Clinical features and risk factors for appendiceal diverticulitis: a comparative study with acute appendicitis.

PURPOSE: Despite their similar clinical characteristics, appendiceal diverticulitis (AD) and acute appendicitis (AA) are pathologically distinct. This study compared the clinical features of AD and AA and identified relevant risk factors. METHODS: Patients who underwent appendectomy with a preoperative diagnosis of either AD or AA were categorized based on histopathological findings. The two groups were compared in terms of various clinical factors. RESULTS: Among the 854 patients included in the study, a histopathological evaluation revealed 49 and 805 cases of AD and AA, respectively. A univariate analysis demonstrated that AD was more prevalent than AA among older, taller, and heavier males. A multivariate analysis revealed that male sex, a white blood cell (WBC) count < 13.5 × 103/µL, an eosinophil count ≥ 0.4%, and a mean corpuscular volume (MCV) ≥ 91.6 fL were significant factors differentiating AD from AA. In addition, pathological AD emerged as an independent risk factor for abscess and/or perforation. CONCLUSIONS: AD was associated with an older age, robust physique, and significant risk of abscess and/or perforation despite a low WBC count. In addition to imaging modalities, the preoperative factors of male sex, a WBC count < 13.5 × 103/µL, an eosinophil count ≥ 0.4%, and a MCV ≥ 91.6 fL may be useful for distinguishing AD from AA.

Comprehensive circulating microRNA profile as a supersensitive biomarker for early-stage lung cancer screening.

PURPOSE:  Less-invasive early diagnosis of lung cancer is essential for improving patient survival rates. The purpose of this study is to demonstrate that serum comprehensive miRNA profile is high sensitive biomarker to early-stage lung cancer in direct comparison to the conventional blood biomarker using next-generation sequencing (NGS) technology combined with automated machine learning (AutoML). METHODS: We first evaluated the reproducibility of our measurement system using Pearson's correlation coefficients between samples derived from a single pooled RNA sample. To generate comprehensive miRNA profile, we performed NGS analysis of miRNAs in 262 serum samples. Among the discovery set (57 patients with lung cancer and 57 healthy controls), 1123 miRNA-based diagnostic models for lung cancer detection were constructed and screened using AutoML technology. The diagnostic faculty of the best performance model was evaluated by inspecting the validation samples (74 patients with lung cancer and 74 healthy controls). RESULTS: The Pearson's correlation coefficients between samples derived from the pooled RNA sample ≥ 0.98. In the validation analysis, the best model showed a high AUC score (0.98) and a high sensitivity for early stage lung cancer (85.7%, n = 28). Furthermore, in comparison to carcinoembryonic antigen (CEA), a conventional blood biomarker for adenocarcinoma, the miRNA-based model showed higher sensitivity for early-stage lung adenocarcinoma (CEA, 27.8%, n = 18; miRNA-based model, 77.8%, n = 18). CONCLUSION: The miRNA-based diagnostic model showed a high sensitivity for lung cancer, including early-stage disease. Our study provides the experimental evidence that serum comprehensive miRNA profile can be a highly sensitive blood biomarker for early-stage lung cancer.

Neurogenic intermittent claudication caused by vasculitis in the cauda equina: an autopsy case report.

