Nazario Portolani

Limited liver resection: a good indication for the treatment of hepatocellular carcinoma in elderly patients.

OBJECTIVEnHepatocellular carcinoma is often diagnosed in elderly people.nnnMETHODSnOne hundred and seventy-five patients older than 70 years were operated on for hepatocellular carcinoma (Group 1). The results were compared with 276 resected patients younger than 70 (Group 2) and to 108 aged patients with chronic liver disease without hepatocellular carcinoma (Group 3).nnnRESULTSnHepatocellular carcinoma in the elderly is more frequently associated with hepatitis C virus, less frequently capsulated and less frequently diagnosed by screening programs than in young patients. After resection, no difference was noted in post-operative complications and in mortality rates (3.2%); major hepatic resection in cirrhosis carried a high risk of death (22%). Five years survival was 42%, comparable with the young surgical patients but significantly lower than the medical patients in Group 3. Recurrence of hepatocellular carcinoma was the main reason of death, but it was suitable for a radical treatment in 37.6% of cases, including surgery, with a mean survival of 31 months.nnnCONCLUSIONSnLiver resection is a valid option for the treatment of hepatocellular carcinoma in the elderly; major resections in cirrhotic old patients must be reserved for selected cases. Recurrence may be suitable of a radical approach, including surgery.

Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications

BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are increasingly recognized entities, whose management remains sometimes controversial, due to the high rate of benign lesions and on the other side to the good survival after resection of malignant ones.MethodsRetrospective analysis of a prospectively collected Western series of IPMN.ResultsForty cases of IPMN were analysed (1992-2007). Most patients were symptomatic (72.5%); cholangio-MRI had the best diagnostic accuracy both for the tumour nature (83.3%) and for the presence of malignancy (57.1%). ERCP was done in 8 cases (20%), and the results were poor. Thirteen patients were treated by pancreatic resection and 27 were maintained in follow-up. Total pancreatectomy was performed in 46% of the cases; in situ and invasive carcinoma were recognized in 15.4% and 38.4% of the cases, respectively. The mean follow-up was 42 months (range 12-72). One only patients with nodal metastases died 16 months after the operation for disease progression, while 91.6% of the operated patients are disease free. Out of the 27 not resected patients, 2 out of 4 presenting a lesion at high risk for malignancy died, while the remaining are in good conditions and disease free, with a mean follow-up of 31 months.ConclusionTherapeutic indication for IPMNs is mainly based upon radiological evaluation of the risk of malignancy. While the main duct tumours should be resected, preserving whenever possible a portion of the gland, the secondary ducts tumours may be maintained under observation, in absence of radiological elements of suspicion such as size larger than 3 cm, or a wall greater than 3 mm or nodules or papillae in the context of the cyst.

Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma: A Western Experience

BackgroundIntrahepatic cholangiocarcinoma (ICC) is an unusual tumour.MethodsThe clinicopathological data of 67 patients with ICC and combined hepatocellular–cholangiocarcinoma (HCC–ICC) are presented.ResultsHCV–HBV infection was present in 37.3% and chronic liver disease in 38.7% of cases, a rate higher than in the normal population; in these patients the cancer was small, often asymptomatic and of combined type. Liver resection was performed in 51 patients; at 1, 3 and 5xa0years, overall survival was 87.9%, 59.0%, and disease-free survival was 47.7% and 78.8%, 51.4%, and 46.7%, respectively. The better results were in the group of cirrhotic patients in whom ICC was diagnosed by a screening program for HCC (5-year survival 76.6%). Nodal metastasis showed negative prognostic value for both overall and disease-free survival; in N+ patients mean survival was 14.7xa0months after liver resection and lymph node dissection.ConclusionViral infection and cirrhosis may be considered risk conditions for ICC and combined HCC–ICC; in resected patients survival was good. Nodal metastases must not be considered a contraindication for liver resection.

Liver Resection for Hepatocellular Carcinoma ≤3 cm: Results of an Italian Multicenter Study on 588 Patients

BACKGROUNDnThe best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm.nnnSTUDY DESIGNnRetrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method.nnnRESULTSnPostoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS.nnnCONCLUSIONSnLiver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.

