Perioperative Systemic Therapy Versus Cytoreductive Surgery and HIPEC Alone for Resectable Colorectal Peritoneal Metastases: Patient-Reported Outcomes of a Randomized Phase II Trial.

BACKGROUND: As part of a randomized phase II trial in patients with isolated resectable colorectal peritoneal metastases (CPMs), the present study compared patient-reported outcomes (PROs) of patients treated with perioperative systemic therapy versus cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone. Also, PROs of patients receiving perioperative systemic therapy were explored. PATIENTS AND METHODS: Eligible patients were randomized to perioperative systemic therapy (experimental) or CRS-HIPEC alone (control). PROs were assessed using EORTC QLQ-C30, QLQ-CR29, and EQ-5D-5L questionnaires at baseline, after neoadjuvant treatment (experimental), and at 3 and 6 months postoperatively. Linear mixed modeling was used to compare five predefined PROs (visual analog scale, global health status, physical functioning, fatigue, C30 summary score) between arms and to longitudinally analyze PROs in the experimental arm. RESULTS: Of 79 analyzed patients, 37 (47%) received perioperative systemic therapy. All predefined PROs were comparable between arms at all timepoints and returned to baseline at 3 or 6 months postoperatively. The experimental arm had worsening of fatigue [mean difference (MD) + 14, p = 0.001], loss of appetite (MD + 15, p = 0.003), hair loss (MD + 18, p < 0.001), and loss of taste (MD + 27, p < 0.001) after neoadjuvant treatment. Except for loss of appetite, these PROs returned to baseline at 3 or 6 months postoperatively. CONCLUSIONS: In patients with resectable CPM randomized to perioperative systemic therapy or CRS-HIPEC alone, PROs were comparable between arms and returned to baseline postoperatively. Together with the trial's previously reported feasibility and safety data, these findings show acceptable tolerability of perioperative systemic therapy in this setting.

Comparing practice and outcome of laparoscopic liver resection between high-volume expert centres and nationwide low-to-medium volume centres.

BACKGROUND: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands. METHOD: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups. RESULTS: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P < 0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P = 0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P = 0.034) and a shorter postoperative hospital stay (3 versus 5 days; P < 0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P < 0.004). CONCLUSION: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group.

Treatment Strategies and Prognosis of Patients With Synchronous or Metachronous Colorectal Peritoneal Metastases: A Population-Based Study.

BACKGROUND: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort. METHODS: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups. RESULTS: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553). CONCLUSION: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.

Appearance of Focal Nodular Hyperplasia after Chemotherapy in Two Patients during Follow-Up of Colon Carcinoma.

Surgical liver resection is a treatment option in patients with resectable colorectal liver metastases. We present two cases of focal nodular hyperplasia (FNH) development after treatment with oxaliplatin during follow-up of colon carcinoma. The first case was a 40-year-old male patient who developed multiple liver lesions suspect for metastatic disease four years after he had undergone laparoscopic right-sided hemicolectomy and adjuvant chemotherapy (capecitabine and oxaliplatin). He underwent a metastasectomy of segments three and four and microwave ablation (MWA) of the lesion in segment one. Pathological analysis demonstrated FNH. The second patient was a 21-year-old woman who presented with multiple liver lesions during follow-up for colon carcinoma. She underwent a laparoscopic right-sided hemicolectomy and was adjuvantly treated with capecitabine and oxaliplatin three years ago. Magnetic resonance imaging (MRI) was performed, and the lesions showed no signs of metastatic disease but were classified as FNH. Therefore, the decision was made to follow up the patient. In conclusion, the development of benign liver lesions could occur during follow-up of colon carcinoma and might be caused by oxaliplatin-induced changes to the liver parenchyma. Hence, it is important to distinguish these from metastatic liver disease.

Increase in the incidence of synchronous and metachronous peritoneal metastases in patients with colorectal cancer: A nationwide study.

