Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer

Gastric cancer(GC) is one of the most frequentlydiagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogenous metastasis from GC, such as vascular invasion, advanced age, differentiation, Borrmann type 1 or 2 and expansive growth. Recently, molecular mechanisms that contribute to metastatic site determination have been elucidated by advanced molecular biological techniques. Investigating the molecules that specifically participate in metastasis establishment in distinct secondary organs will lead to the development of novel biomarkers for patient stratification according to their metastatic risk and strategies for preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC.

Hematogenous umbilical metastasis from colon cancer treated by palliative single-incision laparoscopic surgery

Sister Mary Joseph’s nodule(SMJN)is a rare umbilical nodule that develops secondary to metastatic cancer.Primary malignancies are located in the abdomen or pelvis.Patients with SMJN have a poor prognosis.An 83-year-old woman presented to our hospital with a1-month history of a rapidly enlarging umbilical mass.Endoscopic findings revealed advanced transverse colon cancer.computer tomography and fluorodeoxyglucose-positron emission tomography revealed tumors of the transverse colon,umbilicus,right inguinal lymph nodes,and left lung.The feeding arteries and drainage veins for the SMJN were the inferior epigastric vessels.Imaging findings of the left lung tumor allowed for identification of the primary lung cancer,and a diagnosis of advanced transverse colon cancer with SMJN and primary lung cancer was made.The patient underwent local resection of the SMNJ and subsequent single-site laparoscopic surgery involving right hemicolectomy and paracolic lymph node dissection.Intra-abdominal dissemination to the mesocolon was confirmed during surgery.Histopathologically,the transverse colon cancer was confirmed to be moderately differentiated tubular adenocarcinoma.We suspect that SMJN may occur via a hematogenous pathway.Although chemotherapy for colon cancer and thoracoscopic surgery for the primary lung cancer were scheduled,the patient and her family desired home hospice.Seven months after surgery,she died of rapidly growing lung cancer.

Intussusception due to hematogenous metastasis of hepatocellular carcinoma to the small intestine:A case report

BACKGROUND The commonest sites of extrahepatic metastases from hepatocellular carcinoma(HCC)are the lungs,bones,adrenal glands,and regional lymph nodes.Hematogenous metastasis to the gastrointestinal(GI)tract is a rare condition in patients with HCC,and the prognosis is usually poor.We report,herein,an extremely rare case of a patient with intussusception due to hematogenous metastasis of HCC to the ileum and his long-term survival with multidisciplinary therapy.CASE SUMMARY The patient was a 71-year-old man with a history of chronic hepatitis B,who had undergone three surgeries for HCC.He was treated with sorafenib for peritoneal metastases of HCC.He was admitted to our hospital with chief complaints of abdominal pain and vomiting.Abdominal contrast-enhanced computed tomography imaging revealed a small intestinal tumor,presenting with intussusception and small bowel obstruction.Conservative treatment was started,but due to repeated exacerbation of symptoms,surgery was planned on the 28th d of hospitalization.Partial ileal resection without reducing the intussusception and end-to-end anastomosis was performed.On histological examination,tumor cells were not observed on the serosal surface,but intravascular invasion of tumor cells was seen.Immunohistochemistry was positive for immunohistochemical markers,and a diagnosis of hematogenous metastasis of HCC to the ileum was made.He remains alive 82 mo after the first surgery.CONCLUSION Prognosis of HCC patients with GI tract metastasis is usually poor,but in some cases,multidisciplinary therapy may prolong survival.

