Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

The SMART-ALPPS Protocol: Strategy to Minimize ALPPS Risks by Targeting Invasiveness.

BACKGROUND: The range of procedures with documented feasibility by laparoscopic approach is widening in the setting of liver resections. Many technical limits have been overcome in the attempt to reduce the biological impact of major procedures [1-8]. Similarly, associated liver partition and portal vein ligation for staged hepatectomy (ALPPS)-which could be assumed as the paradigm of maxi-invasiveness-has recently been proposed in a minimally invasive fashion to reduce the impact of this procedure [9-12]. Technical insights to perform laparoscopic ALPPS are provided. METHODS: Perioperative and intraoperative tips for laparoscopic ALPPS are provided within a SMART (Strategy to Minimize ALPPS Risks by Targeting invasiveness) protocol. Stage 1: After volumetric and functional assessment, partial liver transection is performed, keeping intact both the hilum and the caval plane (to prevent adhesions), therefore avoiding portal ligation. No inert material is left inside the abdominal cavity at the end of procedure to keep the liver surfaces apart. Radiologic portography with portal vein embolization is scheduled on postoperative day (POD) 1. Liver volume (pre-PVE: 29%; post-PVE: 52%) and liver function measured through a Technetium-99 hepatobiliary scintigraphy [13] (pre-PVE: 2.15%/min/sqm; post-PVE: 3.67%/min/sqm) of the future remnant liver are reassessed within 10 days to verify whether size and function are adequate. Stage 2: After 2 weeks from the first stage, laparoscopic right hepatectomy is performed following an anterior approach. RESULTS: No conversion to open was required. Operative time was 100 and 300 minutes for stage 1 and 2, respectively. Intraoperative blood loss was 50 and 300 ml for the two procedures. Postoperative course was uneventful; patient was discharged on POD 6 of the second operation. CONCLUSIONS: The implementation of a perioperative protocol to prevent the risk of liver failure by both assessing volume and function of FLR and targeting the invasiveness of the surgical procedure may allow to minimize and control risks of a maximally invasive procedure, such as ALPPS.

Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Laparoscopic repeat liver resection for hepatocellular carcinoma: a multicentre propensity score-based study.

BACKGROUND: In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes. METHODS: Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded. RESULTS: Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P < 0·001), duration of operation (248(156) versus 285(167) min; P < 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086). CONCLUSION: Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.

ANTECEDENTES: Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo. RESULTADOS: El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P < 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P < 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

Propensity Score-Matched Analysis of Pure Laparoscopic Versus Hand-Assisted/Hybrid Major Hepatectomy at Two Western Centers.

BACKGROUND: Laparoscopic major hepatectomy is expanding, but little data exist comparing surgical approaches. The aim of this study was to test the hypothesis that pure laparoscopic liver resection (PLAP) has advantages over hand-assisted (HALS) or hybrid (HYB) resection for major hemi-hepatectomy at two western centers. METHODS: Using propensity score matching, 65 cases of HALS + HYB (18 hand-assisted and 47 hybrid) were matched to 65 cases of PLAP. Baseline characteristics were well matched for gender, age, ASA score, Childs A cirrhosis, right/left hepatectomy, malignancy, tumor size, and type between the groups. RESULTS: The HALS + HYB group had 27 right and 38 left major hepatectomies (n = 65) versus 29 right and 36 left (n = 65) in the PLAP group (p = NS). The median number of lesions resected was 1 in each group, with median size 5.6 cm (HALS + HYB) versus 6.0 cm (PLAP), (p = NS). The HALS + HYB group had shorter OR time (240 versus 330 min, p < 0.01), and less blood loss (EBL 150 ml vs. 300 ml, p < 0.01) versus the PLAP group, respectively. Median length of stay (LOS) was 4 days with HALS + HYB versus 5 days in the PLAP group (p = 0.02). There were no significant differences in use of the Pringle maneuver, transfusion rate, ICU stay, post-op morbidity, liver-specific complications, or R0 resection. Pain regimen/usage in each group is provided. There were no 30/90-day deaths in either group. CONCLUSION: This is the first reported series of propensity score matching of HALS + HYB versus PLAP for major hepatectomy. The HALS + HYB group had non-inferior OR time, blood loss, and LOS versus the PLAP group, while the other perioperative parameters were comparable. We conclude that minimally invasive liver resection with either PLAP or HALS + HYB technique yields excellent results.

Theory of Relativity for Posterosuperior Segments of the Liver.