PURPOSE: Intermittent claudication (IC) refers to leg pain that is induced by walking and relieved by rest. Neurogenic IC is usually associated with lumbar canal stenosis (LCS). We present rare findings from an autopsied patient who had neurogenic IC caused by vasculitis in the cauda equina. METHODS: We performed antemortem neurological and electrophysiological assessments, sural nerve biopsy, and post-mortem examination of the spinal cord and brain. RESULTS: A 61-year-old man noted sudden-onset leg pain that was not associated with any traumatic trigger. His leg pain consistently appeared when the patient walked and quickly faded on stopping. Spine surgery and cardiovascular departments both made a diagnosis of IC. However, magnetic resonance imaging (MRI) did not show LCS, and all ankle-brachial pressure indices were normal. He subsequently developed diffuse muscle weakness of the legs a month after disease onset. Myeloperoxidase antineutrophil cytoplasmic autoantibody was seropositive (140 IU/mL), and a sural nerve biopsy revealed axonal injury and angiitis. MRI showed multiple cerebral infarctions. He was diagnosed with microscopic polyangiitis (MPA) and underwent corticosteroid therapy. He died from complications two months after the onset. A post-mortem study revealed vasculitis in the subarachnoid space of the cauda equina, spinal cord, and brain parenchyma. The cauda equina showed a combined loss of small and large axonal fibres. The lumbar cord displayed central chromatolysis of the lower motor neurons. CONCLUSION: MPA is a rare cause of neurogenic IC when the symptom is acute and multimodal. Small-vessel vasculitis affecting the cauda equina may underlie MPA-associated IC.

Long-term survivor who underwent surgical resections of repeated peritoneal oligometastases from colon cancer : a rare case report.

A 74-year-old woman underwent right hemicolectomy and partial ileal resection for ascending colon cancer with synchronous peritoneal metastasis. Histopathological examination showed moderately differentiated adenocarcinoma with mucinous component, pT4b N3 M1, and Stage IV. Postoperative chemotherapy comprising 36 courses of mFOLFOX6 with bevacizumab was administered. Twenty-two months after the surgery, computed tomography (CT) revealed a 20 mm nodular lesion adjacent to the gastric wall, and laparoscopic resection of the nodule was performed. Thirty-nine months after the second surgery, CT showed a 24 mm nodular lesion involving the liver parenchyma, and partial hepatectomy involving the nodule was performed. Histopathological examination of the nodules resected by the second and third surgeries showed the same features as the primary ascending colon cancer. The nodules were diagnosed as metachronous peritoneal metastases. The patient followed up without chemotherapy after the second and third surgery, showed no recurrence for 26 months after the third surgery. Fortunately, more than 7 years have passed since the primary tumor resection. Hence, surgical resection for synchronous and repeated metachronous peritoneal oligometastases from colon cancer can offer long-term survival. J. Med. Invest. 69 : 302-307, August, 2022.

Diagnosis and clinical implication of collision gastric adenocarcinomas: a case report.

BACKGROUND: Collision tumors are a subtype of simultaneous tumors wherein two unrelated tumors collide or infiltrate each other. Collision gastric adenocarcinomas (CGA) are rare and difficult to diagnose, and their clinical implications remain unclear. Herein, we aimed to reveal diagnostic methods for CGA and provide insight into its implications. CASE PRESENTATION: Among 1041 cases of gastric cancers (GCs) resected between 2008 and 2018, we included cases of confirmed CGA. Patients' backgrounds, preoperative endoscopy findings, macroscopic imaging findings, and histopathology findings [including immunostaining for CK 7, MUC2, and mismatch repair (MMR) proteins] were investigated. The incidence of CGA was 0.5%: 5 of 81 cases having simultaneous multiple GCs. Tumors were mainly in the distal stomach. The CGA in two cases was between early cancers, in two cases was between early and advanced cancers, and in one case was between advanced cancers. There were three cases of collision between differentiated and undifferentiated types and two cases between differentiated types. Immunostaining with CK7 and MUC2 was useful for diagnosing collision tumor when the histology was similar to each other. Among ten GCs comprising CGA, nine tumors (90%) exhibited deficient MMR proteins, suggesting high microsatellite instability (MSI). CONCLUSIONS: CGA is rare and usually found in the distal stomach. Close observation of shape, optimal dissection, and detailed pathological examination, including immunostaining, facilitated diagnosis. CGAs may have high MSI potential.

Non-tumor forming and diffusely spreading invasive pancreatic cancer.

