Survival Rates by Histologic Subtype and Stage in Appendix Cancer

• Five-Year Overall Survival Rates:
  
  

  • Malignant Carcinoid (Neuroendocrine): ~88%
    
    

  • Goblet Cell Carcinoid: ~70%
    
    

  • Colonic-type Adenocarcinoma: ~51%
    
    

  • Mucinous Adenocarcinoma: ~59%
    
    

  • Signet Ring Cell Type: ~25%
    
    

• Median Survival for Mucinous Adenocarcinoma:
  
  

  • Disease-specific survival: 118 months
    
    

  • Overall survival: 88 months
    
    

• Trend in Survival Over Time:
  
  

  • Survival has improved for neuroendocrine tumors but not for adenocarcinoma or mucinous subtypes.
    
    

Factors That Improve Prognosis in Appendix Cancer

1. Early Stage at Diagnosis (Localized Disease)
   
   

2. Younger Age (<50 years)
   
   

3. Well-Differentiated Histology
   
   

4. Mucinous Histology (Better outcomes in localized disease than non-mucinous)
   
   

5. Complete Surgical Resection with lymph node removal (e.g., right hemicolectomy for non-mucinous adenocarcinoma)
   
   

6. Cytoreductive Surgery with HIPEC (for moderate-grade mucinous tumors)
   
   

7. Adjuvant Chemotherapy (Effective in stages I-III, particularly for non-mucinous and poorly differentiated tumors)
   
   

8. Lower CEA Levels and absence of lymphatic/distant spread
   
   

Genetic Factors in Appendix Cancer

• Inheritance:
  
  

  • Most cases are sporadic.
    
    

  • Pathogenic germline variants found in 10-12% of cases.
    
    

  • Lynch syndrome and other hereditary gastrointestinal cancer syndromes may be implicated but are not typically the drivers of tumorigenesis.
    
    

• Microsatellite Instability: Rare (<4%).
  
  

• Genetic Evaluation:
  
  

  • Genetic evaluation is recommended due to the underrecognized prevalence of germline variants, although screening for appendix cancer in hereditary cancer syndromes is not currently advised.
    
    

References

1. Mo S, Zhou Z, Ying Z, et al. Epidemiology of and Prognostic Factors for Appendiceal Carcinomas. Int J Colorectal Dis. 2019;34(11):1915-1924.
   
   

2. Palmer K, Weerasuriya S, Chandrakumaran K, et al. Goblet Cell Adenocarcinoma of the Appendix: Systematic Review and Incidence. Front Oncol. 2022;12:915028.
   
   

3. McClelland PH, Gregory SN, Nah SK, et al. Survival in Mucinous Adenocarcinoma of the Appendix. Ann Surg Oncol. 2024;31(9):6237-6251.
   
   

4. Wang D, Ge H, Lu Y, Gong X. Incidence and Survival Trends in Appendiceal Tumors. PLoS One. 2023;18(11):e0294153.
   
   

5. Aloysius M, Nikumbh T, Singh A, et al. Survival in Non-Mucinous Appendiceal Adenocarcinomas. Surgery. 2023;174(4):759-765.
   
   

6. Liu T, Mi J, Wang Y, et al. Survival Prediction Risk Model for Appendiceal Cancer. Front Med. 2022;9:1022595.
   
   

7. Asare EA, Compton CC, Hanna NN, et al. Efficacy of Chemotherapy in Appendix Adenocarcinomas. Cancer. 2016;122(2):213-221.
   
   

8. Halfter K, Schubert-Fritschle G, Klauschen F, et al. Trends in Appendix Tumors and Prognosis. Colorectal Dis. 2023;25(5):943-953.
   
   

9. Xie X, Zhou Z, Song Y, et al. Prognostic Prediction of Adenocarcinoma of Appendix. Sci Rep. 2016;6:39027.
   
   

10. Foote MB, Walch H, Kemel Y, et al. Impact of Germline Alterations in Appendiceal Adenocarcinoma. Clin Cancer Res. 2023;29(14):2631-2637.
    
