Real world results of venetoclax combined with hypomethylating agents in relapsed/refractory AML.

OBJECTIVE: Relapsed/refractory AML cases are much more resistant to chemotherapy. Venetoclax is a highly sensitive BCL-2 inhibitor. It was aimed to evaluate the effects of venetoclax therapy on real-world R/R AML survival outcomes, the effects of the cytogenetic characteristics of the patients and previous clinical applications on treatment response, and venetoclax treatment toxicity. PATIENTS AND METHODS: The study included patients who only received a venetoclax-based salvage on R/R AML patients from Turkey. The study included a total of 62 patients from 6 different centers in Turkey. Response to 2 cycles of venetoclax treatment was assessed by bone marrow blast rate. The demographic data, cytogenetic characteristics, AML type, MDS type, response rates and overall survival of the patients after venetoclax combination treatment were assessed. Median age of the patients was 65 (19-85). Mean number of prior treatments was 2.67 ±1.75. RESULTS: 13 patients (21%) had a history of allogenic stem cell transplantation. 58 (93.5%) had received HMA therapy before venetoclax. 36 patients (58.1%) had de-novo AML, and 25 (40.3%) previously had MDS. Treatment response was evaluated as complete remission (n = 21, 33.9%), partial response (n = 17, 27.4%), and treatment failure (n = 24, 38.7%). Patients in the TF group were significantly more likely to have poor cytogenetic and to have received allogeneic transplants. The mean estimated overall survival after the venetoclax treatment was 9.13 ± 0.75 months. CONCLUSIONS: The study population consisted of a group of patients who had relapsed or primary refractory disease with poor prognosis, despite numerous rounds of chemotherapy. It is our belief that the high response rates obtained with the combination of venetoclax/HMA, and having obtained positive results with poor risk patients, indicated a promising perspective for R/R AML patients.

Anesthetic management of a neonate with congenital diaphragmatic hernia under high-frequency oscillatory ventilation.

Perioperative management of a neonate with congenital diaphragmatic hernia (CDH) is challenging because of pulmonary hypoplasia, pulmonary hypertension, and respiratory insufficiency. In this report, we present our intra-operative experience in a 4-days old and 3070 grams CDH neonate. He was admitted to neonatal intensive care unit and intubated due to severe respiratory insufficiency. He showed signs of severe pulmonary hypoplasia and his echocardiography revealed a cardiac dextroversion. The patient was relatively stabilized after four days under combined high-frequency oscillatory ventilation (HFOV) and inhaled nitric oxide (iNO). A corrective surgical intervention was sustained with dopamine, dobutamine, fentanyl and midazolam infusions. Ventilator settings were: 9 cmH2O MAP; 15-Hz frequency; 30 cmH2O amplitude and 55% FiO2. Venous-blood gas analysis indicated pH:7.38 pO2:36.2, pCO2:39.2 with SpO2:98%. We believe that HFOV and iNO combination is an effective alternative for the anesthetic management of CDH cases as it provides better gas exchange and less volutrauma.

Comparison of Single-Port Percutaneous Extraperitoneal Repair and Three-Port Mini-Laparoscopic Repair for Pediatric Inguinal Hernia.

AIM: Laparoscopy has been widely used in surgical practice in pediatric age, and many techniques for laparoscopic hernia repair have been described till now. In this study, we compared two laparoscopic techniques performed by two surgeons; each surgeon practicing only one of the two techniques. MATERIALS AND METHODS: A retrospective analysis was performed on the surgical charts, enrolling 71 patients with uncomplicated inguinal hernia. Patients were divided into two groups according to the type of surgery: (Group A, 24 patients aged 2 months-8 years) laparoscopic percutaneous internal ring suturing technique and (Group B, 47 patients aged 35 days-12 years) three-port mini-laparoscopic technique. The hernia sac was ligated at the level of internal ring, using nonabsorbable 4/0-3/0 suture. Any unexpected contralateral opening was repaired in the same manner for both groups. Follow-up period was 4 months-2 years and 9 months-8 years, respectively. Operative time and complications were analyzed. RESULTS: Operation time (19.58 ± 7.06 minutes versus 35.87 ± 10.34 minutes, P < .001) was shorter in the percutaneous repair group. However, when subdivided by unilateral and bilateral presentation, only unilateral operative time was shorter compared to three-port group. There were no recurrences in Group A, while two recurrences occurred in Group B during the learning curve period. A contralateral opening accompanied the presenting unilateral hernia in 3 cases for Group A and 16 for Group B. One patient had to be converted open resulting from epigastric vessel injury, and postop hydrocele formation was seen in another in Group A. No intraoperative complications were seen in Group B. CONCLUSION: The overall experience shows that laparoscopic repair is a reliable approach regardless of the chosen technique. Percutaneous repair seems to be a less invasive method with shorter operative time, but it is not free of complications according to this series.

