Mitochondria as playmakers of apoptosis, autophagy and senescence.

Mitochondria are the key energy-producing organelles and cellular source of reactive species. They are responsible for managing cell life and death by a balanced homeostasis passing through a network of structures, regulated principally via fission and fusion. Herein we discuss about the most advanced findings considering mitochondria as dynamic biophysical systems playing compelling roles in the regulation of energy metabolism in both physiologic and pathologic processes controlling cell death and survival. Precisely, we focus on the mitochondrial commitment to the onset, maintenance and counteraction of apoptosis, autophagy and senescence in the bioenergetic reprogramming of cancer cells. In this context, looking for a pharmacological manipulation of cell death processes as a successful route for future targeted therapies, there is major biotechnological challenge in underlining the location, function and molecular mechanism of mitochondrial proteins. Based on the critical role of mitochondrial functions for cellular health, a better knowledge of the main molecular players in mitochondria disfunction could be decisive for the therapeutical control of degenerative diseases, including cancer.

Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study.

INTRODUCTION: Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines. METHODS: A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years. RESULTS: Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69-87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8-17.7 months). PFS was 14.8 months (range, 13.9-15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1-36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases. CONCLUSION: Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.

Silybin-Induced Apoptosis Occurs in Parallel to the Increase of Ceramides Synthesis and miRNAs Secretion in Human Hepatocarcinoma Cells.

Silybin is a flavonolignan extracted from Silybum marianum (milk thistle) with hepatoprotective, antioxidant, and anti-inflammatory activity. Several studies have shown that silybin is highly effective to prevent and treat different types of cancer and that its antitumor mechanisms involve the arrest of the cell cycle and/or apoptosis. An MTT assay was performed to study cell viability, lipid peroxidation, extracellular NO production, and scavenger enzyme activity were studied by Thiobarbituric Acid-Reactive Species (TBARS) assay, NO assay, and MnSOD assay, respectively. Cell cycle and apoptosis analysis were performed by FACS. miRNA profiling were evaluated by real time PCR. In this study, we demonstrated that Silybin induced growth inhibition blocking the Hepg2 cells in G1 phase of cell cycle and activating the process of programmed cell death. Moreover, the antiproliferative effects of silybin were paralleled by a strong increase of the number of ceramides involved in the modulation of miRNA secretion. In particular, after treatment with silybin, miR223-3p and miR16-5p were upregulated, while miR-92-3p was downregulated (p < 0.05). In conclusion, our results suggest that silybin-Induced apoptosis occurs in parallel to the increase of ceramides synthesis and miRNAs secretion in HepG2 cells.

Sorafenib in elderly patients with advanced hepatocellular carcinoma: a case series.

OBJECTIVE: The management of hepatocellular carcinoma (HCC) in elderly patients is significantly more complicated than in younger patients because of medical comorbidities, advanced status at diagnosis, reduced liver function and altered drug pharmacokinetics. Our objective was a revision of the charts of unselected elderly patients with HCC being treated with a reduced starting dose of sorafenib. METHODS: Activity, adverse events and quality of life were evaluated during the treatment. Sixty patients (47 males and 13 females) aged more than 70 years old (range 70-90, median 76 years) were retrospectively reviewed. RESULTS: One complete and one partial response were achieved in the series (overall response rate 3.3%). Stable disease accounted for 76.6% (46 out of 60 patients). The disease control rate (complete plus partial response plus stable disease) was 80%. Median time to progression (TTP) was 7.0 months (95% CI, 5.2-8.7 months) and median survival was 10.0 months (95% CI, 5.0-14.9 months). Thrombosis correlated to TTP. Full doses of sora-fenib were reached in 11 out of 60 patients (18.3%). The evaluation of quality of life did not show any significant change during the study. CONCLUSIONS: Sorafenib at a reduced dose can be safely used in elderly HCC patients with maintenance of activity and increased tolerability.

Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview.

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV). Continuous oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental factors or cellular mitochondrial dysfunction, has recently been associated with hepatocarcinogenesis. On the other hand, a distinctive pathological hallmark of HCC is a dramatic down-regulation of oxido-reductive enzymes that constitute the most important free radical scavenger systems represented by catalase, superoxide dismutase and glutathione peroxidase. The multikinase inhibitor sorafenib represents the most promising target agent that has undergone extensive investigation up to phase III clinical trials in patients with advanced HCC. The combination with other target-based agents could potentiate the clinical benefits obtained by sorafenib alone. In fact, a phase II multicenter study has demonstrated that the combination between sorafenib and octreotide LAR (So.LAR protocol) was active and well tolerated in advanced HCC patients. The detection of molecular factors predictive of response to anti-cancer agents such as sorafenib and the identification of mechanisms of resistance to anti-cancer agents may probably represent the direction to improve the treatment of HCC.

