Challenges in the management of a splenic pseudocyst by laparoscopic splenectomy in an adult patient: A case report.

INTRODUCTION AND IMPORTANCE: Splenic cysts are classified as true cysts, or pseudocysts, and larger cysts tend to be symptomatic, requiring management which has evolved to include spleen-sparing procedures to minimize the risk of overwhelming post-splenectomy sepsis (OPSS) Pitiakoudis et al. (2011), Hansen and Moller (2004), Knook et al. (2019) [1-3]. Total splenectomy remains the gold standard management, and the importance of this case is the uncommon spontaneous occurrence of a pseudocyst, and the importance to pre-operatively consent and prepare the patient for total splenectomy would intra-operative conditions not allow for spleen-preserving techniques. CASE PRESENTATION: CS, a 21-year-old lady, had two presentations to the emergency department with left upper quadrant abdominal pain. The only abnormality on assessment was a large splenic cyst on CT scan, which increased in size on re-presentation. She was consented for a splenic cyst fenestration, and for total splenectomy and optimized with vaccines would intra-operative conditions not allow for spleen-sparing. During the operation, the planes between the cyst and spleen parenchyma were ill-defined, and decision was made to proceed with total splenectomy to avoid bleeding complications. She recovered well, and was discharged 5 days post-operatively, and histology confirmed a pseudocyst (Figs. 1 and 2). CLINICAL DISCUSSION: The management of splenic cysts remains difficult and with no clear guidelines to uniform treatment. There are multiple spleen-preserving techniques developed to avoid OPSS (Agha RA, Franchi T, Sohrabi C, Mathew G, for the SCARE Group, 2020 [4]), however management remains individualized and case-specific. CONCLUSION: Pseudocysts can occur without splenic trauma or infarct. Management is case-based, and patients with large symptomatic cysts should be consented and prepared for total splenectomy would conditions not be safe for spleen-preserving interventions.

Incidence and management of gallbladder cancer in cholecystectomy specimens: a 5-year tertiary centre experience.

BACKGROUND: Gallbladder cancer (GBC) is an uncommon, but highly aggressive cancer. Half of these cases are diagnosed pre-operatively, and the remaining cases are discovered incidentally on post-cholecystectomy specimens. There is a significant geographical variability in GBC incidence, with increasing age, female sex, and prolonged duration of cholelithiasis being risk factors for GBC. The primary aim was to define the overall local incidence of GBC incidental GBC and management of these cases. The secondary aim was to determine any pertinent risk factors in our case population. METHODS: A retrospective observational study was performed on all the cholecystectomy specimens at the Gold Coast Hospital and Health Service from 1 January 2016 to 2 December 2021. Data was collected via the electronic medical record. The incidence and management of gallbladder cancers was calculated, and association with body mass index (BMI), smoking status, diabetes, inflammatory bowel disease (IBD) was identified. RESULTS: 3904 cholecystectomy specimens were reviewed. GBC was identified in 0.46% of cholecystectomies. 50% of these cases were found incidentally. Abdominal pain was the most common presenting complaint (94.4%). GBC was associated with increased age and BMI and female sex. There was no association between smoking status, diabetes or IBD with an increased incidence of cancer. Tumour staging guided surgical and/or adjuvant chemotherapy. CONCLUSION: GBC is rare. Patients with symptoms are associated with a poor prognosis. Incidental cancers are common, and negative margin resection based on the T stage of the cancer is the most reliable curative option.

Incidence and management of choledocholithiasis on routine intraoperative cholangiogram: a 5-year tertiary centre experience.

