1. Home
  2. adenocarcinoma

adenocarcinoma

Gastric Cancer: A Review

Author/s: 
Anuj Kishor Patel, Nilay S. Sethi

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.

Keywords 
oncology Gastroenterology Stomach Neoplasms adenocarcinoma Helicobacter Infections abdominal pain

Thyroid Cancer: A Review

Author/s: 
Laura Boucai, Mark Zafereo, Maria E Cabanillas

Importance: Approximately 43 720 new cases of thyroid carcinoma are expected to be diagnosed in 2023 in the US. Five-year relative survival is approximately 98.5%. This review summarizes current evidence regarding pathophysiology, diagnosis, and management of early-stage and advanced thyroid cancer.

Observations: Papillary thyroid cancer accounts for approximately 84% of all thyroid cancers. Papillary, follicular (≈4%), and oncocytic (≈2%) forms arise from thyroid follicular cells and are termed well-differentiated thyroid cancer. Aggressive forms of follicular cell-derived thyroid cancer are poorly differentiated thyroid cancer (≈5%) and anaplastic thyroid cancer (≈1%). Medullary thyroid cancer (≈4%) arises from parafollicular C cells. Most cases of well-differentiated thyroid cancer are asymptomatic and detected during physical examination or incidentally found on diagnostic imaging studies. For microcarcinomas (≤1 cm), observation without surgical resection can be considered. For tumors larger than 1 cm with or without lymph node metastases, surgery with or without radioactive iodine is curative in most cases. Surgical resection is the preferred approach for patients with recurrent locoregional disease. For metastatic disease, surgical resection or stereotactic body irradiation is favored over systemic therapy (eg, lenvatinib, dabrafenib). Antiangiogenic multikinase inhibitors (eg, sorafenib, lenvatinib, cabozantinib) are approved for thyroid cancer that does not respond to radioactive iodine, with response rates 12% to 65%. Targeted therapies such as dabrafenib and selpercatinib are directed to genetic mutations (BRAF, RET, NTRK, MEK) that give rise to thyroid cancer and are used in patients with advanced thyroid carcinoma.

Conclusions: Approximately 44 000 new cases of thyroid cancer are diagnosed each year in the US, with a 5-year relative survival of 98.5%. Surgery is curative in most cases of well-differentiated thyroid cancer. Radioactive iodine treatment after surgery improves overall survival in patients at high risk of recurrence. Antiangiogenic multikinase inhibitors and targeted therapies to genetic mutations that give rise to thyroid cancer are increasingly used in the treatment of metastatic disease.

Keywords 
Endocrinology oncology Otolaryngology surgery Surgical Oncology Thyroid Disorders diabetes Endocrine Cancer Targeted and Immune Therapy

Screening for Pancreatic Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Author/s: 
Henrikson, Nora B., Bowles, Erin J. Aiello, Blasi, Paula R., Morrison, Caitlin C., Nguyen, Matt, Pillarisetty, Venu G., Lin, Jennifer S.

Objective: We conducted a systematic evidence review to support the U.S. Preventive Services Task Force (USPSTF) in updating their recommendation on screening for pancreatic cancer. Our review addresses the following Key Questions (KQs):
1. Does screening for pancreatic adenocarcinoma improve cancer morbidity or mortality or all-cause mortality; and 1a) Does screening effectiveness vary by clinically relevant subpopulations (e.g., by age group, family history of pancreatic cancer, personal history of new-onset diabetes, or other risk factors)?
2. What is the diagnostic accuracy of screening tests for pancreatic adenocarcinoma?
3. What are the harms of screening for pancreatic adenocarcinoma?
4. Does treatment of screen-detected or asymptomatic pancreatic adenocarcinoma improve cancer mortality, all-cause mortality, or quality of life?
5. What are the harms of treatment of screen-detected pancreatic adenocarcinoma?
Data Sources: We searched Cochrane Central Register of Controlled Trials, Medline, and PubMed, and reference lists of relevant systematic reviews. We searched for articles published from 2002 to October 3, 2017, and updated our search on April 27, 2018. We also searched ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP), for relevant ongoing studies.
Study Selection: We reviewed 19,596 abstracts and 824 articles against specified inclusion criteria. Eligible studies included those written in English and conducted in adults age 18 years or older with or without risk factors for pancreatic cancer. For key questions on screening, we included imaging-based screening protocols. For key questions on treatment, we included studies of adults with screen-detected or asymptomatic pancreatic adenocarcinoma.

