Open Hemorrhoidectomy With Ligasure™ Under Local or Spinal Anesthesia: A Comparative Study.

BACKGROUND: There is increasing evidence that many anorectal surgical procedures may be performed under local anesthesia. The aim of the present study was to evaluate the safety and efficacy of local anesthesia in the outpatient clinic vs spinal anesthesia in the operating room for open hemorrhoidectomy. METHODS: Sixty-two patients with grade III or IV hemorrhoids underwent open hemorrhoidectomy with LigaSure™ between 2018 and 2020. Of them, 32 procedures were performed in the operating room under spinal anesthesia with hyperbaric bupivacaine and other 30 procedures were undertaken in the outpatient clinic under local anesthesia with ropivacaine. RESULTS: There were no significant differences regarding age, gender, American Society of Anesthesiologists class, and Goligher's grade in between groups. No significant differences were observed in postoperative pain score (P = .85), perioperative complications (P = .51), and reoperation rate (P = .96). No recurrences and no differences in patients' satisfaction degree (P = .76) were documented at long-term follow-up in both study groups. DISCUSSION: Our results suggest that open hemorrhoidectomy with LigaSure™ performed in selected patients under local anesthesia in the outpatient clinic is a well-tolerated, safe, and effective procedure.

Jejunal adenocarcinoma after biliopancreatic diversion. Report of a case.

The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro's technique. The patient developed a marked distension of the biliopancreatic limb caused by a jejunal mass, evolving towards the so called "duodenal blowout". Emergency jejunal resection of the biliopancreatic limb, with creation of a new end-to-side jejunal-ileal anastomosis was necessary. The histological examination resulted in a moderately-differentiated ulcerated adenocarcinoma, with reactive lymph nodes and tumor-free resection margins. Tumors of the gastrointestinal system can arise following malabsorptive operations for morbid obesity, and they may be difficult to diagnose, since the symptoms are often attributed to the anatomical-functional changes resulting from this type of surgery. The case reported herein suggests that there is a need for surveillance in patients complaining of digestive symptoms after malabsorptive bariatric surgery.

Inflammatory Indexes as Predictive Biomarkers of Postoperative Complications in Oncological Thoracic Surgery.

The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15, p = 0.03). A similar significant association with MLR on the fourth postoperative day is found in the open group (rho = -0.15, p = 0.048). NLR and LMR on the fourth postoperative day are associated with postoperative complications in the whole and open groups, respectively. Simple, easy-to-perform and inexpensive, blood cell count indexes may be useful in predicting complications in oncological thoracic surgery. A greater number of broader, prospective, randomized studies are necessary to confirm these findings.

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent.

Alterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM/vitamin E or SAM/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFNα/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis.

Current management of incidental gallbladder cancer: A review.

Early-stage gallbladder cancer (GBC) is mostly discovered incidentally by the pathologist after cholecystectomy for a presumed benign disease. It is the most common malignancy of the biliary tract with a variable incidence rate all over the World. The majority of patients with GBC remain asymptomatic for a long time and diagnosis is usually late when the disease is at an advanced stage. Radical surgery consisting in resection of the gallbladder liver bed and regional lymph nodes seems to be the best treatment option for incidental GBC. However, recurrence rates after salvage surgery are still high and the addition of neoadjuvant/adjuvant chemotherapy may improve outcomes. The aim of the present review is to evaluate current literature for advances in management of incidental GBC, with particular focus on staging techniques and surgical options.

Nuclear localization dictates hepatocarcinogenesis suppression by glycine N-methyltransferase.

