Rational Treatment Choices Research Articles

Baseline circulating tumour DNA and interim PET predict response in relapsed/refractory classical Hodgkin lymphoma.

Reliable biomarkers for early identification of treatment failure in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) are lacking. Circulating tumour DNA (ctDNA) profiling has emerged as a powerful predictive and prognostic tool in several haemopoietic and non-haemopoietic malignancies and may guide rational treatment choices in r/r cHL. To assess the predictive and prognostic value of ctDNA, we performed a retrospective analysis on 55 r/r cHL patients treated with the bendamustine, gemcitabine and vinorelbine (BEGEV) regimen and additionally evaluated the potential utility of integrating ctDNA with interim [18 F]-FDG positron emission tomography (iPET). Baseline ctDNA genotyping in r/r cHL mirrored gene mutations and pathways involved in newly diagnosed cHL. We found that baseline ctDNA quantification and serial ctDNA monitoring have prognostic value in r/r cHL receiving salvage chemotherapy. Lastly, integrating ctDNA quantification with iPET evaluation may improve the early identification of patients at high risk of failing standard salvage therapy, who may benefit from an early switch to immunotherapeutic agents. Collectively, our results support the implementation of non-invasive methods to detect minimal residual disease in recurrent cHL and justify its prospective evaluation in appropriately designed clinical trials.

Nomogram for preoperative estimation of histologic grade in gastrointestinal neuroendocrine tumors.

The treatment strategies and prognosis for gastroenteropancreatic neuroendocrine tumors were associated with tumor grade. Preoperative predictive grading could be of great benefit in the selection of treatment options for patients. However, there is still a lack of effective non-invasive strategies to detect gastrointestinal neuroendocrine tumors (GI-NETs) grading preoperatively. The data on 147 consecutive GI-NETs patients was retrospectively collected from January 1, 2012, to December 31, 2019. Logistic regression was used to construct a predictive model of gastrointestinal neuroendocrine tumor grading using preoperative laboratory and imaging parameters.The validity of the model was assessed by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). The factors associated with GI-NETs grading were age, tumor size, lymph nodes, neuron-specific enolase (NSE), hemoglobin (HGB) and sex, and two models were constructed by logistic regression for prediction. Combining these 6 factors, the nomogram was constructed for model 1 to distinguish between G3 and G1/2, achieving a good AUC of 0.921 (95% CI: 0.884-0.965), and the sensitivity, specificity, accuracy were 0.9167, 0.8256, 0.8630, respectively. The model 2 was to distinguish between G1 and G2/3, and the variables were age, tumor size, lymph nodes, NSE, with an AUC of 0.847 (95% CI: 0.799-0.915), and the sensitivity, specificity, accuracy were 0.7882, 0.8710, 0.8231, respectively. Two online web servers were established on the basis of the proposed nomogram to facilitate clinical use. Both models showed an excellent calibration curve through 1000 times bootstrapped dataset and the clinical usefulness were confirmed using decision curve analysis. The model served as a valuable non-invasive tool for differentiating between different grades of GI-NETs, personalizing the calculation which can lead to a rational treatment choice.

Comparison of adverse effects of trastuzumab with other drug combinations for the treatment of breast cancer: A review