A 78-year-old man presented to our hospital with loss of appetite and epigastric discomfort. Computed tomography (CT) revealed dilation of the main pancreatic duct and three cystic lesions in the pancreatic neck, body, and tail. Endoscopic ultrasonography showed a mural nodule > 5 mm enhanced with Sonazoid in a cyst. Therefore, the patient was diagnosed with intra-ductal papillary mucinous neoplasm (IPMN) and underwent distal pancreatectomy. Macroscopic examination of the cut surface of the resected specimen showed no solid tumors in the pancreatic parenchyma. The histopathological diagnosis of the cysts was IPMN with low-grade dysplasia. Ten months after surgery, the serum carbohydrate antigen 19-9 level was elevated, and CT showed multiple peritoneal and pulmonary nodules, suggesting peritoneal dissemination and lung metastases. Since recurrence of pancreatic cancer was suspected, repeat histopathological examination of the resected specimen was performed, revealing small clusters of atypical epithelial cells diffusely spreading in the pancreatic tissue. The diagnosis was changed to invasive ductal carcinoma (pT2N1bM0, stage IIB). Invasive pancreatic cancer that does not form a solid mass, and shows diffuse spreading with small clusters is extremely rare. Imaging diagnosis and histopathological examination should be carefully performed in such cases.

Neurolymphomatosis in follicular lymphoma: an autopsy case report.

Neurolymphomatosis is a neurological manifestation of lymphoma that involves the cranial or spinal peripheral nerves, nerve roots, and plexus with direct invasion of neoplastic cells. Neurolymphomatosis is rare among patients with low-grade lymphoma. We report an autopsied case of neurolymphomatosis that arose from follicular lymphoma. A 49-year-old woman who presented with pain of her neck and shoulder and numbness of her chin. Computed tomography revealed enlarged lymph nodes in her whole body, and biopsy from the axillary lymph node revealed grade 2 follicular lymphoma. Although the patient underwent chemotherapy, she gradually developed muscle weakness in the upper limbs and sensory disturbances of the trunk and limbs. 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed increased tracer uptake of the cervical nerve roots. Repeated FDG-PET after additional therapy revealed progression of disease within the nerve roots and brachial plexus, whereas gadolinium-contrast magnetic resonance imaging (MRI) showed weak enhancement of the cervical nerve roots without formation of mass lesions. She died after a total disease duration of 12 months. Postmortem observations revealed invasion of lymphoma cells into the cervical nerve roots, dorsal root ganglia, and subarachnoid spaces of the spinal cord. Neurolymphomatosis was prominent at the segments of C6-Th2. Combined loss of axons and myelin sheaths was observed in the cervical nerve roots and posterior columns. Lymphoma cells also invaded the cranial nerves. The subarachnoid and perivascular spaces of the brain demonstrated focal invasion of the lymphoma. Mass lesions were not observed in the central nervous system. The lymphoma cells did not show histological transformation to higher grades, and the density of the centroblasts remained at grade 2. Our report clarifies that low-grade follicular lymphoma can manifest as neurolymphomatosis and central nervous system invasion in the absence of transformation toward higher histological grades. FDG-PET may be more sensitive to non-mass-forming lesions, including neurolymphomatosis, than gadolinium-contrast MRI.

Portal vein leiomyosarcoma invading the pancreatic head.

We encountered a rare case of a pancreatic head tumor protruding into the portal vein, later diagnosed histopathologically as primary leiomyosarcoma of the portal vein. A 59-year-old woman visited our hospital because of an elevated amylase level during a medical checkup. Computed tomography showed a moderately contrasted, well-defined mass of 35-mm diameter in the pancreatic head with protrusion into the portal vein. Endoscopic ultrasonography revealed a well-defined and hypoechoic mass. Fluorodeoxyglucose-positron emission tomography showed a high accumulation of fluorodeoxyglucose in the pancreas head. We performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein resection. Gross findings of the fixed specimen showed a white solid, multinodular mass in the pancreatic parenchyma with protrusion into the portal vein. Histopathological examination showed proliferation of spindle-shaped eosinophilic cells with intricate bundle-like growth, indicating leiomyosarcoma. Examining the tumor location and invasion suggested portal vein as the origin. Although portal vein primary leiomyosarcoma is rare, leiomyosarcoma should be considered as a differential diagnosis in pancreatic head tumors with protrusion into the portal vein. Precise macroscopic and histopathological examinations can help determine the definitive diagnosis and origin of leiomyosarcoma.