    

11. Holowatyj AN, Washington MK, Tavtigian SV, et al. Inherited Cancer Susceptibility in Appendix Cancer. JAMA Oncol. 2022;2798729.

Natural and Conservative Methods for Smoking Cessation

(Evidence-Based Summary with Studies)

Overview

Natural or conservative methods for smoking cessation involve nonpharmacological, behavioral, and psychosocial interventions. These are strongly supported by clinical evidence and are often first-line or adjunctive strategies, especially for those unwilling or unable to use pharmacotherapy.

Key Interventions and Effectiveness

1. Brief Advice from Healthcare Providers

• Effectiveness: Even advice under 1 minute during routine encounters increases quit rates.
  
  

• Recommendation: Provide at every clinical visit.
  
  

• Study: Selby & Zawertailo (2022) showed brief clinician advice significantly improves quit attempts and long-term abstinence 【Selby & Zawertailo, Canadian Journal of Psychiatry, 2022】.
  
  

2. Intensive Interventions (Counseling/CBT/ACT)

• Approaches: Individual or group counseling, CBT, Acceptance and Commitment Therapy (ACT).
  
  

• Effectiveness: Greater session frequency and duration → higher quit success.
  
  

• Study: Krist et al. (2021, JAMA) confirmed behavioral counseling improves 6- and 12-month abstinence, with group or individual formats both effective 【Krist et al., JAMA, 2021】.
  
  

3. Behavioral Skills Training

• Techniques:
  
  

  • Self-monitoring of triggers
    
    

  • Behavioral rehearsal (practice quits)
    
    

  • Assertiveness to resist social cues
    
    

  • Stress management (mindfulness, yoga)
    
    

  • Environmental modifications (smoke-free home, substitute activities)
    
    

• Study: Rigotti et al. (2022, Annals of Internal Medicine) found behavioral training improved abstinence, especially when combined with structured programs 【Rigotti et al., 2022】.
  
  

4. Motivational Interviewing (MI)

• Goal: Enhance motivation/readiness, esp. for ambivalent smokers.
  
  

• Effectiveness: Mixed—some trials show modest benefit, others no added effect.
  
  

• Study: Barua et al. (2018, Journal of Thoracic Disease) systematic review showed MI improved quit attempts but was not consistently superior to counseling 【Barua et al., 2018】.
  
  

5. Social Support

• Formats: Group sessions, peer support, family involvement.
  
  

• Effectiveness: As effective as individual counseling; shared accountability enhances adherence.
  
  

• Study: Selby & Zawertailo (2022) found group-based support increased quit rates and satisfaction 【Selby & Zawertailo, 2022】.
  
  

6. Technology-Based Interventions

• Examples: Automated text programs, quitlines, web-based tools, mobile apps.
  
  

• Effectiveness: Moderate-certainty evidence for improved abstinence; text messaging particularly effective.
  
  

• Study: Rigotti et al. (2022, Annals of Internal Medicine) showed quitlines and text support improved 6-month abstinence; apps had weaker evidence 【Rigotti et al., 2022】.
  
  

7. Financial Incentives (Contingency Management)

• Effectiveness: Increase quit success while incentives are active, but high relapse post-withdrawal.
  
  

• Study: Barua et al. (2018) found incentive-based interventions doubled abstinence rates short-term but relapse common without ongoing rewards 【Barua et al., 2018】.
  
  

8. Ineffective/Unsupported Approaches

• Hypnosis and acupuncture: Insufficient evidence, not recommended.
  
  

• Study: Rigotti et al. (2022) concluded no consistent benefit from these modalities 【Rigotti et al., 2022】.
  
