florida between January 2011 and April 2021. Patients were divided into two groups: treatment biologic therapy prior to surgery and controls. RESULTS: Sixty-five patients (31males, median age 54 [range 23-82] years) were included in the study. Twenty nine (44.6%) were treated with biologic therapy prior to repeat ileocolic resection. No demographic differences were found between the biologic therapy and control groups. In addition, no differences were found in mean time from index ileocolic resection (p = 0.9), indication for surgery (p = 0.11), and preoperative albumin (p = 0.69). The majority of patients (57; 87.7%) were operated on laparoscopically, and mean overall operation time was 225 (SD 49.27) min. Overall, the postoperative complication rate was 43.1% (28 patients) and median length of stay was 5 (range 2-21) days. Postoperative complications were more common in the control group, compared to the biologic therapy group (55.6 vs 27.5%; p = 0.04). Conversion rate (35.7 vs 20.7%; p = 0.24), operation time (223 vs 219 min; p = 0.75), length of stay (5.2 vs 5.9 days; p = 0.4), and readmission (16.6 vs 11.1%; p = 0.72) were similar between the two groups. Multivariate analysis of risk factors for postoperative complications showed that biologic treatment was correlated with a lower risk (HR -0.28, CI 95% -0.5596 to -0.01898, p = 0.03). CONCLUSIONS: Patients treated with biologic therapy for CD who underwent repeat ileocolic resection had fewer postoperative complications.

A network meta-analysis of surgical treatments of complete rectal prolapse.

PURPOSE: Surgical treatment of complete rectal prolapse can be undertaken via an abdominal or a perineal approach. The present network meta-analysis aimed to compare the outcomes of different abdominal and perineal procedures for rectal prolapse in terms of recurrence, complications, and improvement in fecal incontinence (FI). METHODS: A PRISMA-compliant systematic review of PubMed, Scopus, and Web of Science was conducted. Randomized clinical trials comparing two or more procedures for the treatment of complete rectal prolapse were included. The risk of bias was assessed using the ROB-2 tool. The main outcomes were recurrence of full-thickness rectal prolapse, complications, operation time, and improvement in FI. RESULTS: Nine randomized controlled trials with 728 patients were included. The follow-up ranged between 12 and 47 months. Posterior mesh rectopexy had significantly lower odds of recurrence than did the Altemeier procedure (logOR, - 12.75; 95% credible intervals, - 40.91, - 1.75), Delorme procedure (- 13.10; - 41.26, - 2.09), resection rectopexy (- 11.98; - 41.36, - 0.19), sponge rectopexy (- 13.19; - 42.87, - 0.54), and sutured rectopexy (- 13.12; - 42.58, - 1.50), but similar odds to ventral mesh rectopexy (- 12.09; - 41.7, 0.03). Differences among the procedures in complications, operation time, and improvement in FI were not significant. CONCLUSIONS: Posterior mesh rectopexy ranked best with the lowest recurrence while perineal procedures ranked worst with the highest recurrence rates.

Use of indocyanine green fluorescence angiography during ileal J-pouch surgery requiring lengthening maneuvers.

BACKGROUND: The purpose of this study was to review whether routine usage of indocyanine green (ICG) perfusion assessment during complex ileal J-pouch surgery requiring lengthening maneuvers reduces ischemic complications. METHODS: Retrospective chart review of patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) who underwent ileal pouch-anal anastomosis (IPAA) surgery with lengthening maneuvers and intraoperative ICG assessment between January 2015 and January 2021. All patients underwent a double stapled anastomosis and were temporarily diverted. All patients underwent laparoscopic and trans-anal ICG assessment of their J-pouch and anastomosis. All J-pouches were evaluated 6 weeks after surgery via contrast enema and pouchoscopy. RESULTS: One hundred fifty eight patients underwent ileal J-pouch surgery during the study period. Sixteen patients (10%) underwent lengthening maneuvers and intra-operative ICG assessment. Twelve patients underwent surgery for UC and 4 for FAP. Median age was 40.3 years and average body mass index was 24.9 kg/m2. Twelve patients underwent a two-stage procedure and the remaining underwent a three-stage procedure. 93.7% of cases were completed laparoscopically (15/16). All patients underwent scoring of the peritoneum and 43% (7/16) underwent division of the ileocolic or intermediate mesenteric vessels. There was no mortality or pouch ischemia and the leak rate was 12.5%. All patients underwent reversal after an average of 18 ± 7 weeks. CONCLUSION: ICG perfusion assessment appears to be of utility in complex IPAA surgery requiring lengthening maneuvers. Its application may be associated with reduced J-pouch ischemia and leak rate in this unique setting.