BACKGROUND: GNMT (glycine N-methyltransferase) is a tumor suppressor gene, but the mechanisms mediating its suppressive activity are not entirely known. METHODS: We investigated the oncosuppressive mechanisms of GNMT in human hepatocellular carcinoma (HCC). GNMT mRNA and protein levels were evaluated by quantitative RT-PCR and immunoblotting. GNMT effect in HCC cell lines was modulated through GNMT cDNA induced overexpression or anti-GNMT siRNA transfection. RESULTS: GNMT was expressed at low level in human HCCs with a better prognosis (HCCB) while it was almost absent in fast-growing tumors (HCCP). In HCCB, the nuclear localization of the GNMT protein was much more pronounced than in HCCP. In Huh7 and HepG2 cell lines, GNMT forced expression inhibited the proliferation and promoted apoptosis. At the molecular level, GNMT overexpression inhibited the expression of CYP1A (Cytochrome p450, aromatic compound-inducible), PREX2 (Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2), PARP1 [Poly (ADP-ribose) polymerase 1], and NFKB (nuclear factor-kB) genes. By chromatin immunoprecipitation, we found GNMT binding to the promoters of CYP1A1, PREX2, PARP1, and NFKB genes resulting in their strong inhibition. These genes are implicated in hepatocarcinogenesis, and are involved in the GNMT oncosuppressive action. CONCLUSION: Overall, the present data indicate that GNMT exerts a multifaceted suppressive action by interacting with various cancer-related genes and inhibiting their expression.

Surgical treatment of hepatocellular carcinoma in the era of COVID-19 pandemic: A comprehensive review of current recommendations.

The new coronavirus disease 2019 (COVID-19) pandemic has resulted in a global health emergency that has also caused profound changes in the treatment of cancer. The management of hepatocellular carcinoma (HCC) across the world has been modified according to the scarcity of care resources that have been diverted mostly to face the surge of hospitalized COVID-19 patients. Oncological and hepatobiliary societies have drafted recommendations regarding the adaptation of guidelines for the management of HCC to the current healthcare situation. This review focuses on specific recommendations for the surgical treatment of HCC (i.e., hepatic resection and liver transplantation), which still represents the best chance of cure for patients with very early and early HCC. While surgery should be pursued for very selected patients in institutions where standards of care are maintained, alternative or bridging methods, mostly thermoablation and transarterial therapies, can be used until surgery can be performed. The prognosis of patients with HCC largely depends on both the characteristics of the tumour and the stage of underlying liver disease. Risk stratification plays a pivotal role in determining the most appropriate treatment for each case and needs to balance the chance of cure and the risk of COVID-19 infection during hospitalization. Current recommendations have been critically reviewed to provide a reference for best practices in the clinical setting, with adaptation based on pandemic trends and categorization according to COVID-19 prevalence.

Vascular resection for locally advanced pancreatic ductal adenocarcinoma: analysis of long-term outcomes from a single-centre series.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. Radical surgery is the best option for cure and, nowadays, it is performed by many surgeons also in cases of vascular infiltration. Whether this aggressive approach to a locally advanced PDAC produces a survival benefit is under debate. Most data in the literature come from retrospective comparative studies; therefore, it is still unclear if such an extensive surgery for an advanced cancer is justified. METHODS: A retrospective review of patients with PDAC treated at our institution over a 12-year period was performed. Data concerning patients' characteristics, operative details, postoperative course, and long-term survival were retrieved from prospective databases and analysed. Factors associated with poor survival were assessed via Cox regression analysis. RESULTS: A total of 173 patients with PDAC were included in the analysis, 41 subjects underwent pancreatectomy with vascular resection for locally advanced disease, and in 132 patients, only a pancreatic resection was undertaken. Demographics, major comorbidities, and tumour characteristics were similar between the two groups. Length of surgery (P=0.0006), intraoperative blood transfusions (P<0.0001), and overall complications (P<0.0001) were significantly higher in the vascular resection group. Length of hospital stay (P=0.684) and 90-day mortality (P=0.575) were comparable between groups. Overall median survival (P= 0.717) and survival rates at 1, 3, and 5 years (P=0.964, P=0.500, and P=0.445, respectively) did not differ significantly between groups. Age ≥70 years and postoperative complications were independent predictors of lower survival. CONCLUSIONS: Our study confirms that pancreatectomy with vascular resection for a locally advanced PDAC is a complex operation associated with a significant longer operating time that may increase morbidity; however, in selected patients, R0 margins can be obtained with an acceptable long-term survival rate. Older patients are less likely to benefit from surgery.

Laparoscopic versus Open Transverse-Incision Approach for Right Hemicolectomy: A Systematic Review and Meta-Analysis.

