Evangelos Felekouras

Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study.

Study objectives: The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin, Leucovorin and 5-FU as second line therapy, following relapse to Gemcitabine, in patients with advanced adenocarcinoma of the pancreas. Patients and methods: Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study. All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable, locally advanced or metastatic. Treatment consisted of Oxaliplatin 50 mg/m2 (2-hour iv infusion), followed by Leucovorin 50 mg/m2 (i.v. bolus) and 500 mg/m2 5-FU (1-hour iv infusion), administered weekly, until unacceptable toxicity or disease progression. Objective tumour response and toxicity were evaluated according to World Health Organisation (WHO) criteria. Results: A total of 30 patients, 20 men and 10 women, median age 63 years (range 52–71 years) and Karnofsky Performance Status (PS) of ≥50 entered the study. The majority of patients (96%) had locally advanced disease. A total of 380 doses of chemotherapy were delivered, a median of 12 doses per patient. Partial responses were observed in 7 patients (PR 23.3%), stable disease in 9 (SD 30.0%), while 14 patients progressed (PD 46.7%). Improved PS was observed in 18 (42.8%) patients. Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment. The median duration of response was 22 weeks, and median overall survival was 25 weeks, Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16%, anemia 3.2%, thrombocytopenia 3.2%, diarrhea 14.2%, fatigue 16.1% and neurotoxicity 4.2%. Eight patients (27%) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy, while 17 patients required G-CSF support. There were no treatment related deaths. Conclusions: The combination of Oxaliplatin, Leucovorin and 5-FU was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma, previously treated with Gemcitabine. Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients.

Central venulitis in the allograft liver: a clinicopathologic study.

BACKGROUND Central venulitis denotes a histologic lesion of the allograft liver characterized by perivenular and subendothelial mononuclear inflammation of the terminal hepatic venules associated with varying degrees of perivenular hepatocyte dropout. Although this lesion has generally been considered a manifestation of acute rejection, some have suggested that it instead represents tacrolimus hepatotoxicity. METHODS We therefore compared the clinicopathologic features of 30 episodes of isolated central venulitis with 22 episodes of combined central venulitis and typical portal acute rejection occurring in 27 patients. Nineteen of the patients received tacrolimus and eight received cyclosporine as primary immunosuppression. RESULTS No significant differences were found between the two groups, except that isolated central venulitis more often displayed a mild inflammatory component (P=0.007) with small lymphocytes as the predominant cell type (P=0.002). None of the patients had tacrolimus or cyclosporine levels that exceeded the therapeutic range, and none had other clinical evidence of drug toxicity. Usual antirejection therapy was instituted in all but two episodes; response was evident in 93% (28 of 30) of the isolated central venulitis and 86% (19 of 22) of the central venulitis-portal acute rejection group, with histologic regression documented in all follow-up specimens (four and five, respectively). Due to persistent central venulitis, two cyclosporine patients were switched to tacrolimus, with prompt resolution. CONCLUSIONS These findings are inconsistent with the concept that central venulitis represents drug toxicity and indicate instead that it is a form of acute allograft rejection.

Clinical Features of Hypersensitivity Reactions to Oxaliplatin: A 10-Year Experience