BACKGROUND: The accessibility to posterosuperior segments of the liver has traditionally constituted a restrain to adopt the laparoscopic approach in this setting. To overcome this challenge, multiple approaches have been reported in literature. Total transabdominal approach has been previously described for this purpose, even though the rationale to standardly adopt it and a technical depiction of how to achieve an optimal mobilization has never been specifically addressed. METHODS: Total transabdominal purely laparoscopic approach to posterosuperior segments of the liver is presented, with detailed emphasis to the rotational motions targeted in laparoscopy. A literature review is presented to summarize all other possible accesses to posterosuperior area of the liver. The institutional series for the laparoscopic approach to Sg 7, Sg 6+7, and Sg8 is retrospectively described. RESULTS: Three rotational motions of the liver are specifically addressed in a video presentation and described for the laparoscopic total-transabdominal approach; the local institutional series using this approach is presented. Other miscellaneous approaches identified from literature encompassing variations in operative position, transabdominal, transthoracic, and combined approaches are described. CONCLUSIONS: Complete mobilization of the ligaments of the liver leads to a rotation of the transection line in front of the operator's view, allowing to achieve a safe total trans-abdominal laparoscopic approach to the posterosuperior ligaments of the liver, without compromising the vascular inflow control, the possibility to convert to open approach, nor requiring potentially harmful decubitus.

Tips and Tricks for a Laparoscopic Approach to Paracaval Liver Segments.

BACKGROUND: A dramatic spread of laparoscopic liver surgery has been experienced over the last years. The approach to paracaval liver segments 1 and 9 is still poorly described in literature, mainly due to its technical demands. OBJECTIVE: The aim of this article was to introduce a safe and effective approach to paracaval liver segments through laparoscopy. METHODS: A minimally invasive approach to resection of Segments 1 and 9 is presented, and an operative set-up is depicted. A step-by-step technique describing the inferior vena cava (IVC) with left and right hepatic venous junction exposure, segmental pedicle isolation, and parenchymal transection is shown through a video document. RESULTS: Postoperative courses were uneventful, and patients were discharged on postoperative day 3. DISCUSSION: The approach to paracaval liver segments requires accurate preoperative case selection, technical, surgical, and anesthesiological expertise in laparoscopic liver surgery, and adequate instrumentary. CONCLUSION: Paracaval segments of the liver can be approached safely through laparoscopy by teams with extensive expertise in the field of laparoscopic liver surgery; however, suspected malignant infiltration of the IVC or unclear preoperative anatomy still contraindicate this approach.

Randomized clinical trial of open versus laparoscopic left lateral hepatic sectionectomy within an enhanced recovery after surgery programme (ORANGE II study).

BACKGROUND: Laparoscopic left lateral sectionectomy (LLLS) has been associated with shorter hospital stay and reduced overall morbidity compared with open left lateral sectionectomy (OLLS). Strong evidence has not, however, been provided. METHODS: In this multicentre double-blind RCT, patients (aged 18-80 years with a BMI of 18-35 kg/m2 and ASA fitness grade of III or below) requiring left lateral sectionectomy (LLS) were assigned randomly to OLLS or LLLS within an enhanced recovery after surgery (ERAS) programme. All randomized patients, ward physicians and nurses were blinded to the procedure undertaken. A parallel prospective registry (open non-randomized (ONR) versus laparoscopic non-randomized (LNR)) was used to monitor patients who were not enrolled for randomization because of doctor or patient preference. The primary endpoint was time to functional recovery. Secondary endpoints were length of hospital stay (LOS), readmission rate, overall morbidity, composite endpoint of liver surgery-specific morbidity, mortality, and reasons for delay in discharge after functional recovery. RESULTS: Between January 2010 and July 2014, patients were recruited at ten centres. Of these, 24 patients were randomized at eight centres, and 67 patients from eight centres were included in the prospective registry. Owing to slow accrual, the trial was stopped on the advice of an independent Data and Safety Monitoring Board in the Netherlands. No significant difference in median (i.q.r.) time to functional recovery was observed between laparoscopic and open surgery in the randomized or non-randomized groups: 3 (3-5) days for OLLS versus 3 (3-3) days for LLLS; and 3 (3-3) days for ONR versus 3 (3-4) days for LNR. There were no significant differences with regard to LOS, morbidity, reoperation, readmission and mortality rates. CONCLUSION: This RCT comparing open and laparoscopic LLS in an ERAS setting was not able to reach a conclusion on time to functional recovery, because it was stopped prematurely owing to slow accrual. Registration number: NCT00874224 ( https://www.clinicaltrials.gov).

Outcome after laparoscopic and open resections of posterosuperior segments of the liver.

