Laparoscopic transperitoneal hernia repair (TAPP) in emergency: long-term follow-up in a high volume centre.

PURPOSE: Aim of this study was to analyse feasibility, safety and effectiveness of laparoscopic transperitoneal hernia repair (TAPP) approach to inguinal hernias in the emergency setting, with a longer follow-up than the studies present in literature. METHODS: We retrospectively analysed all patients who underwent emergency TAPP hernia repair in San Marco Hospital (Zingonia, Italy), from September 2010 to June 2020. A prospectively collected database of 685 consecutive TAPP hernia repair was reviewed. Feasibility and safety were evaluated through operative time, conversion rate, perioperative mortality, morbidity and prosthesis infection rate. Effectiveness was assessed by recurrence and complication rate, acute (during admission) and chronic (during follow-up) pain by Visual Analogic Scale (VAS), and recovery to normal activity in a long-term follow-up (mean period 1718 days). RESULTS: The final study group included 47 patients. The mean age was 59.6 years (range 22-89), 29 patients were male and 18 were female. The mean operation time was 64 min. Two cases were converted to open approach (4%). In four cases bowel resection became necessary (8.5%). Appendicectomy and omentectomy occurred once and twice, respectively (2% and 4%), and orchiectomy was required in two patients (4%). Seroma was the only postoperative complication that we registered in four patients. During a mean follow-up period of 1718 days, there was no recurrence of the hernia or other complications. Five patients referred mild occasional groin pain (VAS < 3), with quick relief without taking any pain killers. CONCLUSION: TAPP approach is a safe, feasible and effective therapeutic option for groin hernias in emergency setting. No recurrence or severe complications were reported in over 4 years of follow-up.

LKB1 loss is associated with glutathione deficiency under oxidative stress and sensitivity of cancer cells to cytotoxic drugs and γ-irradiation.

The liver kinase B1 (LKB1) gene is a tumor suppressor associated with the hereditary Peutz-Jeghers syndrome and frequently mutated in non-small cell lung cancer and in cervical cancer. Previous studies showed that the LKB1/AMPK axis is involved in regulation of cell death and survival under metabolic stress. By using isogenic pairs of cancer cell lines, we report here that the genetic loss of LKB1 was associated with increased intracellular levels of total choline containing metabolites and, under oxidative stress, it impaired maintenance of glutathione (GSH) levels. This resulted in markedly increased intracellular reactive oxygen species (ROS) levels and sensitivity to ROS-induced cell death. These effects were rescued by re-expression of LKB1 or pre-treatment with the anti-oxidant and GSH replenisher N-acetyl cysteine. This role of LKB1 in response to ROS-inducing agents was largely AMPK-dependent. Finally, we observed that LKB1 defective cells are highly sensitive to cisplatin and γ-irradiation in vitro, suggesting that LKB1 mutated tumors could be targeted by oxidative stress-inducing therapies.

Laparoscopic pancreaticoduodenectomy for tumors of the head of pancreas; 10 cases for a single center experience.

