Target Therapy for Extramedullary Relapse of FLT3-ITD Acute Myeloid Leukemia: Emerging Data from the Field.

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase family member. Mutations in FLT3, as well known, represent the most common genomic alteration in acute myeloid leukemia (AML), identified in approximately one-third of newly diagnosed adult patients. In recent years, this has represented an important therapeutic target. Drugs such as midostaurin, gilteritinib, and sorafenib, either alone in association with conventional chemotherapy, play a pivotal role in AML therapy with the mutated FLT3 gene. A current challenge lies in treating forms of AML with extramedullary localization. Here, we describe the general features of myeloid sarcoma and the ability of a targeted drug, i.e., gilteritinib, approved for relapsed or refractory disease, to induce remission of these extramedullary leukemic localizations in AML patients with FLT3 mutation, analyzing how in the literature, there is an important development of cases describing this promising potential for care.

Diagnostic test assessment. Validation study of an alternative system to detect microsatellite instability in colorectal carcinoma.

The American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) have been recently strongly recommended the evaluation of mismatch repair status (MMS) as molecular biomarkers in colorectal cancer for a better prognostic stratification of patients. This recommendation is emphasized by the recent evidence of Microsatellite Instability (MSI) as a predictive marker for chemotherapy and immunotherapy.In this scenario, the validation of molecular biomarker testing methods seems to be essential to design the most appropriate tailored therapy and the most suitable care strategy, respectively.In this study, we validated an alternative method based on capillary electrophoresis system label-free PCR (Qiaxcel system) to evaluate the MSI Bethesda Panel. We also parallel the results with a standard approach.Our data showed total concordance with the standard approach, with a highly time-efficient and easy procedure combined with high sensitivity for MSI detection.Alternative capillary electrophoresis based on label-free PCR such as the Qiaxel system is a very sensitive and specific method to detect MSI for the management of patients with colorectal cancer. This procedure is adequate and suitable in diagnostic routine for the evaluation of microsatellite repeats compared to standard procedures.

Is the sublay self-gripping mesh effective for incisional ventral hernia repair? Our experience and a systematic review of the literature.

Sublay mesh repair seems to be the most effective method for treating incisional hernias (IHs). The aim of this study was to report our experience with retromuscular repair and self-gripping mesh for the treatment of midline IHs. In addition, we provided a systematic review of the literature regarding the use of this novel combination. All patients undergoing elective IH repair from June 2016 to November 2018 were included. The self-gripping mesh was placed in the sublay position. Demographic data, defect sizes, postoperative complications and follow-up durations were collected. A systematic review of the available literature was conducted in January 2020 using main databases. A total of 37 patients (20/17M/F) were included in this study, and the mean age and body mass index (BMI) were 58 years and 27 kg/m2, respectively. Minor complications occurred in six patients. Long-term follow-up demonstrated recurrence in three patients. Regarding the review, five publications were considered relevant. The highest complication rate was 28.6%, and the recurrence rate varied from 0 to 5.1%. This is the first review of the literature regarding sublay IH repair using a self-gripping mesh. The low rates of postoperative complications and recurrence in our experience and those reported by most of the reviewed articles demonstrate that this is a safe and effective method for repairing IHs.

A retrospective, Italian multicenter study of complex abdominal wall defect repair with a Permacol biological mesh.

Complex abdominal wall defects (CAWDs) can be difficult to repair and using a conventional synthetic mesh is often unsuitable. A biological mesh might offer a solution for CAWD repair, but the clinical outcomes are unclear. Here, we evaluated the efficacy of a cross-linked, acellular porcine dermal collagen matrix implant (Permacol) for CAWD repair in a cohort of 60 patients. Here, 58.3% patients presented with a grade 3 hernia (according to the Ventral Hernia Working Group grading system) and a contaminated surgical field. Permacol was implanted as a bridge in 46.7%, as an underlay (intraperitoneal position) in 38.3% and as a sublay (retromuscolar position) in 15% of patients. Fascia closure was achieved in 53.3% of patients. The surgical site occurrence rate was 35% and the defect size significantly influenced the probability of post-operative complications. The long-term (2 year) hernia recurrence rate was 36.2%. This study represents the first large multi-centre Italian case series on Permacol implants in patients with a CAWD. Our data suggest that Permacol is a feasible strategy to repair a CAWD, with acceptable early complications and long-term (2 year) recurrence rates.

A Retrospective Study on Insertion Torque and Implant Stability Quotient (ISQ) as Stability Parameters for Immediate Loading of Implants in Fresh Extraction Sockets.