Comparative Study of NGS Platform Ion Torrent Personal Genome Machine and Therascreen Rotor-Gene Q for the Detection of Somatic Variants in Cancer.

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.

Adrenal incidentalomas in the laparoscopic era and the role of correct surgical indications: observations from 255 consecutive adrenalectomies in an Italian series.

BACKGROUND: The purpose of our study was to evaluate the impact of laparoscopic adrenalectomy on patients with incidentalomas. We analyzed the results of a multi-centre trial that was performed to evaluate the effectiveness of imaging (computed tomography and magnetic resonance imaging) to obtain a correct preoperative diagnosis. METHODS: We obtained our data from the results of a questionnaire that was distributed by mail or email in May 2005 to several surgical units operating in the Campania Region, Italy. Lap Club, a collaborative laparoscopic surgery study group founded in Naples in 1995, distributed the questionnaire. Thirteen centres participated in the audit. In all, we analyzed 255 adrenalectomies performed on 250 patients. We performed statistical analysis using SPSS software. RESULTS: The distribution of pathologic findings demonstrates that the number of lesions caused by cancer discovered from a preoperative indication of incidentaloma has been even smaller (1/114, 0.8%) than the previous numbers reported in the literature. Moreover, whereas most patients with adrenal cancer had lesions larger than 6 cm (7/8, 87.5%), the majority of patients with adrenal metastases had lesions 6 cm or smaller (10/12, 83.3%). Different indications for adrenalectomy emerged on comparison of endocrine surgery units with general surgery units. This difference appears to be significant (p < 0.001), especially on evaluation of the number of nonfunctioning adenomas and the number of endocrine lesions that were observed and treated. CONCLUSION: Laparoscopy remains the gold standard method for adrenalectomy, but its availability must not obligate physicians to treat with surgery when an incidentaloma is detected through imaging. Adrenal malignancies when metastatic are often 6 cm or smaller. If they are single and they originated from a non-small lung cancer, they must be removed. The endocrine surgery unit remains the best setting to evaluate and treat adrenal gland surgical pathology.

Clinical and pathological factors predictive of response to neoadjuvant chemotherapy in breast cancer: A single center experience.

Neoadjuvant chemotherapy (NAC) of breast cancer (BC) improves outcomes, especially in patients with locally advanced and inflammatory cancer. Further insight into clinic-pathological factors influencing outcomes is essential to define the optimal therapeutic strategy for each category of patients and to predict the response to the treatment. In total, 117 patients with BC were treated with NAC with or without trastuzumab between 2010 and 2015. The histologic response to NAC was defined as a pathological complete response (pCR) when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Relapse-free survival (RFS) was estimated using the Kaplan-Meier method and compared using log rank analysis. P-value <0.05 was considered statistically significant. The median age of the 117 patients enrolled in the present study was 52 years (age range, 35-85 years). The overall response rate (complete and partial responses) assessed by radiological and pathological evaluation were 76 and 72%, respectively. pCR was achieved in 35 out of 117 patients (~30%). In total, 6 patients (5%) developed progressive disease during chemotherapy. The RFS was 85 months (SE=3; 95% CI 79-91). The median was not reached and the mean follow-up time was 55 months (median 52 months; range 11-100 months). In this time, 20 patients (17%) experienced tumor recurrence. From the univariate analysis, the pathological response was significantly associated with receptor-based subtype, menopausal status and T-stage. From the multivariate analysis by using linear multiple regression and including receptor- menopausal status and T-stage, the model was not significant (P=0.062). However, by using the multiple logistic regression, and including age, pCR was significantly associated with ER+ HER2neg (P=0.006), T2 (P=0.043) and T3 (P=0.018). T-stage, menopausal status and receptor status are significantly associated with the pathological response in patients with inoperable BC treated with NAC.

Percutaneous ethanol injection of hyperfunctioning thyroid nodules: long-term follow-up in 125 patients.

OBJECTIVE: The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules. MATERIALS AND METHODS: One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter. RESULTS: Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules < or = 10 mL, 63 (94.0%) of 67; nodules > 10 to < or = 30 mL, 32 (91.4%) of 35; nodules > 30 to < or = 60 mL, 17 (89.5%) of 19; nodules > 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months' follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up. CONCLUSION: PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Surgical treatment of intrathyroid metastases: preliminary results of a multicentric study.