Prevalence, diagnosis, and surgical management of complex ileocolic-duodenal fistulas in Crohn's disease.

BACKGROUND: The aim of the present study was to review the prevalence and surgical management of patients with Crohn's disease (CD) complicated by ileocolic-duodenal fistulas (ICDF). METHODS: We performed a retrospective chart review of CD patients who underwent surgical takedown and repair of ICDF during January 2011-December 2021 at two inflammatory bowel disease referral centers. RESULTS: We identified 17 patients with ICDF (1.3%) out of 1283 CD patients who underwent abdominal surgery. Median age was 42 (20-71) years, 13 patients were male (76%) and median body mass index was 22.7 (18.4-30.3) kg/m2. Four patients (24%) were diagnosed preoperatively and only 2 (12%) were operated on for ICDF-related symptoms. The most common procedure was ileocolic resection (13 patients, 76%) including 4 repeat ileocolic resections (24%). The duodenal defect was primarily repaired in all patients with no re-fistulization or duodenal stenosis, regardless of the repair technique. A laparoscopic approach was attempted in the majority of patients (14 patients, 82%); however, only 5 (30%) were laparoscopically completed. The overall postoperative complication rate was 65% including major complications in 3 patients (18%) and 2 patients (12%) who required surgical re-intervention for abdominal wall dehiscence and postoperative bleeding. Preoperative nutritional optimization was performed in 9 patients (53%) due to malnutrition. These patients had significantly less intra-operative blood loss (485 vs 183 ml, p = 0.05), and a significantly reduced length of stay (18 vs 8 days, p = 0.05). CONCLUSION: ICDF is a rare manifestation of CD which may go unrecognized despite the implementation of a comprehensive preoperative evaluation. Although laparoscopic management of ICDF may be technically feasible, it is associated with a high conversion rate. Preoperative nutritional optimization may be beneficial in improving surgical outcomes in this select group of patients.

Iatrogenic superior mesenteric vein injury: the perils of high ligation.

PURPOSE: The purpose of this review is to highlight the perils and pitfalls associated with high vascular ligation during right colectomies for adenocarcinoma and to identify the various mechanisms of injury to the superior mesenteric vein (SMV) and its tributaries. METHODS: This is a retrospective chart review of 304 right colectomies (159 open and 145 laparoscopic) performed over a period of 10 years (1 June 2006-31 May 2016) for right-sided colonic adenocarcinoma in an academic medical center. RESULTS: During a 10-year study period, we encountered five cases in which significant damage to the SMV and its tributaries occurred. This accounts for a total of 1.6 % of all right colectomies performed for colonic adenocarcinoma. CONCLUSIONS: Iatrogenic superior mesenteric vein injury is a rare, severe, and underreported complication of both open and laparoscopic right colectomy for colonic adenocarcinoma. We identified several mechanisms of injury such as anatomic misperception, excessive traction and pulling on the venous system, extensive tumor involvement of the mesentery, and uncontrolled suturing attempts at hemostasis. We believe that increased awareness of this complication with profound understanding of vascular anatomy and the different mechanisms of injury will allow surgeons to avoid this often devastating complication.

[Injuries to blood vessels near the heart caused by central venous catheters]. / Verletzungen herznaher Gefäße durch zentralvenöse Katheter.