Background and Objectives: There is general agreement on the benefits of laparoscopy for treatment of rectal and left colon cancers, whereas findings regarding the comparison of laparoscopic and open right colonic resections are discordant. The aim of this systematic review and meta-analysis was to assess the outcomes and advantages of laparoscopic versus transverse-incision open surgery for management of right colon cancer. Materials and Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Comparative studies evaluating the results of laparoscopic and transverse-incision open right hemicolectomies were analyzed. The measured outcomes were mean operative time, time to feeding, duration of hospital stay, and number of lymph nodes harvested. Results: A total of 5 studies including 318 patients met the inclusion criteria. Meta-analysis revealed no differences in time to resume oral feeding, hospital stay, and number of lymph nodes harvested in between groups, but mean length of surgery was significantly longer in the laparoscopic group. Conclusion: These data confirm that the preferred approach to right hemicolectomy is yet unclear. Laparoscopy has a longer operative time than transverse-incision open surgery, and no significant short-term benefits were observed for the studied parameters. Well-designed randomized control trials (RCTs) might help to identify the differences between these two techniques for the surgical treatment of right colon cancer.

Perianal mucinous adenocarcinoma with dysplastic polyps of the colon: A case report.

INTRODUCTION: Perianal mucinous adenocarcinoma is rarely encountered in the setting of anal neoplasms. The rarity of the disease and the paucity of publications on this topic are responsible for a lack of diagnostic and therapeutic guidelines. PRESENTATION OF CASE: An 80-year-old man with mucinous adenocarcinoma of the anal canal associated with dysplastic polyps of the colon was treated by multiple endoscopic polypectomies and abdomino-perineal resection of the rectum. We discuss the management of this rare case from the diagnosis up to one-year follow-up. DISCUSSION: Perianal mucinous adenocarcinoma is a very rare entity frequently combined with chronic fistulas. Inflammatory symptoms may mislead its diagnosis, which is often delayed. The unique association between perianal mucinous adenocarcinoma and dysplastic polyps of the colon, that we have reported, may suggest a secondary etiology. High clinical suspicion is important for early and correct diagnosis, which should be based on endoanal ultrasound and/or magnetic resonance imaging followed by deep tissue biopsies. CONCLUSION: We stress the importance of accumulating such cases in the literature. The understanding of the etiopathogenic mechanisms may lead to the development of novel diagnostic and therapeutic protocols.

Management of complex liver cystic hydatidosis: challenging benign diseases for the hepatic surgeon: A case series report from an endemic area.

Hydatid cysts of the liver are benign lesions which require a wide range of surgical strategies for their treatment. We hypothesized that cysts larger than 15 cm, or compressing main vascular structures, or located in both hemilivers should be considered, as well as complicated cysts, in the category of complex hydatid cysts.In a retrospective study including 55 patients, we evaluated the characteristics of complex hydatid cysts, and compared surgical outcomes between patients operated on for complex cysts (Complex Group) and those operated on for non-complex cysts (non-Complex Group).In the Complex Group, 19% of patients had cysto-biliary communication with recurrent cholangitis, 9.5% had cysts eroding the diaphragm or chest wall, or communicating with the bronchial tree, 31% had cysts with contact with main vascular structures, 11.9% had multiple bilobar cysts, 14.3% had giant cysts with organ displacement, and 14.3% had a combination of the above-mentioned types. Type of surgical treatment was different between the two groups (P < .001). Additional procedures were statistically more frequent in the Complex Group (P = .02). Postoperative morbidity was higher in the Complex Group, although not in a significant manner (P = .07). Median hospital stay was longer in the Complex Group (12 vs 7 days, P < .001). No 30-day mortality occurred. Four patients (7.3%), all belonging to the Complex Group, required reoperation for postoperative complications.Surgery for complex hydatid cysts of the liver is potentially burdened by serious complications. This kind of benign liver disease requires skill-demanding procedures and should be treated in centers with expertise in both hepato-biliary surgery and hydatid disease management.

The emerging role of pectoral nerve block (PECS block) in breast surgery: A case-matched analysis.

