Pancreatic adenocarcinoma: A review of recent paradigms and advances in epidemiology, clinical diagnosis and management

Table 1 The expected increase in the number of new cases among various continents by 2040[1]

Population	Number of new cases		Change in number of cases	Change in number of cases due to population
	2020	2040
Africa	17070	34165	+ 100.1%	+ 100.1%
Asia	233701	424138	+ 81.5%	+ 81.5%
Europe	140116	178438	+ 27.4%	+ 27.4%
Latin America and Caribbean	37352	67836	+ 81.6%	+ 81.6%
Northern America	62643	89124	+ 42.3%	+ 42.3%
Oceania	4891	7933	+ 62.2%	+ 62.2%
Totals	495773	801634	+ 61.7%	+ 61.7%

Table 2 The histological features and genetic alterations in pancreatic intraepithelial neoplasia

	PanIN-1	PanIN-2	PanIN-3
Histology	Columnar epithelial cells with basally oriented uniform and round nuclei	More nuclear changes such as loss of nuclear polarity, pleomorphism, hyperchromasia and nuclear pseudostratification	Cribriform pattern, budding cells into lumen and nuclear changes
Genetic changes	K-Ras mutations	CDKN2A mutations	TP53 loss
	Telomere shortening		SMAD4 loss
			BRCA2 loss

PanIN: Pancreatic intraepithelial neoplasia.

Table 3 The outcomes of various latest studies comparing laparoscopic pancreaticoduodenectomy with open procedure

Ref.	Study	Comparison	Outcome
Nickel et al[112], 2020	Meta-analysis of 3 RCTs	LPD and OPD	90-d mortality, post-operative complications and oncological outcomes were similar in both groups
			Blood loss was less for LPD
			Operating time was more for LPD
Yoo et al[113], 2020	Retrospective cohort study 359 patients	LPD and OPD	Post-operative complications and hospital stay were shorter for LPD
			Operative time was longer for LPD
			Recurrence free outcomes andoverall survival rates were similar
Chen et al[114], 2020	Meta-analysis of 6 cohort studies	LPD and OPD for PDA	Number of lymph nodes harvested, number of positive lymph nodes, rate of adjuvant therapy, time to adjuvant therapy, 1 yr survival and 2 yr survival are same for both the groups
Zhou et al[115], 2019	Retrospective cohort study	LPD and OPD	Overall complications and survival were similar between the two groups
Chen et al[116], 2018	Retrospective cohort study of 102 patients	LPD and OPD	Intra-operative blood loss, post-operative recovery and hospital stay were shorter for LPD
			Operative time was longer for LPD
			Post operative complications were similar in both the groups
Dang et al[117], 2020	Retrospective cohort study	LPD and OPD	Intra-operative blood loss, operating time and hospital stay for shorter for LPD
			30 d and 90 d mortality rates were better for LPD
			Long term survival rates were similar
Palanivelu et al[118], 2017	RCT of 68 patients with periampullary carcinoma	LPD and OPD	Intra-operative blood loss and hospital stay for shorter for LPD
			Operative time was longer for LPD
			Post-operative complications were similar in both the groups

RCT: Randomized control trial; LPD: Laparoscopic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy.

Table 4 Studies showing the role of neoadjuvant chemotherapy and chemoradiotherapy in resectable pancreatic adenocarcinoma

Ref.	Type of study	Type of neoadjuvant therapy	Drugs	Results
Tajima et al[177], 2012	Retrospective pilot study	Chemotherapy	Gemcitabine and S1	The 3 yr survival rates of NACT group (55.6%) was higher than control group (29.6%)
O’Reilly et al[178], 2014	Phase II trial non randomized	Chemotherapy	Gemcitabine and oxalipaltin	Resectability was 71%
				Overall survival was 21.7 mo
Motoi et al[179], 2013	RCT- NACT vs direct surgery	Chemotherapy	Gemcitabine and S1	Results awaited
Scott et al[180], 2017	RCT- NACT vs direct surgery	Chemotherapy	FOLFIRINOX	Results awaited
Labori et al[181], 2017	RCT- NACT vs direct surgery	Chemotherapy	FOLFIRINOX	Results awaited
Heinrich et al[182], 2011	RCT- NACT vs direct surgery	Chemotherapy	Gemcitabine and oxalipaltin	Results awaited
Sohal et al[183], 2017	RCT-FOLFIRINOX vs GnP	Chemotherapy	FOLFIRINOX vs Gemcitabine and nab paclitaxel	Results awaited
Turrini et al[184], 2009	Prospective study	Chemoradiotherapy	5-Flurouracil and cisplatin with radiotherpay	Respectability rate is 82.6%
				Median overall survival for resected patients is 23 mo
Golcher et al[185], 2015	RCT- NACRT vs direct surgery	Chemoradiotherapy	Gemcitabine and Cisplatin with radiotherpay	R0 resection rate (52%) and median overall survival after tumor resection (27 mo) was greater NACRT arm
Okano et al[186], 2017	Prospective study	Chemoradiotherapy	S-1 with radiotherapy	1-yr and 2-yr survival rates are 91% and 83% in resectable group

RCT: Randomized control trial; NACT: Neoadjuvant chemotherapy; NACRT: Neoadjuvant chemoradiotherapy; FOLFIRINOX: 5-Flurouracil, irinotecan and oxaliplatin.