BACKGROUND: The incidence of choledocholithiasis on routine intraoperative cholangiogram (IOC) during cholecystectomy is approximately 12%. Cholecystectomy without IOC may lead to undiagnosed choledocholithiasis placing patients at risk of complications such as pancreatitis or cholangitis. This study aims to determine the incidence of choledocholithiasis intraoperatively as well as the associated risk factors and the methods of management. METHODS: A retrospective observational analysis of all laparoscopic cholecystectomies with IOC at the Gold Coast Hospital and Health Service from 1 January 2016 to 2 December 2021 was carried out. Patient demographics, operative data and cholangiogram findings were collected from electronic medical systems. RESULTS: A total of 3904 cholecystectomies were carried out over the study period. 3520 (90.1%) had an IOC, and 474 (13.4%) had positive IOC findings. 158 (33.3%) of the cases were managed intraoperatively with hyoscine butylbromide with or without intravenous glucagon followed by biliary tree flushing alone, 183 (38.6%) received transcystic bile duct exploration (TCBDE) with a success rate of 83% and 167 (35.2%) received endoscopic retrograde cholangiopancreatography (ERCP). Choledocholithiasis was incidental in 44 (9.28%) patients. CONCLUSION: Incidental choledocholithiasis during routine IOC is not uncommon. Management predominantly includes intraoperative TCBDE or postoperatively via an ERCP. This study has not found reliable preoperative factors to predict choledocholithiasis based on preoperative clinical, radiological and biochemical factors. A small proportion of patients received preoperative endoscopic intervention, and the decision-making process requires further investigation.

Spontaneous Cystogastrostomy: A Natural Response.

Pancreatic pseudocysts are a common complication of pancreatitis. Conservative management and repeat imaging are appropriate to monitor spontaneous regression. However, in some cases, rupture and haemorrhage of pseudocysts can lead to life-threatening events requiring urgent intervention. We present a male patient in his 30s who was presented to the emergency department with severe pancreatitis in the context of alcohol excess. Past medical history included pancreatitis with a small pseudocyst and splenic vein thrombosis for which he was anticoagulated six weeks previously. Computer tomography of the abdomen and pelvis showed an interval increase in his pseudocyst with haemorrhage secondary to a suspected splenic artery pseudoaneurysm. He was admitted for attempted embolisation and observation. Serial imaging demonstrated progression of the pancreatic pseudocyst and then spontaneous interval decompression via a transgastric fistula, leading to a natural cystogastrostomy confirmed on subsequent endoscopy. We discuss the uncommon sequelae of a complication of pancreatitis, and consider the hypotheses related to this rare occurrence, with suggestions for management and follow-up of these patients.

Cystic Artery Pseudoaneurysm: Current Review of Aetiology, Presentation, and Management.

BACKGROUND: Cystic artery pseudoaneurysms are rare. Most commonly, they occur secondary to acute cholecystitis or after a cholecystectomy. Complications include haemobilia, biliary obstruction, and haemorrhage. Given the rarity and associated morbidity, a high index of suspicion is required. This article reviews the current literature on cystic artery pseudoaneurysms to investigate its aetiology, clinical presentation, and management options. METHODS: A broad search of the Medline and PubMed databases was carried through. All peer reviewed literatures published in the English language between 1991 and 2020 with keywords "cystic" and "artery" and "pseudoaneurysm" in the title were selected for review. No further exclusion criteria; all studies yielded from the search were included in the results of this review. Additionally, we present a case of cystic artery pseudoaneurysm treated at our centre and included this in our analysis. RESULTS: Sixty-seven case reports were found between 1991 and 2020. Aetiologies: Aetiology of cystic artery pseudoaneurysm was found to be cholecystitis in 41 instances (61.2%), cholecystectomy in 18 instances (26.8%), idiopathic in 6 instances (8.9%) cholelithiasis in 1 instance (1.5%), and pancreatitis in 1 instance (1.5%). Complications: Fifty-two cases were complicated by haemobilia (77.6%), 36 by anaemia (53.7%), 25 by biliary obstruction (37.3%), 13 by haemodynamic shock (19.4%), 9 by haemoperitoneum (13.4%), and 6 by contained rupture (8.9%). Most commonly, patients had two or more of these complications. Management: Forty-four patients were managed with endovascular embolisation (65.7%), 21 with endoscopic intervention (31.3%), 18 with open cholecystectomy (26.9%), 13 with laparoscopic cholecystectomy (19.4%), and 6 with pseudoaneurysm ligation (9%). Delayed presentation postcholecystectomy ranged from 8 days to 3 years. CONCLUSIONS: Cystic artery pseudoaneurysms are rare complications of a common operation. The most common clinical presentation is haemobilia, which can be difficult to diagnose clinically. A high index of suspicion and prompt investigation with targeted imaging and intervention is required. This is especially pertinent in gastrointestinal bleeding postlaparoscopic cholecystectomy as a missed diagnosis could cause significant morbidity.

Intramuscular abdominal hibernoma: case report of a rare tumour and a review of the literature.