Inherited IL-12Rß1 Deficiency in a Child With BCG Adenitis and Oral Candidiasis: A Case Report.

Tuberculosis is a major worldwide problem, and protection from it is achieved mainly by live attenuated bacille Calmette-Guérin vaccine, which is capable of causing disease in immunocompromised host. Oral thrush is abnormal in healthy children, which suggests an underlying immunodeficiency. Mendelian susceptibility to mycobacterial disease is a rare primary immunodeficiency characterized by a selective predisposition to weakly virulent Mycobacteria and Salmonella and also predisposition to chronic mucocutaneous candidiasis. Interleukin 12 receptor ß1 (IL-12Rß1) deficiency is the most common disease of Mendelian susceptibility to mycobacterial disease, and to date only 50 IL-12Rß1 deficient patients with clinical signs of chronic mucocutaneous candidiasis have been reported. We report a 2.5-year-old daughter of consanguineous parents with both regional bacille Calmette-Guérin lymphadenitis and recurrent oral candidiasis carrying biallelic R175W mutation in the IL12RB1 gene, resulting in complete loss of expression of IL-12Rß1. To our knowledge, this is the first report of bacille Calmette-Guérin lymphadenitis with concurrent oral candidiasis displaying such a mutation. New mutations and wide clinical diversities are the indisputable fact of populations with a high rate of consanguineous marriages.

Comparison of the effect of LMA and ETT on ventilation and intragastric pressure in pediatric laparoscopic procedures.

BACKGROUND: The aim of our study was to compare classic laryngeal mask airway (LMA-C) with the endotracheal tube (ETT) in pediatric laparoscopic surgery to evaluate the intragastric pressures (IGP) using intragastric pressure monitoring. We also sought to investigate the related influence on respiratory parameters. METHODS: The Ethics Committee of the Health Institution approved the study protocol. A total of 40 patients, ASA I-II, three and a half months to 12 years old were included in this randomized study. Two study groups were formed: the ETT group and the LMA-C group. A nasogastric tube was inserted following induction to evacuate any intragastric gas and fluid before application of either LMA-C or ETT. The change in IGP was measured with a transducer, which was attached to the nasogastric tube. IGP, peak airway pressures (PAP), SPO2 and ETCO2 were recorded. Repeated ANOVA measures were used to evaluate the change in IGP, PAP, SPO2 and ETCO2 times in both groups. RESULTS: The change in IGP was not significant among the groups except at 15 and 30 minutes (P<0.05). The changes in PAP, SPO2, and ETCO2 levels were not significant. CONCLUSION: The perioperative intragastric pressure evaluation failed to show any significant change in intragastric pressures and ventilation parameters due to the application of LMA-C in this study. We advocate LMA-C application as a feasible anesthetic device in pediatric laparoscopic surgery.

Evidence for medium chain triglycerides in the treatment of primary intestinal lymphangiectasia.

UNLABELLED: Primary intestinal lymphangiectasia is an uncommon congenital anomaly. It is an intrinsic abnormality of the intestinal lymphatics system. Over the years, various treatment options such as diuretics, albumin transfusions and a medium chain triglycerides (MCT) diet as well as surgical options such as resection of isolated segments and peritoneal-venous shunts have been used. An MCT diet, which is a low fat, high protein diet, is increasingly used in the management of this anomaly. AIM: The aim was to review the evidence for medium chain triglycerides as a therapeutic option in patients with primary intestinal lymphangiectasia. MATERIAL AND METHODS: A literature search was performed and individual case details were extracted. We found 55 cases, of which 3 were from our own institute. The cases were divided in 2 groups: Group A (n=27) consisted of patients treated with MCT, and Group B (n=28) consisted patients not treated with MCT. Cases were analysed for symptomatic response to MCT as well as mortality. RESULTS: 17 of 27 cases (63%) treated with MCT had complete resolution of symptoms while only 10 of 28 (35.7%) patients in group B showed complete resolution. Mortality for Group A was 1 out of 27 (3.7%), while mortality in group B was 5 of 28 (17.85%) patients. CONCLUSION: We conclude that, although an MCT diet is not completely curative in all cases, it does improve the symptoms of primary intestinal lymphangiectasia and reduces mortality. Hence it is a valid option in the paediatric age group.