Objectives: This study compares the adverse effects (AEs) associated with trastuzumab in the treatment of human epidermal growth factor receptor 2-positive breast cancer (HER-2 + BC) when used alone or in combination with chemotherapy or with tyrosine kinase inhibitors, so as to aid in rational treatment choices. Materials and Methods: An electronic search was conducted on PubMed using the Mesh terms ‘BC’, ‘HER-2 positive’, ‘metastasis BC, ‘trastuzumab’, and ‘safety’. Data from 32 studies regarding AEs were extracted and categorised as trastuzumab + chemotherapy (T+C), trastuzumab biosimilar (Tb), trastuzumab + tyrosine kinase inhibitors+ chemotherapy (T+TKi+C), and trastuzumab + tyrosine kinase inhibitors (T+TKi). The data are presented as the mean percentage of AEs. The statistical comparison was represented by a box and whisker plot of the interquartile range value of AEs. Results: AEs related to the gastrointestinal tract, skin, nervous, blood, and lymph were reported to be the most common in T+C, T+TKi+C, and T+TKi. Nausea, vomiting, diarrhoea, constipation, neuropathy peripheral, alopecia, rash, anaemia, leucopenia, raised aspartate transaminase and alanine transaminase were the most common complaints. AEs such as myalgia, nasopharyngitis, hypertension, and ejection fraction decrease was reported to be the most common in Tb. Conclusion: This study concluded that biosimilar of trastuzumab is safest for the treatment of HER-2-positive BC. Cardiovascular disorder is often reported in the biosimilar group, but this group has fewer AEs reported as compared with chemotherapy, and tyrosine kinase inhibitors groups related to other systems such as digestive, nervous, and respiratory. The choice of combination is depending on the type of BC and the condition of the patients. The patients must monitor for cardiotoxicity when the biosimilar of trastuzumab is used.

Nitrofurantoin and Fosfomycin, effective oral empirical treatment options against multidrug resistant Escherichia coli

ObjectiveThe present study is designed to monitor antibiotic susceptibility pattern of Escherichia coli to assist in forecasting empirical therapy of urinary tract infection.MethodologyIt is a retrospective cross sectional study. It was carried out at Dow Diagnostic Research and Reference Laboratory for a period of 3 months from February 2017 to April 2017. A data of total 5000 urine culture and sensitivity test reports was taken from the medical record. The data was analyzed by SPSS version 16.ResultsOut of 5000 urine samples processed, 1565 showed significant bacterial growth. Escherichia coli was the most common pathogen isolated. Meropenem, Amikacin, Fosfomycin and Nitrofurantoin respectively were found to be the most sensitive antibiotics against Escherichia coli.Conclusion Fosfomycin and Nitrofurantoin are effective oral antibiotics against Escherichia coli causing urinary tract infection. The present study may help clinicians in making rational choice of empirical treatment of the patients.

A historical journey of searching for uricosuric drugs.

Gout is an auto-inflammatory disease driven by urate deposits with a second co-stimulatory factor evoking an (peri)arthritic fulminant inflammation often with a debute at night; inflammatory signals are enhanced via a NLRP3 pathway. In gout patients, urate metabolism has had a positive balance for a time period of weeks to years before the arthritic syndrome or tophaecous disease becomes manifest. This may be due to katabolism or weight loss, enhanced dietary affluence, and overweight resulting in increased serum urate levels. Also, a decreased urate excretion results in proneness to hyperuricaemia and clinical gout. Pharmacotherapeutically, a negative urate balance should be the aim of clinicians and then the rational choice of treatment with uricosurics seems quite logical and promising, but has not had a thorough attention of pharma, researchers nor of clinicians, though most gout patients were and still are low excretors. Here, an overview on the 70-year-old journey mankind has made in a search for uricosurics resulting so far in only 1 registered uricosuric per continent.

Antibiogram Profiles of Bacteria Isolated from Different Body Site Infections Among Patients Admitted to GAMBY Teaching General Hospital, Northwest Ethiopia.

