​Kembara Xtra - Medicine -Pancreatic Cancer

​Kembara Xtra - Medicine -Pancreatic Cancer 
The fourth most frequent type of cancer-related death in the US is exocrine pancreatic adenocarcinoma, which accounts for 90% of pancreatic cancer cases.
Rarely curable: the lowest 5-year relative survival rate of all malignancies, 10.8% overall
60% of cases affect the head, 20% the body and tail, and 20% the gland diffusely.
Only 11% of diagnoses are localized. Surgical resection has a 5-year survival rate of about 41.6% for localized, small cancers (2 cm) without lymph node metastases and without extension beyond the capsule. The majority of tumors have metastasized at diagnosis and are therefore largely incurable and have a 5-year survival rate of 3%. Ampullary, duodenal, or distal bile duct tumors may mimic pancreatic carcinoma.

Epidemiology
In the years 2003 to 2007, the median age at diagnosis was 70; rare cases were under 40; and incidence increased after the age of 45.
Incidence
Approximately 3.2% of all cancer diagnoses and 7% of cancer deaths are expected in the United States in 2021, according to the American Cancer Society; the lifetime risk is roughly 1 in 64 (1.6%).
 Black and white people are more likely to experience it, with 17.2 and 15.2 men and 14.3 and 11.7 women per 100,000, respectively. There are 12.8 and 10.9 in 100,000 men and 11.1 and 9.3 in 100,000 women, respectively, among Hispanics and Asian/Pacific Islanders.
Prevalence
About 83,777 persons in the US had pancreatic cancer in 2018.

Risk Elements 
Prior partial gastrectomy or cholecystectomy: 2- to 5-fold increased risk 15 to 20 years after gastrectomy. Genetic factors/familial aggregation: 5-10% of patients have a first-degree relative with the disease, which confers a 9-fold increase in risk compared to the general population; subgroup may carry germline mutations of DNA repair genes (BRCA2).
The cumulative risk for hereditary chronic pancreatitis, which is autosomal dominant and highly penetrant, is 10% and 54%, respectively, by the ages of 50 and 75.
RR 30 to 40 for Peutz-Jeghers syndrome
RR 10 to 20 for the familial atypical multiple mole and melanoma syndrome (p16).
Non-O blood type RR 1 to 2; Lynch syndrome, hereditary nonpolyposis colon cancer; sporadic chronic pancreatitis; high dietary fat, red meat, obesity; Helicobacter pylori; heavy alcohol users;

Prevention 

Clinicians shouldn't perform pancreatic cancer screenings on people with average risk factors.
 Patients with genetic syndromes (Peutz-Jeghers syndrome, hereditary pancreatitis, patients with CDKN2A gene mutation, patients with one or more first-degree relatives with pancreatic cancer who also have Lynch syndrome, and patients with mutations in the BRCA1, BRCA2, PALB2, and ATM genes) and patients at high risk for pancreatic cancer should be given consideration for screening.
 High-risk individuals should start getting screened at age 50, which is roughly 10 years after the commencement of the familial condition.
When CKDN2A and PRSS1 mutation carriers have hereditary pancreatitis, screening should begin at age 40. When Peutz-Jeghers syndrome is present, screening should begin at age 35.

Accompanying Conditions 

 Cystic fibrosis, diabetes, and chronic pancreatitis
More than 90% of pancreatic ductal adenocarcinomas have KRAS mutations.
Tumor progression is made possible by the mutational inactivation of tumor suppressors (SMAD4, p53, CDKN2A).
Germline cationic trypsinogen or PRSS1 mutations (hereditary pancreatitis), BRCA2 mutations (typically with hereditary breast-ovarian cancer syndrome), CDKN2 mutations (familial atypical mole, multiple melanoma), or DNA repair gene mutations (such as ATM and PALB2, aside from BRCA2) are some of the subsets of familial pancreatic cancer.
Precursor lesions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasms may be curable in the majority of family pancreatic malignancies.