Hibernoma is a rare benign tumour that was first described by Merkel in 1906. It arises from remnants of brown fat and has a differential diagnosis of lipoma and liposarcoma. This is a case report of a 31-year-old male with a slow-growing mass in the left flank that produced constant pain radiating to the groin. Computerised tomography localised the mass within the external oblique muscle, which showed some heterogeneity and low attenuation. The mass appeared hypodense to muscle on T1 and hyperdense to muscle on T2 weighted magnetic resonance images. Prominent vascularity of the mass was noted. Finally, the lesion was found to be a 'typical' hibernoma on core-needle biopsy. It was surgically resected with a cuff of muscle. He recovered without complication, and there is no clinical evidence of recurrence at 6 months.

TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

Surgery for common bile duct stones--a lost surgical skill; still worthwhile in the minimally invasive century?

PURPOSE: Techniques of laparoscopic bile duct exploration have been reported for over 20 years. Despite the simplicity and success of these procedures, they have failed to become commonplace in most surgical departments, as endoscopic retrograde cholangiopancreatography (ERCP) has become the preferred method for dealing with bile duct stones. There is a risk of surgeons not obtaining or losing these skills, which may still be required as a definitive treatment when ERCP fails or is not available. METHODS AND RESULTS: This paper describes these laparoscopic operations, which can be performed to enable a 'one-stop shop' treatment of common bile duct stones (CBDS) at the time of cholecystectomy. In particular, transcystic basket clearance of the bile duct is possible in two-thirds of cases with very little increase in morbidity compared to routine cholecystectomy. The selection of patients who are most likely to be successfully treated with this technique is defined. Some of the authors have published large study series and prospective randomised trials, further refining the choices available to the surgeon who, when performing operative cholangiography, is already halfway to bile duct exploration. CONCLUSIONS: Surgery may reclaim this lost ground by offering an excellent and safe therapeutic option for many of the symptomatic CBDS.

Surgical management in patients with pancreatic cancer: a Queensland perspective.

BACKGROUND: Little has been published regarding presenting symptoms, investigations and outcomes for patients with pancreatic cancer in Australia. Data from a series of patients undergoing attempted resection in Queensland, Australia, are presented with the aim of assisting development of consistent strategies in disease management. METHODS: We reviewed the medical records of 121 patients who underwent attempted surgical resection and who took part in a case-control study between 2007 and 2009. Information relating to symptoms, investigations, surgical procedures and outcomes was captured. RESULTS: The mean age was 63 years and 60% were men. The most common presenting symptoms were jaundice (64%) and pain (63%). Over 80% of patients had multiple imaging investigations or laparoscopy prior to surgery. Seventy-eight patients (64%) had a completed resection and 23% of these had involved margins. The presence of metastases and/or involvement of vessels or adjacent structures precluded resection in the remaining patients. The 1-year survival for patients whose resections were completed was 77% compared with 51% for those whose tumours were not resectable (P = 0.004). There was no 30-day mortality and 68% of patients were alive 1 year after diagnosis. Resections were performed in 11 different hospitals but over 90% of patients underwent their surgery in one of five high-volume centres. CONCLUSION: The Queensland experience is consistent with that reported internationally. A significant proportion of attempted resections was not completed because preoperative staging underestimated disease extent. Most patients with potentially resectable disease are being treated in high-volume centres.

The EGF 61A/G polymorphism - a predictive marker for recurrence of liver metastases from colorectal cancer.