BackgroundInfections with multi-drug resistant (MDR) bacteria are serious threats to many low-income countries associated with overuse and misuse of antibiotics. This study determined the antibiogram profiles of bacteria isolated from different body site infections among patients admitted to GAMBY Teaching General Hospital, Bahir Dar, Northwest Ethiopia.MethodsA hospital-based cross-sectional study was done between November 2015 and May 2018. Various clinical specimens were sampled from patients and analyzed for aerobic bacterial isolation and Kirby–Bauer disk diffusion susceptibility testing. Chi-square test was calculated to see association among variables, and P-value <0.05 was taken as a cutoff value for statistical significance.ResultsFrom the 716 clinical specimens processed, 134 (18.7%) were culture-positive for aerobic bacterial pathogens. Culture-confirmed positivity was higher in ear discharge (27.3%) and urine (26.3%) samples. The prevalence of infection was significantly highest among females (P = 0.001). Escherichia coli 63 (47.4%) and 10 (7.4%) of Klebsiella spp. from Gram-negative bacteria were the predominant bacterial isolates, while Staphylococcus saprophyticus 17 (12.6%) and S. aureus 14 (10.4%) were from Gram-positive bacteria. Overall, 61.8% of the isolates were found to be MDR. The proportion of MDR among Klebsiella spp., S. aureus and E. coli isolates was 90.9%, 60.9% and 50%, respectively. Gram-positive bacteria demonstrated 20%, 48.6% and 100% of resistance against norfloxacin, ciprofloxacin and clindamycin, respectively. Gram-negative bacteria also revealed from 20% resistance for the antibiotic nitrofurantoin and 100% of resistance for ampicillin and penicillin.ConclusionInfections with bacterial isolates resistant to the majority of antibiotics are a major issue in the study area. Most of the identified bacteria were resistant to the routinely used antibiotics, and MDR isolates are alarmingly high. Therefore, clinicians should practice rational choice of antibiotics and treatment should be guided by antimicrobial susceptibility testing.

Therapeutic effect and clinical cost of multi-disciplinary team model of hepatoblastoma in children

Objective To summarize and analyze the treatment process, long-term efficacy and clinical economics of children's hepatoblastoma (HB) in multi-disciplinary team (MDT) mode, so as to provide basis for the rational choice of diagnosis and treatment. Methods From January 2014 to February 2019, 13 cases of hepatoblastoma in children who completed the whole treatment course in the Pediatric Hematology Tumor Ward of Peking University First Hospital were collected and analyzed, and were followed up until June 30, 2020. There were 9 males and 4 females who were diagnosed and treated according to the MDT process in the hospital. The median age was 16 months (2-54 months), 69.23% (9/13) were under 2 years old. The characteristics, diagnosis and treatment process and treatment effect of the cases were summarized, and the cost of clinical treatment was analyzed. Results According to the pretreatment extent of disease(PRETEXT), there were 1, 9 and 3 children with stages Ⅱ, Ⅲ and Ⅳ. 76.92% (10/13) of the patients had the largest tumor diameter > 10 cm. All the patients received preoperative neoadjuvant chemotherapy (8 patients received 4 cycles of chemotherapy, and 6 patients changed the chemotherapy plan), surgical treatment and postoperative chemotherapy, the tumor volume decreased by more than 50% (64%-95%) in 12 cases, except 1 case with no significant increase of alpha fetal protein and multiple lesions.The median length of stay was 87 days (68-214 days), the median cost of stay was 200 000 yuan (115 000-500 000 yuan), the median length of stay was 7 days (5-17 days), the median cost of stay was 20 000 yuan (15 000-60 000 yuan), and the incidence of postoperative complications was 7.69% (1/13). All the patients were followed up for 16-69 months. All the patients survived. Conclusion Under the MDT mode, the treatment is seamless connection, the long-term prognosis of children with HB is good, and the total hospitalization cost and time are within the acceptable range. Standard preoperative neoadjuvant chemotherapy can significantly reduce the tumor, improve the resection rate, reduce postoperative complications, reduce the total individual expenditure, shorten the total hospital stay, and further improve the long-term disease-free survival rate.

Barium enema findings in total colonic aganglionosis: a single-center, retrospective study