BACKGROUND: Intrathyroid metastases (ITM) are rare and usually have a dismal prognosis. The aim of this study was to detect which neoplasms metastasize most often to the thyroid gland, their clinical features and treatment options. MATERIALS AND METHODS: Retrospective analysis of clinical files of 17,122 patients submitted to surgery for thyroid disease between 1995 and 2005. Twenty-five patients (median age 61 years) were affected by ITM. RESULTS: The site of the primary tumor was: kidney (15), lung (4), colon (3), breast (1), melanoma (1), and unknown in 1 patient. Ten patients (40%) complained of preoperative symptoms, in the others, thyroid involvement was incidentally discovered during the follow-up for the primary cancer. Twenty patients (80%) underwent total thyroidectomy, 3 received thyroid lobectomy and 2 palliative procedures. Morbidity was 16%, mortality was nil. The median follow-up was 24 months. CONCLUSION: ITM should always be suspected in any patient with a previous history of malignancy. Fine-needle agobiopsy (FNAB) with immunohistochemical stains may help in preoperative workup. A long delay between the primary tumor and the recurrence warrants surgery and total thyroidectomy seems to be the treatment of choice because of the multifocality of metastasis to the thyroid gland.

Hepaticojejunostomy in the treatment of iatrogenic biliary lesions following laparoscopic cholecystectomy. A retrospective study on 51 cases.

BACKGROUND/AIMS: Laparoscopic cholecystectomy is characterized by a higher incidence of iatrogenic biliary lesions. The Authors evaluate the role of hepaticojejunostomy in the treatment of iatrogenic biliary lesions following laparoscopic cholecystectomy in 51 patients observed in the Campania region, Italy from 1991 to 2003. METHODOLOGY: The Authors report the data of a retrospective multicentric study of 51 patients -39 women (76.47%), 12 men (13.53%)-reoperated on for major biliary lesions following laparoscopic cholecystectomy. Hepaticojejunostomy in 20 cases (39.21%) and T-Tube plasty in 20 cases (39.21%) were performed. RESULTS: The mean follow-up was 25.01 months. The mean hospital stay was 25.7 days. 1/51 patients (1.9%) died from intraoperative incontrollable hemorrhage while cumulative postoperative mortality was 9.8% (5/51 patients). Therapeutic success rate of hepaticojejunostomy was 70% with a T-Tube plasty success rate of 65%. 9/51 patients (17.64%) were reoperated while in 4/51 (7.84%) a biliary stent was positioned. In 1/51 patients (1.9%) a biliary cirrhosis and in 3/51 (5.7%) a bioumoral cholestasis was observed. CONCLUSIONS: Laparoscopic cholecystectomy causes a higher incidence of iatrogenic biliary lesions. Hepaticojejunostomy gives better long-term results and lower morbidity compared to T-Tube plasty. Management of septic complications in patients with iatrogenic biliary lesions represents the first therapeutic step.

[Locally advanced breast cancer in elderly patients: treatment standardised or tailored to individual needs?]. / Cancro della mammella localmente avanzato nell'età senile: trattamento standardizzabile o modulato?

Breast cancer in elderly patients occurs frequently and is often inadequately managed. Furthermore, for organizational and social reasons, the incidence of locally advanced neoplasms is higher in this age group than in the younger population. The aim of the study was to assess our experience in this specific pathology and review the international literature on this topic. From 2001 to 2005 116 cases of breast cancer in elderly women (70-95 years old) were observed by our surgical units. Of these, 38 were at a locally advanced stage (10--26.3%--stage IIIA, 28--73.7%--stage IIIB). Comorbidity (two or more diseases) existed in 32 patients. A Madden modified radical mastectomy was carried out in all cases. Resection was extended to the chest-wall tissues in cases of local infiltration. Surgical mortality was 10% (4 cases). Eight of the 34 patients discharged died within 24 months (2 of disease progression). Adjuvant chemotherapy was never offered. On the other hand, all patients received hormone therapy (tamoxifen). 10 of the 26 patients (38.4%) surviving over 2 years underwent redo surgery for local relapse of disease. Our conclusions are: 1) breast cancer in elderly patients is often underestimated and undertreated; 2) disease management cannot be standardized, but must be tailored to the single patient; 3) short- and medium-term results are satisfactory; 4) comorbidity must be carefully assessed.