Background: Oxaliplatin has become one of the major cytotoxic agents for the treatment of gastrointestinal tumors. As a result, several cases of the so-called oxaliplatin-associated hypersensitivity reaction have been documented. Patients and Methods: We have retrospectively evaluated and characterized these reactions in our patient group by reviewing the files of 1,224 patients exposed to an oxaliplatin-containing regimen in order to provide useful clinical information for diagnosis and management. Results: Three hundred and eight (308) patients who have never been exposed to platinum compounds developed symptoms compatible with a reaction to oxaliplatin that was verified by manifestation of at least similar symptoms on rechallenging. The reactions occurred after the first 5 courses, with a median course number of 9 (range 1–24). These reactions could be distinguished as (1) mild reactions occurring in 195 (63%) patients manifesting with itching and small area erythema either during treatment or within the next hours, and (2) severe reactions occurring in 113 (37%) patients within minutes of drug infusion manifesting with diffuse erythroderma, facial swelling, chest tightness, bronchospasm and changes in blood pressure. Oxaliplatin withdrawal was not required in patients with a mild reaction. Forty-eight (42%) patients having a severe reaction with appropriate premedication and prolongation of the infusion duration could tolerate 2–4 subsequent courses. For the remaining 65 (58%) patients, oxaliplatin withdrawal was inevitable because of the very severe reactions occurring on rechallenging. In addition, 3 patients presented with thrombocytopenia and 3 others with hemolytic anemia, all reversible upon oxaliplatin discontinuation. Conclusions: Hypersensitivity reactions to oxaliplatin are underestimated. Although the reactions are not frequent during first courses, in extensively pretreated patients, they may become a serious problem. In the majority of patients, drug discontinuation might not be necessary. In patients manifesting a severe reaction, re-exposure to oxaliplatin should be considered only if the patient can tolerate the reaction and there has been clinical benefit from this therapy. Physicians and nursing staff should be aware of the risk and be well prepared.

Association between mutations in the CARD15/NOD2 gene and colorectal cancer in a Greek population

Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example since patients with longstanding IBD are at increased risk for development of colorectal cancer (CRC). Therefore, genetic factors predisposing to or implicated in the chronic inflammatory process in IBD may simultaneously predispose to CRC. Recently CARD15/NOD2 has been associated with IBD, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the CARD15/NOD2 gene, which appear with significantly higher frequency in patients with IBD. In this report, we have examined the frequency of the 3 major mutations R702W, G908R and 3020insC of the CARD2/NOD2 gene in a series of 104 consecutive Greek patients with sporadic colorectal cancer and 100 healthy individuals. The frequency of all the mutations was significantly elevated compared to the control population (R702W, OR=5.00, p=0.023; G908R, OR=2.78, p=0.025; 3020insC, OR=2.44, p=0.017). Patients with advanced stage tumors were more frequently carriers of at least 1 variant in the CARD15/NOD2 gene (p=0.009). Our results suggest that CARD2/NOD2 may be a genetic factor that predispose to sporadic colorectal cancer.

Bile Duct Injuries Associated with Laparoscopic and Open Cholecystectomy: An 11-Year Experience in One Institute

PurposeBile duct injury (BDI) represents the most serious complication of laparoscopic cholecystectomy (LC). The aim of this retrospective single-institution study was to evaluate the real incidence of BDI during laparoscopic and open cholecystectomy (OC) in a tertiary academic center in Athens, Greece.MethodsBetween January 1991 and December 2001, 3 637 patients underwent cholecystectomy in our department; as LC in 2 079 patients (LC group) and as OC in 1 558 patients (OC group). All the LCs were performed or supervised by five staff surgeons and all the OCs were performed or supervised by another five staff surgeons.ResultsThere were 13 BDIs associated with LC (0.62%) and 6 associated with OC (0.38%) (P = 0.317). There was one death associated with BDI after LC. Only two (15.4%) of the BDIs associated with LC occurred within the proposed learning curve limit of 50 LCs per individual surgeon.ConclusionLaparoscopic cholecystectomy is safe and is not associated with a higher incidence of BDI than OC. Moreover, we did not find that the learning curve for LC affected BDI occurrence.

Serous cystadenocarcinoma of the pancreas: report of a case and management reflections.

BackgroundSerous adenomas represent 1-2% of pancreatic neoplasms and typically are asymptomatic not requiring any treatment and simple observation is the option of choice. Although, they carry a realistic risk of malignancy despite the general view that they never become malignant. We report a case, which, according to our best knowledge is the 27th case reported in the literature.MethodsWe reviewed the literature by performing a search in Pub Med and Medline.ResultsA 86-year old patient known to have a serous cystadenoma of the pancreas treated conservatively through a close clinical and radiological follow up which was unattended for 4 years ending up to our emergency department suffering an acute abdomen. Exploratory laparotomy revealed a perforated prepyloric ulcer which was treated accordingly. Patient died some weeks later due to severe medical co morbidities.ConclusionSerous cystic neoplasms of the pancreas carry a realistic risk of malignancy despite the general view that they never become malignant. In our opinion the treatment strategy of serous cystic neoplasms of the pancreas should be aggressive even in cases of remote metastases since prognosis of the disease is satisfactory