BackgroundPreoperative diagnosis of total colonic aganglionosis is important for the rational choice of treatment. The present study aimed to evaluate the diagnostic performance of radiographic signs on preoperative barium enema in patients with total colonic aganglionosis.MethodsForty-four patients [41 (3-659) days] with total colonic aganglionosis, including 17 neonatal patients, who received preoperative barium enema at Beijing Children’s Hospital, from January 2007 to December 2019 were included. All radiographs were retrospectively restudied by 2 pediatric radiologists to ascertain radiographic signs including rectosigmoid index, transition zone, irregular contraction, gas-filled small bowel, microcolon, question-mark-shaped colon and ileocecal valve reflux. Kappa test was performed to assess the accuracy and consistency of the radiographic signs.ResultsThe 2 radiologists showed slight agreement for gas-filled small bowel, microcolon and rectosigmoid index, fair agreement for transition zone and irregular contraction, and moderate agreement for question-mark-shaped colon and ileocecal valve reflux (Kappa values, 0.043, 0.075, 0.103, 0.244, 0.397, 0.458 and 0.545, respectively). In neonatal patients, the 2 radiologists showed moderate agreement for ileocecal valve reflux and substantial agreement for question-mark-shaped colon (Kappa values, 0.469 and 0.667, respectively). In non-neonatal patients, the 2 radiologists showed substantial agreement for ileocecal valve reflux (Kappa value, 0.628). In 36 patients with total colonic aganglionosis extending to the ileum, the accuracies of question-mark-shaped colon, ileocecal valve reflux and the combination of both were 47%, 53%, and 75%, respectively, in one radiologist and 53%, 50% and 72%, respectively, in the other radiologist.ConclusionsIleocecal valve reflux is a relatively reliable radiographic sign for diagnosing total colonic aganglionosis and could improve the diagnostic accuracy upon combination with question-mark-shaped colon.

INDIVIDUAL APPROACH TO THE EXAMINATION OF PATIENTS AND THE CHOICE OF TREATMENT METHODS TOOTH SENSITIVITY

52 patients aged 26 to 54 years (39 women and 13 men) with hypersensitivity of the teeth were examined. Taking into account the individual approach to the examination of patients, the dental status was determined, etiological factors, body features, the presence of somatic pathology, clinical manifestations of hypersensitivity of the teeth were determined, with the determination of the degree, prevalence and intensity of hyperesthesia. The study made it possible to make a rational choice of treatment and prevention measures, taking into account individual General and local manifestations of this pathology.

Clinical analysis of 211 cases of cesarean scar pregnancy

Objective: To investigate the rational choice of early diagnosis and treatment of cesarean scar pregnancy (CSP). M ethods: The clinical data, including age, gravidity, time to previous cesarean section, first symptom, auxiliary examination, regimen, and therapeutic outcomes, of 211 patients with CSP admitted to Sichuan Provincial People’s Hospital from March 2016 to February 2018 were retrospectively analyzed. Results: Of the 211 patients, 165 patients were first diagnosed with CSP in this hospital, and eight of them (4.85%) were misdiagnosed; 46 patients were referred to thus hospital by physicians in other hospitals, and 21 of them (45.65%) were misdiagnosed. After admission, transvaginal color Doppler sonography was performed with a blood β-human chorionic gonadotropin (β-hCG) study to confirm the diagnosis. According to the surgical approaches, 211 patients were divided into six groups: group A: hysteroscopy group (141 patients), group B: uterine artery embolization (UAE) plus hysteroscopy group (38 patients), group C: hysteroscopy plus laparoscopy group (seven patients), group D: UAE with hysteroscopy plus laparoscopy group (six patients), group E: laparotomy group (12 patients), and group F: uterine evacuation group (seven patients). There were no significant differences in age, number of cesarean sections, time from previous cesarean section, days of the missed period, diameter of the gestational sac, or blood β-hCG levels among the six groups (p &gt; 0.05). However, the cure rate, complication rate, mean intraoperative blood loss, mean operative time, mean length of hospital stay, and mean medical cost were all statistically significant between the six groups (p &lt; 0.05). Conclusions: Women who have a history of cesarean section should be vigilant and undergo a transvaginal ultrasound examination as early as possible to exclude CSP and avoid a missed diagnosis or misdiagnosis. For patients at less than or equal to eight weeks of gestation and with a gestational sac diameter less than or equal to 3.0 cm, hysteroscopy is the preferred treatment that is safe and effective. Hysteroscopy combined with laparoscopy and laparotomy are suitable for patients with a high risk of massive bleeding, for instance, patients with a thin anterior myometrium on which abundant blood flow signals are shown, or should be considered as emergency backup plans for other surgical approaches. UAE can effectively reduce intraoperative blood loss but increases the risk of postoperative complications, length of hospital stay, medical costs, and it is suitable for patients with massive bleeding during or after CSP surgery and in need of emergency hemostasis or for patients with a very high risk of bleeding confirmed by a preoperative assessment.