SMARCA4-deficient rectal carcinoma with a sarcomatoid component: a case report.

A new classification of SMARCA4-deficient tumors was proposed recently for thoracic malignancies, and the tumors have some histopathological characteristics similar to those of carcinosarcoma. We encountered a case of SMARCA4-deficient rectal carcinoma with a sarcomatoid component. A 46-year-old man presented to our hospital with a prolapsing anal mass. Colonoscopy revealed an irregular, nodular, and elevated lesion in the rectum, and the biopsy revealed a moderately differentiated adenocarcinoma. Abdominoperineal resection of the rectum was performed. A macroscopic image of the resected specimen showed a complex tumor 3.5 cm × 3 cm in size with a papillary protrusion and an irregular ulcerative lesion. Histopathological examination revealed that the tumor was composed of moderately/poorly differentiated adenocarcinoma and atypical spindle cells. The adenocarcinoma component was positive for epithelial markers (AE1/AE3 and carcinoembryonic antigen) and showed deletion of SMARCA2 and SMARCA4, while the spindle cells expressed mesenchymal markers (α-smooth muscle actin and vimentin). The pathological diagnosis was poorly differentiated adenocarcinoma with a sarcomatoid component, pT3N2bM0, stage IIIc. Although our case had histological characteristics of carcinosarcoma, immunostaining revealed a deficiency of SMARCA4. This case presented a SMARCA4-deficient colorectal carcinoma with a sarcomatoid component, which was histopathologically similar to carcinosarcoma.

Superficial spreading type of early gastric cancer with diagnostic difficulty and positive surgical margin: a case report.

An 83-year-old man visited our hospital because of difficulty swallowing. Gastroscopy revealed multiple ulcers and a reddish depression in the lesser curvature of the middle stomach. The initial biopsy showed regenerative atypia, so a gastroscopy was repeated every 3 months thereafter because of suspected malignancy. A biopsy performed 12 months after the initial gastroscopy revealed a well-differentiated adenocarcinoma. After determination of the planned oral resection line by two negative biopsies, laparoscopic distal gastrectomy was performed. The resected specimen showed a 0 - IIa + IIc lesion composed of well-to-moderately differentiated tubular adenocarcinoma, including hand-shaking-type gastric cancer. The oral resection margin was positive due to widespread mucosal extension; therefore, an additional total gastrectomy was needed. Cases of well-differentiated adenocarcinoma and its superficial extension may be difficult to diagnose via endoscopy and biopsy.

Superficial spreading type of early gastric cancer coexisting with multiple hyperplastic polyps.

We encountered a rare case that involved the superficial spreading type of early gastric cancer coexisting with multiple hyperplastic polyps. An 81-year-old Japanese woman with a history of Helicobacter pylori infection was diagnosed with gastric cancer (cT1bN0M0), which presented as a wide, nodular, aggregated protrusion that was associated with multiple pedunculated and sessile polyps. Distal gastrectomy was performed, and the resected specimen involved an 8 cm × 4 cm nodular aggregated protruding lesion and 15 polyps that were 2-20 mm in size. Histopathological examination revealed that the nodular aggregated protruding lesion was a mucosal adenocarcinoma and that the multiple polyps were hyperplastic. The coexistence of multiple hyperplastic polyps and mucosal adenocarcinoma with nodular aggregated protrusions suggested that the mucosal adenocarcinoma had developed from a fusion of multifocal hyperplastic lesions. This may have occurred via a hyperplasia-carcinoma sequence related to the Helicobacter pylori infection. The superficial spreading type of early gastric cancer has a potential developed from a fusion of multifocal hyperplastic polyps.

