Cirrhotic patients are still at risk of developing hepatocellular carcinoma despite Interferon-induced sustained virological response.

INTRODUCTION: Hepatitis C virus (HCV) infection is a common cause of chronic liver disease and hepatocellular carcinoma (HCC). The prevalence of HCC significantly declines among patients achieving a sustained virological response (SVR) after antiviral therapy with pegylated(PEG)-interferon (IFN) and ribavirin. However, up to 5% of patients with SVR may develop HCC. PATIENTS AND METHODS: We investigated the epidemiological, clinical, biochemical and virological characteristics of a small cohort of patients with chronic hepatitis C (CHC) who developed HCC after being successfully treated with PEG-IFN-α and ribavirin. RESULTS: Between September 2000 and January 2003, 598 patients with CHC underwent a complete course of treatment with PEG-IFN-α and ribavirin; 221 out of 598 (37%) patients obtained a SVR. Throughout the 10-year post-treatment follow up, 13 of 221 ( 5.8% ) SVR patients developed HCC. All 13 patients were male and were affected with Child A liver cirrhosis; in addition, at baseline they were significantly older (p < 0.05) and had higher alpha-fetoprotein levels (p < 0.05) in comparison with those who did not develop HCC. Nine patients (69.3%) developed HCC within the first 3 years after antiviral treatment completion, one patient (7.7%) between 3 and 5 years and 3 subjects (23%) between 5 and 10 years; 12 of 13 had a solitary lesion with a mean diameter of 2.5± 0.5 cm. Eleven cases (84.6%) underwent surgical resection, one (7.7%) received liver transplantation, one (7.7%) received palliative care. CONCLUSIONS: The risk of developing HCC after achieving SVR persists in patients with HCV-related cirrhosis. As a consequence, these patients should continue to undergo long-term surveillance for HCC, in order to early detect and treat it.

Laparoscopic treatment of intrasplenic pancreatic pseudocyst.

INTRODUCTION: Pseudocyst formation commonly follows pancreatitis, but erosion into the spleen is rare and potentially life threatening. We report a case of an intrasplenic pancreatic pseudocyst treated laparoscopically with distal pancreatectomy and splenectomy. METHODS: A 50 year old male with a history of chronic alcoholic pancreatitis, presented with abdominal pain for 3 months, worsening over the past several days. A CT scan showed a broad 9 cm subcapsular fluid collection suspicious for an intra-splenic pseudocyst. The patient underwent laparoscopic distal pancreatectomy and splenectomy. RESULTS: There were no intraoperative complications and the patient was discharged on day 8. The final pathology revealed a benign cystic lesion measuring 9 x 6 x 3 cm that was not communicating with the pancreatic duct, and 2 smaller pseudocysts in the pancreatic body and tail. A previous scan did not reveal any abnormalities in the spleen, and showed the other pancreatic pseudocysts. At 8 month follow up the patients was symptom free, with no new pseudocysts. CONCLUSIONS: Splenic parenchyma involvement is an unusual complication of pancreatic pseudocyst. The optimal treatment is controversial. Percutaneous drainage carries a high recurrence rate and risk of hemorrhage. Open surgery is effective, but associated with significant morbidity. Laparoscopy offers an effective method of treatment without the potential complication of a large abdominal incision.

Lymph node evaluation in gallbladder cancer: which role in the prognostic and therapeutic aspects. Update of the literature.

OBJECTIVE: The widespread use of laparoscopy has changed the outcome of gallbladder cancer as a consequence of increasing referral and incidental discovering of earlier stages cancer. Nevertheless, GBC is still associated with a poor prognosis and lymphnodal involvement is a main prognostic factor, important both for staging and for evaluating surgery quality. No consensus exists about the extension of lymphadenectomy to be performed nor about contraindications to extensive resection. A review of literature was so designed to identify the actual role, extension and limits of lymphadenectomy. MATERIALS AND METHODS: A search on Pubmed and Scopus has been performed using the following keywords: gallbladder cancer, gallbladder neoplasm, surgery, laparoscopy, lymphadenectomy to evaluate the prognostic and the therapeutic role of the lymphadenectomy in gallbladder cancer. The retrieved articles were analyzed aimed to evaluate the impact of lymphectomy and of its extension on overall and disease free survival. RESULTS:  Although no consensus still exists over the extension of ideal lymphadenectomy, some points are already clearly established: a part from T1a neoplasms, that do not require further surgery, and T1b for which a regional lymphectomy (N1) is safe and mandatory, more advanced stages require a more aggressive surgery but the fate of paraortic nodal station is still under evaluation. In fact some Authors still believe that the involvement of these nodes determine a so poor prognosis to make uselessly risky their surgical aggression. Other Authors conversely, show that there is not any difference in survival, among node positive patients, between paraortic node positive and no paraortic node positive patients. CONCLUSIONS: The prognosis of gallbladder cancer remains poor because in most patients the diagnosis is made at an advanced stage. Complete surgical resection provides the only curative treatment option in this disease. In order to improve long-term outcome, several surgeons have advocated aggressive surgical resection, including major hepatectomy, pancreatoduodenectomy and extended lymphadenectomy. Even a para-aortic nodal disease shouldn't discourage from pursuing this objective.