BACKGROUND: Epidermal growth factor (EGF) plays an important role in tumorigenesis. Variations in the DNA sequence of the gene EGF can lead to alterations in EGF activity, which is suspected to influence tumor progression. This retrospective study aimed to investigate the influence of EGF 61A/G polymorphism on the recurrence of liver metastases after hepatic surgery in patients with colorectal cancer. METHODS: EGF 61A/G polymorphism was determined in 268 consecutive patients (175 [65%] men and 93 [35%] women, mean age 62 +/- 10.3 years) who had liver metastases at primary diagnosis and were treated by surgery with curative intent (R0) for liver metastases from colorectal cancer. RESULTS: Overall, 81 of 268 (30%) patients exhibited wild-type EGF 61 A/A, 137 (51%) were heterozygous EGF 61 A/G and 50 (19%) were homozygous EGF 61 G/G. After adjusting for age, sex, UICC stage and tumor location, we observed a trend-wise 1.6-fold increased risk for hepatic recurrence (HR 1.6; 95% CI 1.0-2.5, P = 0.06) in individuals with the G/G genotype compared with carriers of the A-allele. The effect was much more pronounced in younger patients (or= 65 years). Interestingly, male patients with EGF G/G had a 1.6-fold higher risk of recurrence (HR 1.6; 95% CI 1.0-2.5, P = 0.07). A significant correlation (P = 0.033) was detected between Dukes classification and the homozygous 61 G/G genotype. CONCLUSION: Despite the limitations of our study, the retrospective results indicate that carriers of the EGF polymorphism might be at higher risk of developing liver recurrences. If confirmed in subsequent studies, genotyping for the EGF A/G variant might help in identification of patients at high risk of recurrence of liver metastases.

Simultaneous blockade of the epidermal growth factor receptor/mammalian target of rapamycin pathway by epidermal growth factor receptor inhibitors and rapamycin results in reduced cell growth and survival in biliary tract cancer cells.

The prognosis of patients with biliary tract adenocarcinomas (BTA) is still poor due to lack of effective systemic treatment options. Knowledge of the molecular mechanisms involved in the pathogenesis of this disease is of importance for the development of new treatment strategies. We determined the expression of epidermal growth factor receptor (EGFR) and activated mammalian target of rapamycin (p-mTOR) in paraffin-embedded surgical specimens of BTA (n = 89) by immunohistochemistry. Overall survival was analyzed with Cox models adjusted for clinical and pathologic factors. Combined EGFR/p-mTOR expression was significantly associated with relapse-free survival [adjusted hazard ratio for relapse, 2.20; 95% confidence interval (95% CI), 1.45-3.33; P < 0.001] and overall survival (adjusted hazard ratio for death, 2.32; 95% CI, 1.50-3.58; P < 0.001) of the patients. The effect of the EGFR inhibitors erlotinib or cetuximab and the mTOR inhibitor rapamycin on growth and survival of five BTA cell lines was tested in short-term 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and long-term colony formation assays. Simultaneous blockade of EGFR and mTOR in biliary tract cancer cell lines results in a synergistic inhibition of both phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways, leading to reduced cell growth and survival. These results suggest that combined targeted therapy with EGFR and mTOR inhibitors may potentially benefit patients with BTAs and should be further evaluated in clinical trials.

Influence of hepatic resection margin on recurrence and survival in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rare disease in the Western world, hence little is known about its optimal surgical management. We analyzed whether hepatic resection margin is a prognostic factor for local or distant recurrence and survival in patients resected with curative intent. METHODS: Seventy-four patients underwent potentially curative surgery for ICC at our institution from 1994 to 2007. Demographic, and tumor- and surgery-related details including hepatic resection margin were recorded, patients were followed up for recurrence and survival. All patients were resected using modern dissection devices (CUSA or Waterjet). RESULTS: Fifty-nine patients (80%) underwent R0 resection, 15 (20%) had a resection margin greater than 10 mm (wide margin, WM) and 38 (51%) between 1 and 10 mm (close margin, CM). In 14 patients (19%), hepatic resection margin was involved on histological examination; perioperative mortalities were excluded from analysis (n = 7). Forty-seven patients developed recurrence (WM, CM, and R1): hepatic recurrence was observed in 40%, 58%, and 50% of patients; extrahepatic spread occurred in 27, 16, and 14%; and 33, 26, and 36% had no recurrence of disease so far (P = 0.755). There was no difference between groups regarding local versus disseminated hepatic recurrence. Median recurrence free survival was 11.4 months (WM), 9.8 months (CM), and 9.9 months (R1), respectively (P = 0.880). Median overall survival was 27.2 months (WM), 29.7 months (CM), and not reached in the R1 group, (P = 0.350). CONCLUSION: Hepatic resection margin seems to play a minor role in the prognosis of ICC as long as complete tumor clearance can be achieved with a modern liver dissection technique.

Adequate preoperative staging rarely leads to a change of intraoperative strategy in patients undergoing surgery for colorectal cancer liver metastases.