BACKGROUND: Laparoscopic resection of posterosuperior (PS) segments of the liver is hindered by limited visualization and curvilinear resection planes. The aim of this study was to compare outcomes after open and laparoscopic liver resections of PS segments. METHODS: Patients who underwent minor open liver resection (OLR) and laparoscopic liver resection (LLR) between 2006 and 2014 were identified from the institutional databases of seven tertiary referral European hepatobiliary surgical units. Propensity score-matched analysis was used to match groups for known confounders. Perioperative outcomes including complications were assessed using the Dindo-Clavien classification, and the comprehensive complication index was calculated. Survival was analysed with the Kaplan-Meier method. RESULTS: Some 170 patients underwent OLR and 148 had LLR. After propensity score-matched analysis, 86 patients remained in both groups. Overall postoperative complication rates were significantly higher after OLR compared with LLR: 28 versus 14 per cent respectively (P = 0·039). The mean(s.d.) comprehensive complication index was higher in the OLR group, although the difference was not statistically significant (26·7(16·6) versus 18·3(8·0) in the LLR group; P = 0·108). The mean(s.d.) duration of required analgesia and the median (range) duration of postoperative hospital stay were significantly shorter in the LLR group: 3·0(1·1) days versus 1·6(0·8) days in the OLR group (P < 0·001), and 6 (3-44) versus 4 (1-11) days (P < 0·001), respectively. The 3-year recurrence-free survival rates for patients with hepatocellular carcinoma (37 per cent for OLR versus 30 per cent for LLR; P = 0·534) and those with colorectal liver metastases (36 versus 36 per cent respectively; P = 0·440) were not significantly different between the groups. CONCLUSION: LLR of tumours in PS segments is feasible in selected patients. LLR is associated with fewer complications and does not compromise survival compared with OLR.

Liver failure in patients treated with chemotherapy for colorectal liver metastases: Role of chronic disease scores in patients undergoing major liver surgery. A case-matched analysis.

AIM: An accurate and noninvasive tool to predict Chemotherapy Associated Liver Injury (CALI) still lacks. Study aimed to evaluate chronic liver disease scores (Aspartate aminotransferase to Platelet Ratio Index, APRI and Fibrosis-4, FIB-4) as Postoperative Liver Failure (PLF) predictors in patients treated with Oxaliplatin for Colorectal Liver Metastases (CLM). METHODS: 8 patients who developed PLF after major hepatectomy (Group B) were compared to 24 patients who did not develop PLF (Group A) in a case-matched analysis for patients and disease characteristics. ROC curves analysis was performed to assess score accuracy. RESULTS: In Group A number of CT cycles was lower, (6 vs 9, p NS), interval between treatment and surgery was longer (11 vs 7 weeks, p < 0.05) and bevacizumab was more frequently administered (66.7% vs 37.5%, p < 0.05). In Group B median APRI score was 0.53 (range: 0.86-4.26) whereas in Group A was 0.30 (range: 0.06-2.21, p < 0.05). Median FIB-4 score was 2.46 (range: 0.86-13.65) in Group B and 1.58 (range: 0.27-7.68) in Group A (p < 0.001). Multivariate analysis showed a significant correlation between APRI and the onset of PLF. A good accuracy of APRI score was evident in ROC curves with an area under the curve of 0.72 (p 0.003). CONCLUSIONS: APRI score is calculated considering both liver damage and platelet count, it is cost effective and easily available. This study demonstrates that there is a good accuracy in PLF prediction and consequently in CT induced liver damage evaluation.

It's T-ALL about Notch.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subset of ALL with poor clinical outcome compared to B-ALL. Therefore, to improve treatment, it is imperative to delineate the molecular blueprint of this disease. This review describes the central role that the Notch pathway plays in T-ALL development. We also discuss the interactions between Notch and the tumor suppressors Ikaros and p53. Loss of Ikaros, a direct repressor of Notch target genes, and suppression of p53-mediated apoptosis are essential for development of this neoplasm. In addition to the activating mutations of Notch previously described, this review will outline combinations of mutations in pathways that contribute to Notch signaling and appear to drive T-ALL development by 'mimicking' Notch effects on cell cycle and apoptosis.

[Subacromial impingement syndrome and rotator cuff tear. Ultrasonography of 140 cases]. / Sindrome da conflitto sotto-acromiale e lesioni della cuffia dei rotatori. Esperienza ecografica in 140 casi.

