The assessment of minimal residual disease versus that of somatic mutations for predicting the outcome of acute myeloid leukemia patients.

BACKGROUND: In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. METHOD: At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. RESULTS: Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction > 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. CONCLUSIONS: We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity.

Metformin intoxication: Vasopressin's key role in the management of severe lactic acidosis.

Vasopressin is a potent vasopressor used for improving organ perfusion during cardiac arrest, septic and catecholamine-resistant shock; with reference to this, it is useful for the treatment of vasoplegic shock because, restoring organ perfusion pressure by contraction of vascular smooth muscle through a non-catecholamine receptor pathway, it can be employed when catecholamines are ineffective. A 49-yr-old woman was admitted to the Emergency Department after having intentionally taken 95.2g of metformin, 1.6g of pioglitazone and 40 UI of insulin glargine in a suicide attempt. Despite fluid resuscitation, CVVHDF (continuous veno-venous hemodiafiltration) treatment, norepinephrine and epinephrine infusion, she developed a severe lactic acidosis and a catecholamines-refractive vasodilatory shock. Only the vasopressin infusion, in association with catecholamines, gradually stabilized the patient's hemodynamic status.

Duodenal graft complications requiring duodenectomy after pancreas and pancreas-kidney transplantation.

Duodenal graft complications are poorly reported complications of pancreas transplantation that can result in graft loss. Excluding patients with early graft failure, after a median follow-up period of 126 months (range 23-198) duodenectomy was required in 14 of 312 pancreas transplants (4.5%). All patients were insulin-independent at the time of diagnosis. Reasons for duodenectomy included delayed duodenal graft perforation (n = 10, 71.5%) and refractory duodenal graft bleeding (n = 4, 28.5%). In patients with duodenal graft bleeding, a total duodenectomy was performed. In patients with duodenal graft perforation, preservation of a duodenal segment was possible in five patients but completion duodenectomy was necessary in one patient. After total duodenectomy, immediate enteric duct drainage was feasible in seven patients. In two patients, a pancreaticocutaneous fistula was created that was subsequently converted to enteric drainage in one patient. In the other patient, enteric fistulization occurred as a consequence of silent pressure perforation of the draining catheter on the ascending colon. After a mean follow-up period of 52 months (21-125), all patients were alive, well, and insulin-independent. An aggressive and timely surgical approach may permit graft rescue in patients with severe duodenal graft complications occurring after pancreas transplantation. Generalization of these results remains to be established.

Laparoscopic robot-assisted pancreas transplantation: first world experience.

BACKGROUND: Surgical complications are a major disincentive to pancreas transplantation, despite the undisputed benefits of restored insulin independence. The da Vinci surgical system, a computer-assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity of pancreas transplantation. METHODS: Pancreas transplantation was performed by robot-assisted laparoscopy in three patients. The first patient received a pancreas after kidney transplant, the second a simultaneous pancreas kidney transplantation, and the third a pancreas transplant alone. Operations were carried out through an 11-mm optic port, two 8-mm operative ports, and a 7-cm midline incision. The latter was used to introduce the grafts, enable vascular cross-clamping, and create exocrine drainage into the jejunum. RESULTS: The two solitary pancreas transplants required an operating time of 3 and 5 hr, respectively; the simultaneous pancreas kidney transplantation took 8 hr. Mean warm ischemia time of the pancreas graft was 34 min. All pancreatic transplants functioned immediately, and all recipients became insulin independent. The kidney graft, revascularized after 35 min of warm ischemia, also functioned immediately. No patient had complications during or after surgery. At the longer follow-up of 10, 8, and 6 months, respectively, all recipients are alive with normal graft function. CONCLUSIONS: We have shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed by larger series, laparoscopic robot-assisted pancreas transplantation could become a new option for diabetic patients needing beta-cell replacement.

Current perspectives on laparoscopic robot-assisted pancreas and pancreas-kidney transplantation.

Pancreas transplant recipients continue to suffer high surgical morbidity. Current robotic technology provides a unique opportunity to test whether laparoscopy can improve the post-operative course of pancreas transplantation (PT). Current knowledge on robotic pancreas and renal transplantation was reviewed to determine feasibility and safety of robotic PT. Information available from literature was included in this review, together with personal experience including three PT, and two renal allotransplants. As of April 2011, the relevant literature provides two case reports on robotic renal transplantation. The author's experience consists of one further renal allotransplantation, two solitary PT, and one simultaneous pancreas-kidney transplantation. Information obtained at international conferences include several other renal allotransplants, but no additional PT. Preliminary data show that PT is feasible laparoscopically under robotic assistance, but raises concerns regarding the effects of increased warm ischemia time on graft viability. Indeed, during construction of vascular anastomoses, graft temperature progressively increases, since maintenance of a stable graft temperature is difficult to achieve laparoscopically. There is no proof that progressive graft warming produces actual damage to transplanted organs, unless exceedingly long. However, this important question is likely to elicit a vibrant discussion in the transplant community.

Robotic renal transplantation: first European case.

