Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis

BackgroundThe objective of this meta-analysis was to evaluate the effectiveness and safety of lymph node dissection (LND) in patients with intrahepatic cholangiocarcinoma (ICC).MethodsA literature search with a date range of January 2000 to January 2018 was performed to identify studies comparing lymph node dissection (LND+) with non-lymph node dissection (LND-) for patients with ICC. The LND + group was further divided into positive (LND + N+) and negative (LND + N-) lymph node status groups based on pathological analysis.Results13 studies including 1377 patients were eligible. There were no significant differences in overall survival (OS) (HR 1.13, 95% CI 0.94–1.36; P = 0.20), disease-free survival (DFS) (HR 1.23, 95% CI 0.94–1.60; P = 0.13), or recurrence (OR 1.39, 95% CI 0.90–2.15; P = 0.14) between LND + group and LND-group. Postoperative morbidity was significantly higher in the LND + group (OR 2.67, 95% CI 1.74–4.10; P < 0.001). A subset analysis showed that OS was similar between LND + N- and LND-groups (HR 1.13, 95% CI 0.82–1.56; P = 0.450). However when comparing, OS of the LND-group to the LND+N+ group there was a significant increase in OS for the LND-group (HR 3.26, 95% CI 1.85–5.76; P < 0.001).ConclusionsLND does not seem to positively affect overall survival and is associated with increased post-operative morbidity.     

Prognostic significance of and risk prediction model for lymph node metastasis in resectable intrahepatic cholangiocarcinoma: do all require lymph node dissection?

BackgroundLymph node (LN) metastasis portends a worse prognosis following resection of intrahepatic cholangiocarcinoma (ICC); however, lymphadenectomy is not routinely performed, as its role remains controversial. Herein, we developed a risk model for LN metastasis by identifying its predictive factors and assessed a subset of patients who might not benefit from LN dissection (LND).Methods210 patients who underwent curative-intent surgery for ICC were retrospectively reviewed. A preoperative risk model for LN metastasis was developed following identification of its preoperative predictive factors using the recursive partitioning method.ResultsIn the multivariable analysis, CA 19-9 level of >120 U/mL, an enlarged LN on computed tomography, and a tumor location abutting the Glissonean pedicles were independent predictors of LN metastasis. The preoperative risk model classified the patients according to their risk: high, intermediate, and low risks at a rate of LN metastasis on final pathology of 60.9%, 35%, and 2.3%, respectively. In the subgroup analysis among the low-risk patients, performance of LND had no survival advantage over non-performance of LND.ConclusionRoutine LND for preoperatively diagnosed ICC should be recommended to patients at an intermediate and a high risk of developing LN metastasis but may be omitted for low-risk patients.     

Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase?

BACKGROUND/AIMS: The incidence of intrahepatic cholangiocarcinoma (ICC) has been reported to be increasing in the USA. The aim of this study is to examine whether this is a true increase or a reflection of improved detection or reclassification. METHODS: Using data from the Surveillance Epidemiology and End Results (SEER) program, incidence rates for ICC between 1975 and 1999 were calculated. We also calculated the proportions of cases with each tumor stage, microscopically confirmed cases, and the survival rates. RESULTS: A total of 2864 patients with ICC were identified. The incidence of ICC increased by 165% during the study period. Most of this increase occurred after 1985. There were no significant changes in the proportion of patients with unstaged cancer, localized cancer, microscopic confirmation, or with tumor size <5 cm during the period of the most significant increase. The 1-year survival rate increased significantly from 15.8% in 1975-1979 to 26.3% in 1995-1999, while 5-year survival rate remained essentially the same (2.6 vs. 3.5%). CONCLUSIONS: The incidence of ICC continues to rise in the USA. The stable proportions over time of patients with early stage disease, unstaged disease, tumor size <5 cm, and microscopic confirmation suggest a true increase of ICC.     

Prognosis and status of lymph node involvement in patients with adenocarcinoma in situ and minimally invasive adenocarcinoma—a systematic literature review and pooled-data analysis

Background

Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have been brought up that substitute for bronchioloalveolar carcinoma (BAC), according to the new classification of lung adenocarcinoma. There has been increasing opinions that argues for the adjustment of lymph node disposition in patients with such early stage tumors. Therefore, we sought to overview the prognosis and status of lymph node involvement in AIS/MIA patients.

Methods

PubMed, Springer and Ovid databases were searched for relevant studies. Data was extracted and results summarized to demonstrate the disposition of lymph nodes in AIS/MIA.