OBJECTIVE: The tumors of the head of the pancreas are one of the leading causes of cancer-related death in Western countries. The current gold standard for these tumors is a Whipple procedure. This procedure did not change in its surgical steps since when it was initially introduced in 1935. More recently, a laparoscopic approach with similar outcomes has been described. The aim of this paper is to describe the laparoscopic surgical technique performed in our unit, reporting single center postoperative outcomes. PATIENTS AND METHODS: From the 1st January 2013 to the 31st December 2015 a database was created. Data about patients who underwent a laparoscopic pancreaticoduodenectomy (LPD) were collected prospectively. All patients were preoperatively assessed with blood samples, tumor markers, CT chest abdomen and pelvis and/or MRI pancreas. Only patients with specific characteristics were considered eligible for an LPD: performance status 0, body mass index (BMI) less than 30 kg/m2, a small neoplastic lesion (< 3.5 cm) confined to the pancreas, the absence of infiltrated organs and/or blood vessels (T1 or T2). Postoperative data and complications were recorded and described according to the Clavien-Dindo classification and the international study group of pancreatic surgery definitions. RESULTS: In a time interval of 36 months, 31 patients with an initially considered resectable pancreatic cancer were referred. 11 patients were found to have metastasis during the preoperative workout. Only 10 patients were considered eligible for a LPD. Six of them were men (60%). The mean BMI was 25.01 kg/m2 (19.6-29.8). 5 patients, who underwent to LPD did not have any comorbidities. An overall 50% of all patients were jaundice at the time of diagnosis with a mean bilirubin level of 181.3 µmol/L (119.7-307.8). All patients with a direct bilirubin greater than 250 µmol/L underwent a preoperative percutaneous biliary drainage. In the majority of the LPD performed (50%), the histology reported a pancreatic adenocarcinoma. Other postoperative histology described were: IPMN (20%), ampullar neoplasia (20%) and neuroendocrine tumor (10%). Neo-adjuvant chemotherapy was never considered indicated. The reported postoperative complications were: 1 anastomotic bleeding, 2 pancreatic fistula, 1 infected intra-abdominal collection and 1 delay gastric emptying. The pancreatic fistulas were considered grade A and grade B. One fatality after LPD occurred because of an uncontrollable, diffuse severe hemorrhagic gastritis associated with a GJ anastomosis bleeding in the POD 25. The mean hospital stay was 12.3 days (8-25). The mean operative time was 224 min (170-310). There were no intraoperative complications. The main intraoperative blood loss was 220 ml (180-400) and intraoperative blood transfusions were not required. The resection margins were negative (R0) in 100% of cases and the mean lymph nodes harvested were 24 (18-40). The LPD is still a not common practice. Our results are comparable with those reported in literature about the open technique. These remarkable surgical outcomes are probably related to the extremely careful preoperative patient selection performed. The indication for a laparoscopic vs. an open pancreaticoduodenectomy was based on a CT scan pancreas performed less than 30 days before the planned date of surgery and a careful preoperative assessment. A low complication rate and a relative short stay in hospital were associated to a good quality of life in the early postoperative period and an early referral for postoperative chemotherapy. Good clinical outcomes were associated with outstanding oncological results. CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is a feasible surgical procedure. Remarkable oncological and surgical outcomes can be achieved with a morbidity and mortality rate in line with the data reported by the large series of open procedures.

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome.

BACKGROUND: Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. AIM: To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. METHODS: A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. RESULTS: Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5-33.2) in alcoholic and 33.6 months (30.7-36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. CONCLUSIONS: Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) is recommended in patients with cirrhosis. As α-fetoprotein (AFP) is considered a poor surveillance test, we tested the performance of its changes over time. METHODS: Eighty patients were diagnosed with HCC (cases) during semiannual surveillance with ultrasonography and AFP measurement were recruited and matched for age, gender, etiology and Child-Pugh class with 160 contemporary cancer-free controls undergoing the same surveillance training group (TG). As a validation group (VG) we considered 36 subsequent patients diagnosed with HCC, matched 1 : 3 with contemporary cancer-free controls. α-Fetoprotein values at the time of HCC diagnosis (T0) and its changes over the 12 (Δ12) and 6 months (Δ6) before cancer detection were considered. RESULTS: In both TG and VG, >80% of HCCs were found at an early stage. In TG, AFP significantly increased over time only in cases. T0 AFP and a positive Δ6 were independently associated with HCC diagnosis (odds ratio: 1.031 and 2.402, respectively). The area under the curve of T0 AFP was 0.76 and its best cutoff (BC) was 10 ng ml(-1) (sensitivity 66.3%, specificity 80.6%). The combination of AFP >10 ng ml(-1) or a positive Δ6 composite α-fetoprotein index (CAI) increased the sensitivity to 80% with a negative predictive value (NPV) of 86.2%. Negative predictive value rose to 99%, considering a cancer prevalence of 3%. In the VG, the AFP-BC was again 10 ng ml(-1) (sensitivity 66.7%, specificity 88.9%), and CAI sensitivity was 80.6% with a NPV value of 90.5%. CONCLUSIONS: CAI achieves adequate sensitivity and NPV as a surveillance test for the early detection of HCC in cirrhosis.