Liver Resection in Cases of Isolated Hepatic Actinomycosis: Case Report and Review of the Literature

Hepatic actinomycosis is an uncommon entity that forms communicating abscesses and fistulae. We report a 53-y-old immunocompetent male patient with hepatic actinomycosis. Symptoms included intermittent fever, abdominal pain, right upper quadrant tenderness and jaundice. A hepatic tumour mass was found on abdominal sonography and computerized tomography. Two preoperative percutaneous core biopsies of the mass were not diagnostic. The above findings were highly suggestive for liver abscess or purulent primary liver neoplasm. Treatment with intravenous antibiotics was continued for 20 d, but both symptoms and liver ultrasound findings remained unchanged. The patient underwent exploratory laparotomy and right posterior segmentectomy of the liver. Pathological examination of the surgically removed specimen disclosed hepatic actinomycosis. Following operation the patient remains in excellent condition without evidence of recurrence.

Comparison of safety and efficacy of ultrasonic and bipolar thermal energy: an experimental study.

The safety and efficacy of the Ligasure-8 Generator with the new Ligasure V 5-mm forceps (Valleylab, Tyco Healthcare) (LS) and the Ultracision Harmonic Scalpel Generator 300 with the new 5 mm 36p Harmonic Ace forceps (Ethicon Endo-Surgery ING) (UC) are compared. Twenty New Zealand rabbits were randomly allocated into 2 groups and the short gastric vessels were divided with either LS or UC. The speed of each method, the number of the times it had to be applied, gastric perforation rates and histopathologic findings were recorded. Approximately the same number of applications was necessary for the 2 groups. UC was significantly faster but resulted in contained perforation in 3 cases against 1 for LS (difference statistically not significant). A tendency for deeper and more severe histopathologic damages was seen with UC. For routine fast dissection, UC is satisfactory, but where prevention of thermal injury is important, LS may be more appropriate.

Comparison Between Minimally Invasive and Open Pancreaticoduodenectomy: A Systematic Review.

Introduction: Minimally invasive approaches (laparoscopic or robotic) are used in various operations. Our aim was to compare them with the open approach in pancreaticoduodenectomy. Methods: We conducted a search for articles published in MEDLINE database comparing minimally invasive (laparoscopic or robotic) with open pancreaticoduodenectomy on June 15, 2014. Results: Our search yielded 136 articles. We excluded 122 articles and we took into consideration 14 (10 for laparoscopic and 4 for robotic pancreaticoduodenectomies). Most cases were related to malignant diseases and tumors treated with minimally invasive operations tended to be smaller. There were relatively high conversion rates in both laparoscopic (0% to 15%) and robotic procedures (4.5% to 10%). There were no significant differences regarding resection margins, rates of pancreatic fistula formation, bile leak, and delayed gastric emptying, reoperation rates, and intraoperative and postoperative mortality. On the contrary, blood loss was less in minimally invasive than open operations, although this difference was not always significant. Moreover, totally laparoscopic and robotic procedures lasted longer than the open ones, whereas hand-assisted laparoscopic procedures did not. However, the findings regarding the number of the retrieved lymph nodes, the length of hospital stay, and costs were inconclusive and controversial. Conclusions: Laparoscopic and robotic pancreaticoduodenectomy are feasible, safe, and oncologically equivalent alternatives to open pancreaticoduodenectomy. Minimally invasive operations have the advantage of the less blood loss, but totally laparoscopic and robotic procedures last longer than open procedures.

Sequential Administration of 5-Fluorouracil (5FU)/Leucovorin (LV) Followed by Irinotecan (CPT-11) at Relapse versus CPT-11 Followed by 5-FU/LV in Advanced Colorectal Carcinoma

Purpose: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). Patients and Methods: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m2 LV and 425 mg/m2 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m2), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. Results: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6–47.4 weeks) for group A and 32.0 weeks (range, 28.2–35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10–36 weeks) and 12 weeks (range, 10–16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. Conclusions: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.