Balloon extraction of a retained rectal foreign body under fluoroscopy, case report and review.

Rectal foreign body impaction in infancy is extremely rare, and the literature does not describe a standard treatment procedure. Extraction by fiberoptic rectosigmoidoscope is advocated as the treatment of choice but is not free of possible complications. It should be also taken into consideration that the type of foreign body has an impact on the timing of treatment. We report a 50-day-old male presenting with a retained broken tip of a mercury thermometer in the rectum. A novel method of diagnostic approach and treatment is discussed.

Management of ovarian cysts during infancy: autoamputation presenting as a possible pitfall.

The widespread use of routine antenatal ultrasound has relatively increased the frequency of intrauterine diagnosis of ovarian cysts. In utero adnexal torsion may present with subsequent autoamputation in some of these lesions. Prenatal and postnatal ultrasonographic findings, however, may not always be relevant in making the correct diagnosis. The authors report on two cases with prenatally-diagnosed hypoechogenic cystic masses. The cysts failed to resolve after a period of conservative management. A laparoscopic approach revealed ovarian autoamputation presenting as cystic mass. Preoperative ultrasound, abdominal CT and MRI failed to detect the presence of autoamputation. The present report discusses the possibility of an otherwise silent ovarian autoamputation, which may necessitate laparoscopic intervention for correct diagnosis, in neonates presenting with persistent ovarian cysts.

Thoracoscopic assessment of mediastinal tuberculous lymphadenitis in a 4-month-old child.

Isolated mediastinal tuberculous lymphadenitis is a relatively common entity in children, second in frequency after cervical localization. In the absence of an accompanying parenchymal lesion, mediastinal tuberculous lymphadenitis may pose a diagnostic dilemma on admission and must be distinguished from other causes of mediastinal masses. Bronchoscopy is suggested as a diagnostic tool where tuberculosis cannot be excluded by radiology or specific skin tests. Thoracotomy and excision is reported as necessary to treat the obstructive symptoms. In this report, the diagnostic and therapeutic feasibility of thoracoscopic mediastinal node biopsy in a 4-month-old presenting mediastinal tuberculous lymphadenitis is reported.

The effect of antiepileptic drugs on vitamin B12 metabolism.

The effects of antiepileptic drugs (AED) on the serum concentration of vitamin B12, folic acid and homocysteine (HMC), and erythrocyte folic acid levels were determined in 45 epileptic patients (30 women, 15 men; mean age 31.7 years) and 23 healthy volunteers (control group; 18 women, five men; mean age 33.4 years). All patients were either on carbamazepine (CMZ), oxcarbazepine (OXZ), or valporate (VP) monotherapy. Serum vitamin B12 levels were low in 17.8% of patients and 8.7% of the controls (P = 0.299). Serum homocysteine levels were high in 17.8% of the patients (P = 0.008). Fifty percent of the patients who had hyperhomocysteinemia, and 75% of the patients who had low serum vitamin B12 level were on CMZ monotherapy. Peripheral blood smears showed hypersegmented neutrophils and macrocytosis in 13.3%, hypochromia and microcytosis in 26.7%, acanthocytes in 2.2%, and thrombocytosis in 2.2% of all patients. The control group had normal peripheral blood smears, except in four cases that showed hypocromia and microcytosis. Long-term administration of AED may cause elevation of homocysteine and development of subnormal serum vitamin B12 levels. Peripheral blood smear abnormalities were frequently seen in patients receiving antiepileptic treatment (P = 0.022), particularly in patients on CMZ monotherapy (P = 0.281). However, homocysteine, vitamin B12, folic acid levels and peripheral blood smear findings did not correlate with the drugs used (P = 0.665, 0.336, 0.249 for CMZ, OXZ, VP, respectively).

Minimal access surgical repair of Morgagni hernia: the fate of the unresected hernia sac.

Treatment of retrosternal diaphragmatic (Morgagni) hernia is composed of a simple surgical closure of the retrosternal opening either conventionally by open abdominal or thoracic approaches, or more recently, by using minimal access surgery (MAS). Clinical experience using the latter approach is very limited in children. Removal of the hernia sac is a controversial issue, since the sac is said to carry the risk of cyst formation or show spontaneous resolution. This issue represents a 7-year-old boy with Morgagni hernia that was successfully repaired by the MAS approach. The hernia sac was not resected because of adhesion to the adjacent tissues. The patient was readmitted with fluid accumulation within the remaining sac 2 months after the operation. A complete spontaneous resolution was observed within 2 months under conservative follow-up. To our knowledge, the temporary complication described in this paper has not been published in the literature.

