Perioperative outcome and long-term survival for intrahepatic cholangiocarcinoma after portal vein embolization and subsequent resection: A propensity-matched study.

INTRODUCTION: In view of the high therapeutic value of surgical resection for intrahepatic cholangiocarcinomas (ICC), our study addresses the question of clinical management and outcome in case of borderline resectability requiring hypertrophy induction of the future liver remnant prior to resection. METHODS: Clinical data was collected of all primary ICC cases receiving major liver resection with or without prior portal vein embolization (PVE) from a single high-volume center. PVE was performed via a percutaneous transhepatic access. Propensity score matching was performed. Perioperative morbidity was assessed as well as long-term survival with a minimum follow-up of 36 months. RESULTS: No significant difference in perioperative morbidity was seen between the PVE and the control group. For the PVE group, median OS was 28 months vs. 37 months for the control group (p = 0.418), median DFS 18 and 14 months (p = 0.703). Disease progression during hypertrophy was observed in 38% of cases. Here, OS and DFS was reduced to 18 months (p = 0.479) and 6 months (p = 0.013), respectively. In case of positive N-status or multifocal tumor (MF+) OS was also reduced (18 vs. 26 months, p = 0.033; MF+: 9 vs. 36months p = 0.013). CONCLUSION: Our results suggest that the surgical therapy in case of borderline resectability offers acceptable results with non-inferior OS rates compared to cases without preoperative hypertrophy induction and comparable oncological features. In the presence of additional risk factors (multifocal tumor, lymph node metastasis, PD during hypertrophy) the OS is notably reduced.

Correlation Between Sarcopenia and Growth Rate of the Future Liver Remnant After Portal Vein Embolization in Patients with Colorectal Liver Metastases.

PURPOSE: To investigate whether sarcopenia and myosteatosis correlate with the degree of hypertrophy (DH) and kinetic growth rate (KiGR) of the future liver remnant (FLR) in patients with colorectal liver metastases undergoing portal vein embolization (PVE) in preparation for right hepatectomy. MATERIALS AND METHODS: Forty-two patients were included. Total liver volume and FLR volume were measured before and 2-4 weeks after PVE. KiGR of the FLR was calculated. Sarcopenia was assessed using the total psoas muscle volume (PMV), the psoas muscle cross-sectional area (PMCS) and the total skeletal muscle index (L3SMI) at the level of 3rd lumbar vertebra. Degree of myosteatosis was assessed by mean muscle attenuation at L3 (L3MA). Correlations between muscle indices and DH and KiGR were assessed using simple linear regression analyses. RESULTS: Mean DH was 8.9 ± 5.7%, and mean KiGR was 3.6 ± 2.3. Mean PMV was 55.56 ± 14.19 cm3/m3, mean PMCS was 8.76 ± 2.3 cm2/m2, mean L3SMI was 45.6 ± 9.89 cm2/m2, and mean L3MA was 27.9 ± 18.6 HU. There was a strong positive correlation between PMV and DH (R = 0.503, p = 0.001) and PMV and KiGR (R = 0.545, p < 0.001). Furthermore, there was a moderate correlation between PMCS and KiGR (R = 0.389, p = 0.014). L3SMI and L3MA were neither associated with DH (p = 0.390 and p = 0.768, respectively) nor with KiGR (p = 0.188 and p = 0.929, respectively). CONCLUSION: We identified a positive correlation between PMV and PMCS, as markers for sarcopenia, and the KiGR of the FLR after PVE. PMV and PMCS might therefore aid to identify patients who are poor candidates for FLR augmentation using PVE alone.

[Intrahepatic cholangiocarcinoma - current perspectives and treatment algorithm]. / Aktueller Therapiealgorithmus des intrahepatischen cholangiozellulären Karzinoms.

Cholangiocarcinoma (CCC) is the second most common primary malignancy of the liver and is typically diagnosed at advanced disease stages. Among curative treatment options for CCC, radical surgical resection with extrahepatic bile duct resection, hepatectomy, and en-bloc lymphadenectomy are considered the mainstay of curative therapy. The assessment of the functional liver reserve by dynamic liver function tests and the estimation of the remaining future liver volume (future liver remnant, FLR) are of paramount importance. The introduction of novel interventional and surgical techniques, such as portal vein embolization, associating liver partition, and portal vein ligation for staged hepatectomy (ALPPS), have enabled clinicians to achieve resectability even in patients previously deemed unresectable. Radiofrequency ablation (RFA) shows acceptable results in small intrahepatic cholangiocarcinoma (IHCC) in liver cirrhosis and should be evaluated if cirrhosis precludes surgical treatment. Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) alone or in combination with systemic therapy may be applied in cases of surgical irresectability. According to recent results of the British BILCAP trial, adjuvant therapy may be considered after surgical resection in curative intent.