INTRODUCTION: - To investigate the incidence of, factors associated with, and differences between synchronous and metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. METHODS: - Data from the Netherlands Cancer Registry were used. All patients diagnosed with colorectal cancer (CRC) between 1 January and June 30, 2015 were evaluated for synchronous or metachronous CPM (diagnosis ≤90 or >90 days after surgery for primary CRC), and survival in 2019 (median follow-up 38.4 months). RESULTS: - Of 7233 included patients, 409 (5.7%) were diagnosed with synchronous CPM. Factors associated with synchronous CPM were mucinous (OR 2.72 [1.90-3.90]) or signet ring cell (SRC) histology (OR 6.58 [3.66-11.81]), T4 (OR 4.82 [3.68-6.32]), N1 (OR 1.66 [1.20-2.30]), or N2 stage (OR 3.27 [2.36-4.52]), and synchronous systemic metastases (SM) (OR 3.13 [2.37-4.14]). After surgery for primary CRC, 326 patients developed metachronous CPM after a median time of 14.7 months (3-year cumulative incidence: 5.5%). Factors associated with metachronous CPM were younger age (HR 1.63 [1.10-2.42]), mucinous (HR 1.84 [1.20-2.82]) or SRC histology (HR 2.43 [1.11-5.32]), T4 (HR 2.77 [2.07-3.70]), N1 (HR 2.90 [2.18-3.85]), N2 (HR 3.19 [2.26-4.50]), and synchronous SM (HR 1.95 [1.43-2.66]). CONCLUSION: - This population-based study found the highest incidence of CPM currently reported in literature and a strong association between the presence of synchronous SM and both synchronous and metachronous CPM. These findings may contribute to a tailored approach in the follow-up after primary CRC surgery and guide future clinical trials investigating new strategies regarding risk-reduction or early detection of metachronous CPM.

Laparoscopic combined resection of liver metastases and colorectal cancer: a multicenter, case-matched study using propensity scores.

BACKGROUND: Combined laparoscopic resection of liver metastases and colorectal cancer (LLCR) may hold benefits for selected patients but could increase complication rates. Previous studies have compared LLCR with liver resection alone. Propensity score-matched studies comparing LLCR with laparoscopic colorectal cancer resection (LCR) alone have not been performed. METHODS: A multicenter, case-matched study was performed comparing LLCR (2009-2016, 4 centers) with LCR alone (2009-2016, 2 centers). Patients were matched based on propensity scores in a 1:1 ratio. Propensity scores were calculated with the following preoperative variables: age, sex, ASA grade, neoadjuvant radiotherapy, type of colorectal resection and T and N stage of the primary tumor. Outcomes were compared using paired tests. RESULTS: Out of 1020 LCR and 64 LLCR procedures, 122 (2 × 61) patients could be matched. All 61 laparoscopic liver resections were minor hepatectomies, mostly because of a solitary liver metastasis (n = 44, 69%) of small size (≤ 3 cm) (n = 50, 78%). LLCR was associated with a modest increase in operative time [206 (166-308) vs. 197 (148-231) min, p = 0.057] and blood loss [200 (100-700) vs. 75 (5-200) ml, p = 0.011]. The rate of Clavien-Dindo grade 3 or higher complications [9 (15%) vs. 13 (21%), p = 0.418], anastomotic leakage [5 (8%) vs. 4 (7%), p = 1.0], conversion rate [3 (5%) vs. 5 (8%), p = 0.687] and 30-day mortality [0 vs. 1 (2%), p = 1.0] did not differ between LLCR and LCR. CONCLUSION: In selected patients requiring minor hepatectomy, LLCR can be safely performed without increasing the risk of postoperative morbidity compared to LCR alone.

Large variation in the utilization of liver resections in stage IV colorectal cancer patients with metastases confined to the liver.

BACKGROUND: Surgical resection of both the primary tumor and all metastases is considered the only chance of cure for patients with stage IV colorectal cancer. The aim of this study was to investigate change over time in the utilization of liver resections, as well as possible institutional variations. PATIENTS AND METHODS: All patients diagnosed with stage IV colorectal cancer with metastases confined to the liver (n = 1617) between 2004 and 2012 were selected from the population-based Eindhoven Cancer Registry. The proportion of patients undergoing liver resection was investigated. Institutional variation in the period 2010-2012 was analyzed using logistic regression. Kaplan-Meier and Cox regression analyses were used to analyze overall survival. RESULTS: The proportion of patients undergoing liver metastasectomy increased over time from 8% in 2004 to approximately 24% in 2012. There was a wide inter-hospital variation in the proportion of patients that underwent a liver resection (range: 14-34%) in the period 2010-2012. Liver resection was more often performed in younger patients and in rectal cancer patients. Median overall survival in patients undergoing liver resection was 55 months. Adjusted for potential confounders, resection of liver metastases was strongly associated with improved overall survival (HR 0.32, 95%CI 0.25-0.40). DISCUSSION: This study shows that despite the excellent long-term prognosis for patients with stage IV colorectal cancer after liver resection, there is still a large institutional variation in the utilization of this potentially curative therapy.