Management of desmoid disease

Desmoid disease results when the wnt signaling pathway in fibroblasts is constantly active. It is characterized by enlarging tumors and sclerosing sheets of tissue. In patients with familial adenomatous polyposis (FAP) this can happen in the abdomen, the abdominal wall and in extra-abdominal sites. This review describes the clinical sequelae of desmoid disease in patients with FAP and their management. While abdominal wall desmoids cause symptoms due to their increasing size and prominence, they can be resected with a recurrence rate of about 30%. Intra-abdominal desmoid disease often involves the small bowel mesentery and cannot be resected without enterectomy. Various medical options are available for their management but none are predictably successful. A staging system has been developed that predicts mortality and allows rational treatment choices. Specific complications such as obstruction of the ureter and small bowel, small bowel perforation with abscess and fistula, and hemorrhage may need surgical management. Most FAP patients with desmoid disease can live in equilibrium with the desmoids. The keys are to mitigate symptoms while avoiding toxic or dangerous therapy.

EFFICIENCY OF APPLICATION OF COMPLEX TOPICAL DRUGS IN PATIENTS WITH INFLAMMATORY DISEASES OF THE PHARYNX

Infectious-inflammatory diseases of the pharynx are the most common pathological processes in the human population. Correct diagnosis and rational choice of effective treatment are directly correlate with important role of the pharyngeal tube in the life of the organism and a high risk of complications. The vast majority of clinical cases do not require the use of systemic drugs, topical therapy only. However, in the light of new data on the importance of microbial populations (microbiome), working as a functional barrier between the environment and nasopharyngeal mucosa, attention is attracted to topical antiseptics with antiinflammatory and biocenose saving effects, as part of complex therapy in diseases of the throat In the light of this issue, topical drugs based on lysozyme an enzyme, which is a natural antiseptic for the human body, are looking promising. These products are represented by Lysobact® (Bosnalijek, Bosnia and Hercegovina). It has proven anti-inflammatory, immunomodulatory and antiseptic action, and it`s efficacy is meaningful in treatment of the pharynx diseases in patients of different age groups.

Toward a Mechanism-Based Approach to Pain Diagnosis.

The past few decades have witnessed a huge leap forward in our understanding of the mechanistic underpinnings of pain, in normal states where it helps protect from injury, and also in pathological states where pain evolves from a symptom reflecting tissue injury to become the disease itself. However, despite these scientific advances, chronic pain remains extremely challenging to manage clinically. Although the number of potential treatment targets has grown substantially and a strong case has been made for a mechanism-based and individualized approach to pain therapy, arguably clinicians are not much more advanced now than 20years ago, in their capacity to either diagnose or effectively treat their patients. The gulf between pain research and pain management is as wide as ever. We are still currently unable to apply an evidence-based approach to chronic pain management that reflects mechanistic understanding, and instead, clinical practice remains an empirical and often unsatisfactory journey for patients, whose individual response to treatment cannot be predicted. In this article we take a common and difficult to treat pain condition, chronic low back pain, and use its presentation in clinical practice as a framework to highlight what is known about pathophysiological pain mechanisms and how we could potentially detect these to drive rational treatment choice. We discuss how present methods of assessment and management still fall well short, however, of any mechanism-based or precision medicine approach. Nevertheless, substantial improvements in chronic pain management could be possible if a more strategic and coordinated approach were to evolve, one designed to identify the specific mechanisms driving the presenting pain phenotype. We present an analysis of such an approach, highlighting the major problems in identifying mechanisms in patients, and develop a framework for a pain diagnostic ladder that may prove useful in the future, consisting of successive identification of 3 steps: pain state, pain mechanism, and molecular target. Such an approach could serve as the foundation for a new era of individualized/precision pain medicine. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION)-American Pain Society (APS) Pain Taxonomy (AAPT) includes pain mechanisms as 1 of the 5 dimensions that need to be considered when making a diagnostic classification. The diagnostic ladder proposed in this article is consistent with and an extension of the AAPT. We discuss how identifying the specific mechanisms that operate in the nervous system to produce chronic pain in individual patients could provide the basis for a targeted and rational precision medicine approach to controlling pain, using chronic low back pain as our example.

Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane.

The Biological and Clinical Challenge of Liver Cancer Heterogeneity

Primary liver cancer (PLC) consists of two major histological subtypes: hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). PLC is, similar to all major human cancers, clinically and biologically heterogeneous, and highly resistant to treatment. Consequently, 5-year survival rates of PLC in the US has been <20% over the past 40 years with little sign of improvement [1]. Patient ethnicity, underlying liver diseases due to various etiological factors such as viral hepatitis resulting from hepatitis B and hepatitis C infection, parasitic infection, alcoholic liver disease, or obesity, etc., may contribute to molecular and biological heterogeneity [2]. Furthermore, recent application of genomic technologies (e.g., transcriptomic and sequencing analyses) have reinforced the extent of heterogeneity in PLC [2]. In addition, the heterogeneous hepatic microenvironment in PLC resulting from inflammation and varying degrees of liver fibrosis and cirrhosis may also affect tumor biology. The major barrier to improve outcome of patients with PLC is the incomplete understanding of PLC heterogeneity and the inability to subdivide the patients into biologically and genomically unique subgroups harboring well-defined and effective-treatment targets, a central strategy applied by the precision cancer medicine (PCM) approach. PCM utilizes cancer genomic data with precision based on mechanistic understanding of a particular state of tumor biology to facilitate rational treatment choices that are tailored to individual patients. It is paramount to reevaluate current practice guidelines and to apply the PCM strategy for managing PLC patients and designing new clinical trials.

Rational Choice of Treatment for Initial Stages of Gonarthrosis in Patients with Systemic Osteoporosis

Rational Choice of Treatment for Initial Stages of Gonarthrosis in Patients with Systemic Osteoporosis

Rational Choice of Treatment for Initial Stages of Gonarthrosis in Patients with Systemic Osteoporosis

Results of open controlled study of 60 outpatients aged 45-70 years, with systemic osteoporosis (postmenopausal and idiopathic) and I-II stages of gonarthrosis by Kellgren - Lawrence classification are presented. All patients were divided into 2 groups: study group (n=30) and control group (n=30). Additional treatment for gonarthrosis (Artra drug for 3 months) was prescribed only to patients from the study group. It was shown that study drug decreased significantly (p

Intracerebral Hemorrhage in Patients Receiving Oral Anticoagulation Therapy

Intracerebral hemorrhage (ICH) in patients with oral anticoagulation therapy is an increasingly prevalent problem in large part due to the aging population and the increased use of anticoagulants for patients at high risk of thrombosis. Warfarin has been virtually the only outpatient anticoagulant choice until fairly recently. The development of subcutaneously injected heparinoids, and more recently, of direct thrombin inhibitors, has made the treatment and prognostication of ICH in anticoagulated patients more difficult. In this review, we will review the current state of diagnosis, prognostication, and treatment for patients with this often-devastating type of bleeding. We will focus on warfarin therapy, because the preponderance of evidence comes from studies of warfarin treatment. Where there is evidence, we will contrast warfarin with some of the newer treatment modalities. We review the evidence of the 4 major reversal agents for warfarin, vitamin K, prothrombin complex concentrates, activated factor VII, and fresh frozen plasma as well as rational treatment choices. We offer possible treatments for the newer anticoagulants based on the limited evidence available. Finally, we review recommendations from the major societies and studies that support early and aggressive therapies in intensive care units with dedicated neurological specialists.