Rectal foreign body insertion as a rare cause of persistent lumbosacral plexus injury.

Rectal foreign body insertion is a common condition in emergency surgery, which often requires surgical intervention. Here we report a clinical case of rectal foreign body insertion as a rare cause of persistent lumbosacral plexus injury. A 72-year-old man presented to the emergency department complaining of acute bilateral paraplegia with loss of sensation in both legs, as well as total urinary retention. The patient underwent abdominal computed tomography, which showed a rectal foreign body measuring 13 × 11.5 × 10 cm in the lower abdomen and pelvis. Extraluminal assistance through a median laparotomy was required after unsuccessful attempts at transanal recovery alone. After removal of the foreign body, the rectal wall and anorectal sphincter were massively dilated, with severe bruising of the rectal mucosa on proctoscopy. A protective loop-ileostomy was performed. The sacral plexus is located posteriorly in the pelvis. Physiologically, the nerves are well protected by surrounding anatomical structures. Post-traumatic lumbosacral plexus injuries with paraplegia, urinary retention and anorectal sphincter insufficiency occur quite frequently after heavy traffic accidents. Lumbosacral plexus injury as a result of rectal foreign body insertion is rare. Severe neurological deficits through rectal foreign body insertion are rare but known medical conditions. To the best of our knowledge, this is the first reported case of severe and persistent post-traumatic lumbosacral plexus injury through a rectal foreign body.

An undigested cherry tomato as a rare cause of small bowel obstruction.

Small bowel obstruction due to undigested fibre from fruits and vegetables is a rare but known medical condition. We report a case of small bowel obstruction caused by a whole cherry tomato in a patient without a past medical history of abdominal surgery. A 66-year-old man presented to the emergency department complaining of lower abdominal pain with nausea and vomiting. His last bowel movement had occurred on the morning of presentation. He underwent abdominal computed tomography (CT), which showed a sudden change of diameter in the distal ileum with complete collapse of the proximal small bowel segment. Laparoscopy confirmed a small bowel obstruction with a transition point close to the ileocaecal valve. An enterotomy was performed and a completely undigested cherry tomato was retrieved. To our knowledge, this is the first reported case of a small bowel obstruction caused by a whole cherry tomato.

Pharmacogenetic profiling of CD133 is associated with response rate (RR) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), treated with bevacizumab-based chemotherapy.

Recent studies suggest CD133, a surface protein widely used for isolation of colon cancer stem cells, to be associated with tumor angiogenesis and recurrence. We hypothesized that gene expression levels and germline variations in CD133 will predict clinical outcome in patients with metastatic colorectal cancer (mCRC), treated in first-line setting with 5-fluorouracil, oxaliplatin and bevacizumab (BV), and we investigated whether there is a correlation with gene expression levels of CD133, vascular endothelial growth factor (VEGF) and its receptors. We evaluated intra-tumoral gene expression levels by quantitative real-time (RT) PCR from 54 patients and three germline variants of the CD133 gene by PCR-restriction-fragment length polymorphism from 91 patients with genomic DNA. High gene expression levels of CD133 (>7.76) conferred a significantly greater tumor response (RR=86%) than patients with low expression levels (7.76, RR=38%, adjusted P=0.003), independent of VEGF or its receptor gene expression levels. Gene expression levels of CD133 were significantly associated with VEGF and its receptors messenger RNA levels (VEGFR-1 (P<0.01), -2 and -3, P<0.05). Combined analyses of two polymorphisms showed a significant association with progression-free survival (PFS) (18.5 months vs 9.8 months, P=0.004) in a multivariate analysis as an independent prognostic factor for PFS (adjusted P=0.002). These results suggest that CD133 is a predictive marker for standard first-line BV-based treatment in mCRC.

A let-7 microRNA-binding site polymorphism in 3'-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy.