Reciprocal hematogenous osteomyelitis of the femurs caused by Anaerococcus prevotii:A case report

BACKGROUND Haematogenous osteomyelitis is an extremely rare disease occurring in adults,especially in developed countries.It is clearly a systemic infection,because bacteraemia spreads over proximal and distal long bones or paravertebral plexuses,resulting in acute or chronic bone infection and destruction.CASE SUMMARY A 46-year-old Caucasian male was complaining of a left thigh pain.It is known from the anamnesis that the patient developed severe pneumonia three months ago before the onset of these symptoms.The patient was diagnosed with haematogenous osteomyelitis,which developed a turbulent course and required complex combination therapy.The primary pathogen is thought to be Anaerococcus prevotii,which caused pneumonia before the onset of signs of osteomyelitis.Unfortunately,due to the complexity of identifying anaerobes and contributing nosocomial infections,the primary pathogen was not extracted immediately.After the manifestation of this disease,pathological fractures occurred in both femurs,as well as purulent processes in the lungs and molars accompanied.The patient received broad-spectrum antibiotic therapy and countless amounts of orthopaedic and reconstructive surgeries,but no positive effect was observed.The patient underwent osteosynthesis using an Ilizarov’s external fixation apparatus,re-fixations,external AO,debridements,intramedullary osteosynthesis with a silver-coated intramedullary nail,abscessotomies.The right femur healed completely after the pathological fracture and osteomyelitis did not recur.Left femur could not be saved due to non-healing,knee contracture and bone destruction.After almost three years of struggle,it was decided to amputate the left limb,after which the signs of osteomyelitis no longer appeared.CONCLUSION To sum it all up,complicated or chronic osteomyelitis requires surgery to remove the infected tissue and bone.Osteomyelitis surgery prevents the infection from spreading further or getting even worse up to such condition that amputation is the only option left.

Hematogenous Osteomyelitis by Acinetobacter Baumannii: Case Report and Literature Review

Skeletal infection with Acinetobacter baumanii is a rare condition and found mainly among soldiers injured in war. Multidrug resistant (MDR) Acinetobacter baumanii (A. baumanii) osteomyelitis is difficult to treat and requires long course of intravenous antibiotics. Most of reported cases in the literature are the consequences of direct inoculation of the pathogen. Here in, we report the first case of A. Baumannii osteomyelitis disseminated through hematogenous route and the therapeutic approach for this rare infection. Clinical Presentation: A 46 year old African-American male patient with human immunodeficiency virus (HIV) and end- stage renal disease on hemodialysis, who developed persistent MDR A. baumanii bacteremia in the hospital, thought to be secondary to the hemodialysis catheter, necessitating replacement of the catheter. Three months after his discharge to a skilled nursing facility (SNF), he developed left leg swelling without noticeable pain or fever. MRI revealed findings consistent with chronic osteomyelitis of left tibia and intra operative bone culture grew MDR A. baumannii. The patient had good outcome after three surgical debridements and prolonged period (7 Months) of dual antimicrobial therapy. Discussion: While in most documented cases of A. baumannii osteomyelitis, entry appears to require direct inoculation;our case suggests that this pathogen can seed into bone hematogenously in the setting of immunosuppression, persistent bacteremia and possibly in the presence of underlying bone infarcts. Clinicians need to be aware of this rare possible consequence of A. baumannii bacteremia. In conclusion, combination of multiple surgical debridements and dual antimicrobial therapy for a long period may result in a good outcome.

Waist subcutaneous soft tissue metastasis of rectal mucinous adenocarcinoma: A case report

BACKGROUND Rectal mucinous adenocarcinoma(MAC)is a rare pathological type of rectal can-cer with unique pathological features and a poor prognosis.It is difficult to diag-nose and treat early because of the lack of specific manifestations in some aspects of the disease.The common metastatic organs of rectal cancer are the liver and lung;however,rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding.CASE SUMMARY In this report,the clinical data,diagnosis and treatment process,and postope-rative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed.The patient underwent surgical treatment after admission and recovered well after surgery.The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis.CONCLUSION Subcutaneous soft tissue metastasis of rectal MAC is rare,and it can suggest that the tumor is disseminated,and it can appear even earlier than the primary ma-lignant tumor,which is occult and leads to a missed diagnosis and misdiagnosis clinically.When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer,a ma-lignant tumor should be considered.