Precision Oncology: An Overview

In this Special Series issue, Journal of Clinical Oncology presents a systematic assessment of cancer genomic information and its accelerating clinical impact. In the scientific literature and lay press, the relevant discipline is often called personalized, or precision, cancer medicine. The word personalized conveys the sense that cancer genomic data may facilitate rational treatment choices that are tailored to individual patients. The term precision refers to prospects for enhanced molecular resolution, mechanistic clarity, and therapeutic cogency that may accompany clinical implementation of genomics technologies. We have chosen the term genomics-driven cancer medicine in recognition of the fact that knowledge that emanates specifically from the cancer genome will likely continue to direct the opening act of precision oncology as it plays out in clinical and translational studies over the next several years. Although precision medicine will inevitably permeate many diseases (both cancer and noncancer), oncology arguably sits at its vanguard. One obvious reason is the fact that cancer is a genomic disease: most cancers harbor a cocktail of mutated (or otherwise altered) oncogenes and tumor suppressors that work in concert to specify the molecular pathways that lead to their genesis, maintenance, and progression. Toward this end, oncology research has benefitted immensely from the proliferation of worldwide efforts to characterize the genomes of thousands of cases spanning nearly all major cancer types. As described in the opening article of this Special Series issue, the same technologic and analytic advances that have enabled a comprehensive catalogue of cancer genes are becoming increasingly malleable for advanced clinical diagnostics. Together with the expanding compendium of targeted anticancer agents in clinical development or active use, oncology has served as a proving ground for the genomics-driven framework that is unique among medical specialties. Conceptually, the implementation of genomics-driven cancer medicine might seem straightforward (Fig 1): first, characterize the genomes of patients’ tumors using state-of-the-art technologies; second, filter the genomic data through a knowledge base of existing and emerging anticancer drugs; and third, present an annotated list to the treating oncologist that can be incorporated into clinical decision making. However, multiple challenges must be addressed to bring this ambitious goal to fruition. To begin with, high-quality genomic information must be obtained consistently in the diagnostic setting— often from sparse amounts of archival tumor tissue. The article by MacConaill reviews the remarkable technologic advances that make large-scale genomic data generation feasible in a clinical setting. Although questions persist regarding the extent of genomic data needed, the cost-effectiveness of various platforms, and how rapidly clinical genomic data can be delivered, it seems clear that available technologies for genome characterization are fast becoming equipped to meet the demands of precision oncology. The analytic challenges that accompany comprehensive genomic data have proven more problematic. The somatic and germline alterations that are relevant to each cancer must be identified with high

Surgical treatment of Budd-Chiari syndrome: analysis of 221 cases

Budd-Chiari syndrome (B-CS) refers to post-hepatic portal hypertension and/or inferior vena cava hypertension caused by obstruction of blood flow at the portal cardinal hepatic vein. The treatments of B-CS include operations on pathological membrane lesions, shunting and combined operations. Studies have shown that China, Japan, India and South Africa have a high incidence of B-CS. In China, the Yellow River Basin in Henan, Shandong, Jiangsu and Anhui Provinces also have a high incidence, around 10 per 100 000. The clinical data of 221 B-CS patients were analyzed retrospectively. We focused on pathological types, surgical methods, effectiveness and complications of treatment, and follow-up. Based on imaging findings such as color ultrasonography, angiography or magnetic resonance angiography, the 221 patients were divided into 3 types (five subtypes): type Ia (72 patients), type Ib (20), type II (72), type IIIa (33), and type IIIb (24). Surgical procedures included balloon membranotomy with or without stent (65 patients), improved splenopneumopexy (18), radical resection of membrane and thrombus (17), inferior vena cava bypass [29, with cavocaval transflow (13) and cavoatrial transflow (16)], mesocaval shunt (41), splenocaval shunt (25), splenoatrial shunt (12), splenojugular shunt (6), and combined methods (8). The complication rate was 9.05% (20/221) and the perioperative death rate was 2.26% (5/221). All of the patients were followed up from 6 months to 5 years. The success rate was 84.6% (187/221), and the recurrence rate was 8.9% (9/101) and 13.5% (13/96) after 1- and 5-year follow-up, respectively. The rational choice of surgical treatment based on B-CS pathological typing may increase the success rate and decrease the recurrence.