BACKGROUND: To date, insertion torque value (ITV) and implant stability quotient (ISQ) obtained by the Osstell instrument are common clinical methods to assess the initial stability of an implant for a predictable loading procedure. The aim of this current study is to evaluate the ITV and ISQ as stability parameters as part of the decision-making protocol in the adoption of immediate loading in fresh extraction sockets. MATERIALS AND METHODS: A total of 41 tapered implants were allocated into two groups: the test group (n = 11; 3 males and 8 females; mean age: 62.8 ± 10.7) which received 18 implants as type 1 fresh extraction sockets after teeth removal and the control group (n = 7; 4 males and 3 females; mean age: 65.4 ± 9.7) which received 23 implants placed in healed sockets for a period of at least 3 months. Both the ITV and ISQ data were recorded at the time of insertion (t 0). Since ITV (test group) and ITV/ISQ (control group) values were useful for the immediate loading protocol, a screw-retained temporary crown was immediately loaded. ISQ values were recorded after a healing period of 4 months (t 1). RESULTS: ITV mean values at t 0 in test and control groups were, respectively, 48.61 ± 15.39 and 70.47 ± 14.71, whereas ISQ mean values were 57.55 ± 1.93 and 72.86 ± 5.25, respectively, showing a statistically significant difference (p value < 0.001). ISQ mean values at t 1 in either the test or the control group were 68.68 ± 4.20 and 74.54 ± 4.17, not showing a statistical difference. The implant survival rate was 100% in both groups, and no surgical and prosthetic complications were reported during the study. CONCLUSION: In conclusion, this study remarked the presence of a residual gap that influenced the ISQ during implant insertion in fresh extraction sockets making this parameter not sufficient for a conclusive decision in the immediate loading, whereas the ITV alone showed to be the best parameter for a final substantial decision.

Intestinal obstruction due to congenital bands in adults who have never had abdominal surgery Two case reports and a review of the literature.

Congenital abdominal bands are a very rare entity and are often silent for a person's entire life. In a very few circumstances, however, they can manifest with clinical symptoms. Diagnosis of these bands is very challenging as the patient has never submitted for abdominal surgery and imaging, laboratory tests and clinical examination can be silent or unspecific. Two patients were admitted to and operated on in our hospital between June 2017 and July 2018. All patients had a bowel obstruction at the time of presentation, presenting no emission of faeces or gas. Conservative therapy was tried in one case, and surgical intervention was required. At surgery, both patients were found to have congenital bands causing the occlusion. The postoperative courses were uneventful. Small bowel obstruction (SBO) by congenital bands remains a challenging disease for surgeons. Diagnosis of SBO has to be suspected even if radiology does not indicate any relevant features. Laparoscopy should be the preferred approach, but if not feasible, then open surgery can resolve the case. KEY WORDS: Adhesions, Congenital bands, Intestinal occlusion, Laparoscopy.

miR-155 regulative network in FLT3 mutated acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) represents a heterogeneous disorder with recurrent chromosomal alterations and molecular abnormalities. Among AML with normal karyotype (NK-AML) FLT3 activating mutation, internal tandem duplication (FLT3-ITD), is present in about 30% of patients, conferring unfavorable outcome. Our previous data demonstrated specific up-regulation of miR-155 in FLT3-ITD+ AML. miR-155 is known to be directly implicated in normal hematopoiesis and in some pathologies such as myeloid hyperplasia and acute lymphoblastic leukemia. METHODS AND RESULTS: To investigate about the potential influence of miR-155 de-regulation in FLT3-mutated AML we generated a transcription factors regulatory network and combined this with data from multiple sources that predict miR-155 interactions. From these analyses, we derived a sub-network, called "miR-155 module" that describes functional relationship among miR-155 and transcription factors in FLT3-mutated AML. We found that "miR-155 module" is characterized by the presence of six transcription factors as central hubs: four miR-155 regulators (JUN, RUNX1, FOSb, JUNB) and two targets of miR-155 (SPI1, CEBPB) all known to be "master" genes of myelopoiesis. We found, in FLT3-mutated AML, a significant down-regulation of miR-155 target genes CEBPB and SPI1 and up-regulation of miR-155 regulator genes JUN and RUNX1. We also showed that PKC412-related FLT3 inhibition, in MV4-11 cell line, causes down-regulation of miR-155 and increased level of mRNA and protein of miR-155 target SPI1. We showed in experiments of miR-155 mimic in K562 cell line, a high increase of miR-155 and an inverse correlation with the mRNA levels of its targets SPI1 and CEBPB. Moreover silencing of miR-155 in primary AMLs causes mRNA up-regulation of its target SPI1 and CEBPB. CONCLUSION: Our results suggest that activating mutation of FLT3 in AML can lead, through the induction of JUN, to an increased expression of miR-155, which then causes down-regulation of SPI1 and CEBPB and consequently may causes block of myeloid differentiation.

