Progress and current perspectives of diagnosis and treatment of hepatoid adenocarcinoma of the stomach

Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Endoscopic techniques for diagnosis and treatment of gastroentero-pancreatic neuroendocrine neoplasms:Where we are

BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-enteropancreatic neuroendocrine neoplasms(GEP-NENs).AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 15 years,using both medical subject heading(MeSH)terms and free-language keywords:gastro-enteropancreatic neuroendocrine neoplasms;endoscopy;ultrasound endoscopy;capsule endoscopy;double-balloon enteroscopy;diagnosis;therapy;staging.RESULTS In the diagnostic setting,endoscopic ultrasonography(EUS)represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric,duodenal and rectal NENs.The diagnosis of small bowel NENs(sbNENs)has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy,which allow for direct visualization of the entire small bowel;however,data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive.From a therapeutic point of view,endoscopic removal is the treatment of choice for the majority of gastric NENs(type 1/2),for well-differentiated localized nonmetastatic duodenal NENs<1 cm,confined to the submucosa layer and for<10 mm,stage T1–T2,rectal NENs.EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs.Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.

A modified method for locating parapharyngeal space neoplasms on magnetic resonance images: implications for differential diagnosis

The parapharyngeal space(PPS) is an inverted pyramid-shaped deep space in the head and neck region, and a variety of tumors, such as salivary gland tumors, neurogenic tumors, nasopharyngeal carcinomas with parapharyngeal invasion, and lymphomas, can be found in this space. The differential diagnosis of PPS tumors remains challenging for radiologists. This study aimed to develop and test a modified method for locating PPS tumors on magnetic resonance(MR) images to improve preoperative differential diagnosis. The new protocol divided the PPS into three compartments: a prestyloid compartment, the carotid sheath, and the areas outside the carotid sheath. PPS tumors were located in these compartments according to the displacements of the tensor veli palatini muscle and the styloid process, with or without blood vessel separations and medial pterygoid invasion. This protocol, as well as a more conventional protocol that is based on displacements of the internal carotid artery(ICA), was used to assess MR images captured from a series of 58 PPS tumors. The consequent distributions of PPS tumor locations determined by both methods were compared. Of all 58 tumors, our new method determined that 57 could be assigned to precise PPS compartments. Nearly all(13/14; 93%) tumors that were located in the pre-styloid compartment were salivary gland tumors. All 15 tumors within the carotid sheath were neurogenic tumors. The vast majority(18/20; 90%) of trans-spatial lesions were malignancies. However, according to the ICA-based method, 28 tumors were located in the pre-styloid compartment, and 24 were located in the post-styloid compartment, leaving 6 tumors that were difficult to locate. Lesions located in both the pre-styloid and the post-styloid compartments comprised various types of tumors. Compared with the conventional ICA-based method, our new method can help radiologists to narrow the differential diagnosis of PPS tumors to specific compartments.

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.

Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract

Mixed neuroendocrine non-neuroendocrine neoplasms(MiNENs)are a hetero-geneous group of malignant neoplasms that can settle in the gastroenteropan-creatic tract.They are composed of a neuroendocrine(NE)and a non-NE compo-nent in at least 30%of each tumour.The non-NE component can include different histological combinations of glandular,squamous,mucinous and sarcomatoid phenotypes,and one or both of the components can be low-or high grade malignant.Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion,and the lack of specific clinical trials is the main reason why their management is difficult.The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data.It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that,due to their low incidence,will require long recruitment periods.

Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer

The Agatsuma et al’s study shows that despite the evidence of the benefits of an early colorectal cancer(CRC)diagnosis,through screening in asymptomatic subjects,up to 50%of candidates reject this option and many of those affected are diagnosed later,in advanced stages.The efficacy of screening programs has been well-established for several years,which reduces the risk of CRC morbidity and mortality,without taking into account the test used for screening,or other tools.Nevertheless,a significant proportion of patients remain unscreened,so understanding the factors involved,as well as the barriers of the population to adherence is the first step to possibly modify the participation rate.These barriers could include a full range of social and political aspects,especially the type of financial provision of each health service.In Japan,health services are universal,and this advantageous situation makes it easier for citizens to access to these services,contributing to the detection of various diseases,including CRC.Interestingly,the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities,and symptomatic and cancer screening groups showed similar early-stage diagnosis.

Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

AIM To reveal better diagnostic markers for differentiating neuroendocrine tumor(NET) from solid-pseudopapillary neoplasm(SPN), focusing primarily on immunohistochemical analysis.METHODS We reviewed 30 pancreatic surgical specimens of NET(24 cases) and SPN(6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pancytokeratin, E-cadherin, progesterone receptor,vimentin, α-1-antitrypsin, CD10, and β-catenin.RESULTS E-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.CONCLUSION E-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Pathological differential diagnosis of solid-pseudopapillary neoplasm and endocrine tumors of the pancreas

AIM:To investigate differential points of solid-pseudo-papillary neoplasm (SPN) of the pancreas and pancre-atic endocrine tumor (PET).METHODS:Ten cases of SPN and fourteen cases of PET were studied in this retrospective study. Clinical and pathologic features,immunostaining reactions and β-catenin gene mutations were analyzed.RESULTS:The mean age of SPN patients was 25.6 years and these patients had no specific symptoms. The mean diameter of the tumors was 11.0 cm,9/10 cases were cystic or a mixture of solid and cystic structures,and there was hemorrhage and necrosis on the cut surface in 8/10 (80%) cases. Characteristic pseudo-papillary structure and discohesive appearance of the neoplastic cells were observed in all 10 (100%) cases. The results of immunostaining showed that nuclear expression of β-catenin and loss of E-cadherin in all the cases,was only seen in SPN. Molecular studies discov-ered that 9/10 (90%) cases harbored a point mutation of exon 3 in β-catenin gene. On the other hand,the mean age of PET patients was 43.1 years. Eight of 14 cases presented with symptoms caused by hypoglyce-mia,and the other 6 cases presented with symptoms similar to those of SPN. The mean size of the tumors was 2.9 cm,most of the tumors were solid,only 3/14 (21%) were a mixture of solid and cystic structures,and macroscopic hemorrhage and necrosis were much less common (3/14,21%). Histologically,tumor cells were arranged in trabecular,acinar or solid patterns and demonstrated no pseudopapillary structure and discohesive appearance in all 14 (100%) cases. The results of immunostaining and mutation detection were completely different with SPN that membrane and cytoplastic expression of β-catenin without loss of E-cadherin,as well as no mutation in β-catenin gene in all the cases. CONCLUSION:Both macroscopic and microscopic features of SPN are quite characteristic. It is not difficult to distinguish it from PET. If necessary,immunos-taining of β-catenin and E-cadherin is quite helpful to make the differential diagnosis.

Plexiform fibromyxoma:Review of rare mesenchymal gastric neoplasm and its differential diagnosis

Plexiform fibromyxoma(PF)is a very rare mesenchymal neoplasm of the stomach that was first described in 2007 and was officially recognized as a subtype of gastric mesenchymal neoplasm by World Health Organization(WHO)in 2010.Histologically,PF is characterized by a plexiform growth of bland spindle to ovoid cells embedded in a myxoid stroma that is rich in small vessels.The lesion is usually paucicellular.While mucosal and vascular invasion have been documented,no metastasis or malignant transformation has been reported.Its pathogenesis is largely unknown and defining molecular alterations are not currently available.There are other mesenchymal tumors arising in the gastrointestinal tract that need to be differentiated from PF given their differing biologic behaviors and malignant potential.Histologic mimics with spindle cells include gastrointestinal stromal tumor,smooth muscle tumor,and nerve sheath tumor.Histologic mimics with myxoid stroma include myxoma and aggressive angiomyxoma.Molecular alterations that have been described in a subset of PF may be seen in gastroblastoma and malignant epithelioid tumor with gliomaassociated oncogene homologue 1(GLI1)rearrangement.The recent increase in publications on PF reflects growing recognition of this entity with expansion of clinical and pathologic findings in these cases.Herein we provide a review of PF in comparison to other mesenchymal tumors with histologic and molecular resemblance to raise the awareness of this enigmatic neoplasm.Also,we highlight the challenges pathologists face when the sample is small,or such rare entity is encountered intraoperatively.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge

Diagnosing early-stage pancreatic cancer(PC)remains a clinical challenge.Hence,studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative.This article aims to un-derscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC,thereby improving its management and prognosis.

Underwater endoscopic mucosal resection for neoplasms in the pyloric ring of the stomach: Four case reports

BACKGROUND Tumors located in the pylorus are technically more complex to resect by endoscopic resection,as the anatomical characteristics of this region can affect the adequate assessment of margins and performance of the procedure.We reported the results of underwater endoscopic mucosal resection(UEMR)of benign mucosal neoplasms located in the pyloric ring.CASE SUMMARY This case series describes 4 patients with 4 mucosal neoplasms located in the pyloric ring.The diameter of each neoplasm was less than 15 mm.We performed UEMR for the lesions.Water immersion enabled slight floating of the lesions,resulting in easy identification.We achieved en bloc resection with a snare and electrosurgical unit.All procedure were performed within 3 min without adverse events.Pathologic examination showed low-grade dysplasia with clear resection margins in one case and hyperplastic polyps in three cases.CONCLUSION UEMR can be an effective and safe treatment method for neoplasms in the gastric pyloric ring.

Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography

BACKGROUND Solid pseudopapillary neoplasms of the pancreas(SPN)share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes(PDAC with cystic changes),which may result in unnecessary surgery.AIM To investigate the value of computed tomography(CT)in differentiation of SPN from PDAC with cystic changes.METHODS This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes,confirmed through pathological diagnosis.Quantitative and qualitative analysis was performed,including assessment of age,sex,tumor size,shape,margin,density,enhancement pattern,CT values of tumors,CT contrast enhancement ratios,“floating cloud sign,”calcification,main pancreatic duct dilatation,pancreatic atrophy,and peripancreatic invasion or distal metastasis.Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes,and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination.RESULTS When compared to PDAC with cystic changes,SPN had a lower age(32 years vs 64 years,P<0.05)and a slightly larger size(5.41 cm vs 3.90 cm,P<0.05).SPN had a higher frequency of“floating cloud sign”and peripancreatic invasion or distal metastasis than PDAC with cystic changes(both P<0.05).No significant difference was found with respect to sex,tumor location,shape,margin,density,main pancreatic duct dilatation,calcification,pancreatic atrophy,enhancement pattern,CT values of tumors,or CT contrast enhancement ratios between the two groups(all P>0.05).The area under the receiver operating characteristic curve of the combination was 0.833(95%confidence interval:0.708-0.957)with 78.6%sensitivity,81.3%specificity,and 80.4%accuracy in differentiation of SPN from PDAC with cystic changes.CONCLUSION A larger tumor size,“floating cloud sign,”and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)

Breast cancer is the most common cancer among women worldwide.It has been estimated that about 416000 new cases and over 117000 deaths of breast cancer occurred in China in 2020.Among the new cases of breast cancer diagnosed each year,3-10%have distant metastasis at the time of initial diagnosis.In addition,approxi-mately 30%of patients with early-stage breast cancer may eventually experience recurrence or metastases.The 5-year survival rate of patients with advanced breast cancer is only 20%with a median overall survival of 2-3 years.Although advanced breast cancer remains incurable at present,new therapeutic options and multidisci-plinary treatment could be utilized to alleviate symptoms,improve quality of life,and prolong patients’survival.The choice of treatment regimens for patients with advanced breast cancer is very important,and the optimal treatment strategy beyond the first-and second-line therapy is often lacking.Herein,the China Advanced Breast Cancer Guideline Panel discussed and summarized recent clinical evidence,updated the guidelines for the diag-nosis and treatment of advanced breast cancer based on the 2020 edition,and formulated the“Guidelines for diagnosis and treatment of advanced breast cancer in China(2022 edition)”for clinicians’reference.

DIAGNOSIS AND SURGICAL TREATMENT OF 103 PATIENTS WITH EARLY ESOPHAGEAL CANCER AND CARDIAC CANCER OF STOMACH

Screening of the general population for esophageal cancer and gastric cardia cancer using an occult blood bead detector supplemented by fiberogastroscopy was able to detect 103 cases with early esophageal cancer and gastric cardia cancer at Yangzhong County where the incidence was high from Apr. 1986 to Feb. 1992. Among them, there were 47 cancers of esophagus and 56 cancers of gastric cardia through pathological verification.. They took 17.1% (103/604) of the correspouding esophageal and gastric cardia caucers. We thought that about 90% of early esophageal and gastric cardia cancers have symptoms. We should couduct screening for high risk group in the area where the incidence is high at regular intervals. Besides, it is also important to strengthen propaganda for cancer prevention and self-protection for population, to emphasize the diagnosis and recognition of early cancer for medical workers.

Research Progress of TCM Tongue Diagnosis in Spleen and Stomach Disease

According to the theory of traditional Chinese medicine,the tongue is thought to be an outer manifestation of the status of the viscera.It can be divided to spleen-stomach area,liver-gall area,kidney area,and heart-lung area.The tongue coating is formed by stomach-Qi.the tongue,especially spleen-stomach area,and the tongue coating may reflect the status of the spleen and stomach.This article summarizes the research overview of TCM tongue diagnosis in spleen and stomach disease.

Some recent works on diagnosis and treatment of gastric cancer

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