Data Analysis: We conducted dual, independent critical appraisal of all provisionally included studies and abstracted study details and results from fair- and good-quality studies. Because of the limited number of studies and the population heterogeneity, we provided a narrative synthesis of results and used summary tables to allow for comparisons across studies. After confirming that the yield of different imaging modalities was similar across studies, we calculated a pooled diagnostic yield across studies and produced forest plots to illustrate the range of effects seen across studies. For harms of screening (KQ3) and harms of treatment (KQ5), we stratified results by procedural and psychosocial harms.
Results: We included 13 unique prospective cohort screening studies (24 articles) reporting results for 1,317 people. Studies were conducted in the U.S., Canada, and Europe, and all screening populations except one small comparison group were exclusively in persons at elevated familial or genetic risk for pancreatic cancer. No studies reported on the effect of screening for pancreatic adenocarcinoma on cancer morbidity, mortality, or all-cause mortality (KQ1); and no studies reported on the effectiveness of treatment for screen-detected pancreatic adenocarcinoma (KQ4).

Thirteen fair quality studies reported on the diagnostic accuracy of screening tests for pancreatic adenocarcinoma (KQ2). Across these studies, 18 cases of pancreatic adenocarcinoma were detected.. Twelve of 18 cases (66.7%) were detected at stage I or II or classified as “resectable.” Pooled yield for all screening tests to detect pancreatic adenocarcinoma on initial screening in high-risk populations was 7.8 per 1000 (95% confidence interval, 3.6 to 14.7); and for total yield including both initial and repeat screening, it was 15.6 per 1000 (95% CI, 9.3 to 24.5).

Harms of screening for pancreatic adenocarcinoma
Procedural harms of screening were evaluated in eight screening studies (n=675); psychological harms were assessed in two studies (n=277). Details on the assessment of harms were variably reported. In two studies (n=277) in which 150 individuals received ERCP as a diagnostic followup test, 15 people (10%) reported acute pancreatitis, nine of which required hospitalization. No evidence of increased worry, distress, depression, or anxiety after screening was reported, compared to before screening.

Harms of treatment of screen-detected pancreatic adenocarcinoma
Of the 57 people who underwent surgery across all studies, six studies (n=32 people receiving surgery) assessed harms of treatment of screen-detected pancreatic adenocarcinoma (KQ5), with 7 harms detected in two studies. Methods of assessing harms were variably reported. Harms included one person experiencing stricture to the hepaticojejunal anastomosis at 11 months after surgery, one with unspecified post-operative complications, 2 with post-operative fistula and 3 cases of diabetes. In the two studies that systematically assessed harms in all surgical patients (n=12 people receiving surgery), no harms were reported.

Limitations: No randomized trials of screening were identified. The body of evidence includes observational screening studies with limited sample sizes and focused on populations with known familial risk, many with a substantial proportion of people with known genetic mutations. No studies included a clinical followup or unscreened comparison group, limiting assessment of diagnostic accuracy. Of those studies that reported harms of screening or treatment, limitations included inadequate description of the methods of assessing harms, including whether all participants were systematically assessed.

Conclusions: Imaging-based screening in groups at high familial risk can detect pancreatic adenocarcinoma with limited evidence of minimal harms. However, the clinical impact of screening is not well documented. There is insufficient evidence to assess benefits or harms of surgical intervention for screen-detected pancreatic adenocarcinoma.

Keywords 
pancreatic cancer obesity risk factors patient care
Subscribe to adenocarcinoma