Results

Twenty-three studies consisting of 6,137 lung adenocarcinoma were included. AIS/MIA accounted for 821 of the total 6,137. All included patients received curative surgery. After a review of the summarized data we found that only one patient (with MIA) had N1 node metastasis, N2 disease was not found in any of the included patients. In concordance with this, studies that reported 5-year disease free survival (5-year DFS) have almost 100% rate.

Conclusions

Our findings indicated that patients with AIS/MIA have good survival prognosis after surgical resection, and that recurrence and lymph node metastasis in these patients is rare. Therefore, we strongly encouraged further studies to determine the role of different lymph node disposition strategies.     

Solitary recurrence of hilar cholangiocarcinoma in a mediastinai lymph node two years after curative resection

We recently encountered an unusual case of hilar cholangiocarcinoma in which a solitary recurrence in a mediastinal lymph node occurred two years after curative resection of the primary tumor. A 64-year old woman was admitted to our hospital with a complaint of right hypochondrial discomfort. After imaging studies demonstrated a hilar cholangiocarcinoma in the left hepatic duct, a curative resection of the tumor was performed, consisting of a left hepatic lobectomy along with caudate lobectomy, regional lymph node dissection, and resection of the extrahepatic bile duct. No nodal metastasis was observed histologically. Two years after surgery, the patient was found to have a nodule in the posterior mediastinum, which was thoracoscopically resected. No other swollen lymph nodes, local recurrence, or distant metastasis were noted. Histologically, the nodule proved to be a metastatic lymph node, and adjuvant chemoradiation therapy was initiated. The patient remained well for the four years following her first operation and had no evidence of disease recurrence 28 mo after her second operation. To our knowledge, this case is the first report of solitary recurrence in a mediastinal lymph node after curative resection of hilar cholangiocarcinoma.     

Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence?

Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma that accounts for about 10%-20% of the total cases. Infection with hepatitis B virus (HBV) is one of the most important predisposing factors leading to the formation of iCCA. It has been recently estimated based on abundant epidemiological data that the association between HBV infection and iCCA is strong with an odds ratio of about 4.5. The HBV-associated mechanisms that lead to iCCA are under intense investigation. The diagnosis of iCCA in the context of chronic liver disease is challenging and often requires histological confirmation to distinguish from hepatocellular carcinoma. It is currently unclear whether antiviral treatment for HBV can decrease the incidence of iCCA. In terms of management, surgical resection remains the mainstay of treatment. There is a need for effective treatment modalities beyond resection in both first- and second-line treatment. In this review, we summarize the epidemiological evidence that links the two entities, discuss the pathogenesis of HBV-associated iCCA, and present the available data on the diagnosis and management of this cancer.     

Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?

BACKGROUND: Recent studies with infliximab indicate the therapeutic potential of tumour necrosis factor alpha blockade in spondyloarthropathy (SpA). Because defective host defence is implicated in the pathogenesis of SpA, the potential side effects of this treatment due to impact on the antimicrobial defence are a major concern. OBJECTIVE: To report systematically the adverse events seen in a large cohort of patients with SpA treated with infliximab, with special attention to bacterial infections. PATIENTS AND METHODS: 107 patients with SpA were treated with infliximab for a total of 191.5 patient years. All serious and/or treatment related adverse events were reported. RESULTS: Eight severe infections occurred, including two reactivations of tuberculosis and three retropharyngeal abscesses, and six minor infections with clear bacterial focus. One patient developed a spinocellular carcinoma of the skin. No cases of demyelinating disease or lupus-like syndrome were seen. Two patients had an infusion reaction, which, however, did not relapse during the next infusion. Finally, three patients with ankylosing spondylitis developed palmoplantar pustulosis. All patients recovered completely with adequate treatment, and infliximab treatment had to be stopped in only five patients with severe infections. CONCLUSIONS: Although the global safety of infliximab in SpA is good compared with previous reports in rheumatoid arthritis and Crohn's disease, the occurrence of infections such as tuberculosis and retropharyngeal abscesses highlights the importance of careful screening and follow up. Focal nasopharyngeal infections and infection related symptoms, possibly induced by streptococci, occurred frequently, suggesting an impairment of specific host defence mechanisms in SpA.     

Localization of isolated lymph node metastases in esophageal cancer--does it influence the sentinel node concept?

