Alberto Porcu

Asymptomatic Gastric Perforation by a Toothpick

Background: Many cases of gastric perforation with peritonitis, pylephlebitis, hepatic abscesses, or lethal bleeding, caused by ingested long and sharp objects, are reported in the literature. Methods: During a right hepatectomy for a giant hemangioma, a wooden toothpick was found between the two layers of the hepatogastric ligament. It was not possible to find the passage of the foreign body through the gastric wall. The patient did not report any correlated symptoms. Results: There was no sign of inflammation around the toothpick, which was enveloped in thin scar tissue. The removal of the foreign body was performed without complications. Conclusions: The peculiarity of our case is the total absence of symptoms during and after the perforation. Despite the benign evolution of our case, toothpicks must be considered as potentially dangerous, like other pointed objects, and, therefore, removed immediately.

Primary umbilical endometriosis: case report and discussion on management options

INTRODUCTION We report a recently observed case of primary umbilical endometriosis (UE), with the main aim to discuss the management of this rare condition. PRESENTATION OF CASE A 24-year-old woman complained of a painful nodule on her umbilical region, bleeding with her menstrual cycle. Ultrasonography showed a hypoechoic superficial mass in the umbilicus and no signs of intra-abdominal endometriosis. Excision of the nodule under local anesthesia was performed. Histopathological analysis confirmed the diagnosis of umbilical endometriosis. Neither symptoms nor signs of local recurrence have been observed after 24 months. DISCUSSION UE should be taken into account in differential diagnosis of umbilical disorders even in young nulliparous women with no typical symptoms of pelvic endometriosis. Although there is a substantial agreement about the necessity of surgery, treatment options are either local excision of the lesion or removal of the whole umbilicus with or without laparoscopic exploration of the peritoneal cavity. The decision should be tailored for the individual patient, taking into consideration the size of the lesion, the duration of symptoms and the presence of possible pelvic endometriosis. CONCLUSION Local excision saving the umbilicus may be the treatment of choice in patients with small UE lesions.

Spontaneous regression of hepatocellular carcinoma: report of a case.

The widespread use of ultrasound in screening programmes for chronic liver disease has led to early diagnosis of hepatocellular carcinoma (HCC), and to the observation of some cases of tumour spontaneous regression. This is a rare event whose underlying mechanism is still unclear. We present here a case of spontaneous regression of HCC in a 71-year-old woman with chronic hepatitis and discuss possible aetiologies. None of the causative mechanisms proposed for spontaneous regression of HCC is completely satisfactory, so further studies are necessary to improve understanding of this unusual biological event. Therefore, we stress the importance of accumulating all such cases in the literature, because the clarification of aetio-pathogenic mechanisms may lead to the development of new treatment strategies for HCC.

99mTc-Tetrofosmin Pinhole-SPECT (P-SPECT) and Radioguided Sentinel Node (SN) Biopsy and in Breast Cancer Axillary Lymph Node Staging

We compared 99mTc-Tetrofosmin P-SPECT with radioguided SN biopsy in 101 T1/T2 BC pts to predict axillary lymph node status. The day before surgery all pts underwent lymphoscintigraphy (LS) to mark the SN, following subdermal injection of 99mTc-colloidal sulphur surrounding the breast lesion. LS was combined with pre and intraoperative gamma probe. Previously, all pts had also undergone P-SPECT. ALND was performed in all cases. The SN(s) was detected in 97/101 cases (96%) by LS and gamma probe; in the 4 missed cases P-SPECT predicted lymph node status. In the 97 comparable cases, radioguided SN biopsy showed a slightly higher accuracy than P-SPECT (94.8% vs 93.8%), but a higher false-negative rate (14.3% vs 8.6%); P-SPECT had a higher NPV (95.2% vs 92.5%). The two procedures when combined achieved 100% accuracy. Radioguided SN biopsy alone had 100% accuracy only in pts with BC < 15 mm. P-SPECT had 3 false negative cases, 2 of which were micrometastatic SNs, and 3 false positives. P-SPECT identified 81.2% of cases with a single node, determined the exact number of nodes in 82.6% of cases with 1 to 3 node and correctly classified 93.7% of pts as having < or = 3 or > 3 metastatic nodes. Radioguided SN biopsy seems indicated in selected, early stage, small BC pts, while P-SPECT shows a high sensitivity independent of primary tumor size, giving additional important preoperative prognostic information. The two procedures combined provided a better axillary lymph node status prediction in T1/T2 carcinomas, and could thus improve ALND pt selection.

Labial mucosa and combined labial/bladder mucosa free graft for urethral reconstruction

One-stage urethral reconstruction was performed using a free graft of labial mucosa and combined labial/bladder mucosa. We present the results of this technique in 12 cases that had a minimum follow-up period of 3 years. Eleven patients had medium penile or posterior hypospadias and one had chordee penis without hypospadias. Urethroplasty with labial mucosa was performed by two techniques: labial mucosa used alone or combined with bladder mucosa. The labial mucosa was harvested from the inner surface of the upper and/or lower lip, depending on which method was used. Seven patients, six with medium penile or posterior hypospadias and 1 with chordee without hypospadias, were given a labial mucosa graft alone; the urethral gap was 3.5 to 6 cm. The other five cases, all with posterior hypospadias, were treated by combined labial/bladder mucosa graft urethroplasty: the urethral gap was 6 to 13 cm. Follow-up (at 3 to 4 1/2 years) showed no complications apart from a urethral fistula in one patient and mild stenosis on the anastomosis in four cases, which required urethral dilatations in the first month after surgery.