Clinicopathological characteristics of De Garengeot hernia: six case reports and literature review.

BACKGROUND: De Garengeot hernia, wherein the appendix is present within a femoral hernia, is a rare disease; therefore, the clinicopathological features remain to be clarified. This study aimed to reveal the clinicopathological characteristics of De Garengeot hernia. CASE PRESENTATION: Six patients who underwent appendectomy and herniorrhaphy between 1999 and 2018 were included. The incidence of De Garengeot hernia was 3.2% among the 182 femoral hernias that required surgery during the study period. The median age of the patients was 78 years, and five patients were women. The median body mass index was 20.1. Patients frequently had fever or elevated CRP level. Preoperative diagnoses based on computed tomography were femoral (n = 3), inguinal (n = 2), and De Garengeot (n = 1) hernias. Emergency and elective surgeries were performed in four and two patients, respectively. Histopathological examination of the resected appendix showed gangrenous appendicitis (n = 3), perforated appendicitis (n = 2), and appendiceal ischemia (n = 1) in the patients. Postoperatively, one patient developed sepsis. CONCLUSIONS: Preoperative diagnosis of De Garengeot hernia is often difficult, and patients frequently have severe appendicitis. Precise diagnosis is required, and emergency surgery should be considered depending on the severity of appendicitis.

Mucosal prolapse syndrome-like inflammatory polyp protruding from the appendiceal orifice masquerading as an appendiceal neoplasm: A rare case report.

We describe a case of a mucosal prolapse syndrome (MPS)-like inflammatory polyp protruding from the appendiceal orifice, mimicking an appendiceal neoplasm. A 48-year-old man presented with lower abdominal pain and elevated white blood cell count and C-reactive protein level. Computed tomography showed a swollen appendix with multiple small saccular lesions and periappendiceal fat stranding and small saccular lesions in the ascending colon and cecum. Ultrasonography showed a swollen appendix 25 mm in diameter with multiple saccular structures and a periappendiceal high-echoic area, suggesting appendiceal diverticulitis. Colonoscopy revealed an erythematous lesion protruding from the appendiceal orifice. An ileocecal resection was performed based on a preoperative diagnosis of appendiceal diverticulitis and tumor. Histopathological examination of the appendix showed multiple mucosal herniations with infiltration of inflammatory cells, indicating appendiceal diverticulitis. The tumor was characterized by glandular duct hyperplasia and stromal expansion with smooth muscle hyperplasia and was diagnosed as an inflammatory polyp resembling an MPS lesion. Although several studies have shown the macroscopic and endoscopic appearance of MPS-like inflammatory lesions associated with colonic diverticular disease, this case was the first to present an inflammatory polyp associated with appendiceal diverticulitis in which the lesion protruding from the appendiceal orifice was masquerading as an appendiceal neoplasm.

IgG4 plasma cell myeloma: Clinicopathological characteristics and diagnosis.

Plasma cell myeloma (PCM) is usually associated with the presence of M-protein in the serum and urine of patients, and about half of the PCM cases exhibit the IgG M-protein and increased gamma-globulin fraction on membrane electrophoresis. The IgG4 subclass is located in the beta-2 fraction on membrane electrophoresis. The aim of this study was to develop a method to evaluate IgG4-producing PCM (IgG4-PCM) and its clinicopathological characteristics. We found three cases of IgG4-PCM among 80 cases of IgG-producing PCM by membrane electrophoresis, which were confirmed by IgG4 immunostaining. None of the cases had a clinical history of IgG4-related disease, although they exhibited high levels of serum IgG4. A bone marrow aspiration specimen had an increased number of plasma cells with a relatively mature morphology. No cases exhibited lymphoplasmacytic inflammation, obliterative phlebitis or fibrosis. Immunohistochemistry revealed that tumor cells expressed CD138 and IgG4 and showed monoclonal expression of kappa. We revealed that IgG4-PCM might not be associated with IgG4-related disease and that the detection of M-protein with beta-globulin fraction by electrophoresis may be useful for screening IgG4-PCM.