Laparoscopic cholecystectomy: ultrasonic energy versus monopolar electrosurgical energy.

OBJECTIVE: Nowadays, laparoscopic cholecystectomy (LC) is undoubtedly considered the "gold standard" in the surgical treatment of symptomatic gallstones, gallbladder adenomas and acute cholecystitis. Among the alternative energy sources proposed (monopolar, bipolar electric scalpel, radiofrequency sealers) with the aim to dissect and/or seal, the ultrasonic energy has been frequently adopted, however without a widespread acceptance among surgeons for routine or emergency laparoscopic cholecystectomy. This study investigates the possible beneficial aspects of ultrasonic dissection and its efficacy in the closure of the cystic artery and duct. PATIENTS AND METHODS: Patients were retrospectively divided into 2 groups according to the instruments used for division of the cystic artery and duct as well as for dissection of the liver bed: 121 patients in whom dissection and coagulation were performed using monopolar coagulation and 43 patients who were all treated with the ultrasonically activated scalpel harmonic ACE (Ethicon Endo-Surgery) as the sole instrument used in the whole procedure. RESULTS: The mean operative time, was significantly shorter in the harmonic group than in the traditional group (35.36 + 10.15 min vs. 55.6+12.10 vs. respectively; p < 0.0001). The rate of gallbladder perforation was significantly higher in the traditional group than in the harmonic group 20.66% (25 patients) vs. 6.98% (3 patients), respectively; p < 0.05). Intraoperative volume blood loss was significantly more in the traditional group than in the HS group (29.32+14.21 vs. 12.41+8.22; p < 0.0001). The mean amount of postoperative drainage was not significantly different among the two group (18.41+6.54 vs. 15.96+8.69 ml, p > 0.05). No considerable visceral injury has been recorded in either group. The postoperative parameters observed included postoperative hospital stay and morbidity for each group. The hospital stay was not significantly shorter in harmonic group (48.15+4.29 vs. 49.06+2.94 h, p > 0.05). The overall morbidity rate was 14.02 % (not significant). CONCLUSIONS: The use of the harmonic scalpel shows some statistically significant advantages limited to a few intraoperative parameters. We conclude that a wider use of harmonic scalpel not offers such advantages to make it the reference technique.

Dissemination metastasis after laparoscopic colorectal surgery versus conventional open surgery for colorectal cancer: a metanalysis.

PURPOSE: The purpose of this systematic review is to evaluate and compare the risk of dissemination metastasis (wound, port-side metastases and peritoneal seeding) after laparoscopic colorectal surgery and conventional open surgery for colorectal cancer. MATERIALS AND METHODS: The Authors searched relevant randomized controlled trials between January 1998 and July 2012. RESULTS: Wound, port-site metastases and peritoneal seeding were rare and no significant differences occurred between the two groups. The port-site and extraction site recurrence were likely to be the results of suboptimal surgical techniques and occurred in the early phase of the learning curve. The authors also found no significant differences in overall, local and distant recurrences. No significant differences between laparoscopic and open surgery were found in cancer-related mortality during the follow up period of the study (7 RCTs, 3525 patients, 12.8% vs. 14.00%; OR (fixed) 0.83, 95% CI 0.68-1.02), with no significant heterogeneity (p = 0.35). CONCLUSIONS: The literature supports the implementation of laparoscopic surgery into daily practice. Laparoscopic surgery can be used for safe and radical resection of cancer in the right, left, sigmoid colon and rectum. However further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

Clinical presentation and outcome of squamous cell carcinoma of the anus in HIV-infected patients in the HAART-era: a GICAT experience.

