Is port-site resection necessary in the surgical management of gallbladder cancer?

INTRODUCTION: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed "benign" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry. METHODS: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. RESULTS: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. CONCLUSION: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment.

Complex liver resection for hepatic tumours involving the inferior vena cava.

BACKGROUND: Resection of liver tumours with involvement of inferior vena cava (IVC) is considered to have a high surgical risk. AIM: We retrospectively reviewed 23 patients who underwent hepatectomy with IVC resection in two West-European liver surgery Units. METHODS: The tumours included liver metastases (n = 13), hepatocellular carcinoma (n = 4), intrahepatic cholangiocarcinoma (n = 3), liver haemangioma (n = 1), primary hepatic lymphoma (n = 1) and recurrent right adrenal gland carcinoma (n = 1). RESULTS: IVC resection was associated with right hepatectomy in 8 cases, extended right hepatectomy in 9 cases, extended left hepatectomy in 3 cases, minor liver resection in 2 cases, and right hepatectomy with nephrectomy in one case. In 16 patients the IVC wall involvement was <30% of its circumference, and a tangential vena cava resection was performed. In 7 patients (30%) with >50% involvement, a caval segment was resected and replaced with a 20 mm ringed polytetrafluoroethylene graft. R0-resection was achieved in all patients. Median intraoperative blood loss was 1.100 ml (range 490-15,000). Fourteen patients were transfused with a median of 3 PRC units per patient (range 1-25). Major complications occurred in 9 patients. Postoperative stay in ICU was 2.3 ± 3.4 days (range 1-14) and hospital stay was 17.3 ± 2.6 days (range 5-62). In 14 patients, final pathology demonstrated microscopic IVC infiltration. CONCLUSIONS: In selected patients with malignant involvement of the liver and IVC, surgical resection en bloc with IVC is the only possibility to achieve R0 resection, with acceptable mortality and morbidity, in units specialized in liver surgery.

Plasma cholinesterase correlations in acute surgical and critical illness.

AIM: The properties of plasma cholinesterase (CHE) are partly undiscovered. Equally unknown are the correlations between changes in CHE and other blood variables during the acute phase response related to acute surgical and critical illness. METHODS: Data from 432 measurements of CHE and other variables performed in 92 patients were systematically evaluated and processed by regression analysis. RESULTS: There was a strong direct correlation between CHE and albumin (r=0.77, P<0.0001). CHE was also directly correlated to cholesterol, iron binding capacity, hematocrit, prothrombin activity, and inversely correlated to bilirubin and to presence of sepsis or liver dysfunction (P<0.0001 for all). Postoperatively CHE decreased to about 60% of the preoperative value, remaining directly related to it (r=0.69, P<0.0001), and decreasing further in the presence of sepsis or liver dysfunction, with slow reversal of the decrease during recovery from illness. In parenterally fed septic patients the decrease in CHE was moderated by increasing the amino acid dose (P<0.0001). CONCLUSION: In acute surgical and critical illness CHE mostly behaves as a negative acute phase reactant, independently of the modifications related to other already known factors. This should be taken into account when interpreting the implications of decreased CHE in the clinical setting.

Lymphoepithelial cyst of the pancreas: case report and review of the literature.

BACKGROUND AND STUDY AIMS: Lymphoepithelial cyst of the pancreas (LCP) is a rare, benign cyst mimicking pseudocyst or cystic neoplasm. Literature describing LCP is limited to case or brief series reports, and the natural history of this condition is largely unknown. A literature review was carried out in order to elucidate the clinical, pathological and biochemical features of LCP. The aim of this study was to define diagnostic criteria and treatment. METHODS: A Medline and Pubmed search was conducted by using the key-words "lymphoepithelial cyst" and "pancreas". The articles found were accurately examined and all details regarding clinical and pathological features were included in a data-base. Furthermore, a case recently observed in our unit was added to the review. RESULTS: Ninety-two cases of LCP were found in the worldwide literature, including the case that we observed. LCP occurs more frequently in males (M:F=5.5:1), its preferred site is the tail of the pancreas, and its size ranges between 2 and 10centimetres. Histologically, it is a true cyst delineated by a keratinizing squamous epithelium surrounded by lymphoid tissue. LCP is asymptomatic in the majority of cases and preoperative diagnosis is complicated by a lack of specific radiological features of the disease. An accurate preoperative diagnosis can only be made by obtaining cytological specimens and placing them in the hands of a pathologist who is familiar with the cytological appearances of the disease. CONCLUSIONS: LCP is a rare lesion worldwide, without any prevalence in different countries or in different ethnic groups. Understanding the features of LCP, making an accurate diagnosis and differentiating it from cystic neoplasm preoperatively is vital, as when it is diagnosed certainly, a conservative treatment is justified. Otherwise, radical surgery in the form of pancreatic resection is required to exclude the diagnosis of pancreatic cystic neoplasm.