Laparoscopic implementation of the Altemeier procedure for recurrent rectal prolapse. Technical note.

INTRODUCTION: Many surgical options exist to treat rectal prolapse with different indications, feasibility and results in urgent and complicated cases. These include perineal or abdominal approaches including rectopexy with or without resection. Perineal approaches have reduced surgical invasivity and hospital stay if compared to transabdominal approaches by open surgery or laparoscopy. Up to now there was still a clear dividing line for surgical treatment between the perineal approach, used more for complicated emergency case while the transabdominal open, or laparoscopic approach more common in elective surgery, but more complex to perform. PRESENTATION OF CASE: A 37 year old female patient affected by psychiatric disease presented with an unreducible second recurrence of a complicated rectal prolapse. The patient was treated with a third Altemeier procedure but now performed under laparoscopic control. The patient recovered promptly without any complication or recurrence up to the 24 months follow-up. DISCUSSION: To the best of our knowledge, this is the first case report describing the combined laparoscopic-perineal approach for the treatment of a complicated recurrence of rectal prolapse. The technical feasibility, the rapidity, the optimal outcome and the rationale behind this option all suggest that this laparoscopic assistance certainly allows an implementation of the effectiveness, safety and results of an established effective perineal approach. CONCLUSION: This combined approach has the advantage of maintaining the simplicity and rapidity of conventional perineal surgery, adding the advantages of abdominal control and avoiding the risks, the invasivity, and the longer duration of more complex laparoscopic procedures.

Our early experiences with single-incision laparoscopic surgery: the first 32 patients.

BACKGROUND: Most of the laparoscopic surgeons have been attempting to reduce incisional morbidity and improve cosmetic outcomes by using fewer and smaller ports. Single-incision laparoscopic surgery (SILS) is a new laparoscopic procedure. Herein we would like to present our experiences. PATIENTS AND METHODS: Between January 2009 and October 2009, data of the 32 patients who were operated through SILS are evaluated prospectively. There were 22 females and 10 males with a mean age of 45.1±14.8 years. Ten splenectomies for idiopathic thrombocytopenic purpura, 16 cholecystectomies for acute cholecystitis or asymptomatic gallstones, 3 appendectomies for acute appendicitis, one distal pancreatosplenectomy for Renal Cell Cancer metastases, 1 adrenalectomy for Conn Syndrome and 1 case of liver resection for hepatic adenoma were carried out. The most common splenectomy indication was idiopathic thrombocytopenic purpura, cholecystectomy indication was acute cholecystitis (n=8), and asymptomatic cholelithiasis (n=8), appendectomy indication was acute appendicitis, distal pancreatosplenectomy indication was renal cell cancer metastases, adrenalectomy indication was Conn syndrome and liver resection indication was left hepatic mass in between segments 1 and 2. SILS was carried out successfully in 31 patients. Only in 1 patient conversion was required owing to bleeding. RESULTS: All procedures were carried out through a 2-cm umbilical incision. There was no mortality and morbidity recorded. CONCLUSIONS: In experienced hands of minimally invasive surgeons, SILS incision laparoscopic surgery could be carried out successfully in a wide range of surgical operations. However, to be able to show the differences between Standard laparoscopic surgery and single SILS, prospective randomized comparative studies are required.

Appendicular tuberculosis: the resurgence of an old disease with difficult diagnosis.

Gastrointestinal tuberculosis (TB) is quite rare, representing only 3% of all extra-pulmonary cases. Blind gut and ileum are the most common gastrointestinal localizations, while appendix involvement is infrequent. Appendix involvement is usually related to symptoms of acute appendicitis since the caseous necrosis may lead to adhesions and surgical complications such as perforation. For this reason patients with suspected appendicular TB usually undergo surgery even without a secure diagnosis. In these cases, due to the absence of specific symptoms and signs, the diagnosis is delayed after surgery, thus resulting in a high percentage of important, and sometimes lethal, complications. Histopathological examination is often the only way to reach a diagnosis and to establish specific antibiotic therapy, while an early diagnosis could avoid surgical treatment. We report a case of appendicular TB not only for its rarity but also to discuss the difficulty in its diagnosis.

Prospective randomized comparison of clinical results between hand-assisted laparoscopic and open splenectomies.