A kidney from a 56-year-old mother was transplanted to her 37-year-old daughter laparoscopically using the daVinci HDSi surgical system. The kidney was introduced into the abdomen through a 7-cm suprapubic incision used also for the uretero-vescical anastomosis. Vascular anastomoses were carried out through a total of three additional ports. Surgery lasted 154 min, including 51 min of warm ischemia of the graft. Urine production started immediately after graft reperfusion. Renal function remains optimal at the longest follow-up of 3 months. The technique employed in this case is discussed in comparison with the only other two contemporary experiences, both from the USA. Furthermore, possible advantages and disadvantages of robotics in kidney transplantation are discussed extensively. We conclude that the daVinci surgical system allows the performance of kidney transplantation under optimal operative conditions. Further experience is needed, but it is likely that solid organ transplantation will not remain immune to robotics.

Postoperative intra-abdominal pressure and renal function after liver transplantation.

HYPOTHESIS: Intra-abdominal hypertension frequently threatens renal function early after orthotopic liver transplantation (OLT). DESIGN: A prospective study of consecutive patients who underwent OLT. SETTING: The intensive care unit of a National Health Service teaching hospital. PATIENTS AND MAIN OUTCOME MEASURES: The intra-abdominal pressure (IAP) of 108 consecutive patients who underwent OLT was postoperatively measured 3 times a day for 72 hours using the urinary bladder technique. Intra-abdominal hypertension was defined as an IAP of 25 mm Hg or higher. RESULTS: Thirty-four patients (31%) had a high IAP. Acute renal failure developed in 17 recipients (16%), 11 (65%) of whom had intra-abdominal hypertension (P<.01), with a mean +/- SD IAP of 27.9 +/- 9.9 mm Hg vs 18.6 +/- 5.2 mm Hg in those without acute renal failure (P<.001). The subjects with a high IAP were more frequently administered loop diuretics to maintain adequate diuresis (P<.001) and had a low mean arterial pressure on the day of surgery (P<.01), despite the fact that they were given more intravenous fluids (P<.01) and did not differ in the need for inotropic drugs. Logistic regression analysis showed that intraoperative transfusions of more than 15 U, respiratory failure, and intra-abdominal hypertension (P<.01) were independent risk factors for renal failure. The length of intensive care unit stay was similar in the patients with a normal and a high IAP, but mortality was higher among the latter (P =.02). CONCLUSIONS: Intra-abdominal hypertension is common after OLT and is significantly associated with renal failure, reduced urinary output, and intensive care unit mortality. It is, therefore, worth monitoring IAP in those undergoing OLT.

Intra-abdominal pressure monitoring in liver transplant recipients: a prospective study.

OBJECTIVE: No data are available on the incidence and clinical relevance of increased intra-abdominal pressure after orthotopic liver transplantation. This study assessed abdominal hypertension in a population of transplanted patients as this may be an important cofactor in early postoperative complications. DESIGN AND SETTING: Prospective clinical study in an intensive care unit of a national health system teaching hospital PATIENTS AND MEASUREMENTS: Abdominal pressure was measured every 6 h using the urinary bladder method and was considered elevated when it was 25 mmHg or higher. Hemodynamic status was evaluated at the same times. Renal function was assessed on the basis of hourly urinary output by calculating serum creatinine on postoperative days 2 and 4 and the filtration gradient; patient outcomes were also considered. RESULTS: Intra-abdominal hypertension was observed in 32% of cases; the subjects with high abdominal pressure had significantly lower mean artery pressure values but did not differ in terms of central venous pressure or cardiac output. High intra-abdominal pressure was more frequently associated with renal failure, a lower filtration gradient, delayed postsurgical weaning from ventilation, and a worse outcome. CONCLUSIONS: Abdominal hypertension is frequent after liver transplantation and may be associated with a complicated post-operative course.

Renal failure and abdominal hypertension after liver transplantation: determination of critical intra-abdominal pressure.

There is growing interest in measuring intra-abdominal pressure (IAP) in postsurgical and critically ill patients because increased pressure can impair various organs and functions. The aim of this study was to evaluate the effect of different IAP levels on the postoperative renal function of subjects undergoing orthotopic liver transplantation. IAP was measured every 8 hours with the urinary bladder pressure method for at least 72 hours after surgery. At the end of the study, the patients were classified on the basis of their IAP values: < or = 18 mm Hg (group A), 19 to 24 mm Hg (group B), > or = 25 mm Hg (group C). The three groups were compared in terms of the incidence of acute renal failure (defined as blood creatinine > 1.5 mg/dL or an increase in the same of > 1.1 mg/dL within 72 hours of surgery), hourly diuresis, blood creatinine, the filtration gradient, hemodynamic variations, and outcome. The incidence of renal failure was higher among the subjects in group C (P < .05 versus group A and < .01 versus group B), who also had higher creatinine levels (P < .01), a greater need for diuretics (P < .01) and a worse outcome (P < .05). Receiver Operator Characteristic curve analysis showed that an abdominal pressure of 25 mm Hg had the best sensitivity/specificity ratio for renal failure. An intra-abdominal pressure of > or = 25 mm Hg is an important risk factor for renal failure in subjects undergoing liver transplant.