Esophageal muscle cell interaction with biopolymers.

BACKGROUND: The in vitro interactions of esophageal smooth muscle cells (SMCs) with synthetic absorbable polymers were tested and artificial muscle tissues harvested from subcutaneous implantation were examined. MATERIAL/METHODS: Esophageal tissue samples from adult and fetal (25-day gestational age) rabbits were cut into small pieces and cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. Growing cells were identified as SMCs by immunostaining for anti-actin and anti-myosin antibodies. Equal volumes of agar gel and medium were mixed and used for 3-D culture. 5x10(5) cells and 1 mg polyglycolic acid (PGA) and poly-lactide-co-glycolide acid (PLGA) fibers were seeded in six-well tissue culture plates. On days 2 and 7 growing cells were counted by a hemocytometer and cell-polymer interactions were evaluated with light microscopy. Adult and fetal SMCs were seeded onto the PGA and PLGA scaffolds, cultivated for two weeks, and implanted subcutaneously on the backs of the rabbits. Cell-polymer implants were retrieved after four weeks and muscle formation was evaluated histologically and immunohistochemically. RESULTS: Growing cells stained positive for actin and myosin proteins. Cell-polymer interactions were poor after 24 hours, whereas intensive attachment to the fibers was detected 48 hours following cultivation. Both fiber materials supported cell proliferation. PLGA scaffolds improved muscle formation more efficiently than PGA, and fetal and adult SMCs showed similar mass quality. CONCLUSIONS: Scaffolds are important as cell-carrying vehicles, and material-cell interactions should be tested before application. A 3-D culture prepared with agar gel and medium is practical for testing material toxicity.

Incomplete duodenal obstruction in a newborn.

A case of newborn with incomplete duodenal obstruction caused by superior mesenteric artery syndrome has been presented with this report. A full term, 1-day-old baby girl was referred to our hospital because of recurrent bilious vomiting since birth and upper gastrointestinal barium study revealed the incomplete obstruction at the 3rd part of the duodenum with a vertical abrupt cutoff. The diagnosis of superior mesenteric artery syndrome was made with ultrasonography and duodenojejunostomy was carried out. Although it is extremely rare, superior mesenteric artery syndrome should also be considered as one of the rare cause of incomplete duodenal obstruction in newborn period.

Multifocal tuberculosis of the chest wall without pulmonary involvement.

Skeletal tuberculosis (TB) is usually seen in association with a primary pulmonary focus. However, it is being increasingly recognized that the former may be encountered without the latter, particularly in children. Sternal lesions have been frequently reported in infants, presumably secondary to Bacillus Calmette-Guerin (BCG) vaccination. Herein we report a case of rib TB and a cold abscess in a child who had previously had sternal TB ; that diagnosis had been missed at the time. Timely treatment of apparently solitary skeletal lesions may reduce the number of multifocal cases of skeletal TB in children.

Bronchobiliary fistula detected with hepatobiliary scintigraphy.

Bile leakage into the thoracic cavity is a rare complication of invasive cancer. A 12-year-old boy was diagnosed with undifferentiated sarcoma of the right lobe of the liver invading the diaphragm. An extended right hepatectomy and total resection of the mass was performed, leaving a patchy tumoral invasion at the anterior diaphragmatic surface. Surgery was followed with a combined chemotherapy regimen. In the sixth postoperative month, he was readmitted with bilious expectoration. Tc-99m mebrofenin hepatobiliary scintigraphy revealed radiotracer accumulation in the right hemithorax. Bile leakage into the right thoracic cavity was diagnosed based on the hepatobiliary scintigraphic findings. For this patient; hepatobiliary scintigraphy, which is routinely used to visualize the liver and biliary tree, provided a noninvasive mean for the precise diagnosis of a bronchobiliary fistula. The fistula was then confirmed and corrected with surgery. The patient recovered uneventfully.

Peritoneal tuberculosis with elevated serum CA 125 level mimicking advanced ovarian carcinoma in an adolescent.

Differential diagnosis between tuberculous peritonitis and peritonitis carcinomatosis is extremely difficult in patients with ascites, peritoneal implants and elevated CA 125 level. A 16-year-old girl presented with abdominal distention, intermittent fever and weight loss. Physical examination and radiologic studies revealed massive ascites, generalized peritoneal thickening and slightly enlarged right ovary with a cystic mass and left pleural effusion. Serum CA 125 was 939 U/L (normal range: 0-35 U/L) and other tumor markers including alpha fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) were within normal range. Acid-fast stain and culture were negative for Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy were performed with the presumptive diagnosis of peritonitis carcinomatosis, and histologic examination revealed multiple granulomas with epithelioid cells and caseification necrosis which confirmed tuberculosis. Quadruple anti-tuberculosis treatment was administered and the patient's clinical findings and serum CA 125 level returned to normal. In conclusion, tuberculous peritonitis should be considered in the differential diagnosis of patients with ascites and elevated serum CA 125. This marker may be useful in monitoring treatment response.