BACKGROUND/AIMS: As demonstrated for different malignancies the detection of sentinel nodes (SNL) helps to individualize the indication for lymphadenectomy. In esophageal cancer, the lymphatic spread involves three distinct anatomical compartments. This study analyses the localization of single lymph node metastases in esophageal cancer and discusses the possible theoretical impact on SNL navigation. METHODOLOGY: 143 patients with esophageal carcinoma were included in this retrospective analysis. All patients underwent transthoracic en-bloc esophagectomy with 2-field lymphadenectomy. A meticulous work-up of all resected lymph nodes allowed a specific assignment to defined nodal groups of the abdominal and mediastinal compartment. Of 143 patients, 80 (55.9%) were classified as pN1. RESULTS: Twenty four of 80 patients had one single (n=15 patients) or two single (n=9 patients) lymph node metastases (total of 33 nodal metastases). Twenty four of these 33 lymph node metastases (73%) were located in the abdominal compartment. 9 of 13 patients (69%) with esophageal carcinomas above the tracheal bifurcation had isolated abdominal lymph node metastases. The overall rate of skip metastasis to the abdominal compartment was 55%. CONCLUSIONS: Isolated lymph node metastases in esophageal cancer are predominantly located in the abdominal compartment along the lesser curvature and the left gastric artery. Therefore, SNL navigation in esophageal cancer has to focus on this region and requires initial laparotomy/laparoscopy irrespective of the type of esophageal resection.     

Gas embolism in laparoscopic hepatectomy: what is the optimal pneumoperitoneal pressure for laparoscopic major hepatectomy?

Laparoscopic hepatectomy (LH) has become popular as a surgical treatment for liver diseases, and numerous recent studies indicate that it is safe and has advantages in selected patients. Because of the magnified view offered by the laparoscope under pneumoperitoneal pressure, LH results in less bleeding than open laparotomy. However, gas embolism is an important concern that has been discussed in the literature, and experimental studies have shown that LH is associated with a high incidence of gas embolism. Major hepatectomies are done laparoscopically in some centers, even though the risk of gas embolism is believed to be higher than for minor hepatectomy due to the wide transection plane with dissection of major hepatic veins and long operative time. At many high-volume centers, LH is performed at a pneumoperitoneal pressure less than 12 mmHg, and reports indicate that the rate of clinically severe gas embolism is low. However, more studies will be necessary to elucidate the optimal pneumoperitoneal pressure and the incidence of gas embolism during LH.     

Total pancreatectomy for pancreatic ductal adenocarcinoma: review of the National Cancer Data?Base

Background

Total pancreatectomy is infrequently performed for pancreatic cancer. Perceived operative mortality and questionable survival benefit deter many surgeons. Clinical outcomes, described in single-center series, remain largely unknown.

Methods

The National Cancer Database was queried for cases of pancreatic ductal adenocarcinoma undergoing total pancreatectomy (1998–2011). Univariate survival analyses were performed for 21 variables: demographic (8), tumor characteristics (5), surgery outcomes (6), and adjuvant therapy (2). The Log-rank test of differences in Kaplan–Meier survival curves was used for categorical variables. Variables with p < 0.05 were included in a multivariate analysis. Cox proportional hazards regression was used to analyze continuous variables and multivariate models.

Results

2582 patients with staging and survival data made up the study population. 30-day mortality was 5.5%. Median overall survival was 15 months, with 1, 3, and 5-year survival rates of 60%, 22%, and 13%, respectively. Age, facility type, tumor size and grade, lymph node positivity, margin positivity, and adjuvant therapy significantly impacted survival in multivariate analysis.

Conclusion

Although total pancreatectomy is a reasonable option for selected patients with pancreatic ductal adenocarcinoma, survival of the entire group is limited. Operative mortality is improved from prior reports. Greater survival benefits were seen in younger patients with smaller, node negative tumors resected with negative margins in academic research centers.     

Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality?

Summary. Recent evidence has been accumulated showing that anti‐HCV‐positive serologic status is significantly associated with lower survival in dialysis populations, but the mechanisms underlying this negative relationship are still unclear. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus (HCV) infection on all‐cause and disease‐specific mortality of patients on regular dialysis. The relative risk of all‐cause, cardiovascular and liver disease‐related mortality was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random effect pooled estimates for mortality with HCV across the published studies. We identified fourteen observational studies involving 145 608 unique patients on long‐term dialysis. Pooling of study results demonstrated that anti‐HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all‐cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25–1.47. Stratified analysis showed that the adjusted RR for liver disease‐related death was 3.82 (95% CI, 1.92; 7.61); heterogeneity statistics, R_i = 0.58 (P‐value by Q‐test = 0.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10; 1.45); no heterogeneity was found (NS). This meta‐analysis of observational studies indicates that anti‐HCV‐positive patients on dialysis have an increased risk of either liver or cardiovascular disease‐related mortality compared with anti‐HCV‐negative patients. Further studies are in progress to understand better the link between HCV and cardiovascular risk among patients on maintenance dialysis.     

Assessment of the uvulo-glossopharyngeal dimensions in patients with β-thalassemia major

Objectives

Thalassemia patients present varying degrees of craniofacial characteristics, while the morphology of the upper airway is less studied. The purpose of this study was to compare the uvula-glossopharyngeal dimensions (UGDs) of patients with β-thalassemia major (BTM) with non-thalassemic subjects who had similarities in the maxillo-mandibular skeletal pattern.