Depending on the location of the tumor, the majority of cases are diagnosed after the onset of symptoms. Pancreatic head tumors, which make up 60–70% of all cases, restrict the periampullary bile duct and result in obstructive jaundice.
Weight loss is 90%, pain is 75% (progressive midepigastric dull aching that frequently spreads to the back), malnutrition is 75%, jaundice is 70%, anorexia is 60%, pruritus is 40%, diabetes mellitus is 50%, weakness, weariness, and malaise are 30% to 40% of the symptoms, and back pain, alcoholic stools, dark urine, and steatorrhea are prevalent.
● When an elderly person develops acute pancreatitis or develops diabetes for the first time, pancreatic cancer is a concern.
Uncommon conditions include GI bleeding, severe pancreatitis, duodenal blockage, and unexplained thrombophlebitis.

clinical assessment 

Virchow node (left supraclavicular) and Sister Mary Joseph node (umbilical) in metastatic disease; palpable rectal shelf; muscle wasting and malnutrition; palpable abdominal mass or ascites in 20%; Jaundice: 70% if tumor obstructs bile duct; 10% with body or tail carcinoma; Courvoisier sign, hepatomegaly; GI bleeding from tumor erosion; portal hypertension-related bleeding; Pancreatic pan

Differential diagnoses include chronic pancreatitis, pancreatic cancer that has spread to the duodenum, cholangiocarcinoma, lymphoma, islet cell tumor, sarcoma, and cystic neoplasms.
Conditions that are not cancerous include choledocholithiasis, acute or chronic pancreatitis, biliary tract strictures, adenomas, and chronic mesenteric ischemia.

Laboratory Results 
Cross-sectional imaging (often starting with a CT scan)EUS-guided biopsy is the best method for tissue; it has a sensitivity of 75%–90% and a specificity of 100% for mass diagnosis.
Routine laboratory testing may reveal anemia, reduced serum albumin, and high serum bilirubin and alkaline phosphatase (all indicators of cholestasis).
Initial examinations (lab, imaging)
The majority of patients don't need their serum tumor markers (CA19-9) measured for diagnosis or treatment.
Use in predicting outcomes and responses to adjuvant chemotherapy has been suggested by some data.
It is not advised to use CEA and CA19-9 as screening assays.
Individuals with Lewis-negative blood group antigen phenotype (5-10%) are unable to synthesize CA19-9; elevations can occur in benign pancreatic or biliary disorders as well as nonpancreatic malignancies; MUC5AC aids in differentiating. Elevated CA19-9 antigen has 80% sensitivity and 90% specificity.


Tests in the Future & Special Considerations
CA19-9 may reveal tumor development that is progressive. Recurrence is not excluded by a normal CA19-9.
For diagnosis and staging, a pancreatic protocol using thin section, multiphase, multidetector helical CT is the preferred method: Abdominal ultrasonography (US): a popular initial test to evaluate jaundice and duct dilatation; less sensitive than CT for pancreatic masses; 85–90% sensitivity; 90–95% specificity; for evaluation of distant metastasis and prediction of resectability
Endoscopic retrograde cholangiopancreatography (ERCP): 90% sensitivity; 95% specificity for ductal cancer; useful if endoscopic stent is indicated for biliary obstruction; EUS: accurate for tissue biopsy, local tumor and node staging, predicting vascular invasion (90% specificity; 73% sensitivity); MRI: no advantage over contrast-enhanced CT; MR cholangiopancreatography: 90% sensitivity; 95% specificity. Preferred in certain circumstances, including those involving the gastric outlet, duodenal stenosis, surgical rearrangement (Billroth II), ductal disruption, and to detect bile duct obstruction following a failed ERCP.

Other/Diagnostic Procedures
Percutaneous fine-needle biopsy under US or CT guidance: 98-100% specificity; sensitivity of 80-90%.
EUS-guided biopsy has a sensitivity of 85% to 90% and a specificity of about 100% for pancreatic mass.
Laparoscopic staging with US: 92% sensitivity, 88% specificity, and 89% accuracy
Positive peritoneal cytology predicts unresectability with a positive predictive value of 94%, a specificity of 98%, and a sensitivity of 25%.
PET scan: minimal anatomic information; 90% sensitivity; 70% specificity
● Stage Ia of the tumor staging system: T1 N0 M0 (tumor 2 cm)
- T2 N0 M0 (tumor >2 cm and 4 cm) for stage Ib.
- T3 N0 M0 (tumor >4 cm), Stage IIa
- Stage IIb: T1–T3 N1 M0 (where N1 denotes metastases in 1–3 local lymph nodes).
- Stage III: T1-T3 N2 M0 (N2 is metastases in 4 regional lymph nodes), T4 any N M0 (Tumor affects common hepatic artery, superior mesenteric artery, and/or celiac axis, independent of size).
- Stage IV: Distant Metastases, any T any N
ALERT for Test Interpretation
Similar discomfort, weight loss, jaundice, and an inflammatory lump on imaging can all be symptoms of chronic pancreatitis.

