Recent progress in pancreatic cancer

Abstract

Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.

Keywords: medical oncology; molecular biology; pancreatic neoplasms; radiation oncology; radiology.

Figure 1

Patients, such as the one shown here, with Familial Atypical Multiple Mole Melanoma syndrome have increased numbers of melanocytic nevi and an increased risk of melanoma and pancreatic cancer.

Figure 2

A) Histopathology of a ductal adenocarcinoma of the pancreas. Note the atypical glands embedded in the desmoplastic stroma. B) Intraductal papillary mucinous neoplasms (IPMNs) are characterized by an intraductal growth of neoplastic mucin-producing cells that typically form papillae (both hematoxylin and eosin stain).

Figure 2

A) Histopathology of a ductal adenocarcinoma of the pancreas. Note the atypical glands embedded in the desmoplastic stroma. B) Intraductal papillary mucinous neoplasms (IPMNs) are characterized by an intraductal growth of neoplastic mucin-producing cells that typically form papillae (both hematoxylin and eosin stain).

Figure 3

CT of pancreatic cancer. A resectable pancreatic cancer with a well-defined fat plane around the artery (arrow).

Figure 4

CT of pancreatic cancer. A) Abutment, defined as less than 180-degree involvement of the celiac axis (arrow), is considered Stage III borderline resectable. B) Greater than 180-degree involvement of the arteries (arrow) is defined as encasement and is considered Stage III locally advanced or unresectable.

Figure 4

CT of pancreatic cancer. A) Abutment, defined as less than 180-degree involvement of the celiac axis (arrow), is considered Stage III borderline resectable. B) Greater than 180-degree involvement of the arteries (arrow) is defined as encasement and is considered Stage III locally advanced or unresectable.

Figure 5

Abutment of an artery, in this case the common hepatic artery, by tumor. Note that the tumor extends to the border of the artery but does not invade or narrow the vessel. On CT scan imaging this is seen as less than 180 degree involvement of the vessel and is considered to be borderline resectable. At operation this degree of involvement would allow the artery to be separated from the tumor, although it would likely leave microscopic cancer cells at the margin. Borderline resectable patients should undergo neoadjuvant therapy. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 6

Encasement of an artery, in this case the common hepatic artery, by tumor. Note that the tumor surrounds and narrows the artery. On CT scan imaging this is seen as greater than 180 degree involvement of the vessel and is considered to be locally advanced unresectable. At operation this degree of involvement would not allow separation of the tumor from the artery and would likely result in an R2 resection. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 7

Tumor involving the superior mesenteric vein (SMV), including numerous small tributaries of the vein. Since there is no single target vessel below the necessary region of resection this is considered unresectable. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 8

Flow chart diagraming a general approach to the treatment of pancreatic cancer. © Johns Hopkins University; used with permission.

Figure 9

The organs resected in a pancreatoduodenectomy (PD) include a portion of the stomach, the entire duodenum, the proximal 20–30 cm of jejunum, the common bile duct, gall bladder, the head and uncinate of the pancreas along with the associated regional lymph nodes. In the pylorus preserving version of the PD the duodenum is divided just beyond the first portion and the stomach and pylorus are preserved. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 10

Illustrations of standard (A) and pylorus-preserving (B) pancreatoduodenectomies (PD). Three anastomoses are necessary to reestablish gastrointestinal function. In the typical reconstruction shown here the end of the pancreas and end of the common hepatic duct are connected to the same limb of jejunum. Downstream from this the stomach is connected to the jejunum in a standard PD (A) or for a pylorus preserving version the duodenum is connected to the jejunum (B). Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 11

Focal tumor involvement of the portal vein-superior mesenteric vein confluence. Note that the tumor invades the vessel in a location that does not involve numerous small tributaries of the superior mesenteric vein (SMV) nor does it extend high on the portal vein. Since there is a single target vessel (dark lines) above and below the necessary region of resection this is considered to be resectable. The inset shows a primary anastomosis of the portal vein (PV) and SMV after en bloc resection of the vessel with the splenic vein tied off. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 12

(A) Short-Segment encasement of the common hepatic artery. (B) Although arterial encasement is most often considered to be locally advanced, short segment encasement of the common hepatic artery is amenable to resection and primary anastomosis. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 13

Tumor encasing the celiac artery, proximal hepatic artery and splenic artery. Although arterial encasement is most often considered to be locally advanced unresectable this configuration of vessel involvement allows en bloc resection of the proximal hepatic, celiac and splenic arteries (dark line marks transection margin of artery) in combination with a distal pancreatectomy. This is called the Appleby procedure. (B) The gastroduodenal artery (GDA) must be preserved since perfusion of the liver is by retrograde flow through this vessel to the common hepatic artery. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 14

Stereotactic body radiation therapy plan delivering 33 Gy to the pancreatic tumor over 5 treatments. Breath hold during treatment and pancreatic tumor markers (fiducials) allows for small margins (3 mm) and accurate targeting of the tumor. Notice the low dose of radiation (colored lines) to the bowel and adjacent normal structures.

Figure 15

Retrocrural and antecrural nerve blocks are effective approaches to alleviating pain caused by pancreatic cancer. Top illustrates a mid-sagittal view and the bottom an axial view with the patient prone. Note the position of the needle tip in the antecrural versus retrocrural positions. Blue represents the injected anesthetic. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.

Figure 16

Pain medication can also be delivered intrathecally into the cerebrospinal fluid (CSF) using a catheter attached to a surgically implanted pump. Blue represents the injected anesthetic. Illustration by Corinne Sandone. Illustration by Corinne Sandone. © Johns Hopkins University; used with permission.