Injuries to blood vessels near the heart can quickly become life-threatening and include arterial injuries during central venous puncture, which can lead to hemorrhagic shock. We report 6 patients in whom injury to the subclavian artery and vein led to life-threatening complications. Central venous catheters are associated with a multitude of risks, such as venous thrombosis, air embolism, systemic or local infections, paresthesia, hemothorax, pneumothorax, and cervical hematoma, which are not always immediately discernible. The subclavian catheter is at a somewhat lower risk of catheter-associated sepsis and symptomatic venous thrombosis than approaches via the internal jugular and femoral veins. Indeed, access via the subclavian vein carries a substantial risk of pneumo- and hemothorax. Damage to the subclavian vein or artery can also occur during deliberate and inadvertent punctures and result in life-threatening complications. Therefore, careful consideration of the access route is required in relation to the patient and the clinical situation, to keep the incidence of complications as low as possible. For catheterization of the subclavian vein, puncture of the axillary vein in the infraclavicular fossa is a good alternative, because ultrasound imaging of the target vessel is easier than in the subclavian vein and the puncture can be performed much further from the lung.

Characterization of the symbiont Rickettsia in the mirid bug Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae).

Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae) is an omnivorous insect used for biological control. Augmentative release and conservation of N. tenuis have been used for pest control in tomato crops. Intracellular bacterial symbionts of arthropods are common in nature and have diverse effects on their hosts; in some cases they can dramatically affect biological control. Fingerprinting methods showed that the symbiotic complex associated with N. tenuis includes Wolbachia and Rickettsia. Rickettsia of N. tenuis was further characterized by sequencing the 16S rRNA and gltA bacterial genes, measuring its amount in different developmental stages of the insect by real-time polymerase chain reaction, and localizing the bacteria in the insect's body by fluorescence in situ hybridization. The Rickettsia in N. tenuis exhibited 99 and 96% similarity of both sequenced genes to Rickettsia bellii and Rickettsia reported from Bemisia tabaci, respectively. The highest amount of Rickettsia was measured in the 5th instar and adult, and the symbionts could be detected in the host gut and ovaries. Although the role played by Rickettsia in the biology of N. tenuis is currently unknown, their high amount in the adults and localization in the gut suggest that they may have a nutritional role in this insect.

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up.

OBJECTIVES: In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re-evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia. METHODS: This was a retrospective review of the records of 30 consecutive fetuses with tachycardia documented on M-mode echocardiography between January 2004 and December 2010 at Wilhelmina Children's Hospital, a tertiary referral university hospital. Patients were subdivided into those diagnosed with supraventricular tachycardia and those with atrial flutter (AF) and presence of hydrops was noted. Other variables investigated included QTc interval measured on maternal electrocardiogram before and after initiation of antiarrhythmic therapy, fetal heart rhythm and heart rate pre- and postnatally, oral maternal drug therapy used, time to conversion to sinus rhythm (SR), percentage of fetuses converted following transplacental treatment, maternal adverse effects, presence or absence of tachycardia as noted on postnatal ECG, postnatal therapy or prophylaxis and neonatal outcome. Findings are discussed with reference to the literature. RESULTS: A total of 28 patients (18 with SVT, 10 with AF) were treated with sotalol as first-line therapy. Fetal hydrops was present in six patients (five with SVT, one with AF). All hydropic patients converted antenatally to SR (67% with sotalol as a single-drug therapy, 33% after addition of flecainide). Of the non-hydropic patients, 91% converted to SR (90% with sotalol only, 10% after addition of flecainide or digoxin). In 9% (with AF) rate control was achieved. There was no mortality. No serious drug-related adverse events were observed. Postnatally, rhythm disturbances were detected in 10 patients, two of whom still had AF. In eight, SVT was observed within 3 weeks postnatally, and in five of these within 72 hours. CONCLUSIONS: Sotalol can be recommended as the drug of first choice for treatment of fetal AF and has been shown to be an effective and safe first-line treatment option for SVT, at least in the absence of hydrops. Postnatal maintenance therapy after successful prenatal therapy is not necessarily indicated, as the risk of recurrence is low beyond 72 hours of age.

Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis.