No role for pancreatic resection in metastatic illness; surgical resection is the only chance of cure.
Nonmetastatic pancreatic cancer can be surgically removed, be marginally surgically removed, or be locally progressed.
Extrapancreatic dissemination, encasement or blockage of major arteries, and distant metastases are criteria for unresectability.
Patients can be referred to clinical trials.

Stages I and II medication - radical pancreatic resection plus chemotherapy - ESPAC-3 trial following resection: no appreciable difference in overall survival between 5-fluorouracil (5-FU)/folinic acid and gemcitabine
- ESPAC-4: Gemcitabine plus capecitabine outperforms gemcitabine by itself.
- The current standard of care is postoperative gemcitabine alone or in conjunction with 5-FU-based chemoradiation; preoperative neoadjuvant treatment trials are ongoing.
- In situations of pancreatic cancer that is just barely treatable, think about preoperative chemotherapy and radiation.
Stage III - Standard: gemcitabine-based chemotherapy for six months; optional chemoradiation (capecitabine and irradiation) is debatable.
- FOLFIRINOX, a combination of gemcitabine, nab-paclitaxel, leucovorin, and fluorouracil. These treatment plans are utilized with patients who have few or no performance limitations.
- Implantation of radioactive materials or intraoperative radiation therapy
First-line treatment for stage IV patients is FOLFIRINOX, which combines gemcitabine with nab-paclitaxel, capecitabine, and erlotinib. Gemcitabine alone is advised for patients with an ECOG PS of 2 or a comorbidity that precludes aggressive treatments.
- Palliative decompression, supportive care, and pain-relieving operations (celiac or intrapleural block) comprise second-line therapy.
 Endoscopic expandable metal stent implantation instead of surgery for duodenal blockage○ Biliary obstruction: Endoscopic biliary stenting is as effective as surgical hepaticojejunostomy and is safer than percutaneous implantation.
Treatment with larotrectinib or entrectinib is advised for malignancies containing NTRK fusions.
Patients who test positive for mismatch repair deficiency or significant microsatellite instability are advised to use pembrolizumab.
Options for ongoing treatment include chemotherapy or the PARP inhibitor olaparib in patients with BRCA1 or BRCA2 mutations who have already had first-line platinum-based chemotherapy without disease progression for at least 16 weeks.
Gemcitabine combined with nab-paclitaxel
Fluorouracil combined with irinotecan or oxaliplatin

Pancreaticoduodenectomy, the Whipple surgery, and en bloc resection of the head of the pancreas, distal common bile duct, duodenum, jejunum, and gastric antrum are popular surgical procedures.
- Distal pancreatectomy for body and tail cancers - Total pancreatectomy
 Unusual procedures
- Regional pancreatectomy and pylorus-preserving pancreaticoduodenectomy - Palliative bypass - Biliary decompression - Gastrojejunostomy - Duodenal endoprosthesis - Obstruction

At two to three months after the start of therapy, the treatment received a follow-up evaluation. Contrast-enhanced CT is favored. Regular PET scans are not advised. Imaging cannot be replaced with CA19-9.

Diet 
Pancreatic enzymes and fat-soluble vitamins might need to be replaced.

90% of people who are diagnosed with pancreatic cancer pass away from the illness, mostly from metastatic disease. 5-year survival rates are 30% for node-negative patients and 10% for node-positive patients.
Median life expectancy: 10 to 20 months
Complete surgical resection can result in a 5-year survival rate of 18–24% for localized disease and small tumors (2 cm) without lymph node involvement and without expansion beyond the capsule.
The outlook is brighter for cystadenocarcinomas than for common pancreatic malignancies.