Anatomical variant of origin of ophthalmic artery: case report.

We report on one case of variant origin of right ophthalmic artery (OA) from C4 choroidal segment of the right supraclinoid internal carotid artery. A 41-year-old woman affected by bitemporal hemianopsia performed Magnetic Resonance Imaging with gadolinium showing tuberculum sellae meningioma. During angiography we observed this variant of origin of OA. At surgical dissection, we observed this variant in carotid cistern.

Liver resection for intrahepatic stones in congenital bile duct dilatation.

OBJECTIVE: This study reports our clinical experience with liver resection for congenital dilatation of the intrahepatic bile duct and intrahepatic gallstones to evaluate results and define indications for treatment. PATIENTS AND METHODS: We studied the clinical data of patients who underwent hepatic resection for intrahepatic lithiasis from January 1992 to December 2008 and assessed the immediate and long-term results of these interventions. RESULTS: Of 49 treated patients, 47 underwent liver resection. In the majority of cases, the disease was limited to the left lobe and left hepatectomy was the most commonly performed surgical procedure. The operative mortality was zero with morbidity in 24.5% of patients. Cholangiocarcinoma was diagnosed in six cases (12.2%). In 91.6% of cases the long-term results were good or satisfactory. CONCLUSION: Treatment goals in all cases should be the elimination of intrahepatic stones, the prevention of recurrent lithiasis, and prevention or cure of cholangiocarcinoma. Surgical excision is the best possible treatment for symptomatic patients with localized disease and atrophy of the affected liver.

Liver resections for hilar cholangiocarcinoma.

Hilar cholangiocarcinoma (HC) is a rare tumor which has to be distinguished by intrahepatic cholagiocarcinoma invading hepatic hilum because the former has better prognosis then the latter. Patients with HC are difficult to manage because many challenging issues remain in the treatment of this tumour regarding correct diagnosis and therapeutic strategy. HC is resectable in about 30% of cases, but operative risk is highly influenced by septic complications of preoperative biliary drainage and by the need of major liver resection associated with biliary resection. We report the results of 43 resected patients (28 M/15 F; mean age 60 years, range 33-78), accounting for 29% of 149 patients with HC. Symptomless jaundice was the most common clinical presentation (87%; 130 patients). Biliary stricture was classified according to the Bismuth-Corlette classification as type 1 in 3 patients (7%); type 2 in 12 patients (28%); type 3 in 28 patients (65%). Ten patients underwent preoperative right portal vein embolization. Main biliary confluence excision associated with major hepatectomy was performed in 40 patients (93%), with R0 resection rate by 77%. Postoperative mortality rate was 6.9% (3 patients). Morbidity rate was 52.5% (21 patients), being biliary fistula (38%) and liver failure (19%) the most frequent complications. Five-year overall and disease-free survival rate were 36.1% and 28.2, respectively. Surgical resection remains the only chance of cure for patients with HC. However, due to the complexity of surgery immediate results remain unsatisfactory with morbidity and mortality rates higher than those reported after liver resection for other malignancies. This is mainly related to septic complications, strictly linked to complications of preoperative biliary drainage. Selective biliary drainage, careful management of biliary drains, drainage of excluded ducts in case of cholangitis, bile culture guided antibiotic use and preoperative portal vein embolization are important factors to reduce the risk of cholangitis and of postoperative complications. Because of the significant perioperative risk, the demanding operative management and the rarity of this tumor, patients with HC should be referred to tertiary surgical centers.

Gas in portal circulation and pneumatosis cystoides intestinalis during chemotherapy for advanced rectal cancer.