BACKGROUND: Diagnostic tools used prior to hepatic surgery have significantly advanced during the last decade. We investigated the value of preoperative staging on detection of additional resectable hepatic lesions in metastatic colorectal cancer patients. METHODS: One hundred ninety-four consecutive resections for colorectal liver metastases between January 2002 and December 2005 were prospectively analyzed. Data on imaging (multidetector computed tomography [MDCT] and magnetic resonance imaging [MRI]) were compared to intraoperative findings by intraoperative sonography and bimanual palpation together with histopathological examination. Univariate and multivariate analysis of factors influencing recurrence was performed. RESULTS: In 16 (8.2%) resections, additional lesions were detected intraoperatively. In 11 cases (5.7%), these were small (<1 cm) and subcapsular. Detection of additional tumors was associated with shorter median recurrence free survival (5.4 vs. 13.4 months; P < .001) even though all lesions were resected and risk of recurrence was stratified by the Fong score. Patients treated with neoadjuvant chemotherapy did not generally have an increased risk of additional tumors; however, intraoperative detection of new lesions was associated with inferior outcome in this subgroup (median RFS 4.6 vs. 18.3 months in responders, P < .001). CONCLUSION: Preoperative imaging with contrast-enhanced MDCT and MRI is efficient and very seldom leads to changes in intraoperative strategy. Patients exhibiting additional resectable hepatic lesions upon surgery have a high risk for early recurrence and should be monitored closely during follow-up.

Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma.

PURPOSE: The mammalian target of rapamycin (mTOR) is a protein kinase that plays a key role in cellular growth and homeostasis. Because its regulation is frequently altered in tumors, mTOR is currently under investigation as a potential target for anticancer therapy. The purpose of our study was to determine the prognostic value of activated mTOR (p-mTOR) in patients with biliary tract adenocarcinoma (BTA), in order to strengthen the rationale for targeted therapy of BTA using mTOR inhibitors. EXPERIMENTAL DESIGN: We determined expression of p-mTOR in paraffin-embedded surgical specimens of BTA by immunohistochemistry with a monoclonal antibody to phosphorylated mTOR. Overall survival was analyzed with a Cox model adjusted for clinical and pathologic factors. RESULTS: Immunostaining for p-mTOR was positive in 56 of 88 (64%) tumors. Activated mTOR was not associated with any of the clinical or pathologic variables of the patients but predicted overall survival of the patients. Overall survival was significantly shorter in patients with p-mTOR-positive tumors as compared with patients with p-mTOR-negative tumors (hazard ratio for death 2.57; 95% confidence interval, 1.35-4.89; P = 0.004). Multivariate Cox proportional hazards regression analyses identified p-mTOR to be an independent prognostic factor for death (adjusted hazard ratio for death, 2.44; 95% confidence interval, 1.24-4.80; P = 0.01). CONCLUSIONS: Patients with BTA and p-mTOR-positive tumors have a significantly shorter overall survival than patients with p-mTOR-negative tumors and may benefit from targeted therapy with mTOR inhibitors in the future.

E-cadherin and beta-catenin expression in normal, inflamed and cancerous gallbladder tissue.

BACKGROUND: Changes of the E-cadherin/beta-catenin complex during cell-cell interactions result in the loss of cell adhesion and may account for the ability of cancer cells to metastasize. Gallbladder carcinoma (GBC) can develop during chronic inflammation from normal tissue. The aim of this study was to investigate the expression of E-cadherin and beta-catenin in normal gallbladder mucosa, inflamed gallbladder tissue and GBC. MATERIALS AND METHODS: Tissue from 10 GBC, 10 chronic cholecystitis and 10 healthy gallbladders were used to evaluate the expression of E-cadherin and beta-catenin by immunohistochemistry. RESULTS: The beta-catenin membranous expression decreased between cholecystitis and malignant tissue, as well as between normal epithelium and carcinoma. The E-cadherin membranous expression was reduced in normal gallbladder epithelia compared to carcinoma and also from inflammation to GBC. The cytoplasmatic beta-catenin expression did not show any significant difference. Cytoplasmatic E-cadherin was significantly different from normal gallbladders to carcinomas and between normal tissue and inflammation. No significant difference of the nuclear P-catenin expression could be observed. E-cadherin was not detected intra-nuclear in any tissue. CONCLUSION: Significant differences of E-cadherin and beta-catenin were detected between normal, inflamed and cancerous tissues. These changes of the protein expressions and the associated loss of adhesive mechanisms might lead to a cancerous pathway in GBC.