  

Conclusion

The strongest evidence supports:
✅ Brief clinician advice
✅ Counseling (individual/group, CBT, ACT)
✅ Behavioral skills training & environmental modifications
✅ Social support
✅ Technology-based interventions (text, quitlines, web tools)
✅ Financial incentives (short-term effectiveness)

Effectiveness is dose-dependent: more intensive, longer-duration engagement → higher abstinence rates.

References

1. Selby P, Zawertailo L. Behavioral Interventions for Tobacco Cessation. Can J Psychiatry. 2022.
   
   

2. Krist AH, Davidson KW, Mangione CM, et al. Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation. JAMA. 2021;325(3):265–279.
   
   

3. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC Expert Consensus on Tobacco Cessation Treatment. J Thorac Dis. 2018;10(Suppl 9):S1138-S1173.
   
   

4. Rigotti NA, Chang Y, Regan S, et al. Comparative Effectiveness of Smoking Cessation Interventions. Ann Intern Med. 2022;175(4):472–482.

Secondhand Smoke (SHS), Thirdhand Smoke (THS), and Health Risks

Evidence-Based Summary with Studies

1. Causal Link Between SHS and Lung Cancer

• SHS = known human carcinogen (American College of Chest Physicians).
  
  

• Living with a smoker ↑ lung cancer risk 20–30%.
  
  

• Causes thousands of lung cancer deaths annually.
  
  

• Elevated risk for small cell lung cancer (OR > 3.0); also for adenocarcinoma and squamous carcinoma.
  
  

• Dose-response: higher exposure → greater risk.
  
  

• Childhood/household exposure especially harmful.
  
  

Key Studies:

1. Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of Lung Cancer: ACCP Guidelines. Chest. 2013;143(5 Suppl):e1S-e29S. doi:10.1378/chest.12-2345.
   👉 https://doi.org/10.1378/chest.12-2345
   
   

2. Elkefi S, Zeinoun G, Tounsi A, et al. Second-Hand Smoke Exposure and Risk of Lung Cancer Among Nonsmokers in the US. Int J Environ Res Public Health. 2025;22(4):595. doi:10.3390/ijerph22040595.
   👉 https://doi.org/10.3390/ijerph22040595
   
   

3. Possenti I, Romelli M, Carreras G, et al. SHS Exposure and Lung Cancer Risk in Never-Smokers. Eur Respir Rev. 2024;33(174):240077. doi:10.1183/16000617.0077-2024.
   👉 https://doi.org/10.1183/16000617.0077-2024
   
   

4. Hackshaw AK, Law MR, Wald NJ. Accumulated Evidence on Lung Cancer & ETS. BMJ. 1997;315(7114):980-8. doi:10.1136/bmj.315.7114.980.
   👉 https://doi.org/10.1136/bmj.315.7114.980
   
   

5. Kim CH, Lee YC, Hung RJ, et al. Exposure to SHS and Lung Cancer by Histology. Int J Cancer. 2014;135(8):1918-30. doi:10.1002/ijc.28835.
   👉 https://doi.org/10.1002/ijc.28835
   
   

6. Štěpánek L, Ševčíková J, Horáková D, et al. Public Health Burden of SHS. Int J Environ Res Public Health. 2022;19(20):13152. doi:10.3390/ijerph192013152.
   👉 https://doi.org/10.3390/ijerph192013152
   
   

2. Other Health Effects of SHS

• Respiratory: COPD, chronic cough, asthma in children, lower respiratory infections.
  
  

• Cardiovascular: Coronary heart disease, stroke.
  
  

• ENT: Otitis media in children.
  
  

• Mechanisms: DNA adduct formation, oxidative stress, chronic inflammation.
  