Traumatic lesions of the diaphragm. Our experience in 33 cases and review of the literature

Abstract We reviewed 33 consecutive patients with diaphragmatic injuries. Twenty-nine were admitted in emergency conditions after blunt (22 patients) or penetrating injury, presenting shock, dyspnoea, coma or acute abdomen in 21 cases; major associated lesions were found in 23 patients. Four patients presented acute complications of visceral herniation 2, 4, 84 and 216 months after the trauma. The diagnosis was preoperative in 23 cases, intraoperative in 9; in one case it was missed at laparotomy, becoming evident the day after. The sensibility of preoperative chest x-ray and CT was 86% and 100% in presence of visceral herniation, 14% and 0% in absence of visceral hernia. The diaphragmatic repair was always obtained by direct suture, following 20 haemostatic procedures (liver, spleen, mesenterium) and two bowel resections. The mortality rate was 24.4%; the morbidity rate was 48%. Traumatic lesions of the diaphragm are generally expression of particularly severe trauma whose outcome is mainly influenced by the associated lesions. They are also correlated to specific morbidity and mortality, so the surgical exploration is mandatory whenever this injury is suspected, considering that the preoperative diagnosis relies on visceral dislocation. Associated lesions influence the surgical strategy but a direct suture is usually effective in preventing specific complications.

Lynch Syndrome from a surgeon perspective: retrospective study of clinical impact of mismatch repair protein expression analysis in colorectal cancer patients less than 50 years old

BackgroundIn clinical practice, unexpected diagnosis of colorectal cancer in young patients requires prompt surgery, thus genetic testing for Lynch Syndrome is frequently missed, and clinical management may result incorrect.MethodsPatients younger than 50xa0years old undergoing colorectal resection for cancer in the period 1994-2007 were identified (Group A, 49 cases), and compared to a group of randomly selected patients more than 50 (Group B, 85 cases). In 31 group A patients, immunohistochemical expression analysis of MLH1, MSH2 and MSH6 was performed; personal and familial history of patients with defective MMR proteins expression was further investigated, searching for synchronous and metachronous tumors in probands and their families.ResultsFifty-one percent of patients did not express one or more MMR proteins (MMR-) and should be considered Lynch Syndrome carriers (16 patients, group A1); while only 31.2% of them were positive for Amsterdam criteria, 50% had almost another tumor, 37.5% had another colorectal tumor and 68% had relatives with colorectal tumor. This group of patients, compared with A2 group (< 50xa0years old, MMR+) and B group, showed typical characteristics of HNPCC, such as proximal location, mucinous histotype, poor differentiation, high stage and shorter survival.ConclusionsThe present study confirms that preoperative knowledge of MMR proteins expression in colorectal cancer patients would allow correct staging, more extended colonic resection, specific follow-up and familial screening.

Emergency Celiac Revascularization for Supramesocolic Ischemia During Pancreaticoduodenectomy: Report of a Case

Occlusive atherosclerotic disease of the celiac artery may be diagnosed late during pancreatic resection, inducing a sudden ischemic threat to the liver, stomach, pancreas, and new anastomoses. Failure to identify and correct the insufficient supramesocolic flow can result in serious morbidity. We report the case of a 64-year-old man in whom sudden and unexpected visceral ischemia occurred while Whipple’s procedure was being performed to resect a cephalopancreatic mass. We diagnosed occlusion of the celiac trunk and achieved celiac revascularization by performing an end-to-side transposition of the celiac artery onto the superior mesenteric artery, which had been dissected during the lymphadenectomy. We describe this technique as an alternative treatment for acute supramesocolic ischemia caused by celiac axis occlusion. It is important that surgeons performing pancreatic surgery are aware of the possibility of this complication because the test occlusion of the gastroduodenal artery, which must always precede its ligation, can be negative.

Sequential multidisciplinary treatment of hepatocellular carcinoma: The role of surgery as rescue therapy for failure of percutaneous ablation therapies

The recurrence of hepatocellular carcinoma (HCC) after percutaneous ablation is poorly evaluated.