Chronological Changes in Appendiceal Pathology Among Patients Who Underwent Appendectomy for Suspected Acute Appendicitis.

BACKGROUND: Given recent advances in imaging and the development of diagnostic parameters, the rate of unnecessary appendectomy (i.e., negative appendectomy) has been decreasing. However, the incidence of acute appendicitis (AA) in elderly patients is rising due to the aging of society. We aimed to identify chronological changes in demographics and appendiceal pathology among patients who underwent appendectomy for suspected AA. METHODS: Data from 881 patients who underwent appendectomy for suspected AA between January 2006 and December 2017 were analyzed. The final diagnosis was based on intraoperative findings, pathological reports, and clinical course. Negative appendectomy was defined as the absence of appendiceal diseases including inflammation, fibrosis, and neoplasm. We compared demographics and appendiceal pathology between early (2006-2011) and late study phases (2012-2017). RESULTS: The mean age of patients with pathologically proven AA (n = 761) was significantly greater in the late phase than in the early phase (38.6 ± 19.8 years vs. 44.0 ± 20.3 years, p = 0.0002), and the ratio of patients with AA aged ≧ 75 years was also increased (from 5.6 to 8.6%, p = 0.1120). The incidences of complicated appendicitis (defined as perforated or gangrenous appendicitis) and appendiceal diverticulitis (AD) were increased in the late phase compared to those in the early phase (61.3% vs. 77.2% and 3.7% vs. 6.6%, respectively). The negative appendectomy rate was significantly reduced in the late phase compared to that in the early phase (10.0% vs. 2.5%, p < 0.0001). CONCLUSIONS: During a 12-year period, the mean age of patients with AA and the incidences of complicated appendicitis and AD increased, whereas the negative appendectomy rate decreased.

Diagnosis of appendiceal diverticulitis by multidetector computed tomography.

PURPOSE: Because appendiceal diverticulitis (AD) has a high risk of perforation, precise diagnosis is important for patients with suspected acute appendicitis (AA). In this study, we aimed to reveal the characteristics of computed tomography (CT) images of AD. METHODS: CT images were comparatively analyzed in patients who underwent appendectomy and had histopathologically proved AD (n = 23) or AA (n = 365) to reveal specific findings of CT image for AD and determine sensitivity and specificity of CT for AD. RESULTS: Univariate analysis showed that maximal diameter of the appendix in AD was significantly smaller than that in AA. Multivariate analysis showed that saccular structure of the appendix wall, cecum or ascending colon diverticulum and peri-appendiceal or -cecal fluid collection were significant independent indicators of AD. Based on that saccular structure of the appendix wall which was the most important specific finding, the sensitivity and specificity of CT for AD were 48% and 99%, respectively. CONCLUSION: The saccular structure of the appendix wall, cecum or ascending colon diverticulum and peri-appendiceal or -cecal fluid collection in CT suggest AD in patients with suspected AA. The sensitivity and specificity of CT for diagnosing AD were 48% and 99%, respectively.

[Classic Hodgkin lymphoma developing early after treatment of follicular lymphoma].

There are few reports of a patient presenting with combined follicular lymphoma (FL) and classical Hodgkin lymphoma (cHL). A 37-year-old Japanese man was diagnosed with FL with generalized lymphadenopathy and treated with R-CHOP. Four months later, he presented with fever, elevated lactic acid dehydrogenase (LDH), and pancytopenia. Consequently, he was diagnosed with cHL in the bone marrow. Identical clonality of FL and cHL tumor cells suggested identical immunoglobulin heavy chain gene rearrangements. He was treated with salvage chemotherapy and high-dose chemotherapy with autologous hematopoietic stem cell transformation (HDT-ASCT), which has led to complete remission and no recurrence for more than two years after transplantation. Our case suggests that HDT-ASCT may be an effective treatment for this rare clinical condition.