Complications After Laparoscopic Cholecystectomy: A Video Evaluation Study of Whether the Critical View of Safety was Reached.

BACKGROUND: Achieving the critical view of safety (CVS) before transection of the cystic artery and duct is important to reduce biliary duct injury in laparoscopic cholecystectomy. To gain more insight into complications after laparoscopic cholecystectomy, we investigated whether the criteria for CVS were met during surgery by analyzing videos of operations performed at our institution. METHODS: All consecutive patients who underwent a completed laparoscopic cholecystectomy between 2009 and 2011 were included. The videos of the operations of patients with complications were independently reviewed and rated by two investigators with a third consulted in the event of a disagreement. The reviewers answered consecutive questions about whether the CVS criteria were met. Patients who underwent an elective laparoscopic cholecystectomy and had no complications were used as a control group for comparison. RESULTS: Of the 1108 consecutive patients who had undergone a laparoscopic cholecystectomy during the study period, 8.8 % developed complications (average age 51 years) and 1.7 % had bile duct injuries [six patients (0.6 %) had a major bile duct injury, type B, D, or E injury]. In the 65 surgical videos available for analysis, CVS was reached in 80 % of cases according to the operative notes. However, the reviewers found that CVS was reached in only 10.8 % of the cases. Only in 18.7 % of the cases the operative notes and video agreed about CVS being reached. CVS was not reached in any of the patients who had biliary injuries. In the control group, CVS was reached significantly more often in 72 %. CONCLUSIONS: In our institutional series of laparoscopic cholecystectomies with postoperative complications, CVS was reached in only a few cases. Evaluating surgical videos of laparoscopic cholecystectomy cases are important and we recommend its use to improve surgical technique and decrease the number of biliary injuries.

Resection of liver metastases in patients with breast cancer: survival and prognostic factors.

AIMS: Patients with breast cancer metastasized to the liver have a median survival of 4-33 months and treatment options are usually restricted to palliative systemic therapy. The aim of this observational study was to evaluate the effectiveness and safety of resection of liver metastases from breast cancer and to identify prognostic factors for overall survival. METHODS: Patients were identified using the national registry of histo- and cytopathology in the Netherlands (PALGA). Included were all patients who underwent resection of liver metastases from breast cancer in 11 hospitals in The Netherlands of the last 20 years. Study data were retrospectively collected from patient files. RESULTS: A total of 32 female patients were identified. Intraoperative and postoperative complications occurred in 3 and 11 patients, respectively. There was no postoperative mortality. After a median follow up period of 26 months (range, 0-188), 5-year and median overall survival after partial liver resection was 37% and 55 months, respectively. The 5-year disease-free survival was 19% with a median time to recurrence of 11 months. Solitary metastases were the only independent significant prognostic factor at multivariate analysis. CONCLUSION: Resection of liver metastases from breast cancer is safe and might provide a survival benefit in a selected group of patients. Especially in patients with solitary liver metastasis, the option of surgery in the multimodality management of patients with disseminated breast cancer should be considered.

[Radiofrequency ablation of colorectal metastases to the liver: results since the first application in the Netherlands]. / Radiofrequente ablatie van colorectale levermetastasen: resultaten vanaf de eerste toepassing in Nederland.