Right Colon Cancer Missed by Virtual Colonoscopy in HNPCC Patient

the diagnostic accuracy of virtual colonoscopy in patients at high risk of colon cancer due to Lynch syndrome. Hereditary nonpolypoid colon cancer (HNPCC) is the most common hereditary colorectal cancer syndrome and is estimated to account for 3–5% of colorectal cancer cases [1]. It is due to inherited mutations in genes involved in DNA mismatch repair, the defect of which causes a lifetime risk for developing colorectal cancer of 70–80% in the absence of colonoscopic screening, with a mean age of diagnosis of 44 years [2]. Current recommendations for those patients include colonoscopy every 1–2 years beginning at age 20–25 [3]. Computed tomographic colonography (CTC), also called virtual colonoscopy, has been proposed as a screening method for colorectal cancer, with the approval of the American Gastroenterological Association and the American College of Surgeons; the technology has undergone major advances in recent years, and it is actually accepted that diagnostic accuracy is comparable to that of optical colonoscopy for polyps ≥8–9 mm in size [4]. Due to its being less invasive, CTC should represent an alternative to colonoscopy for routine surveillance of subjects with a high risk for colorectal cancer. It has been reported that CTC and colonoscopy have a similar ability to identify individuals with large polyps in patients at increased risk for colorectal cancer [5]. However, in the only published study specifically focusing on patients with HNPCC, the per-patient sensitivity for detecting all lesions with CTC was 0.25 and 0.29 by two radiologists and the specificities 0.82 and 0.76. For lesions of 10 mm or larger, the sensitivities were 0.6 and 1.0 and the specificities 0.96 by each examiner. In this study, there were 2 patients out of 87 with cancer, and both radiologists did recognize the cancer correctly [6]. We report the case of a 46-year-old female, having her mother, grandmother, and four out of five brothers affected by colorectal cancer, in five of whom was diagnosed before 50 years of age. Formal diagnosis of HNPCC was made on the basis of Amsterdam criteria; a retrospective immunohistochemical analysis of two available cases showed the absence of MSH1 and MSH6 expression, and microsatellite instability, and genetic testing of living brothers confirmed the inherited absence of mismatch repair proteins in all but one of them. Previous colonoscopy was made in our patient G. L. Baiocchi :G. A. M. Tiberio :N. Portolani : S. M. Giulini Surgical Clinic, Department of Medical and Surgical Sciences, Brescia University, Brescia, Italy

HER-2/Neu and Topoisomerase-II-α Expression and Genic Amplification in Pancreatic Adenocarcinoma

Dear Sir, We read with interest the paper by Sharif et al. in the 2008 November issue of Digestive Diseases and Sciences [1]. Despite significant advances in staging and clinical management, pancreatic cancer remains an often incurable disease; the limited effectiveness of the therapies presently available raise the interest toward new therapeutic strategies, such as those blocking the signal transduction pathways involved in tumor progression [2]. ErbB receptors and topoisomerase II-a are among the known transducers that were recently analyzed. The expression of these molecules in the tumor could have important therapeutic implications and open the way to the use of a target therapy with monoclonal antibodies. Most published studies, mainly based upon immunohistochemical (IHC) evaluation of HER-2/neu, have unfortunately shown a very variable over-expression percentage in pancreatic cancer (17–82%), to the point that the usefulness of this method for the determination of protein expression remains questionable [3, 4]. This great variability of the HER-2/neu expression can be attributed to at least two factors. On the one hand, the immunohistochemical technique, which is the most widely used as it is less expensive and easier to apply, is not presently standardized and is greatly influenced by the different tissue processing systems. On the other hand, the HER-2/neu over-expression does seem to be an early event in the pancreatic carcinogenetic process (HER-2/neu is expressed mainly in hyperplastic intraductal lesions and in wellto-moderately differentiated carcinomas) and therefore it would be necessary to correlate the samples to the clinical history according to how early the stage is [5]. In their paper, Sharif et al. report the analysis of a large series of HER2 gene amplification status and its association with tumor characteristics and survival in pancreatic cancer. Our group also analyzed the role of HER-2/neu in 13 cases of pancreatic ductal adenocarcinoma, including 7 males and 6 females, with an average age of 68.2 years; nodal metastases were found in 6 cases, microscopic vascular infiltration in 10 cases and perineural infiltration in 11 cases. The average survival time was 16.9 months (range 10–28 months). Analysis on resected specimens was done both with IHC and the fluorescent in situ hybridization (FISH) technique, using the latter as a control since it is presently considered the gold standard in the determination of the HER-2/neu status [6]. The same cases were subjected to a contemporaneous assessment of the expression and of the amplification of topoisomerase II-a, the gene of which is mapped next to the HER-2 gene in chromosome 17. This vicinity justifies the frequent co-amplification of the genes [7]. IHC for HER-2 was done with the Hercept Test (DAKO Cytomation, Carpinteria, CA, USA), employed with little differences from the manufacturers recommendations. Slides were deparaffinized and rehydrated in graded solutions of ethanol and distilled water. Endogenous peroxidase was blocked, followed by sequential application of HER-2 primary antibody for 60 min and NovoLink Polymer for 30 min (NovoLink Polymer Detection System; Novocastra Laboratories, Newcastle, UK). The immunoprecipitate was visualized by treatment with chromogen for 10 min and counterstained by hematoxylin. The expression was evaluated by two observers following the scoring system suggested by the FDA guidelines (3? implies complete and intense membrane staining of [10% of the tumor cells; G. L. Baiocchi (&) V. Villanacci E. Rossi F. Gheza N. Portolani S. M. Giulini Surgical Clinic, Brescia University, Brescia, Italy e-mail: baiocchi@med.unibs.it