OBJECTIVES: Acute abdominal symptoms with CT scan evidence of intramural gas in bowel walls (pneumatosis cystoides intestinalis, PCI) and of gas in the portal venous blood (PBG) in patients undergoing chemotherapy may represent a worrisome picture, suggestive of bowel necrosis. This picture remains a major clinical clue and the reporting of new cases may help to share awareness and experience on management. We describe a patient with acute abdominal symptoms and evidence of PCI with PBG under cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy for metastatic adenocarcinoma of the rectosigmoid junction. METHODS: After admission for mucositis with diarrhea and profound dehydration, and subsequent emergency laparotomy for derotation of an intestinal volvulus, on the tenth postoperative day the patient developed fever and abdominal pain, with CT scan evidence of PCI with PBG. The exam of the abdomen did not suggest major problems requiring emergency surgery, and antibiotic treatment with close monitoring were performed, followed by rapid improvement. RESULTS: Twelve days later, after resumption of oral diet, the patient unexpectedly suffered a spontaneous jejunal microperforation, requiring emergency laparotomy and bowel resection. Pathology showed that the perforation was within an area of ulceration involving the inner superficial layer of the bowel. Subsequently recovery was normal and at present, after 15 months, the patient is well and continuing chemotherapy. CONCLUSIONS: This is probably the first report of PCI with PBG related to intestinal toxicity during cetuximab, oxaliplatin, tegafur-uracil and folinic acid chemotherapy in a patient with advanced rectal carcinoma, followed by delayed small bowel perforation. It provides an example of the challenges involved in the management of this type of patient.

Isolation and characterization of CD133+ cell population within human primary and metastatic colon cancer.

BACKGROUND: "Cancer stem cells" (CSC) have been identified as a minority of cancer cells responsible for tumor initiation, maintenance and spreading. Although a universal marker for CSC has not yet been identified, CD133 has been proposed as the hallmark of CSC in colon cancer. The aim of our study was to assess the presence of a CD133+ cell fraction in samples of colon cancer and liver metastasis from colon cancer and evaluate their potential as tumor-initiating cells. METHODS: Tissue samples from 17 colon cancers and 8 liver metastasis were fragmented and digested using collagenase. Cell suspensions were characterized by flow cytometry using anti-CD133, CD45 and CD31 antibodies. CD133+ cells were also isolated by magnetic cell sorting and their tumor-initiating potential was assessed versus the remaining CD133- fraction by soft-agar assay. RESULTS: Our results confirmed the existence of a subset of CD133+ tumor cells within human colon cancers. Interestingly, CD133+ cells were detectable in liver metastasis at a higher percentage when compared to primary tumors. Soft-agar assay showed that CD133+ cell fraction was able to induce larger and more numerous colonies than CD133-cells. CONCLUSION: Our findings data that the CD133+ colon cancer cells might play an important role in both primary tumors as well as in metastatic lesions thus warranting further studies on the role(s) of this subset of cells in the metastatic process.

Preoperative right portal vein embolisation: indications and results.

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy of right portal vein embolisation (PVE) in inducing contralateral liver hypertrophy before extended hepatectomy. MATERIALS AND METHODS: Twenty-six consecutive patients, 14 with liver metastases (ten from colorectal cancer; four from carcinoid tumours) and 12 with biliary cancers (ten Klatskin tumours; one gallbladder tumour; one intrahepatic cholangiocarcinoma) with insufficient predicted future remnant liver (FRL) underwent right PVE to induce hypertrophy of the contralateral hemiliver prior to surgical resection. Total liver volume, tumour volume and FRL volume were calculated on a 3D workstation. The ratio of the FRL to the total functional liver volume was <30% in all patients. RESULTS: The FRL volume increased by 5%-25% (15% on average) after right PVE in patients with liver metastases and by 9%-19% (14% on average) in patients with biliary cancers. In all patients, the ratio of FRL to functional liver volume was >or=30% after right PVE. No postoperative deaths due to severe liver failure occurred in the 20 patients who underwent extended hepatectomy. CONCLUSIONS: Right PVE extends the indications for hepatectomy in patients with liver metastases and those with biliary cancers who have an insufficient potential hepatic functional reserve.

Liver dysfunction and sepsis determine operative mortality after liver resection.

BACKGROUND: Liver failure is the principal cause of death after hepatectomy. Its progression towards death and its relationship with sepsis are unclear. This study analysed predictors of mortality in patients with liver dysfunction and the role of sepsis in the death of these patients. METHODS: The study focused on patients with liver dysfunction, excluding those with vascular thrombosis, after liver resection at one of two centres between 1998 and 2006. RESULTS: Liver dysfunction occurred after 57 (4.5 per cent) of 1271 hepatectomies. Fifty-three patients without vascular thrombosis were included in the analysis, with a mortality rate of 23 per cent. Independent predictors of death were age (odds ratio (OR) 1.18 per year increase; P = 0.017), cirrhosis (OR 54.09; P = 0.004) and postoperative sepsis (OR 37.58; P = 0.005). Sepsis occurred in 15 patients (28 per cent), seven of whom died. Intestinal pathogens were isolated in 12 patients with sepsis. The risk of sepsis was significantly increased in those with surgical complications (11 of 16 versus four of 37; P < 0.001). CONCLUSION: Sepsis plays a key role in the death of patients with liver dysfunction after hepatectomy. Early recognition and aggressive treatment of sepsis may reduce mortality.