To evaluate the benefits of pectoral nerve block (PECS block) in breast cancer surgery, we compared outcomes of 100 patients receiving PECS vs 107 without PECS. Intraoperative use of fentanyl (P < .001) acetaminophen (P = .02), morphine (P < .01), and nonsteroidal anti-inflammatory drugs (NSAIDS) (P < .01) was lower in the PECS group. Occurrence of postoperative nausea and vomiting (PONV) was lower in the PECS group (P = .04). On postoperative day 1, the use of acetaminophen (P = .23), morphine (P = .83), and NSAIDS (P = .4) did not differ. Twenty-one patients received surgery with PECS block plus sedation alone. PECS block can reduce intraoperative use of opioids and analgesic drugs, and is associated with reduced occurrence of PONV. Selected patients can receive breast-conserving surgery with PECS plus sedation, avoiding general anesthesia.

In situ reconstruction with autologous graft in the treatment of secondary aortoenteric fistulas: A retrospective case series.

Infections caused by secondary aortoenteric fistulas (SAEF) may be extremely complex and threaten patient's life. We report our surgical approach to SAEF consisting in removal of the infected graft and in situ reconstruction using an autologous venous graft. Seven consecutive patients with SAEF treated with graft removal and in situ reconstruction using an autologous venous graft from 2008 to 2017 were reviewed. Six of seven patients (86%) survived 30-day. In one case a graft thrombosis and acute lower limb ischemia occurred requiring re-operations. All patients received injective antibiotic therapy for 20 days, followed by oral therapy for 3 months. There were no major complications at long-term follow-up. Our results suggest that superficial femoral vein reconstruction of the abdominal aorta for SAEF is effective with an acceptable in-hospital mortality and low rate of major complications. We stress the importance of the deep femoral veins to create the graft because the large saphenous vein is often affected by significant intimal hyperplasia that can cause steno-occlusive complications.

Laparoscopic versus open transverse-incision right hemicolectomy: a retrospective comparison study.

BACKGROUND: The optimal surgical approach to right colon cancer is still under debate. The aim of the present study was to compare the short- and long-term outcomes of laparoscopic and transverse-incision open approaches to right hemicolectomy for colon cancer. METHODS: Data on 99 adult patients with right-side colon cancer undergoing either laparoscopic or open transverse-incision right hemicolectomy at two different university hospitals, between January 2013 and December 2016, were retrospectively reviewed. Data concerning patients' characteristics, operative details and post-operative recovery were retrieved from prospective databases and analysed. RESULTS: Forty-nine subjects were operated on laparoscopically, while 50 through an open transverse incision. Operating time was significantly longer in the laparoscopic group compared with the open group (182 versus 105 min; P < 0.01). Patients treated laparoscopically had a shorter time to first bowel movement, while time to resume a normal diet and post-operative length of hospital stay were comparable in between groups. The median number of lymph nodes harvested was higher in the laparoscopic group (25.6 versus 18.6; P < 0.01), but no significant difference in overall survival between groups was detected. At long-term follow-up, the incidence of incisional hernia was higher in the laparoscopic group as compared to the open group (24.5% versus 0%; P = 0.0002). CONCLUSION: Our results show that laparoscopic right hemicolectomy when compared to the transverse-incision open procedure may guarantee the same oncological radicality, but short-term functional benefits are still unclear. Randomized control studies are warranted to better clarify the comparison of these two approaches for right-sided colon cancers.

MicroRNA-203 impacts on the growth, aggressiveness and prognosis of hepatocellular carcinoma by targeting MAT2A and MAT2B genes.