OBJECTIVE: To provide an overview of the morbidity, mortality and survival following the introduction of radiofrequency ablation (RFA) of colorectal liver metastases in the Netherlands. DESIGN: Prospective, descriptive study. METHOD: Between June 1999 and December 2003 in eight hospitals in the Netherlands, 87 patients treated by RFA for colorectal liver metastases were included in the study. The outcome measures were morbidity, 30-day mortality and the percentage local recurrence. RESULTS: In 104 RFA procedures, 199 metastases were ablated; 31 procedures were performed percutaneously and 73 by laparotomy. In 29 procedures, RFA was combined with partial liver resection. The overall postoperative morbidity rate was 19% and the RFA-related morbidity was 14%. 1 patient died following right hemihepatectomy and RFA in the remaining parenchyma (mortality: 1%). Median survival following RFA was 25 months, with a median progression-free survival of 13 months. The overall local recurrence rate was 46%. Since January 2004, this percentage has decreased to approximately 6. Diameter and central location of the metastases were independent risk factors for the development of a local recurrence. CONCLUSION: RFA is an alternative treatment for patients who are not eligible for partial liver resection. The high local recurrence rate in this series reflects the limited experience with this technique during its introduction in the Netherlands. In specialised centres the percentage local recurrence is now 5. Treatment by RFA should always be weighed against the option of partial liver resection and possible (neoadjuvant) chemotherapy. RFA should therefore preferably be carried out in a centre with expertise in the field of liver surgery.

Assessment of systemic inflammatory response (SIR) in patients undergoing radiofrequency ablation or partial liver resection for liver tumors.

INTRODUCTION: Local therapies for liver tumors are considered to be safe. However, cryoablation (CA) has been associated with an exaggerated systemic inflammatory response (SIR). Aim of this study was to assess the degree of SIR after radiofrequency ablation (RFA) in comparison with major (MR) or minor (mR) liver resection. MATERIAL AND METHODS: Thirty-nine patients were treated with RFA (n = 11), MR (n = 10) or mR (n = 18). SIR parameters [white blood count (WBC) and C-reactive protein (CRP)], proinflammatory mediators [IL-6, TNF-alpha and sPLA2], liver damage parameters [AST/ALT] and platelet counts were determined at different time points. The volume of ablated liver was calculated on the first CT after RFA in order to correlate ablated liver volume with liver enzyme release and SIR. All data are expressed as median values with quartiles [25%, 75%]. RESULTS: RFA induced a moderate SIR, as demonstrated by a significant elevation of CRP (77 mg/L vs 3 mg/L), IL-6 (96 pg/ml vs 4 pg/ml) and sPLA2 (41 ng/ml vs 7 ng/ml, p < 0.05). Peak point values of SIR (WBC and CRP at 24 vs 48 h and 48 vs 72 h) and proinflammatory response parameters (24 vs 48 h) occurred earlier after RFA than after mR or MR. Time-to-time comparison revealed even increased levels of CRP (77 mg/L [59, 160]) 24h after RFA when compared to patients undergoing major or minor resection (50 mg/L [28, 66] and 59 mg/L [24, 91], respectively) and increased levels of IL-6 (67 pg/ml [42, 131]) 4 h after RFA when compared to patients undergoing minor resection (29 pg/ml [20, 55]). Postoperative levels of AST and LDH correlated significantly with the ablated liver volume 1h after RFA (RC = 0.860 and RC = 0.868, respectively, p < 0.05). CONCLUSION: RFA induced a moderate SIR of the same magnitude as in patients undergoing partial liver resection. None of the patients showed signs of an exaggerated SIR, as has been reported after cryoablation.

Adverse effects of radiofrequency ablation of liver tumours in the Netherlands.

BACKGROUND: Radiofrequency ablation (RFA) is a new treatment for liver tumours. Complications encountered after RFA in the Netherlands were evaluated in the present study. METHODS: Between June 1999 and November 2003 patients undergoing RFA of irresectable liver tumours in eight medical centres were registered prospectively. RESULTS: One hundred and forty-three RFA procedures were performed in 122 patients. RFA was combined with partial hepatectomy in 37 instances. Death occurred after two procedures (1.4 per cent), and was mainly due to concomitant partial hepatectomy. A total of 19 major complications occurred after ten procedures, including biliary tract damage (seven patients), liver failure (four), hepatic abscess (three), peritoneal infection (two), intrahepatic haematoma (one), hepatic artery aneurysm (one) and pulmonary embolism (one). Twenty-four minor complications were related to concomitant partial hepatectomy or laparotomy. The overall complication rate was 20.3 per cent and the rate of complications related directly to RFA was 9.8 per cent. CONCLUSION: The procedure-specific complication rate was almost 10 per cent and it is recommended that RFA should be performed only by an experienced team comprising a hepatobiliary surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary stricture, hepatic vascular damage and hepatic abscesses were the most common major complications.