Total gastrectomy for type 1 gastric carcinoid: an unusual surgical indication?

Gastric carcinoid is a relatively rare neoplasm with peculiar features which differentiate it from the intestinal and pulmonary carcinoid and, obviously, from gastric adenocarcinoma. Gastric carcinoids are divided into three different types: Type 1, associated with gastric atrophy and megaloblastic anemia; Type 2, associated with Zollinger-Ellison syndrome within a type 1 multiple endocrine neoplasia (MEN); and Type 3, sporadic tumor not associated with other lesions, particularly invasive and with poor prognosis. Type 1 carcinoid is usually asymptomatic and casually detected at endoscopy due to aspecific symptoms or to screening in patients with atrophic gastritis. It is generally small, multifocal and located in the gastric fundus, has no tendency for vascular invasion and is associated with a benign course. Therefore, the recommended treatment, for lesions < 10 mm and in a number < 5, is endoscopic resection with strict follow-up. We report a case of a woman with a type 1 gastric carcinoid in which, for the presence of an extended micro-polyposis of the fundus a total gastrectomy was necessary for treatment. Pathology revealed vascular invasion at the level of the major lesion of 8 mm of diameter. In conclusion this finding, unknown before surgery, emphasizes the need for careful assessment also in the presence of apparently less important gastric carcinoid lesions.

Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases.

We have previously reported that neoadjuvant therapy with modified FOLFIRI enabled nearly a third of patients with metastatic colorectal cancer (mCRC) to undergo surgical resection of liver metastases. Here, we present data from the long-term follow-up of these patients. Forty patients received modified FOLFIRI: irinotecan 180 mg m(-2), day 1; folinic acid, 200 mg m(-2); and 5-fluorouracil: as a 400 mg m(-2) bolus, days 1 and 2, and a 48-h continuous infusion 1200 mg m(-2), from day 1. Treatment was repeated every 2 weeks, with response assessed every six cycles. Resected patients received six further cycles of chemotherapy postoperatively. Nineteen (47.5%) of 40 patients achieved an objective response; 13 (33%) underwent resection. After a median follow-up of 56 months, median survival for all patients was 31.5 months: for non-resected patients, median survival was 24 months and was not reached for resected patients. Median time to progression was 14.3 and 5.2 months for all and non-resected patients, respectively. Median disease-free (DF) survival in resected patients was 52.5 months. At 2 years, all patients were alive (8 DF), and at last follow-up, eight were alive (6 DF). Surgical resection of liver metastases after neoadjuvant treatment with modified FOLFIRI in CRC patients achieved favourable survival times.

Liver resections for hepatocellular carcinoma in chronic liver disease: experience in an Italian centre.

AIM: Liver resection (LR) and transplantation are the best options for treatment of hepatocellular carcinoma (HCC). We retrospectively analysed the experience obtained with LR for HCC in chronic liver disease patients. METHODS: Up until May 2005, 248 patients with HCC were evaluated, and 113 resected. Of these, 97 with chronic liver disease, who underwent a total of 100 resections, form the basis of this study. Age of the patients was 65.6+/-9.2 years (range 32-81, male/female 76/21). In 77 cases there was unifocal and in 23 multinodular tumour; in 61 the size of the tumours was < or =5 cm and in 39>5 cm. Limited resections were performed in 15 cases, resections of 1-2 segments in 51, and major hepatectomies in 34. RESULTS: Blood transfusions were required in 28 cases. Three patients died postoperatively, from liver failure and/or sepsis. Seventeen patients had nonlethal complications (mostly liver dysfunction, often with signs of amplified inflammatory response, including ARDS, without evident sources of sepsis). The 5- and 10-year survival rates were 44% and 24%, respectively. Decreased survival was significantly related to increasing number of tumour nodules and degree of liver fibrosis/presence of cirrhosis, and with the expression of markers of carcinogenesis in a sub-group who received this assessment. At 5 years the rate of liver HCC recurrence was 46%, however, death was unrelated to recurrence in 41% of non-survivors. CONCLUSIONS: Surgery for HCC achieves acceptable early and long-term results. However, the patterns affecting perioperative outcome must be better understood, and the high recurrence rate warrants further trials to assess preventive treatments after LR.