The role of laparoscopy in pancreatic surgery.

Carcinoma of the pancreas is extremely common, with a five-year mortality rate of about 95-99%. Radical surgery requires good technical skill and can cause complications and operative mortality, but should be avoided in patients with extrapancreatic involvement. Advances in dynamic spiral CT-scan have decreased the number of unnecessary laparotomies. VLS is indicated in cases of pancreatic mass deemed resectable or "doubtful" by CT-scan. Direct laparoscopic visualization can be combined with intraoperative laparoscopic ultrasonography (LUS), which has shown a positive predictive value of resectability of 91%. Laparoscopic pancreatoduodenectomy (LPD) shows a high rate of complications and should be performed by very well-trained surgeons. Laparoscopic distal pancreatectomy (LDP) with an "en bloc" splenectomy and spleen preservation should be performed.

Surgical treatment of differentiated thyroid carcinoma: a retrospective study.

A retrospective study was carried out to assessed reliability of the prognostic factors (histology, age, sex, and stage), and standard procedures for the surgical treatment of differentiated thyroid cancers (DTC). From the 144 DTC cases reviewed with follow-up ranging from 1 to 25 years (m = 6.33 years), total mortality for cancer was found to be 55% (8 patients), with a predictive positive value for recurrence of 95.4% and 91.8% at 12 and 24 months, respectively. Median survival was 8.8 years (range 1 to 25 years). The multivariate analysis showed that factors such as age > 45 years, histology of intermediate malignancy, size up to 1.5 cm, and presence of metastases, significantly worsened the prognosis, regardless of the intervention that was carried out. We suggest total thyroidectomy for the treatment of benign pathologies and confirmed or suspected cases of cancer. We reserve loboisthmectomy for the treatment of benign pathologies confined to one lobe or those with FNAB suggesting a follicular neoplasm.

Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review).

Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age.

Role of perineural invasion as a prognostic factor in laryngeal cancer.

The diffusion of laryngeal cancer cells in the perineural space is a parameter associated with a negative prognosis, high loco-regional recurrence and low disease-free survival rates. The spread of tumor cells on the perineural sheath highlights the histopathological and clinically aggressive behavior of this type of tumor, which may extend proximally or distally in the nerve for >10 cm. Therefore, the surgical resection margin is generally insufficient to treat patients with laryngeal cancer presenting with perineural invasion (PNI) with surgery alone. In PNI, the minor laryngeal nerves are frequently involved, rather than the superior and inferior laryngeal nerves. The aim of the present study was: i) To evaluate the prognostic importance of PNI; ii) to correlate the rate of infiltration with factors associated with the tumor, including histotype, site and tumor-node-metastasis stage, and with the type of surgery (total or partial laryngectomy); and iii) to evaluate the rate of disease-free survival according to the outcome of combined surgery and radiotherapy (RT) treatment, by means of retrospective analysis. The results of the present study highlighted the importance of performing a closer clinical and instrumental follow-up in patients with laryngeal cancer whose histopathological examination is positive for PNI. In such cases, it is important to complement the surgical therapeutic treatment with adjuvant RT.

Usefulness of the LigaSure vessel sealing system during superficial lobectomy of the parotid gland.

OBJECTIVE: To evaluate the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. DESIGN: Prospective study of the surgical procedures in the LigaSure Vessel Sealing System and comparison with a conventionally treated control group. SETTING: Secondary care academic referral center. Patients Thirty-five patients with a parotid gland benign tumor were randomly allocated to 2 superficial lobe parotidectomy groups: 17 using the LigaSure procedure (group A) and 18 using the conventional method (group B). MAIN OUTCOME MEASURES: During the past few years, different methods of achieving hemostasis in parotid gland surgery have been tested as means of decreasing operative time and facial nerve injuries by controlling bleeding. With the whole LigaSure Vessel Sealing System, we experienced the usefulness of the LigaSure Precise instrument in superficial lobectomy of the parotid gland. RESULTS: No statistically significant differences were noted between the 2 groups in mean age, tumor diameter, length of hospital stay, time to return to work, or number of adverse events during or after surgery. Operative time was significantly shorter in group A than in group B (P < .001). Total operative time for conservative partial parotidectomy with traditional excision ranged from 115 to 235 minutes (mean, 155.8 minutes). Using the LigaSure system, the mean operative time was 136.4 minutes. Salivary fistulas were more common in group A (3 of 17 patients), with no cases in group B. CONCLUSIONS: The LigaSure method is comparable with but not superior to the conventional method. The main advantages of the LigaSure system are its "sutureless technique" and operative time savings; however, the cost is considerably higher.