INTRODUCTION: Squamous cell carcinoma of the anus (SCCA) is a relatively uncommon cancer. In the HIV-positive patients the introduction of the highly active antiretroviral therapy (HAART) did not change the incidence of SCCA. BACKGROUND AND OBJECTIVES: This paper describes the Italian Cooperative Group on AIDS and Tumours (GICAT) experience on HIV-positive patients with SCCA. The purposes of this retrospective study were: first to describe the clinical presentation and outcome of HIV-positive patients with SCCA, second to compare them with the ones reported in the literature. PATIENTS AND METHODS: Between July 2000 and March 2010 we retrospectively collected epidemiological, clinical and survival data from 65 patients with SCCA in HIV infection enrolled within the GICAT. RESULTS: Fifty-three (81.5%) patients were male. The majority of patients (40%) were homosexual Forty-three patients (66.1%) were diagnosed with HIV before 1996. Thirty-five patients (54%) had CD4-positive cells count > 200 / mm3 and 28 patients (43%) had viral load > 50 cp / ml at the time of SCCA diagnosis. The median time difference between HIV and SCCA diagnosis was 120 months (range 10-282 months). Sixty-one patients (96.8%) received HAART at SCCA diagnosis. Fifty-two patients (80%) had performance status (PS) 0-1 at the time of SCCA diagnosis. Twenty-seven patients (41.5%) underwent surgery with curative intent. Thirty-five patients (53.9%) were given combined modality therapy (CMT) consisting of pelvic radiotherapy with concurrent chemotherapy. No grade 3/4 haematological or extra-haematological effects were observed in our patients. CONCLUSIONS: In summary, despite the retrospective nature of analysis, the absence of patient strict criteria of inclusion/exclusion, our data on HIV-positive patients with SCCA, compared both to general population and to small reports on HIV-positive patients present in the literature, are promising.

Safety and efficacy of radiotherapy treatment in elderly patients with localized prostate cancer: a retrospective analysis.

The purpose of this study was to evaluate the feasibility and the activity of radiotherapy treatment in patients aged ≥75 with prostate cancer (PC). From January 2000 to December 2007, 107 consecutive patients aged ≥75 years received radiotherapy with radical intent for PC. Eighty-one patients received radiotherapy in combination with a 6 months androgen suppression therapy. Variables considered were age, stage, co-morbidities according to the adult co-morbidity evaluation index (ACE-27) and performance status (PS). The median age was 79.1 years (range 76-87). The 23.4% of patients showed no co-morbidities, while the 46.7% had mild, 23.4% moderate, and 6.5% severe co-morbidities, respectively. All patients completed the planned radiation treatment. At a median follow-up of 37.8 months, the 5-year overall survival rate was 78%. There was a better survival for patients with no or mild co-morbidities (p<0.0001) and a good PS (p=0.009). The actuarial disease-free survival at 60 months was 75.8%. Difference in acute and late toxicity rate was detected between ACE-27 classes for diarrhea and marginally for urinary toxicity, but no difference was detected for different age. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with radical radiotherapy. Further prospective trials are needed to confirm these results.

Safety and feasibility of radiotherapy treatment in elderly non-small-cell lung cancer (NSCLC) patients.

The purpose of this study was to evaluate the feasibility and activity of radiotherapy (RT) treatment in elderly patients with locally advanced lung cancer. From January 2002 to December 2007, 51 consecutive patients (43 men and 8 women) aged > or = 65 received RT for locally advanced lung cancer, 22 with radical intent and 16 in adjuvant setting. Thirty-six patients received chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery vs. no surgery, radiation dose and chemotherapy. The median age was 74.7 years (range 65-91). Of the patients, 15.7% had no co-morbidity, 41.2% mild, 25.5% moderate, and 17.6% had severe co-morbidities. Sixteen subjects (31.4%) underwent surgery. All patients completed the planned radiation schedule, while chemotherapy was reduced in 16 patients. At a median follow-up of 22 months, the 2- and 3-year overall survival rates were 46.5% and 35.4%, respectively. Patients with no or mild co-morbidities (p < 0.0001) and a good performance status (p < 0.0001) had a better survival. The actuarial progression-free survival at 2 and 3 years was 41.4% and 38.2%, respectively. Acute lung toxicity rates were different between patients with different ACE-27 indexes, whereas late toxicity was not influenced. In conclusion, in elderly patients, the compliance with RT is good and the rate of toxicity is acceptable. Patients with no or mild co-morbidities have a significantly better survival. The increasing severity of co-morbidities may sufficiently shorten the remaining life expectancy, cancel the gains obtained by RT and increase the acute lung toxicity. Further prospective trials are needed to confirm these results.

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients.

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

FOLFOX2 in the treatment of advanced colorectal cancer: a comparison between elderly and middle aged patients.

The effectiveness of chemotherapy in elderly patients is still a matter of debate. We analyzed the toxicity and efficacy of the original FOLFOX2 regimen in middle aged and elderly patients affected by metastatic colorectal cancer. Consecutive patients with metastatic CRC and measurable disease were eligible. Seventy-eight partially pretreated patients were enrolled: 58 patients were defined as middle aged (<70 years) and 20 were elderly patients (>70 years). Elderly patients in comparison to middle-aged patients in a higher percentage were males. No significant differences were found in hematological and non-hematological toxicity between the two groups. No significant differences were found in the response rates, time to progression (5.9 vs. 6.0 months respectively), or median overall survival (20.9 and 21.8 months, respectively) between middle aged and elderly patients. The FOLFOX2 regimen provides equivalent feasibility, efficacy, and survival gain in middle-aged and in elderly patients with metastatic CRC.