Follow-up of bone mineral density and body composition in adolescents with restrictive anorexia nervosa: role of dual-energy X-ray absorptiometry.

BACKGROUND/OBJECTIVES: Restrictive Anorexia nervosa (ANR) is an eating disorder (ED) characterized by a low bone mineral content (BMC) and by an alteration in body composition (reduction and abnormal distribution of fat mass-FM and lean mass-LM). The aim of our study was to address whether bone and body composition changes could be influenced by hormonal status and sport in female adolescents with restrictive anorexia nervosa-ANR. SUBJECTS/METHODS: Prospective study on 79 adolescents with ANR submitted to Dual Energy X-Ray Absorptiometry-DXA at baseline-T0 and after 12 months-T12. Among the 46/79-58.2% patients that completed the study, we evaluated total and regional FM and LM%, as well as lumbar bone mineral density (BMD) and Z-score, linking them to clinical variables: menarche/amenorrhea/hormonal therapy and physical activity. RESULTS: At T0: body mass index (BMI)=16.4±1.4 kg/m2 with low levels of FM% (21.7±5.7) low BMC in 12/46-26.0% (mean Z-score: -1.21±1.27, with higher values related to physical activity-P=0.001). At T12: a significant increase in BMI-P=0.001, with LM reduction and FM increase (more evident in the trunk-P<0.001); regarding bone, no significant changes were observed, though a tendency in terms of improvement associated with resumption of menses. CONCLUSIONS: After 1 year, weight recovery was not associated with a reestablishment of bone values; by contrast, it was associated with an increase and a distortion in FM distribution, more evident in trunk region (potential and adjunctive risk factor for the relapse of the psychiatric condition). The complexity of these clinical findings suggested DXA, a low-dose and low-cost technique, in long-term monitoring of ANR patients.

Small bowel obstruction caused by mesh migration. Case report.

INTRODUCTION: Endoscopic hernia repair methods have become increasingly popular over the past 15 years. Nonetheless, there is no consensus regarding an optimal fixation method. Transabdominal sutures and titanium tacks or staples are the most traditional ones. CASE REPORT: We present a case of mechanic small bowel obstruction due to mesh migration occurring one year and a half after incisional hernia repair with polytetrafluoroethylene mesh fixed by spiral tacks. DISCUSSION: Titanium spiral tacks are dangerous because of their sharp components, which can damage organs such as the small intestine, by causing microperforations. The type of prosthesis used has also contributed to the intraluminal migration, since polytetrafluoroethylene mesh is very flexible and poorly integrates in the abdominal wall. CONCLUSION: A prosthesis of a different material combined with a different fixation system such as absorbable tacks, biological glue, or mechanical tacks without sharp components, would have obviated mesh migration.

Screening for lung cancer using low-dose spiral CT: 10 years later, state of the art.

Ten years after the first papers on this subject, this editorial represents a brief review on lung cancer screening with low-dose spiral CT. The aim is to present the main theoretical and practical problems related to lung cancer screening, the historical background and results of observational studies and the main ongoing randomised controlled trials. In particular, the National Lung Screening Trial (NLST), which was interrupted early, is discussed. The opinion of the authors is that too many questions are still awaiting an answer.

Natural history of honeycombing: follow-up of patients with idiopathic pulmonary fibrosis treated with single-lung transplantation.

PURPOSE: Although honeycombing is one of the key features for the diagnosis of idiopathic pulmonary fibrosis (IPF), its origin and evolution are still poorly understood. The aim of our study was to analyse the natural history of honeycombing in patients treated with single-lung transplantation. MATERIALS AND METHODS: We considered seven patients who underwent single-lung transplantation; two of them (28.6%) were excluded from our analysis because they died in the posttransplantation period, whereas the remaining five (71.4%) were evaluated with computed tomography (CT) over 67.6±38.56 months. Each CT scan was assessed for disease extension and cyst size (visual score and size of target cysts); CT scans acquired after 2006 were also assessed for native lung volume. RESULTS: All patients showed disease progression (with a concurrent reduction in lung volume in two, 40%) and a progression of honeycombing, with increased number and size of cysts in four (80%). We observed dimensional changes in all target cysts (enlargement or reduction); three patients (60%) also had radiological evidence of complications, such as spontaneous rupture with pneumothorax and development of mycetomas within the cysts. CONCLUSIONS: Honeycombing is a dynamic process in which the overall trend is represented by a dimensional increase in cystic pattern; however, single cysts may have a different evolution (enlargement, reduction or complications). This behaviour could be explained by the variety of the pathogenetic processes underlying honeycombing, with cysts that may present abnormal communication with the airway, including the development of a check-valve mechanism.