Efficacy of magnetic resonance cholangiopancreatography in detecting common bile duct lithiasis: our experience.

It has been shown that magnetic resonance cholangiopancreatography (MRCP) has a diagnostic accuracy comparable to that of ERCP. The aim of this study was to compare the diagnostic accuracy of MRCP in patients with suspected choledocholithiasis, but with negative ultrasonography findings. Among 404 patients undergoing videolaparocholecystectomy for cholelithiasis, 48 with risk factors for coledocholithiasis were evaluated. All the patients with risk factors underwent preoperative hepatobiliary ultrasonography and MRCP. Patients were assigned to one of 2 main groups: A) patients with common bile duct stones at ultrasonography (15/48: 31%) and B) patients without evidence of common bile duct stones on ultrasonography (33/48: 69%), with B comprising two subgroups: B1) MRCP-positive for stones (7/33:21%) and B2) negative US and MRCP (26/33:79%). MRCP showed 100% sensitivity and 100% specificity. The high sensitivity of MRCP allows us to recommend a greater use of the procedure with avoidance of unnecessary ERCP, which should be reserved for therapeutic purposes only.

[Surgical treatment of iatrogenic bile duct injuries following laparoscopic cholecystectomy: analysis of long-term results. Retrospective clinical study in 51 patients operated in the Campania region from 1991 to 2003]. / Trattamento chirurgico delle lesioni iatrogene della via biliare in seguito a colecistectomia videolaparoscopica: analisi dei risultati a distanza. Studio clinico retrospettivo in 51 pazienti operati nella regione Campania dal 1991 al 2003.

An higher incidence rate of iatrogenic bile duct injuries is reported in cholecystectomy performed with the laparoscopy than with the laparotomy approach. The aim of this study was to provide a multicentre report on surgical treatment and the outcome of biliary complications during and following laparoscopic cholecystectomy. A questionnaire was mailed to all surgeons with experience in laparoscopic cholecystectomy in the Campania region. Data were collected from January 1991 to December 2003. Each patient was requested to indicate age, gender, associated diseases, site and type of lesion, surgical experience, diagnosis, treatment and complications. Twenty-six surgeons answered the questionnaire. Fifty-one patients (36 F/15 M; mean age: 42.5 +/- 11.9, range 13-91 years) with bile duct injuries following laparoscopic cholecystectomy were reported. The most frequent lesions were main bile duct partial or total transection. The intraoperative mortality rate was 1/51 (1.9%) due to a complex biliary and vascular injury. The postoperative mortality rate of revision surgery was 5/50 (10%). T-tube positioning (n = 20) and Roux-en-Y hepato-jejunostomy (n = 20) were the procedures most frequently performed. The complication rate in patients treated with the T-tube was significantly higher than in those treated with hepatico-jejunostomy. Surgical treatment of biliary injuries following laparoscopic cholecystectomy was characterized by unusually high mortality and morbidity for a non-neoplastic disease. Roux-en-Y hepato-jejunostomy remains the procedure of choice for these injuries.

Laparoscopic cholecystectomy in the morbidly obese.

In the early days of video-assisted laparoscopic cholecystectomy (VLC), obesity was considered a contraindication for the procedure. We reviewed charts from 304 patients undergoing VLC; 90 patients were obese, and among these, according to a classification currently used by medical nutritionists and based on BMI, 45 were overweight (BMI > or = 25 < or = 29.9), 27 were considered conventionally obese (BMI > or = 30 and < 40) and 18 morbidly obese (BMI > or = 40). In this study we considered only the morbidly obese patients (5 males and 13 females). The average age was 42.3 years (range: 21-65) and the average weight 275 Ib (range: 186-331 Ib). Six patients had previously undergone abdominal surgery. All patients were symptomatic for gallstones, and 5 of them were suffering from acute cholecystitis. Mean operative time was 20 minutes (range: 10-45 minutes) longer than that of non-obese patients. No open conversion was necessary. No major postoperative morbidity and no cases of mortality occurred. The mean hospital stay and resumption of normal diet were similar to those of non-obese patients. Regardless of the higher postoperative risks after open cholecystectomy in obese patients (pulmonary complications, thromboembolism, wound infections and cardiovascular complications), we suggest VLC as the procedure of choice for cholecystectomy in these patients.