PURPOSE: Diets rich in plant-derived polyphenols such as olive oil (OO) and/or catechins such as epigallocatechin 3-gallate (EGCG) have been shown to reduce the incidence of cardiovascular diseases, potentially by improving endothelial function, an important surrogate for atherosclerosis. The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing, yet unknown. METHODS: Eighty-two patients with early atherosclerosis (presence of endothelial dysfunction) were enrolled in this double-blind, randomized trial with 52 completing the study. The aim of the study was to compare the effect of a daily intake of 30 ml simple OO, with 30 ml of EGCG-supplemented OO, on endothelial function as well as on inflammation and oxidative stress after a period of 4 months. Endothelial function was assessed noninvasively via peripheral arterial tonometry (Endo-PAT®). RESULTS: After 4 months, when OO and EGCG-supplemented OO groups were combined, OO significantly improved endothelial function (RHI, 1.59 ± 0.25-1.75 ± 0.45; p < 0.05). However, there were no significant differences in results between the two olive oil groups. Interestingly, with OO supplementation there was a significant reduction in inflammatory parameters: sICAM (196 to 183 ng/mL, p = < 0.001); white blood cells (WBCs) (6.0 × 109/L-5.8 × 109/L, p < 0.05); monocytes (0.48 × 109/L to 0.44 × 109/L, p = 0.05); lymphocytes (1.85 × 109/L to 1.6 × 109/L, p = 0.01); and platelets (242-229 × 109/L, p = 0.047). CONCLUSIONS: Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function. The current study supports one potential mechanism for the role of olive oil, independent of EGCG, modestly supplemented to a healthy cardiovascular diet.

Expression and prognostic significance of hsa-miR-142-3p in acute leukemias.

OBJECTIVES: The microRNA 142 (miR-142) is expressed at high levels in mature hematopoietic cells and has a crucial role during T-lymphocyte development. Its role in leukemogenesis is unclear. PATIENTS AND METHODS: Expression of miR-142 was analyzed in acute myeloid and lymphoblastic leukemia cells (de novo, cell lines). Data were compared to expression in CD34+ hematopoietic cells. Based on the miR-142 expression, clinical data such as overall survival was analyzed. RESULTS: MiR-142 expression in all leukemia cell lines and 86 % of the de novo samples was higher than in CD34+ cells. This difference could be detected in both, myeloid and lymphoid neoplastic cells. In AML patients with intermediate cytogenetic risk a high miR-142 expression was associated with a better overall survival. CONCLUSIONS: MiR-142 expression in acute lymphoblastic as well as myeloid leukemia cells is higher than in CD34+ cells. Additionally, miR-142 expression might have prognostic relevance in AML-patients with otherwise an intermediate cytogenetic risk.

Immunohistochemical localization of the angiotensin-(1-7) receptor Mas in the murine forebrain.

Apart from the well-known biologically active angiotensin II, other biologically active angiotensins have been discovered, including angiotensin IV and angiotensin-(1-7). Some years ago, we and others discovered that the Mas proto-oncogene encodes a receptor that is essential for angiotensin-(1-7) signaling. Angiotensin-(1-7) is not only expressed in the periphery but also within the brain. Based on that, we examined the distribution of Mas within the murine brain, using an antibody directed against the 3(rd) cytoplasmic loop of the receptor protein. Strongest Mas protein expression was detected in the dentate gyrus of the hippocampus and within the piriform cortex. However, Mas protein expression is not restricted to these areas, since Mas immunopositive neurons were also seen in different parts of the cortex, hippocampus, amygdala, basal ganglia, thalamus and hypothalamus. Based on the expression of Mas protein in the cortex and the limbic system, angiotensin-(1-7) signaling may play a role in synaptic plasticity, learning, memory and emotion, as has been described for angiotensin II and IV.

Immune responses to RHAMM in patients with acute myeloid leukemia after chemotherapy and allogeneic stem cell transplantation.

Leukemic blasts overexpress immunogenic antigens, so-called leukemia-associated antigens like the receptor for hyaluronan acid-mediated motility (RHAMM). Persistent RHAMM expression and decreasing CD8+ T-cell responses to RHAMM in the framework of allogeneic stem cell transplantation or chemotherapy alone might indicate the immune escape of leukemia cells. In the present study, we analyzed the expression of RHAMM in 48 patients suffering from acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Furthermore, we correlated transcripts with the clinical course of the disease before and after treatment. Real-time quantitative reverse transcriptase polymerase chain reaction was performed from RNA of peripheral blood mononuclear cells. T cell responses against RHAMM were assessed by tetramer staining (flow cytometry) and enzyme-linked immunospot (ELISPOT) assays. Results were correlated with the clinical outcome of patients. The results of the present study showed that almost 60% of the patients were RHAMM positive; specific T-cells recognizing RHAMM could be detected, but they were nonfunctional in terms of interferon gamma or granzyme B release as demonstrated by ELISPOT assays. Immunotherapies like peptide vaccination or adoptive transfer of RHAMM-specific T cells might improve the immune response and the outcome of AML/MDS patients.