Misdiagnosis of a multi-organ involvement hematogenous disseminated tuberculosis as metastasis:a case report and literature review

Background:Tuberculosis(TB)is a great mimicker and diagnostic chameleon,and prone to be diagnosed as malignancy.Even though many reports have described the differences between pulmonary TB and lung cancer,the atypical systemic hematogenous disseminated TB(HDTB)is very rare and more confusing in clinical practice.Case presentation:A 73-year-old man,HIV-negative,was hospitalized to the local county hospital because of chest pain,low-grade fever,asthenia,anorexia and weight loss for the pasting two months.The CT findings of the two lungs showed multiple round or round-like nodules of different sizes,with clear boundaries and partial fusion.The level of serum CA19–9 was significantly higher than normal,and progressively increased.There were multiple enlarged lymph nodes in the neck,mediastinum,abdominal cavity and pelvic cavity.The symptoms were diagnosed as hematogenous spread of gastrointestinal tumor in the local county hospital.However,when transferred to our provincial hospital,through comprehensive dynamic analysis,this patient was diagnosed as atypical systemic HDTB,no cancer at all.Through routine anti-TB therapy for one year,the patient was recovered very well at the follow-up of half year after withdrawal.Conclusions:In the past,most TB misdiagnosis cases involved in single organ and were finally confirmed through invasive examination.This case enriched clinical experiences in the diagnosis of atypical HDTB.We encouraged clinicians to establish a dynamic thinking for diagnosis and treatment and emphasized the value of biopsy and 18FFDG-PET in distinguishing TB and cancer.

Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis

Aim:To investigate whether tumor cells in a lymph node(LN)can invade from the marginal sinus into extranodal veins via vessel branches that communicate with intranodal veins and whether this can be a starting point for hematogenous metastasis at the early stage of LN metastasis.Methods:Vascular and lymphatic networks of LNs in MXH10/Mo-lpr/lpr mice were investigated using three-dimensional micro-computed tomography and histological methods.Flow in the blood vessel networks of LNs was investigated by fluorescence microscopy.Tumor cells were injected into the subiliac LNs of MXH10/Mo-lpr/lpr mice to induce metastasis to the proper axillary LNs.Tumor development in the proper axillary LN was detected using an in vivo bioluminescence imaging system.A two-dimensional image of the proper axillary LN microvasculature was reconstructed using a contrast-enhanced high-frequency ultrasound system.Results:Extranodal veins communicated with intranodal veins via branches that penetrated the capsule,and blood flowed from intranodal veins to extranodal veins.Tumor cells that had metastasized to the marginal sinus invaded these communicating veins to develop hematogenous metastases.Conclusion:Metastatic LNs that would be considered by clinical imaging to be stage N0 can be a starting point for hematogenous metastasis.The study findings highlight the need for the development of novel techniques for the diagnosis and treatment of early-stage LN metastasis,i.e.,when standard diagnostic imaging might incorrectly classify the LN as stage N0.

Alterations of blood serum parameters in patients with chronic hematogenous osteomyelitis

Objective:To examine metabolic disorders of major components of organic basis of bone tissue in patients with chronic hematogenous osteomyelitis and response to surgical treatment.Methods:The cubital vein puncture was conducted to take blood for analysis in patients with chronic hematogenous osteomyelitis.The activity of collagenase and hyaluronidase,elastin,elastase and total content of glycosaminoglycans were measured in blood serum.Results:The study revealed an enhancement of catabolic phase of metabolism of the main components in bone organic matrix during the relapse of inflammation.It was evidenced by indicators reflecting the synthetic and catabolic phases of the main components of the connective tissue collagen and glycosaminoglycans.The effective therapeutic treatments led to the reduction and normalization of studied compounds.Conclusions:The initial development of hematogenous osteomyelitis happens in a background of metabolic disorders of the main components of organic matrix of bone tissue,and normalizes upon effective therapy.