We investigated the role of rotator cuff impingement in causing tears of supraspinatus and biceps tendons and the comparative reliability of plain radiography and sonography (US). One hundred forty patients with symptoms referrable to the rotator cuff were examined with plain radiography and US of the shoulder. US findings were correlated with MR or double contrast arthrography results in 10 patients and 39 patients were submitted to surgery (acromionplasty). Radiographic studies were performed first and diagnosed rotator cuff impingement (63 patients) caused by abnormal acromial margins or size (23 patients), by acromioclavicular joint protrusion (17 patients), by anterior acromial osteophytosis (10 patients), or by massive periarthritic calcifications (13 patients). In the same 140 patients. US showed normal cuffs in 46 cases, tendonitis in 34, calcific tendonitis in 13, partial-thickness cuff tears in 13, full-thickness cuff tears in 20 and biceps tendon tears in 14 cases. Six of 13 partial tears were studied with MRI, with 4 true positives and 2 false positives. US diagnosis was confirmed by arthrography in 4 complete tears. Twenty-nine of 39 patients undergoing acromionplasty were examined only with plain radiography and US. US accurately diagnosed all 20 massive full-thickness tears, with no false positives nor false negatives (US versus surgery and arthrography). Eleven true positives, 2 false positives and no false negative were observed in 13 partial-thickness cuff tears (US versus surgery and MRI). These findings suggest that rotator cuff US and plain radiography are easily performed, reproducible routine examinations to study the whole rotator cuff and the acromioclavicular joint in the many patients who need an accurate, safe, painless, rapid and cost-effective differential diagnosis, leaving it up to the surgeon to consider MRI or arthrography. Rotator cuff impingement tendonitis, overuse or calcific tendonitis, partial-thickness cuff tears and full-thickness tears ranging from light to severe cause similar shoulder pain and weakness on arm raising. The differential diagnosis must distinguish all these common causes of shoulder dysfunction and cuff problems from other conditions. We conclude that US and plain radiography are accurate routine tests of rotator cuff integrity and rotator cuff impingement.

Death of two subjects due to imipramine and desipramine metabolite accumulation during chronic therapy: a review of the literature and possible mechanisms.

In two unrelated cases, a 7-year-old boy and a 21-year-old woman died suddenly while receiving chronic imipramine therapy. In the boy, concentrations of imipramine were: Left femoral blood 0.5 mg/L, right femoral blood 1.2 mg/L, aorta blood 1.0 mg/L, liver 68 mg/Kg, and for the active metabolite, desipramine, left femoral blood 6.7 mg/L, right femoral blood 9.9 mg/L, aorta blood 8.7 mg/L, liver 400 mg/Kg. In the woman, the imipramine concentrations were: Femoral blood 0.6 mg/L, liver 37 mg/Kg, and of the active metabolite, desipramine, femoral blood 3.74 mg/L, liver 261 mg/Kg. In both cases, the scene investigation strongly indicated that neither individual had ingested an acute overdose. The very high ratios of desmethyl metabolite to parent drug are consistent with this observation. Impaired metabolism due to a genetically determined "slow metabolizer" phenotype of cytochrome CYP2D6, and/or concurrent therapy with phenothiazines, is suggested as a possible mechanism for the apparent fatal accumulation of these tricyclic antidepressants.

[A new digital radiology system. The technical considerations and clinical experience]. / Un nuovo sistema di radiologia digitale. Considerazioni tecniche ed esperienza clinica.

The authors report their experience with a new digital X-ray film processing system, particularly used in the diagnosis of breast, chest, joint and bone pathologic conditions. The technical features of the system are described, and the results are reported which appear as the most significant in mammography, with better visualization of both microcalcifications and small detail images. The above results are due to the possibility of broad contrast variations and of processing basal X-ray images. The possibility is also stressed of improving the diagnostic value of a technically incorrect radiograph, especially if overexposed, with subsequent dose saving.

[Urography with non-ionic contrast media. Multicenter experience on the optimization of the technic]. / Urografia con mezzi di contrasto non ionici. Esperienza multicentrica sulla ottimizzazione della tecnica.

The authors report the results of a multicentric experience based on 1200 urograms performed with nonionic contrast medium. The global diagnostic reliability is evaluated, together with the specific reliability for kidneys, ureters, and bladder, according to the various pathologies. The eventual need of radiographs of completion is showed. In searching for an optimization of the technique for nonionic contrast medium, a panoramic radiograph performed 10' after the end of the injection is pointed out as the key-moment of the test, being extremely rich in information, so as to help defining the most appropriate technique to continue the examination. For its excellent tolerability and high reliability, the nonionic contrast medium is recommended also in routine IVP, not only in risk patients.

[Ureteral duplication and anomalous symptomatology. Presentation of a case]. / Duplicità ureterale a sintomatologia anomala. Presentazione di un caso.

The authors report a case of unilateral ureteral duplication with extravesical ureteral orifice evaluated with sonography and confirmed by surgery. The peculiarity of the case is founded on the anomalous clinical findings with poorly significant uroculture and the apparent discrepancy between sonographic and urographic finding. The important rule of sonographic evaluation in early diagnosis of kidney malformations is confirmed.