  

Key Studies:
7. Tarlo SM, Altman KW, Oppenheimer J, et al. Occupational & Environmental Contributions to Chronic Cough. Chest. 2016;150(4):894-907. doi:10.1016/j.chest.2016.07.029.
👉 https://doi.org/10.1016/j.chest.2016.07.029

8. Tsai J, Homa DM, Gentzke AS, et al. SHS Among Nonsmokers – US 1988-2014. MMWR. 2018;67(48):1342-1346. doi:10.15585/mmwr.mm6748a3.
   👉 https://doi.org/10.15585/mmwr.mm6748a3
   
   

9. Agraval H, Yadav UCS. Molecular Mechanisms of Passive Smoking-Induced Respiratory Diseases. Respir Med. 2025;108279. doi:10.1016/j.rmed.2025.108279.
   👉 https://doi.org/10.1016/j.rmed.2025.108279
   
   

10. Homa DM, Neff LJ, King BA, et al. Disparities in SHS Exposure – US 1999-2012. MMWR. 2015;64(4):103-8.
    👉 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6404a7.htm
    
    

11. Brody DJ, Faust E, Tsai J. SHS Exposure Among Adults – US 2015-2018. NCHS Data Brief. 2021;(369):1-8.
    👉 https://www.cdc.gov/nchs/products/databriefs/db369.htm
    
    

3. Thirdhand Smoke (THS) and “Scent of Smoke”

• Odor alone = not a proven health risk if no particulate/gas exposure.
  
  

• THS defined: toxins deposited on surfaces/dust, later re-emitted or absorbed.
  
  

• Risks: Potentially carcinogenic; children most vulnerable (inhalation, dermal, ingestion).
  
  

• Consensus: Only measurable exposure = health risk; odor detection ≠ exposure.
  
  

Key Studies:
12. Wang SQ, Bao LJ, Li TY, Zeng EY. Health Risk of Nitrosamines in SHS/THS. J Hazard Mater. 2024;480:136446. doi:10.1016/j.jhazmat.2024.136446.
👉 https://doi.org/10.1016/j.jhazmat.2024.136446

13. Martins-Green M, Adhami N, Frankos M, et al. Cigarette Smoke Toxins on Surfaces & Health. PLoS One. 2014;9(1):e86391. doi:10.1371/journal.pone.0086391.
    👉 https://doi.org/10.1371/journal.pone.0086391
    
    

📌 Conclusion

• SHS = established cause of lung cancer, cardiovascular disease, COPD, asthma, and infections.
  
  

• Risk increases with intensity/duration of exposure.
  
  

• Children and domestic partners of smokers face the highest risk.
  
  

• THS = emerging concern, especially for children, but odor alone without measurable exposure is not proven harmful.

Top 30 Injections Reference

Summary – Injection Site Selection & Drug Properties

• Hydrophilic (water-soluble) drugs → prefer highly vascular or moderate-flow areas (deltoid, thigh, abdomen) for rapid or steady absorption.
  
  

• Lipophilic/depot (oil-based) drugs → require large, deep muscles (ventrogluteal, dorsogluteal) for slow, sustained release.
  
  

• SubQ fat → low vascularity → ideal for stable, prolonged absorption (insulin, GLP-1 agonists, anticoagulants).
  
  

• Deltoid → fastest IM absorption, good for small-volume hydrophilic injections (vaccines).
  
  

• Ventrogluteal → safest large-muscle IM, excellent for depot injections.
  
  

• Dorsogluteal → depot-capable but higher nerve/vessel risk.
  
  

• Vastus lateralis → reliable absorption, especially in infants/children.
  