Role of ^(18)F-FDG PET/CT in detection of hematogenous metastases of advanced differentiated thyroid carcinoma: a systematic review and meta-analysis

The aim of this study was to collect the evidence on the performance of 2-deoxy-2-[^(18)F]fluoro-D-glucose(^(18)F-FDG)Positron Emission Tomography/Computed Tomography(PET/CT)in terms of detection rate(DR)and diagnostic accuracy in identifying hematogenous metastases in patients with differentiated thyroid cancer and compare its performance with that of other imaging techniques.A comprehensive PubMed/MEDLINE database research was carried out to retrieve studies documenting the performance of^(18)F-FDG PET/CT in depicting hematogenous metastases in patients with differentiated thyroid cancer.Statistical analysis was performed on a per-patient and per-lesion basis.The literature search yielded 15 articles to be included in the systematic review.^(18)F-FDG PET/CT showed a pooled DR of 85.08%on a per-patient analysis and 89.70%on a per-lesion analysis.For bone lesions,a high DR(81.78%)was found for^(18)F-FDG PET/CT.For the sub-group analysis of lung lesions,pooled DR was 92.77%for^(18)F-FDG PET/CT,95.02%for CT,and 64.93%for magnetic resonance imaging(MRI).On a per-patient analysis,^(18)F-FDG PET/CT demonstrated a pooled sensitivity(SS)of 87.3%[95%confidence interval(CI):77.3%-94%]and a pooled specificity(SP)of 95.6%(95%CI:87.6-99.1).On a per-lesion analysis(328 metastases),PET/CT showed a pooled SS and SP of 86.3%(95%CI:73.5%-93.5%)and 93.4%(95%CI:71.7%-98.8%)in the detection of hematogenous metastases.The presented systematic review and meta-analysis favor the use of^(18)F-FDG PET/CT in the detection of hematogenous metastases in patients with differentiated thyroid cancer.The limited literature warrants further studies to confirm our findings.

Emergency caudate lobectomy for ruptured hepatocellular carcinoma with multiple primary cancers

We report a case of metachronous multiple primary malignancies involving both rectum and liver with colonic metastasis from hepatocellular carcinoma(HCC) through hematogenous pathway.A 72-year-old woman was admitted to the emergency department with right upper abdominal pain for 4 h.Considering her surgical history of Mile's procedure plus liver resection for rectal cancer with liver metastasis three years ago and the finding of urgent computed tomography scan on admission,the preoperative diagnosis was spontaneous rupture of rectal liver metastasis located in caudate lobe and colonic metastasis from rectal cancer. The patient underwent an emergency isolated caudate lobectomy at a hemorrhagic shock status.Pathology reported a primary HCC in the caudate lobe and colonic metastasis of HCC with tumor embolus in the surrounding vessels of the intestine.No regional lymph node involvement was found.It is hypothesized that HCC may disseminate hematogenously to the ascending colon,thus making it a rare case.

Septic Chronic Multifocal Osteomyelitis in Children: A Challenging Presentation of Osteomylitis in a Low Income Country

Background: The aim of this study was to describe the clinical, biological and x-ray presentation of Septic Chronic Multifocal Osteomyelitis (SCMO) and discuss the therapeutic difficulties of this pathology in an African Sub-Saharan teaching hospital. Patients and Methods: A retrospective study was conducted in the Orthopedics and Trauma department of the university teaching hospital of Bobo-Dioulasso (Burkina Faso). Over a period of two years, we selected all cases of chronic osteomyelitis. We studied the epidemiological, diagnostic and therapeutic aspects of SCMO cases. Results: Eleven cases of SCMO were identified. The mean age of the patients was 11.8 years and the sex ratio was 1.75. There were 7 rural patients. The mean time to visit the hospital was 158 days. The most common reasons for consultation were pain (10 cases), swelling (9 cases), and fever (7 cases). Two were sickle cell patients. The most affected bones were the femur (10 cases), the tibia (9 cases) and the fibula (6 cases). The most frequent specific radiological lesions were sequestra (6 cases) followed by pandiaphysitis. Staphylococcus aureus was the most common aetiology. Treatment combined antibiotherapy and surgery (sequestrectomy and/or bone curettage and/or fistulectomy). Hip dislocations, pathological fractures and bone defect complicated the course of this disease. The therapeutic results was good in 3 patients and bad in 5 patients;the other 3 patients were lost to follow-up. Conclusion: Septic chronic multifocal osteomyelitis is a rare but formidable form of osteomyelitis in children. Therapeutic outcomes are often poor in hospitals with limited resources. The best strategy is prevention through early diagnosis and aggressive treatment of acute osteomyelitis.