Emboli rate during and early after carotid endarterectomy after a single preoperative dose of 120 mg acetylsalicylic acid--a prospective double-blind placebo controlled randomised trial.

PURPOSE: To investigate whether a single pre-operative dose of 120 mg acetylsalicylic acid (ASA) decreased either (1) emboli rate, as detected by transcranial Doppler (TCD), during and early after carotid endarterectomy (CEA) and (2) clinical intra- and post-operative signs suggestive of embolism or increased bleeding tendency. DESIGN: Prospective, double-blind placebo controlled trial. PATIENTS AND METHODS: One-hundred consecutive patients were randomised to receive either 120 mg ASA (n = 48) or placebo (n = 49) by suppository on the night before CEA; three patients were excluded. Emboli were counted and expressed as emboli rate (ER). The incidence of bleeding complications was assessed. Surgeons were asked to indicate which patients had received ASA or placebo. RESULTS: There were no significant differences between the ASA and placebo groups in ER in the intraoperative and postoperative periods. ER higher than 0.9 min(-1) was associated with a significantly increased risk of complications (26 vs. 0%, P < 0.01). No extra bleeding complications were observed in the ASA group. Surgeon assessment of whether or not ASA had been administered had a sensitivity of 42% and a specificity of 70%. CONCLUSION: A single pre-operative dose of ASA (120 mg) did not reduce significantly the emboli rate during and after CEA and surgeons could not correctly identify whether or not ASA had been administered.

DNA quantitation of distal bile duct carcinoma measured by image and flow cytometry.

OBJECTIVE: To evaluate discrepancies between flow cytometry (FCM) and image cytometry (ICM), ploidy incidence and relation between DNA ploidies and survival in distal bile duct carcinomas (DBDCs). STUDY DESIGN: Forty-four archival tumor samples from patients with DBDC who underwent subtotal pancreatoduodenectomy from 1985 to 1996 were examined for DNA ploidy using FCM and ICM. RESULTS: Overall, 59% (26/44) of the tumors were aneuploid by at least one of the two techniques. We detected more cases of aneuploidy with ICM than FCM in formalin-fixed, paraffin-embedded DBDCs, 62% (21/34) versus 33% (13/40), respectively. When results could be compared, moderate strength of agreement (kappa = .45) was demonstrated. No correlation was found between DNA ploidy by FCM, ICM or combined FCM-ICM and survival time (P = .80, P = .35, and P = .54, respectively). CONCLUSION: Approximately 59% of DNA histograms contained aneuploid cell populations. Although ICM, as compared to FCM, is more sensitive in assessing the ploidy status of DBDC, both methods were complementary. Most discrepancies between FCM and ICM were due to the dilution of aneuploid populations by non-neoplastic diploid cells. DNA ploidy assessment in DBDC did not offer the possibility of improving the ability to predict survival.

Genomic alterations in distal bile duct carcinoma by comparative genomic hybridization and karyotype analysis.

We report genomic abnormalities identified in 14 human primary common bile duct carcinomas analyzed by cytogenetics or comparative genomic hybridization, or both. Combining the results of the two methods of analysis, 11 chromosomal arms were observed to be gained in whole or in part, and 9 chromosomal arms were lost in whole or in part in at least four tumors each. The most frequently lost chromosomal regions were, in decreasing order: 18q (eight tumors); 6q and 10p (seven tumors each); 8p, 12q, and 17p (six tumors each); and 7q, 12p, and 22q (four tumors each). The most frequently gained regions were 8q and 20q (six tumors each); 12p, 17q, and Xp (five tumors each); and 2q, 6p, 7p, 11q, 13q, and 19q (four tumors each). These results are similar to those we have previously reported in pancreatic cancer and suggest that carcinomas of the common bile duct and pancreas share a number of genetic changes.

p53 expression as a prognostic determinant in resected distal bile duct carcinoma.