Subjects and methods

The material for this cross-sectional retrospective study consisted of lateral cephalograms of 40 BTM patients (23 males, 17 females, aged 9.5?±?0.97 years). These were compared with lateral cephalograms of a control group of 40 non-thalassemic subjects (23 males, 17 females, aged 11.0?±?0.87 years). The control group was chosen so that they had similarities with the BTM patients in the following cephalometric variables: SNA (in degree), SNB (in degree), ANB (in degree), and anterior facial height (N-Me).

Results

The following UGDs in thalassemic subjects were significantly shorter in patients with BTM: tongue length (P?<?0.05), the distance between the hyoid bone and the mandibular plane (P?<?0.01), and the vertical distance between hyoid bone and the C3-RGN line (line connecting third vertebra and retrognathion) (P?<?0.05). The middle airway space in BTM patients was significantly wider (P?<?0.05), and a trend was observed for the wider inferior airway space (P?=?0.07).

Conclusions

Based on this study, some UGDs in BTM patients were significantly different, compared to non-thalassemic subjects who had a similar maxillo-mandibular skeletal pattern. These findings may have implications for the long-term treatment of BTM patients; however, since groups were not exactly age-matched, the observed differences between groups could be attributed to either BTM, age, or both. Additional studies with age-matched subjects are needed to investigate the relationship between BTM and UGDs.     

Delay in surgical treatment of patients with hilar cholangiocarcinoma: does time impact outcomes?

BackgroundSubstantial time elapses before patients with hilar cholangiocarcinoma (HCC) receive surgical treatment because of time-consuming preoperative staging and other interventions, including biliary drainage and portal vein embolization. Prolonged times potentially lead to unresectability and the formation of metastases, yet these issues have not been investigated previously in HCC. This study aimed to evaluate the time between onset of symptoms and the provision of ultimate treatment in patients with HCC and the impact of the length of time on outcomes.MethodsDelays in the treatment of consecutive patients with HCC were evaluated by contacting general practitioners (GPs) and extracting data from hospital files. Time periods were correlated with resectability, occurrence of metastasis, tumour stage and survival using logistic and Cox regression analyses.ResultsTreatment times in 209 consecutive HCC patients were evaluated. The median time from first GP visit until presentation at the tertiary centre was 35 days. Time until treatment was longer when initial symptoms did not include jaundice (non-specific symptoms, P < 0.001). Duration of workup and preoperative biliary drainage at the tertiary centre prior to final surgical treatment resulted in an additional median time of 74 days. No correlation was found between treatment time in weeks and resectability [odds ratio (OR) 1.010, 95% confidence interval (CI) 0.985–1.036], metastasis (OR = 0.947, 95% CI 0.897–1.000), tumour stage (OR = 1.006, 95% CI 0.981–1.031) or survival in resected patients (hazard ratio = 0.996, 95% CI 0.975–1.018).ConclusionsThe time that elapses between the presentation of symptoms and final treatment in patients with HCC is substantial, especially in patients with non-specific symptoms. This time, however, does not affect resectability, metastasis, tumour stage or survival, which suggests that preoperative optimization should not be omitted because of potential delays in treatment.     

Indeterminate colitis: a review of the concept--what's in a name?

The precise diagnosis of colitis cannot always be established with the available diagnostic tools. The subgroup of patients with an uncertain diagnosis has been classified as "indeterminate colitis" (IC). The definition of "indeterminate," however, has changed over the years. Originally, IC was proposed by pathologists for colectomy specimens, usually from patients operated on for severe colitis, showing overlapping features of ulcerative colitis (UC) and Crohn's disease (CD). Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, and other features allowing a diagnosis of either UC or CD. Therefore, it is difficult to compare different studies. An International Organization of Inflammatory Bowel Diseases (IOIBD) working party confirmed 1) the ambiguous nature of the term, and 2) proposes an updated classification for the category of patients with an unclear diagnosis. According to this, the term IBD unclassified (IBDU) is confirmed, as suggested by the Montreal Working Party 2005 for patients with clinically chronic colitis, that clearly have IBD but when definitive features of CD or UC are absent. In resected specimens the term "colitis of uncertain type or etiology" (CUTE) is preferred. It is accepted that most of the time this may have a prefix, such as severe, chronic. The classification of IBD varies when based only on biopsies rather than on a colectomy specimen. The vast majority of these have severe colitis. For those that cannot bear to abandon the highly ambiguous term IC, if it is used at all, this is where it can be used parenthetically.