PURPOSE: recent studies have found that KRAS mutations predict resistance to monoclonal antibodies targeting the epidermal growth factor receptor in metastatic colorectal cancer (mCRC). A polymorphism in a let-7 microRNA complementary site (lcs6) in the KRAS 3' untranslated region (UTR) is associated with an increased cancer risk in non-small-cell lung cancer and reduced overall survival (OS) in oral cancers. We tested the hypothesis whether this polymorphism may be associated with clinical outcome in KRAS wild-type (KRASwt) mCRC patients treated with cetuximab monotherapy. PATIENTS AND METHODS: the presence of KRAS let-7 lcs6 polymorphism was evaluated in 130 mCRC patients who were enrolled in a phase II study of cetuximab monotherapy (IMCL-0144). Genomic DNA was extracted from dissected formalin-fixed paraffin-embedded tumor tissue, KRAS mutation status and polymorphism were assessed using direct sequencing and PCR restriction fragment length polymorphism technique. RESULTS: KRAS let-7 lcs6 polymorphism was found to be related to object response rate (ORR) in mCRC patients whose tumors had KRASwt. The 12 KRASwt patients harboring at least a variant G allele (TG or GG) had a 42% ORR compared with a 9% ORR in 55 KRASwt patients with let-7 lcs6 TT genotype (P = 0.02, Fisher's exact test). KRASwt patients with TG/GG genotypes had trend of longer median progression-free survival (3.9 versus 1.3 months) and OS (10.7 versus 6.4 months) compared to those with TT genotypes. CONCLUSIONS: these results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients, which warrants validation in other clinical trials.

Genetic variations in angiogenesis pathway genes associated with clinical outcome in localized gastric adenocarcinoma.

BACKGROUND: Angiogenesis has been attributed to be a well-recognized aspect of human cancer biology. As such, proteinase-activated receptor (PAR)-1, endostatin (ES) and interleukin-8 (IL-8) mediate the regulation of early-onset angiogenesis and in turn impact the process of tumor-growth and disease progression. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissues were obtained from 137 patients with localized gastric cancer at University of Southern California and Memorial Sloan-Kettering Cancer Center medical facilities. DNA was extracted and genotyping was carried out using PCR-restriction fragment length polymorphism-based protocols. RESULTS: In false discovery rate-adjusted univariate analysis, PAR-1 -506 ins/del (P < 0.001), ES +4349 G>A (P = 0.004), and IL-8 -251 T>A (P < 0.0001) were associated with time to tumor recurrence (TTR). Further, PAR-1 -506 ins/del and IL-8 -251 were associated with overall survival (OS). After adjusting for covariates, IL-8 remained significantly associated with TTR (adjusted P = 0.003) and OS (adjusted P = 0.049), whereas ES was significantly associated with TTR (adjusted P = 0.026). CONCLUSIONS: Polymorphisms in PAR-1, ES, and IL-8 may serve as independent molecular prognostic markers in patients with localized gastric adenocarcinoma. The assessment of the patients' individual risk on the basis of interindividual genotypes may therefore help to identify patient subgroups at high risk for poor clinical outcome.

Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer.

BACKGROUND: Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy. PATIENTS AND METHODS: Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism and 5'-end [gamma-(33)P] ATP-labeled PCR protocols. RESULTS: Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T-251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T-251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001). CONCLUSION: High expression variants of VEGF C+936T and IL-8 T-251A were associated with shorter time to tumor recurrence, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence.

Comparative analysis of four histopathological classification systems to discriminate benign and malignant behaviour in gastrointestinal stromal tumors.

UNLABELLED: The prognostic value of the four most common histopathological classification systems in gastrointestinal stromal tumors (GISTs) was evaluated retrospectively. PATIENTS AND METHODS: Twenty-five consecutive patients with resected GIST and a follow-up of five years or more for surviving patients were included in this analysis. All the tumors were c-KIT (CD117) positive and were additionally re-evaluated for the number of mitoses per 50 high-power fields (HPF) and Ki-67 proliferation index. The four most commonly applied histopathological classification systems of the WHO, Franquemont (modified by using the Ki-67 proliferation index), Fletcher and Miettinen were applied to each patient. RESULTS: The survival of patient groups classified by Franquemont (p = 0.03) and the WHO (p = 0.031) were of prognostic relevance, while the grouping of patients by classifications according to both, Fletcher and Miettinen did not show a significant prognostic value. CONCLUSION: The classification systems of Franquemont (modified) or WHO appear to be advantageous for the evaluation of malignant potential and clinical outcome in patients with GISTs. Our data are merely hypothesis generating and should be validated in larger clinical studies.