AIMS: To determine the incidence and prognostic value of p53 immunopositivity in resectable distal bile duct carcinoma (DBDC). METHODS: Forty-seven paraffin-embedded archival tumour samples of patients with DBDC, who underwent subtotal pancreatoduodenectomy from 1985 to 1996, were immunohistochemically examined for p53 positivity, using the anti-p53 antibody D07. RESULTS: Nineteen (40%) of the 47 tumours demonstrated positive (>30%) p53 protein immunostaining. Focally positive or negative staining was seen in the remaining 28 (60%) cases. Patients in this low p53 category survived significantly longer than those in the high p53 category, with median survival durations of 29 and 13 months respectively (P=0. 039). p53 positivity was independent of age, sex, tumour size, radicality of resection, histopathological grading, lymph-node status, perineural invasion and vasoinvasive growth. CONCLUSIONS: This study indicates that low (0-30%) p53 expression is a favourable prognostic factor in patients with resected DBDC.

Prognostic value of cell proliferation (Ki-67 antigen) and nuclear DNA content in clinically resectable, distal bile duct carcinoma.

BACKGROUND: The aim of this study was to investigate the prognostic value of cell proliferation (Ki-67 antigen) and DNA content in patients resected for distal bile duct carcinoma (DBDC). METHODS: Formalin-fixed tumor specimens of 35 patients with resected DBDC and a long-term clinical follow-up were analyzed. MIB-1 antibody was used for Ki-67 antigen detection to determine the proportion of proliferating cells. DNA content was measured using flow cytometry. RESULTS: A significant correlation was found between a low MIB-1 index (<20%) and survival (P <.05). Of the 35 tumor specimens, 34 specimens were evaluable by flow cytometry: 22 carcinomas were diploid (65%), and 12 were aneuploid (35%). The median DNA index of aneuploid tumors was 1.36 (range, 1.09 to 1.76). No correlation of DNA-ploidy with survival time was found. CONCLUSION: In contrast to DNA-ploidy pattern, Ki-67 antigen expression showed prognostic significance in resectable DBDC. A Ki-67 positive ratio of > or =20% was associated with decreased survival time.

Diagnostic and prognostic value of incidence of K-ras codon 12 mutations in resected distal bile duct carcinoma.

BACKGROUND AND OBJECTIVES: The K-ras gene is one of the most extensively investigated oncogenes in a wide variety of human tumors, but has rarely been studied in distal bile duct carcinoma (DBDC). We sought to investigate the diagnostic and prognostic value of K-ras codon 12 mutations in this type of tumor. METHODS: Forty-seven patients who had undergone resection for DBDC were analyzed to reveal the incidence of K-ras codon 12 mutations, the locus most frequently involved. A rapid and simple two-step, semi-nested polymerase chain reaction (PCR) technique was used to detect mutations in paraffin-embedded tumor samples. RESULTS: The PCR mismatch amplification technique demonstrated that 35 (75%) of the 47 tumors harbored a point mutation in codon 12 of the K-ras oncogene. Patients with mutated tumors had no statistically different survival time compared to those patients without a mutation in the tumor. In contrast, negative microscopic margins proved to be a significant prognosticator. CONCLUSIONS: K-ras codon 12 mutations are common in DBDC and may be useful in the diagnosis and early detection of these tumors. However, no prognostic value of these mutations could be identified in this analysis. The results of this study also suggest that negative surgical margins remain the mainstay of prognostication in resectable DBDC. However, due to the small number of patients included in this study, the results obtained should be interpreted with care.

The modified Pirogoff amputation for traumatic partial foot amputations.

OBJECTIVE: To describe our experience with a modification of the Pirogoff amputation, in the treatment of serious injuries to the hind foot. DESIGN: Retrospective study. SETTING: University hospital, The Netherlands. SUBJECTS: Six patients who required amputation of the hind foot after serious injury. INTERVENTIONS: The modified Pirogoff amputation (amputation of the foot at the ankle with part of the calcaneus left in the lower end of the stump) was done four times as an emergency and twice electively between 1979 and 1991. RESULTS: All the patients were satisfied with their stumps at follow up (7 months-13 years). None had stump pain or phantom pain and they were able to walk about indoors without using the prosthesis. CONCLUSION: We recommend the Pirogoff amputation as the treatment of choice in the management of partial traumatic amputation and other injuries of the foot, should a transmetatarsal amputation be impossible and about 5 cm of the sole of the foot can be preserved.