Squamous cell carcinomas of the head and neck in Fanconi anemia: risk, prevention, therapy, and the need for guidelines.

Fanconi anemia (FA) is a rare recessive DNA repair disorder that is clinically characterized by congenital malformations, progressive bone marrow failure, and increased incidence of malignancies, especially acute myeloid leukemia and squamous cell carcinomas of the head and neck (HNSCCs) and the anogenital regions. On a cellular level, typical features of the disorder are a high degree of genomic instability and an increased sensitivity to bi-functionally alkylating agents. So far, germ-line defects in 15 different FA genes have been identified. Some of these FA genes are also established as tumor susceptibility genes for familiar cancers.In recent years, the prevention and therapy of HNSCCs in FA patients has become more important as the percentage of patients surviving into adulthood is rising. HNSCCs appear in very young FA patients without common risk factors. Since cisplatin-based chemotherapy in combination with radiotherapy, essential parts of the standard treatment approach for sporadic HNSCCs, cannot be used in FA patients due to therapy-associated toxicities and mortalities even with reduced dosing, surgery is the most important treatment option for HNSCCs, in FA patients and requires an early and efficient detection of malignant lesions. So far, no uniform treatment protocol for the management of HNSCCs in FA patients exists. Therefore, we propose that the information on affected FA patients should be collected worldwide, practical therapeutic guidelines developed and national treatment centers established.

Elastography of the uterine cervix: implications for success of induction of labor.

OBJECTIVES: To perform a preliminary investigation into the use of elastography for cervical assessment, in order to determine the effectiveness of this method for the evaluation of cervical consistency. METHODS: Elastography of the uterine cervix was performed in 29 patients before induction of labor, with tissue surrounding the internal os described using a numeric scale called the elastography index (EI). A color map from purple to red was produced with the hardest tissues displayed as purple and assigned a score of 0 points and progressively softer tissues displayed as blue (1 point), green (2 points), yellow (3 points) and red (4 points). The EI of tissue around the internal os, in the middle part of the cervical canal and around the external os were analyzed in relation to the success of induction of labor using the t-test. RESULTS: The mean EI of the internal os in the group of patients with successful induction of labor was 1.23, while in the group with failed induction of labor it was 0.39 (Student's t-test, P=0.024). No difference was found for the EI of the middle part of the cervical canal or for the EI of the external os in relation to the success of induction of labor (P>0.05). CONCLUSION: Elastography of the uterine cervix may be an objective method for assessment of softening of tissue in the region of the internal os before induction of labor. Standardization of the cervical properties observed on elastography during pregnancy may help to guide the use of prostaglandins or oxytocin for induction of labor.

Pancreatic graft survival despite partial vascular graft thrombosis due to splenocephalic anastomoses.

Thrombotic complications following pancreas transplantation are still the most common cause of nonimmunologic graft loss. The aim of this study was to analyze pancreatic graft function after partial arterial graft thrombosis and the investigation of the pancreatic arterial anatomy with regard to intraparenchymal anastomoses. We retrospectively analyzed the data for 175 consecutive pancreas transplants performed between January 2002 and October 2007. Selective Y-graft angiography was performed in 10 and rubber-milk injection in 5 fresh pancreas specimens. Thrombosis of one leg of the Y-graft was diagnosed in 18 (10.3%) patients. Only one of these patients with thrombosis of the splenic artery required exogenous insulin. Sufficient graft perfusion was demonstrated in all of the remaining grafts. One graft was lost due to acute rejection. In all specimens angiography showed an excellent perfusion of the pancreaticoduodenal arcade, even after selective cannulation of the splenic artery. Arterial collaterals between the gastroduodenal, splenic artery and the superior mesenteric artery were demonstrated. Our results demonstrate that global perfusion of the pancreatic graft and sufficient graft function is sustained after the thrombotic occlusion of one branch of the Y-graft by a complex system of intraparenchymal anastomoses. These anatomical findings may have consequences for resection strategies in pancreas surgery.