BACKGROUND: Although some studies have compared laparoscopic and hand-assisted laparoscopic splenectomy (HALS) in splenomegaly cases, no study has analyzed the differences between HALS and open splenectomy (OS). This study aimed to compare the HALS and OS techniques in splenomegaly cases. METHODS: This prospective study included 27 patients undergoing splenectomy for splenic disorders at the Department of General Surgery, Istanbul Medical Faculty between February and October 2007. Open splenectomy was performed for 14 patients and HALS for the remaining 13 patients. RESULTS: The end points compared included incision length, operative time, intraoperative blood loss, postoperative drain output and duration, postoperative pain scores, length of postoperative hospitalization, and perioperative complications. The authors found benefits of HALS over OS for incision length, postoperative pain score, postoperative drain output and duration, and hospital stay. The main advantages of the HALS technique over OS were less postoperative pain (p = 0.0002), shorter hospital stay (p = 0.004), and shorter abdominal incision (p = 0.012). CONCLUSIONS: For splenomegaly, HALS significantly facilitates the surgical procedure and reduces the hospital stay while maintaining the advantages of OS such as tactile sense as well as easy and atraumatic manipulation of enlarged spleens.

Laparoscopic resection of a large GIST of the stomach: is it preferable in elderly patients? A case report.

Gastrointestinal stromal tumour (GIST) of the stomach is extremely rare in the elderly. Surgical resection of the stomach by partial gastrectomy or wedge resection is the standard treatment. Today the resection can also be performed laparoscopically, especially in the case of small tumours as well as for larger GIST though there are unclearly defined oncological limits. The authors report the successful treatment of a large 7.5 cm GIST of the stomach by laparoscopic wedge resection in a 78-year-old patient. The GIST was almost entirely located intraperitoneally between the stomach and the spleen and could be radically resected with a minimal touch technique. The patient recovered promptly and manifested no recurrence at a 2-year follow-up. The authors focus on the main factors supporting the indication for laparoscopic resection of large gastric GIST, especially in the elderly. The surgical risk/benefit ratios of the different approaches, the surgeon's skills in laparoscopically respecting the rules of oncological surgery, and informed consent of the patient in relation to the limited scientific evidence concerning the main risk factors of recurrence are all important considerations.

Asymptomatic congenital intrapericardial diaphragmatic hernia and epigastric hernia in the adult.

The congenital intrapericardial hernia is a rare kind of diaphragmatic hernia. It is due to an embryologic defect of the central tendon of the diaphragm, often accompanied by other congenital malformations. This work presents a unique case report in the literature of the congenital association between intrapericardial diaphragmatic hernia and epigastric hernia in an adult woman. In spite of herniation of the colon and omentum the patient was completely asymptomatic, requesting surgery for an epigastric hernia for aesthetic reasons. The defect of the diaphragm was sutured and the abdominal wall was repaired with a prosthetic mesh.

[Pancreatic trauma: a case report]. / Il trauma del pancreas: a proposito di un caso clinico.

Pancreatic trauma is a rare event, accounting for approximately 3% of all blunt abdominal traumas. The related mortality is quite high, around 5-30%, mostly due to the associated haemorrhagic lesions and to the delay in establishing the diagnosis, while pancreatic damage is directly responsible for death in only 5-10% of cases. We report here on a case of severe pancreatic trauma, underestimated initially and treated surgically at a later stage. The literature shows that the main difficulty in cases of pancreatic trauma is still related to failure recognizing the injury or to the frequent delay in diagnosing the condition, above all in haemodynamically unstable patients. In these cases, as in the one treated in this report, the clinical evidence and the priority accorded to the treatment of the shock are factors that tend to limit thorough examination. In haemodynamically stable patients, on the other hand, the multislice CT-scan and MR pancreatography-wirsungography are useful for the diagnosis. The treatment can be either conservative or surgical, depending on the extent of the damage, especially to the Wirsung duct. Surgical treatment with preservation of the entire pancreatic parenchyma, as performed in our case, even if technically demanding, makes it possible to maintain the function of the pancreas, thus reducing the risk of metabolic complications.

Hepatocarcinoma, gallstone disease and gallbladder carcinoma: a case report of a rare incidental association.

We report a rare case of a patient operated on with a diagnosis of hepatic tumour and gallstone disease, which postoperatively was found to be a hepatocellular carcinoma associated with a gallbladder carcinoma. Spiral CT at admission showed only a hepatic mass in the 4th segment, compatible with hepatocellular carcinoma and gallbladder lithiasis. Cholecystectomy was performed followed by a wedge resection of the 4th segment of the liver. The histopathological examination revealed a well-differentiated hepatocellular carcinoma and, surprisingly, an adenocarcinoma of the gallbladder confined to the mucosa. The association of a hepatocellular carcinoma and gallbladder adenocarcinoma is extremely rare. This association, together with an analysis of the literature showing the increased incidence of gallstones in cirrhotic patients and the consequent greater surgical risk when undergoing subsequent cholecystectomy after liver resection, would suggest that cholecystectomy should be performed routinely during liver resection for hepatocellular carcinoma or cirrhosis, even for minor resections and when there are no evident signs of gallbladder disease.