Clinical and Laboratory Characteristics of Patients with Nontuberculous Mycobacterium Bloodstream Infection in a Tertiary Referral Hospital in Beijing, China

Background： Nontuberculous Mycobacterium （NTM） bloodstream infection （BSI） is relatively rare. We aimed in this study to evaluate the clinical characteristics, laboratory evaluation, and outcomes of patients with NTM BSI. Methods： We retrospectively reviewed the clinical records of inpatients with NTM BSI at our institution between January 2008 and January 2015 and recorded clinical parameters including age, gender, underlying disease, clinical manifestation, organs involved with NTM disease, species of NTM, laboratory data, treatment and outcome of these patients. We also reviewed the reported cases and case series ofNTM BSI by searching PubMed, EMBASE, and Wanfang databases. Data of normal distribution were expressed by mean ~ standard deviation （SD）. Data of nonnormal distribution were expressed by median and interquartile range （IQR）. Results： Among the ten patients with NTM BSI, the median age was 51 years （IQR 29-57 years） and three patients were males. Eight patients were immunocompromised, with underlying diseases including human immunodeficiency virus （HIV） infection （one patient）, rheumatic diseases （two patients）, breast cancer （one patient）, myelodysplastic syndrome （two patients）, and aplastic anemia （two patients）. Other organ（s） involved were lung （two patients）, endocardium （two patients）, brain, spinal cord, and soft tissue （one each patient）. The median lymphocyte was 0.66 x 109/L （IQR 0.24-1 .93 × 10^9/L）. The median cluster of differentiation 4 （CD4） cell count was 179/ mm^3 （IQR 82-19/mm^3）. Five patients died （three with hematological diseases, one with breast cancer, and one with rheumatic disease）, three recovered, and two were lost to follow-up. Conclusions： We reported all cases in our hospital diagnosed with bloodstream NTM infection that was rarely reported. In this group of patients, patients usually had a high fever and could have multiple organ involvements. All patients with poor prognosis had underlying diseases.

Analysis of the Microbiome Based on 16S rRNA Gene Signature in Women with Preterm versus Term Birth

Objective: To characterize and compare the microbiome signature in the maternal, intrauterine, and fetal environments and the associated bacterial species in women who experienced preterm birth and term birth.Methods: A total of 140 women with singleton pregnancies were enrolled in this study. Among them, 31 experienced spontaneous preterm delivery (gestational age < 37 weeks), and 28 of them experienced vaginal delivery at term. Maternal peripheral blood, saliva, and vaginal discharge samples and fetal membrane, amniotic fluid, and cord blood samples were collected immediately after delivery under sterile conditions. DNA was isolated from the fetal membrane and umbilical cord blood samples, and the V3-V4 region of the bacterial 16S rRNA gene was sequenced. The sequence data were quality-filtered, chimera-checked, and organized into operational taxonomic units (OTUs) based on phylogeny. Principal coordinate analysis of beta diversity measures was used for visualization. The linear discriminant analysis effect size (LEfSe) algorithm and Wilcoxon test were used to differentiate the microbiomes found in the fetal membranes and cord blood in the cases of preterm birth.Results: OTU analysis based on the 16S rRNA gene showed similar microbiomes in the maternal peripheral blood, amniotic fluid, fetal membranes, and cord blood. However, the LEfSe algorithm revealed significantly different bacterial compositions in the fetal environment between the preterm and term groups, with some of the bacterial species originating from the maternal peripheral blood or saliva.Conclusions: The bacteria in the intrauterine and fetal environments may originate from other body sites through hematogenous transmission, and may cause the occurrence of preterm birth.