High-dose therapy followed by autologous stem-cell transplantation with and without rituximab for primary treatment of high-risk diffuse large B-cell lymphoma.

BACKGROUND: We aimed to determine safety and efficacy of rituximab (R) in combination with repetitive high-dose therapy (HDT) as primary treatment for diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Patients aged 18-60 years and elevated lactate dehydrogenase were treated with four cycles of MegaCHOEP and transplantation of autologous stem cells after cycles 2, 3 and 4. Rituximab (375 mg/m²) was given before each cycle and 12 and 33 days after start of the last cycle of chemotherapy. Sixty-four patients given R-MegaCHOEP were compared with 29 patients who had received identical treatment without rituximab. RESULTS: Overall survival (OS) and event-free survival (EFS) after 3 years were significantly improved in patients treated with R-MegaCHOEP (OS: 78.7% versus 55.0%, P = 0.045; EFS: 72.7% versus 47.2%, P = 0.013). In a Cox regression model adjusted for performance status and stage, relative risk of treatment failure was lower (relative risk 0.5, P = 0.041) and OS was better (relative risk 0.4, P = 0.054) for patients given R-MegaCHOEP. Grade 3/4 infections were more frequent in the R-MegaCHOEP group (18.5% versus 6.0%, P = 0.003). CONCLUSIONS: The addition of rituximab to MegaCHOEP significantly improved outcome in young patients with high-risk DLBCL. The higher incidence of grade 3/4 infections needs consideration when rituximab and HDT regimens are combined.

Invasive zygomycosis in patients with graft-versus-host disease after allogeneic stem cell transplantation.

Invasive mold infections are a threat to immunosuppressed patients such as patients with graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Up to 10% of SCT recipients develop invasive aspergillosis (IA). Invasive zygomycosis (IZ) may occur during treatment against IA. Here we report 4 SCT patients with GVHD diagnosed with IZ. All patients had received myeloablative hematopoietic SCT and developed chronic GVHD requiring systemic immunosuppression. Underlying diseases were acute lymphocytic leukemia (2), osteomyelofibrosis, and multiple myeloma. All patients had developed pulmonary infiltration that led to initiation of antifungal therapy. Treatment for IA was voriconazole, caspofungin, or itraconazole. Organs involved with zygomycosis were lung, nasal sinus, skin, and kidney. Treatment with liposomal amphotericin and posaconazole was initiated in all patients, and 2 patients also had surgical debridement as well. Despite intensive treatment, no patient survived. IZ is becoming more common in patients with GVHD on successful treatment for IA. Even non-specific symptoms are suspicious in this group of patients and need to be evaluated by vigorous diagnostics. Despite effective antifungals and surgical intervention, the prognosis is grim in patients with active GVHD, as immunoreconstitution is mandatory for successful management.

Minimizing circulatory arrest by using antegrade cerebral perfusion for aortic arch reconstruction in infants causes fewer postoperative adverse events.

BACKGROUND: Because deep hypothermic circulatory arrest (DHCA) carries a risk for neurological damage, antegrade cerebral perfusion (ACP) is used increasingly for aortic arch surgery in infants. We assessed the short-term effects of minimal DHCA (< 30 minutes) versus prolonged DHCA (> 30 minutes) during biventricular aortic arch reconstruction. METHODS: Twenty-six infants (< 3 months of age) who had undergone aortic arch reconstruction were retrospectively analyzed: 15 infants without DHCA (group A) and 11 infants with DHCA (group B). Group B was further divided into < 30 minutes DHCA (group B1, n = 6), and >or= 30 minutes DHCA (group B2, n = 5). Additionally, minimal DHCA (group A + B1) was compared to prolonged DHCA (group B2). RESULTS: In the minimal DHCA group (A + B1), 29 % of the patients had a postoperative adverse event, compared to 80 % in the prolonged DHCA group (B2) ( P < 0.05). Average length of stay in hospital was 25 days shorter for the minimal DHCA group (15 days versus 40 days, P < 0.01). CONCLUSION: Minimal DHCA results in fewer adverse events and a reduced length of stay, compared with prolonged DHCA. Therefore, during aortic arch surgery in infants, DHCA should be minimized by using antegrade cerebral perfusion.