Corticotropin releasing factor-1 receptor antagonist, CP-154,526, blocks the expression of ethanol-induced behavioral sensitization in DBA/2J mice.

RATIONALE: Manipulation of glucocorticoid receptor signaling has been shown to alter the acquisition and expression of ethanol-induced locomotor sensitization in mice. It is unknown if other components of the hypothalamic-pituitary-adrenal (HPA)-axis modulate locomotor sensitization resulting from repeated ethanol administration. In the present investigation, we determined if pretreatment with an i.p. injection of CP-154,526, a selective corticotropin releasing factor (CRF) type-1 receptor antagonist, would block the acquisition and/or expression of ethanol-induced locomotor sensitization in male DBA/2J mice. METHODS: To assess the role of the CRF1 receptor in the acquisition of behavioral sensitization, mice were pretreated with an i.p. injection of CP-154,526 30 min before each of 10 sensitizing i.p. injections of ethanol. To determine the role of the CRF1 receptor in modulating the expression of ethanol-induced sensitization, mice that had previously been sensitized to the locomotor stimulant effects of ethanol were pretreated with CP-154,526 30 min before an i.p. injection of ethanol on the test day. In a third study, ethanol-naïve mice were pretreated with CP-154,526 30 min before an initial i.p. injection of ethanol to determine the combined effects of the CRF1 receptor antagonist and ethanol on locomotor activity. Blood ethanol concentrations were assessed at the termination of sensitization studies. RESULTS: Pretreatment with CP-154,526 blocked the expression of ethanol-induced locomotor sensitization in DBA/2J mice but did not prevent the acquisition of sensitization. The ability of CP-154,526 to block the expression of ethanol-induced locomotor sensitization was not attributable to alterations in blood ethanol levels or possible sedative effects produced by the combined administration of CP-154,526 and ethanol. CONCLUSIONS: These data provide novel evidence that CRF1 receptor signaling modulates the expression of ethanol-induced locomotor sensitization, and add to a growing literature suggesting a role for neurochemicals and hormones associated with the HPA-axis in behavioral sensitization resulting from repeated exposure to drugs of abuse.

Involvement of protein kinase A in ethanol-induced locomotor activity and sensitization.

RATIONALE: Mutant mice lacking the RIIbeta subunit of protein kinase A (regulatory subunit II beta(-/-)) show increased ethanol preference. Recent evidence suggests a relationship between heightened ethanol preference and susceptibility to ethanol-induced locomotor sensitization. It is currently unknown if protein kinase A signaling modulates the stimulant effects and/or behavioral sensitization caused by ethanol administration. To address this question, we examined the effects of repeated ethanol administration on locomotor activity RIIbeta(-/-) and littermate wild-type (RIIbeta(+/+)) mice on multiple genetic backgrounds. METHODS: Over three consecutive days, mice were given single i.p. saline injections and immediately placed in a locomotor activity apparatus to establish a composite baseline for locomotor activity. Next, mice maintained on a hybrid 129/SvEvxC57BL/6J or pure C57BL/6J genetic background were given 10 i.p. ethanol injections before being placed in the activity apparatus. Each ethanol injection was separated by 3-4 days. To determine if changes in behavior were specific to ethanol injection, naïve mice were tested following repeated daily saline injections. The effects of ethanol injection on locomotor behavior were also assessed using an alternate paradigm in which mice were given repeated ethanol injections in their home cage environment. RESULTS: Relative to RIIbeta(+/+) mice, RIIbeta(-/-) mice, regardless of genetic background, consistently showed significantly greater ethanol-induced locomotor activation. RIIbeta(-/-) mice also showed increased sensitivity to ethanol-induced locomotor sensitization resulting from repeated administration, an effect that was dependent on genetic background and testing paradigm. Increased locomotor activity by RIIbeta(-/-) mice was specific to ethanol injections, and was not related to altered blood ethanol levels. CONCLUSIONS: These data provide novel evidence implicating an influence of protein kinase A signaling on ethanol-induced locomotor activity and behavioral sensitization. The observation that RIIbeta(-/-) mice are more sensitive to the effects of repeated ethanol administration suggests that normal protein kinase A signaling limits, or is protective against, the stimulant effects of ethanol and the plastic alterations that underlie behavioral sensitization.