Gastric lymphangioma coexisting with mucosal gastric cancer: a rare case report.

We describe a case of gastric lymphangioma coexisting with mucosal gastric cancer. A 76-year-old man was diagnosed with an advanced gastric cancer (cT2N0M0, Stage I) presenting a nodular protruded lesion with irregular central depression. The surgically resected specimen showed a 4 × 3 cm sessile protruded lesion in the anterior wall of the lower stomach. Histopathological examination revealed a mucosal adenocarcinoma was located immediately above the lymphangioma and was elevated by the cystic component of lymphangioma without admixture, which suggested that the two components arose separately. The mucosal adenocarcinoma was masquerading as an advanced gastric cancer due to the protrusion by the lymphangioma.

Macrophage-mediated complications after stem cell transplantation.

Complications after hematopoietic stem cell transplantation (HSCT) especially graft versus host disease (GVHD) are serious events and the keys to success of HSCT. Pathological diagnosis of complications is critical but sometimes not definite in GVHD diagnosis. In this review, we focus on the role of macrophages in HSCT complications. In the early period after HSCT, residual recipient macrophages have important roles for engraftment and rejection. Hemophagocytosis is the main feature of activated recipient macrophages. Skin lesions after HSCT are usually skin GVHD but mimicking histology of interface dermatitis is hardly differentiated. Macrophages and lymphocytes of these lesions were studied and increased numbers of macrophages were significantly associated with overall survival of HSCT. It could be suggested macrophages were good predictive markers for skin GVHD-like lesions. Intestinal type transplantation-associated microangiopathy (i-TAM) is an independent pathogenesis from GVHD with serious prognosis. Activated macrophages in these lesions are important and key to the pathogenesis of i-TAM. These activated macrophages are predominantly residual recipient tissue-resident macrophages. Cryptogenic organizing pneumonitis is a lung complication around day 100 after HSCT caused by activated alveolar macrophages. They are donor-derived tissue-resident macrophages. Residual recipient and donor-derived macrophages work in different ways in HSCT complications.

Mesenchymal-epithelial transition gene amplification and protein overexpression in stage IV pulmonary adenocarcinoma.

BACKGROUND: In non-small cell lung cancer (NSCLC), MET gene copy number gain, including gene amplification and chromosome 7 polysomy, is reportedly associated with patient prognosis. Although relationship between MET copy number gain and poor prognosis has been suggested in surgically resected non-small cell lung cancer, the clinical significance of MET copy number gain and protein overexpression in patients with advanced unresectable tumor is unclear. METHODS: We assessed MET copy number gain and protein expression using fluorescence in situ hybridization and immunohistochemistry in 88 patients with clinical stage IV pulmonary adenocarcinoma receiving chemotherapy, immunotherapy or palliative care. RESULTS: We found MET amplification, polysomy 7 and high MET protein expression in 10.2, 18.2 and 62.5% of 88 cases, respectively. Gene amplification and high protein expression were not significantly associated. A univariate analysis showed that MET amplification-positive patients had increased overall survival (HR 0.335, 95% CI: 0.119-0.945; P = 0.0388). Although it was not statistically significant in the multivariate analysis of the whole cohort, with the removal of patients who did not receive any treatment other than palliative care, MET amplification independently improved the overall survival (HR 0.178, 95% CI: 0.041-0.770; P = 0.0209). Chromosome 7 polysomy and high MET protein expression did not affect the overall survival. CONCLUSIONS: Although MET amplification-positive tumor is considered aggressive, our results suggest that it has a more favorable prognosis than amplification-negative cases in stage IV pulmonary adenocarcinoma with medical treatment.