Hepatocellular carcinoma (HCC) is characterized by the down-regulation of the liver-specific methyladenosyltransferase 1A (MAT1A) gene, encoding the S-adenosylmethionine synthesizing isozymes MATI/III, and the up-regulation of the widely expressed methyladenosyltransferase 2A (MAT2A), encoding MATII isozyme, and methyladenosyltransferase 2B (MAT2B), encoding a ß-subunit without catalytic action that regulates MATII enzymatic activity. Different observations showed hepatocarcinogenesis inhibition by miR-203. We found that miR-203 expression in HCCs is inversely correlated with HCC proliferation and aggressiveness markers, and with MAT2A and MAT2B levels. MiR-203 transfection in HepG2 and Huh7 liver cancer cells targeted the 3'-UTR of MAT2A and MAT2B, inhibiting MAT2A and MAT2B mRNA levels and MATα2 and MATß2 protein expression. These molecular events were paralleled by an increase in SAM content and were associated with growth restraint and apoptosis, inhibition of cell migration and invasiveness, and suppression of the expression of CD133 and LIN28B stemness markers. In contrast, MAT2B transfection in the same cell lines led to a rise of both MATß2 and MATα2 expression, associated with increases in cell growth, migration, invasion and overexpression of stemness markers and p-AKT. Altogether, our results indicate that the miR-203 oncosuppressor activity may at least partially depend on its inhibition of MAT2A and MAT2B and show, for the first time, an oncogenic activity of MAT2B linked to AKT activation.

Adrenal cavernous hemangioma: a case report.

BACKGROUND: Adrenal cavernous hemangiomas are very rare benign tumors that usually present as incidental findings on abdominal imaging. Preoperative differential diagnosis from other benign or malignant adrenal neoplasms may be challenging. CASE PRESENTATION: A 70-year old man was referred for an 8-cm abdominal mass incidentally discovered on a contrast-enhanced computed tomography (CT) performed to investigate a pulmonary nodule. Biochemical tests ruled out any endocrine dysfunction and iodine 123 metaiodobenzylguanidine whole body scintiscan single-photon emission CT excluded a pheocromocitoma. Findings on magnetic resonance imaging were non-specific and the patient was elected for a left adrenalectomy. Histopathological diagnosis revealed a cavernous hemangioma. A portion of the resected tissue was tested for drug sensitivity to mitotane, doxorubicin, and sunitinib. CONCLUSIONS: Adrenal hemangioma is a rare disease but should be included in the differential diagnosis of adrenal tumors. The surgical resection is generally required to exclude malignant disease, resolve pressure-related symptoms, and prevent retroperitoneal hemorrhage. Although specific features in diagnostic imaging are often lacking, if the diagnosis is established preoperatively a laparoscopic adrenalectomy can be performed due to the benign nature of the lesion. Doxorubicin and sunitinib were both capable of reducing primary culture cell viability, this suggest that similar drugs may be useful in the medical treatment of adrenal hemangiomas.

Alterations of methionine metabolism in hepatocarcinogenesis: the emergent role of glycine N-methyltransferase in liver injury.

The methionine and folate cycles play a fundamental role in cell physiology and their alteration is involved in liver injury and hepatocarcinogenesis. Glycine N-methyltransferase is implicated in methyl group supply, DNA methylation, and nucleotide biosynthesis. It regulates the cellular S-adenosylmethionine/S-adenosylhomocysteine ratio and S-adenosylmethionine-dependent methyl transfer reactions. Glycine N-methyltransferase is absent in fast-growing hepatocellular carcinomas and present at a low level in slower growing HCC ones. The mechanism of tumor suppression by glycine N-methyltransferase is not completely known. Glycine N-methyltransferase inhibits hepatocellular carcinoma growth through interaction with Dep domain-containing mechanistic target of rapamycin (mTor)-interacting protein, a binding protein overexpressed in hepatocellular carcinoma. The interaction of the phosphatase and tensin homolog inhibitor, phosphatidylinositol 3,4,5-trisphosphate-dependent rac exchanger, with glycine N-methyltransferase enhances proteasomal degradation of this exchanger by the E3 ubiquitin ligase HectH. Glycine N-methyltransferase also regulates genes related to detoxification and antioxidation pathways. It supports pyrimidine and purine syntheses and minimizes uracil incorporation into DNA as consequence of folate depletion. However, recent evidence indicates that glycine N-methyltransferase targeted into nucleus still exerts strong anti-proliferative effects independent of its catalytic activity, while its restriction to cytoplasm prevents these effects. Our current knowledge suggest that glycine N-methyltransferase plays a fundamental, even if not yet completely known, role in cellular physiology and highlights the need to further investigate this role in normal and cancer cells.