The relationship between albumin, other plasma proteins and variables, and age in the acute phase response after liver resection in man.

A large series of plasma albumin (ALB, g/dl) and simultaneous blood and clinical measurements were prospectively performed on 92 liver resection patients, and processed to assess the correlations between ALB, other plasma proteins, additional variables and clinical events. The measurements were performed preoperatively and at postoperative day 1, 3 and 7 in all patients, and subsequently only in those who developed complications or died. In patients who recovered normally ALB was 4.3 +/- 0.4 g/dl (mean +/- SD) preoperatively, 3.7 +/- 0.7 at day 1 and 3, and 3.9 +/- 0.4 at day 7. In patients with complications its decrease was more prolonged. In non-survivors it was 3.4 +/- 0.4 preoperatively, 3.0 +/- 0.4 at day 1, and then decreased further. Regression analysis showed direct correlations between ALB and pseudo-cholinesterase (CHE, U/l, nv 5300-13000), cholesterol (CHOL, mg/dl), iron binding capacity (IBC, mg/dl), prothrombin activity (PA, % of standard reference) and fibrinogen, an inverse correlation with blood urea nitrogen (BUN, mg/dl) for any given creatinine level (CREAT, mg/dl), and weaker direct correlations with hematocrit, other variables and dose of exogenous albumin. An inverse relationship found between ALB and age (AGE, years) became postoperatively (POSTOP) also a function of outcome, showing larger age-related decreases in ALB associated with complications (COMPL: sepsis, liver insufficiency) or death (DEATH). Main overall correlations: CHE = 287.4(2.014)(ALB), r = 0.73; CHOL = 16.5(1.610)(ALB) (1.001)(ALKPH), r = 0.71; IBC = 68.6(1.391)(ALB), r = 0.64; PA = 13.8 + 16.0(ALB), r = 0.51; BUN = 21.3 + 20.2(CREAT) - 6.2(ALB), r = 0.91; ALB = 5.0-0.013(AGE) - {0.5 + 0.003(AGE)( COMPL ) + 0.012(AGE)( DEATH )}( POSTOP ), r = 0.74 [p < 0.001 for each regression and each coefficient; ALKPH = alkaline phosphatase, U/l, nv 98-279, independent determinant of CHOL; discontinuous variables in italics label the change in regression slope or intercept associated with the corresponding condition]. These results suggest that altered albumin synthesis (or altered synthesis unable to compensate for albumin loss, catabolism or redistribution) is an important determinant of hypoalbuminemia after hepatectomy. The correlations with age and postoperative outcome support the concept that hypoalbuminemia is a marker of pathophysiologic frailty associated with increasing age, and amplified by the challenges of postoperative illness.

No evidence of hematopoietic stem cell mobilization in patients submitted to hepatectomy or in patients with acute on chronic liver failure.

BACKGROUND: Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. METHODS: We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. RESULTS: White blood cell counts remained in the normal range (4.1-9.8 x 10(9)/L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. CONCLUSIONS: Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.

Nuclear and cytoplasmic expression of survivin in 67 surgically resected pancreatic cancer patients.

Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumour. The present study investigated the prognostic role of apoptosis and apoptosis-involved proteins in a series of surgically resected pancreatic cancer patients. All patients affected by pancreatic adenocarcinoma and treated with surgical resection from 1988 to 2003 were considered for the study. Patients' clinical data and pathological tumour features were recorded. Survivin and Cox-2 expression were evaluated by immunohistochemical staining. Apoptotic cells were identified using the TUNEL method. Tumour specimen of 67 resected patients was included in the study. By univariate analysis, survival was influenced by Survivin overexpression. The nuclear Survivin overexpression was associated with better prognosis (P = 0.0009), while its cytoplasmic overexpression resulted a negative prognostic factor (P = 0.0127). Also, the apoptotic index was a statistically significant prognostic factor in a univariate model (P = 0.0142). By a multivariate Cox regression analysis, both the nuclear (P = 0.002) and cytoplasmic (P = 0.040) Survivin overexpression maintained the prognostic statistical value. This is the first study reporting a statistical significant prognostic relevance of nuclear and cytoplasmic Survivin overexpression in pancreatic cancer. In particular, patients with high nuclear Survivin staining showed a longer survival, whereas patients with high cytoplasmic Survivin staining had a shorter overall survival.