Treatment and outcome of intrahepatic cholangiocellular carcinoma.

BACKGROUND: Treating intrahepatic cholangiocarcinoma (ihCCC) tumor resection leads to the best patient survival. The aim of this study was to investigate prognostic factors in resected patients. METHODS: This was a clinical observational series of 31 resected patients with ihCCC. Univariate analysis of clinical and pathologic factors in relation to patient survival and tumor recurrence were performed. Possible benefit of chemotherapy, although not given randomly, was investigated separately. RESULTS: The median follow-up time was 37.3 months. Of 31 resected patients a tumor-free resection (R0) was achieved in 26; 2 patients died postoperatively. Chemotherapy was administered to 19 patients. Overall survival was significantly better in patients with R0 resection, negative lymph nodes, a solitary tumor, and a width of resection margin greater than 3 mm. Recurrence-free survival was prolonged in patients with negative lymph nodes, early International Union Against Cancer (UICC) stages and solitary tumors. In UICC stages III and IV, patients receiving chemotherapy experienced a better overall survival. CONCLUSIONS: Impact of various parameters on recurrence-free and overall survival was identified; a possible beneficial effect of adjuvant chemotherapy in advanced tumor stages was observed. A prospective, randomized trial is necessary to fully evaluate the role of adjuvant therapy.

Resection of hilar cholangiocarcinomas: pivotal prognostic factors and impact of tumor sclerosis.

The well-known poor prognosis of proximal bile duct cancer is due to its unfortunate anatomical location and its late diagnosis. Successful tumor resection, which is considered to be optimal treatment, depends on many factors. Eighty-eight patients suffering from proximal bile duct cancer underwent surgical exploration at our institution between 1977 and 1998. In 37 patients the tumor was resectable; in the remaining 51 patients exploratory laparotomy or a palliative operation was performed. The median survival after tumor resection was 18.6 months, but median survival after a palliative procedure or an exploratory laparotomy was only 3.4 months (p < 0.001). A curative R0 resection was possible in 11 patients, an R1 resection was performed in 22 patients, and 4 patients had an R2 resection. The median survival rate after R0 resection was 83.6 months, 12.3 months after R1 resection, and 2.7 months after R2 resection (p < 0.001). Survival after resection in patients with negative lymph nodes (n = 30) was significantly longer than in those with positive lymph nodes (n = 7) (p = 0.022). Grade of tumor sclerosis tended to have an influence on resectability rate (p = 0.076). The pattern of tumor growth was without statistical influence. Multivariate analysis revealed resection (p < 0.001) as the only significant prognostic marker for patient survival. Radical resection is the only therapy that provides a chance for long-term survival, with sclerosis of the cancer tending to have an influence on univariate analysis.

Low p27Kip1 expression is an independent prognostic factor in gallbladder carcinoma.

BACKGROUND: The cyclin-dependent kinase inhibitor p27Kip1 is an important regulator of the cell cycle and low expression of p27Kip1 is associated with poor prognosis in a variety of malignant diseases. The objective of the current study was to determine the prognostic value of this protein in patients with gallbladder carcinoma. MATERIALS AND METHODS: We studied p27Kip1 expression in 55 unselected patients with gallbladder carcinoma by means of immunohistochemistry and evaluated its impact on overall survival. RESULTS: Low p27Kip1 expression (< 50% nuclear staining) was observed in 36 out of 55 (65%) samples. Comparison with clinical parameters of the patients showed that low p27Kip1 expression was significantly associated with a higher T classification (p = 0.02), lymph node metastasis (p = 0.04), distant metastasis (p = 0.007) and an advanced TNM stage (p = 0.009). Kaplan-Meier analyses revealed that patients with low p27Kip1 expression had a significantly shorter overall survival than patients with high p27Kip1 expression (median 0.3 years vs. 0.8 years; p = 0.001). Cox proportional hazards regression analyses identified p27Kip1 (p = 0.002) and residual tumour stage (p = 0.001) to be independent prognostic factors for death. CONCLUSION: The results of our study suggest that low p27Kip1 expression is an independent prognostic factor associated with poor prognosis in patients with gallbladder carcinoma.