  

Deltoid (upper arm – IM, ≤1 mL)

1. Influenza vaccine – 0.5 mL (15 µg antigen/strain) → Neutralizing antibodies → prevents viral entry
   
   

2. COVID-19 vaccines – 0.3 mL Pfizer (30 µg mRNA); 0.5 mL Moderna (50 µg) → Spike protein defense
   
   

3. Tdap/Td – 0.5 mL → Antibodies + memory cells → toxin protection
   
   

4. Hepatitis B vaccine – 1 mL adult (20 µg); 0.5 mL child (10 µg) → Prevents viral attachment
   
   

5. HPV vaccine – 0.5 mL (9-valent, 20–40 µg L1/strain) → Blocks HPV infection
   
   

6. Pneumococcal vaccine – 0.5 mL (25 µg polysaccharide/serotype) → Opsonizing antibodies
   
   

7. Shingles (Shingrix) – 0.5 mL (50 µg gE + adjuvant) → T-cell immunity
   
   

8. MMR (IM booster) – 0.5 mL (≥1,000 TCID50 live virus) → Adaptive immunity
   
   

9. Vitamin B12 – 1,000 mcg/mL; inject 1 mL → DNA synthesis, RBC maturation
   
   

Ventrogluteal (hip – IM, ≤3 mL)

10. Ceftriaxone – 250–1,000 mg (350 mg/mL; 1–3 mL) → Cell wall inhibition
    
    

11. Penicillin G benzathine – 1.2–2.4 M units (600,000 U/mL; 2–4 mL) → Long-acting bactericidal
    
    

12. Haloperidol decanoate – 50–200 mg (100 mg/mL; 0.5–2 mL) → Dopamine blockade
    
    

13. Medroxyprogesterone (Depo-Provera) – 150 mg (150 mg/mL; 1 mL) → Ovulation suppression
    
    

14. Iron dextran – 100 mg (50 mg/mL; 2 mL) → Restores hemoglobin synthesis
    
    

15. Hydroxocobalamin – 1,000 mcg (1,000 mcg/mL; 1 mL) → Myelin & methylation support
    
    

Dorsogluteal (buttock – IM, ≤3 mL)

16. Testosterone cypionate – 50–200 mg (200 mg/mL; 0.25–1 mL) → Androgen receptor agonist
    
    

17. Risperidone LAI – 25–50 mg (12.5–25 mg/mL; 1–2 mL) → Dopamine/serotonin blockade
    
    

18. Paliperidone palmitate – 39–234 mg (39 mg/0.25 mL to 234 mg/1.5 mL) → Antipsychotic effect
    
    

Vastus Lateralis (outer thigh – IM, ≤2 mL adults)

19. Pediatric vaccines – 0.5 mL → Adaptive immunity
    
    

20. Epinephrine autoinjector – 0.3 mg adult / 0.15 mg child (1 mg/mL) → ↑ BP, bronchodilation
    
    

21. Naloxone IM – 0.4–2 mg (0.4 mg/mL; 1–5 mL) → Opioid reversal
    
    

Subcutaneous (≤1 mL)

22. Insulin – U-100 (100 units/mL; 0.1–1 mL, 10–100 units) → ↑ Glucose uptake
    
    

23. GLP-1 agonists – Semaglutide 0.25–2.0 mg (1.34 mg/mL; 0.19–1.5 mL); Liraglutide 1.2–1.8 mg (6 mg/mL; 0.2–0.3 mL) → Stimulate insulin
    
    

24. Heparin – 5,000 units (1,000 U/mL; 1 mL) → Antithrombin activation
    
    

25. Enoxaparin (Lovenox) – 40 mg (100 mg/mL; 0.4 mL) or 1 mg/kg (0.6–1 mL) → Factor Xa inhibition
    
    

26. Dalteparin – 2,500–5,000 units (2,500 U/mL; 1–2 mL); Fondaparinux 2.5 mg (2.5 mg/0.5 mL) → Antithrombin potentiation
    
    

27. Allergy immunotherapy – 0.05–0.5 mL (diluted vials) → Immune tolerance
    
    

28. Varicella vaccine – 0.5 mL (≥1,350 PFU live virus) → Protective antibodies
    
    

29. MMR vaccine (SubQ) – 0.5 mL (≥1,000 TCID50 live virus) → Adaptive immunity
    
    

30. Zoster vaccine live (Zostavax) – 0.65 mL (≥19,400 PFU VZV) → T-cell immunity