Post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia: role of follow-up CT.

PURPOSE: Our aim was to evaluate the evolution of 20 patients with H1N1 pneumonia, focusing our attention on patients with severe clinical and radiological findings who developed post-acute respiratory distress syndrome (post-ARDS) pulmonary fibrosis. MATERIALS AND METHODS: Twenty adult patients (nine women and 11 men; mean age 43.5 ± 16.4 years) with a diagnosis of H1N1 infection confirmed by pharyngeal swab came to our attention from September to November 2009 and were followed up until September 2010. All patients were hospitalised in consideration of the severity of clinical findings, and all underwent chest X-ray. Twelve of them underwent at least one computed tomography (CT) scan of the chest. RESULTS: In 75% of cases (15/20), there was complete resolution of the clinical and radiological findings. Twenty-five percent of patients (5/20) developed acute respiratory distress syndrome (ARDS), which progressed to predominantly peripheral pulmonary fibrosis in 10% (2/20; one died and one had late-onset pulmonary fibrosis, documented on day 68). Moreover, in one patient with a CT diagnosis of pulmonary fibrosis, we observed progressive regression of radiological findings over 4 months of follow-up. CONCLUSIONS: In patients with H1N1 pneumonia, post-ARDS pulmonary fibrosis is not a rare complication. Therefore, a CT scan should be performed in all patients with severe clinical findings. Our study demonstrated that in these patients, fibrosis could present a different spatial distribution and a different temporal trend, with delayed late onset; moreover, in one case, the signs of interstitial lung disease partially regressed over time. Therefore, CT should be considered not only in the diagnostic stage, but also during the follow-up.

Selective arterial embolisation for bone tumours: experience of 454 cases.

PURPOSE: The authors present the experience of a single institution with selective arterial embolisation for primary and metastatic bone tumours. MATERIALS AND METHODS: A total of 365 patients were treated with 454 embolisation procedures from December 2002 to April 2010. Embolisation was the primary treatment for benign bone tumours, adjuvant treatment to surgery for benign and malignant bone tumours and palliative treatment for bone sarcomas and metastases. Indications for repeat embolisation included pain or imaging evidence of progressive disease: 105 patients had repeat embolisation at the same location at an interval of 1-3 months; 260 patients had one embolisation, 78 had two and 29 had three or more. In all patients, N-2-butyl cyanoacrylate (NBCA) in 33% lipiodol was the embolic agent used. RESULTS: A total of 419 of the 454 embolisations (93%) were technically successful. In 35 cases, embolisation was not feasible because of poor lesion vascularisation (21 patients with bone metastases and two with aneurysmal bone cysts), origin of the Adamkiewicz artery in the embolisation field (four patients with bone metastases and one with aneurysmal bone cyst), atheromatosis and arteriosclerosis (five patients with bone metastases) and anatomical and technical problems such as small-calibre vessels, many branches and acute vessel angles (two patients with bone metastases). A clinical response was achieved in 406 of the 419 procedures (97%), and no response in 13 procedures in patients with pelvis and sacrum tumours. Complications included postembolisation syndrome in 81 patients (22%), transient paraesthesias in 41 (11%), skin breakdown and subcutaneous necrosis at the shoulder and pelvis in five (1.4%) and paresis of the sciatic nerve in one (0.3%). CONCLUSIONS: We recommend embolisation as primary or palliative treatment or an adjunct to surgery for tumours of variable histology. Strict adherence to the principles of transcatheter embolisation is important. Arteries feeding the tumour and collaterals must be evaluated carefully and catheterised superselectively to protect the normal tissues. NBCA is considered the most appropriate embolic agent for small-vessel occlusion without major complications.