Both de novo synthetized and exogenous fatty acids support the growth of hepatocellular carcinoma cells

Although it is well established that fatty acids (FA) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma (HCC), inhibition of Fatty Acid Synthase (FASN) cannot completely repress HCC cell growth in culture. Thus, we hypothesized that uptake of exogenous FA by cancer cells might play an important role in the development and progression of HCC. Lipoprotein lipase (LPL) is the enzyme that catalyses the hydrolysis of triglycerides into free fatty acids (FFA) and increases the cellular uptake of FA.

A functional mammalian target of rapamycin complex 1 signaling is indispensable for c‐Myc‐driven hepatocarcinogenesis

Amplification and/or activation of the c‐Myc proto‐oncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c‐Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c‐Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c‐Myc‐dependent hepatocarcinogenesis. Specifically, we found that ablation of Raptor, the unique member of mTORC1, strongly inhibits c‐Myc liver tumor formation. Also, the p70 ribosomal S6 kinase/ribosomal protein S6 and eukaryotic translation initiation factor 4E‐binding protein 1/eukaryotic translation initiation factor 4E signaling cascades downstream of mTORC1 are required for c‐Myc‐driven tumorigenesis. Intriguingly, microarray expression analysis revealed up‐regulation of multiple amino acid transporters, including solute carrier family 1 member A5 (SLC1A5) and SLC7A6, leading to robust uptake of amino acids, including glutamine, into c‐Myc tumor cells. Subsequent functional studies showed that amino acids are critical for activation of mTORC1 as their inhibition suppressed mTORC1 in c‐Myc tumor cells. In human hepatocellular carcinoma specimens, levels of c‐Myc directly correlate with those of mTORC1 activation as well as of SLC1A5 and SLC7A6. Conclusion: Our current study indicates that an intact mTORC1 axis is required for c‐Myc‐driven hepatocarcinogenesis; thus, targeting the mTOR pathway or amino acid transporters may be an effective and novel therapeutic option for the treatment of hepatocellular carcinoma with activated c‐Myc signaling. (Hepatology 2017;66:167–181).

Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice.

BACKGROUND & AIMS Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy without effective treatment options. MLN0128, a second generation pan-mTOR inhibitor, shows efficacy for multiple tumor types. We evaluated the therapeutic potential of MLN0128 vs. gemcitabine/oxaliplatin in a novel ICC mouse model. METHODS We established a novel ICC mouse model via hydrodynamic transfection of activated forms of AKT (myr-AKT) and Yap (YapS127A) protooncogenes (that will be referred to as AKT/YapS127A). Genetic approaches were applied to study the requirement of mTORC1 and mTORC2 in mediating AKT/YapS127A driven tumorigenesis. Gemcitabine/oxaliplatin and MLN0128 were administered in AKT/YapS127A tumor-bearing mice to study their anti-tumor efficacy in vivo. Multiple human ICC cell lines were used for in vitro experiments. Hematoxylin and eosin staining, immunohistochemistry and immunoblotting were applied for the characterization and mechanistic study. RESULTS Co-expression of myr-AKT and YapS127A promoted ICC development in mice. Both mTORC1 and mTORC2 complexes were required for AKT/YapS127A ICC development. Gemcitabine/oxaliplatin had limited efficacy in treating late stage AKT/YapS127A ICC. In contrast, partial tumor regression was achieved when MLN0128 was applied in the late stage of AKT/YapS127A cholangiocarcinogenesis. Furthermore, when MLN0128 was administered in the early stage of AKT/YapS127A carcinogenesis, it led to disease stabilization. Mechanistically, MLN0128 efficiently inhibited AKT/mTOR signaling both in vivo and in vitro, inducing strong ICC cell apoptosis and only marginally affecting proliferation. CONCLUSIONS This study suggests that mTOR kinase inhibitors may be beneficial for the treatment of ICC, even in tumors that are resistant to standard of care chemotherapeutics, such as gemcitabine/oxaliplatin-based regimens, especially in the subset of tumors exhibiting activated AKT/mTOR cascade. Lay summary: We established a novel mouse model of intrahepatic cholangiocarcinoma (ICC). Using this new preclinical model, we evaluated the therapeutic potential of mTOR inhibitor MLN0128 vs. gemcitabine/oxaliplatin (the standard chemotherapy for ICC treatment). Our study shows the anti-neoplastic potential of MLN0128, suggesting that it may be superior to gemcitabine/oxaliplatin-based chemotherapy for the treatment of ICC, especially in the tumors exhibiting activated AKT/mTOR cascade.

NEONATAL ACUTE APPENDICITIS IN AN INGUINAL-HERNIA

Acute appendicitis is very rare in the newborn, representing only 0.1%–0.2% of childhood cases. The usual form is intra-abdominal appendicitis with perforation and diffuse peritonitis. It is exceptional to find neonatal acute appendicitis developing inside a patent processus vaginalis. We describe a case of this kind in an 18-day-old infant who survived and is doing well.

Conservative approach to Hepatic Portal Venous Gas: A case report

Highlights • Hepatic Portal Venous Gas (HPVG) is a rare condition often associated with a significant underlying pathologies.• The mechanism underlying the passage of the gas from the intestine into the mesenteric, then portal, venous system is not fully understood.• The high mortality rate made HPVG a cause of mandatory explorative laparotomy throughout the last fifty years of the twentieth century.• The frequent presence of benign conditions underlying this condition has diverted the common therapeutic approach to more cautious options.