Lumbar teratoma presenting intradural and extramedullary extension in a neonate.

BACKGROUND CONTEXT: The association of teratomas and spinal malformations such as spina bifida, partial sacral agenesis, hemivertebrae, and diastematomyelia has been described in the literature. Reported cases, however, are mainly presacral or sacrococcygeal with an extremely rare presentation of intradural extension. PURPOSE: A case of lumbar teratoma with an intradural extension and extramedullary component and the clinical outcome following surgical treatment are reported. STUDY DESIGN/SETTING: To our knowledge, among the reported teratoma cases with an intradural extension and extramedullary component, our case has a distinguishing feature regarding the involvement of the lumbar spine. It is also the first case, showing no neurological deficit during the postoperative period. METHODS: A full-term, female infant presented with a 30 x 30 x 10 mm lumbar mass covered with normal skin. The mass contained an irregular, bone-like, hard and mobile material accompanying cystic components. Magnetic resonance imaging revealed a total closure defect of the first and second lumbar laminae and a subcutaneous mass with intradural extension. The lesion was found to penetrate the dural sac through an extended exposure from T12 to L3. There was no firm attachment of the intradural, extramedullary component of the lesion. Total removal of the tumor was achieved. RESULTS: The patient was discharged on day 7 without any neurological deficit or sign of hydrocephalus. The pathological examination showed a benign teratoma containing mature cartilage, muscle, adipose tissue, and glandular tissue. Follow-up at 2 years showed no recurrence or neurological deficit and a normal sphincter tone. Urodynamic evaluation was within normal limits. CONCLUSION: Accompanying a spinal dysraphic state, the mature teratoma in our case may support the idea of a tumor actually arising from a dysraphism and growing outward to produce the mass.

A continuous debate on contralateral processus vaginalis: evaluation technique and approach to patency.

We present our experience with the transinguinal diagnostic laparoscopy and discuss its efficacy in evaluating the contralateral side in unilateral inguinal hernias. The possible influence of the initial side of hernia, age and gender on recognized bilateralism were also evaluated in two study groups (diagnostic laparoscopy vs clinical diagnosis). In this retrospective study, we evaluated 36 bilateral, 158 left-sided and 303 right-sided consecutive inguinal hernia cases. A total of 211 out of 461 unilateral cases underwent hernia repair and transinguinal laparoscopic evaluation of the contralateral side. Complications and difficulties of the technique, the mean duration of laparoscopy and operative times were additionally analyzed from operation charts. In this study, bilateralism was determined by transinguinal laparoscopy in Group 1 (children with a contralateral patent processus vaginalis) and clinically in Group 2 those who had a metachronous hernia. The patients were also analyzed according to the side of the inguinal hernia, age and gender in both groups. We found an overall positive contralateral patency in 41 cases (19.4%). We failed to perform a successful diagnostic laparoscopy in six cases (2.7%). No anesthetic or surgical complications were noted. Transinguinal laparoscopy did not add any considerable time to the mean operation time. The incidence of bilateralism in Group 1 was higher in girls than boys. Clinically detected bilateralism was significantly higher in 0-6 month age group and contralateral patency detected via laparoscopy was high in all other age groups. We may conclude that transinguinal diagnostic laparoscopy is a feasible technique in children. We advocate its use as a tool with minimal complication risk even in the hands of novice.

Ectopic thoracic kidney in a child with congenital diaphragmatic hernia.

Thoracic ectopic kidney with partial or complete renal protrusion above the level of the diaphragma into the posterior mediastinum is the rarest form of all ectopic kidneys with an incidence of less than 1 per 10,000 cases. We present a newborn with right congenital diaphragmatic hernia associated with thoracic ectopic kidney. The diagnosis of ectopia was made prior to surgery. Gerota's fascia of kidney was used to close the diaphragmatic defect. Since this renal anomaly is usually asymptomatic, it does not require any specific treatment. However, a close examination of function and anatomy of the kidney prior to surgery of hernia is important and beneficial. We discuss the embryological context and the importance of renal scintigraphy in patients with ectopic kidney.