Open Distal Pancreatectomy for Pancreatic Cancer

Abstract 

Distal pancreatectomy is a procedure performed most often for pancreatic tumors—both benign and malignant—but can also be indicated in the treatment of pancreatitis. The operation can be performed with an en-bloc resection of the spleen, or with splenic preservation—splenectomy is indicated for oncologic resection. The operative approach—laparoscopic, robotic, or open—is dictated by the patient and clinical scenario at hand. In this case, we perform an open distal pancreatectomy with splenectomy in a patient who has undergone neoadjuvant treatment for pancreatic adenocarcinoma. This is a unique case of a patient undergoing surgical resection after initial diagnosis of metastatic disease. The patient is a 69-year-old woman who initially presented with abdominal pain and bloating, and was found to have a 2-cm suspicious tumor in the body of her pancreas and biopsy-proven single liver metastasis. She was treated with an extended course of neoadjuvant chemotherapy, and re-staging scans showed significant response. Chemoradiation was completed and the liver metastasis was no longer visible on imaging. Twenty-seven months after diagnosis she was taken to the operating room for distal pancreatectomy and splenectomy; no liver or peritoneal metastases were seen. Her postoperative course was overall uneventful, and she recovered well. Final surgical pathology demonstrated complete pathological response with no evidence of disease seen and 0/11 lymph nodes positive for malignancy. She is currently being followed with CT scans and tumor markers every three months by her medical oncology team, and as of now, February 2022, there is no evidence of recurrence.

Case Overview

Background

Despite its relatively low incidence, pancreatic cancer is the fourth leading cause of death from cancer in the US.¹ Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of pancreatic cancer, with a small proportion of patients harboring slower-growing malignant endocrine tumors. Risk factors include advanced age, male sex, diabetes, history of smoking, pancreatitis, and certain genetic susceptibility loci, among others. R0 surgical resection of these tumors offers the only chance of curative treatment. At diagnosis, pancreatic cancers are categorized as unresectable/disseminated, locally advanced, borderline resectable or upfront resectable (see Table 1), which largely depends on tumor involvement of the local vasculature and presence of distant metastases.² The majority of pancreatic cancers (60–70%) arise in the head of the gland, with the remainder in the body and tail.¹ Relevant in distal pancreatectomy, the involvement of the splenic vasculature is not a contraindication to surgical resection. Unfortunately, the majority of pancreatic cancer patients will have distant spread of disease at the time of diagnosis; this is seen at an even higher rate in those with tumors of the pancreatic body and tail as small masses in this part of the pancreas are typically asymptomatic. Ultimately only 5–7% of individuals with PDAC in the body/tail of the pancreas will undergo surgery.³ 

Table 1: Criteria for tumor staging in pancreatic cancer. Source: Current Surgical Therapy, Neoadjuvant and Adjuvant Therapy for Pancreatic Cancer2

For patients with upfront resectable disease without high risk features, surgery is the recommended first-line treatment option, as per 2019 NCCN guidelines, and is supported by recent clinical trials.^4">4 Options for surgical management of pancreatic adenocarcinoma include pancreaticoduodenectomy (Whipple procedure) for lesions in the head, and distal pancreatectomy with splenectomy for lesions of the body and tail.  First-line therapy for borderline resectable and locally advanced disease is with neoadjuvant treatment (NAT), consisting of FOLFIRINOX or gemcitabine-nab-paclitaxel.3 A growing body of literature supports NAT in PDAC, such that a number of clinical trials are examining NAT prior to surgical resection in upfront resectable disease.^5, 6 The pros and cons of such an approach are discussed in more detail below.

Outcomes of treatment vary based on the stage of the tumor at patient presentation and the extent of surgical resection. The overall 5-year survival rate for all patients with pancreatic cancer is around 10%. This varies from patients with successful R0 resection, which portends an approximately 30% 5-year survival rate in node-negative disease and 10% 5-year survival in node-positive disease, to patients with disseminated disease at diagnosis, with practically no possibility of long-term survival.¹

Focused History of the Patient

The patient is a 69-year-old woman with a significant smoking history, HLD, HTN and GERD who presented initially with abdominal pain, weight loss and bloating. Workup included a CT scan which revealed a pancreatic body mass measuring 2.1 cm and a liver lesion. The tumor marker CA 19-9 was elevated at 69 U/mL. CT Chest to complete staging was negative for metastatic disease. US-guided liver biopsy revealed adenocarcinoma. The patient then underwent 4 cycles of FOLFIRINOX. Re-staging scans demonstrated an increase in size of liver lesions and a decrease in the pancreatic mass, and she was changed to gemcitabine/abraxane for four cycles.  Repeat CT then showed decrease in both the liver and pancreatic masses.  A total of 17 cycles of gem/abraxane were administered, with CT showing stable disease and CA 19-9 of 5 U/mL. She was then moved to gemcitabine monotherapy. She tolerated chemotherapy remarkably well with minimal side effects—experiencing insomnia and neuropathy.

A long course (5 weeks) of chemoradiation was then offered given ongoing stable disease. Concurrent capecitabine with radiotherapy (RT) was administered. Liver imaging with MRI disclosed no evidence of disease at the completion of treatment. The primary tumor had decreased remarkably in size as well. Consensus of multidisciplinary discussion was that surgical management with distal pancreatectomy and splenectomy was an appropriate next step, although unconventional, in a patient initially diagnosed with Stage IV pancreatic cancer, given her durable response and lack of evidence of metastatic disease on repeat imaging, and low tumor-marker level.

Physical Exam

At presentation, the patient showed no evidence of jaundice, palpable abdominal masses, or abdominal surgical scars. 

Imaging

CT scan at diagnosis demonstrated a heterogeneous, irregular low-attenuation pancreatic mass in the body of the pancreas measuring 2.1 cm x 2.1 cm with pancreatic ductal dilation and atrophy of the parenchyma of the pancreas, suspicious for pancreatic malignancy.  A 9-mm heterogenous low-attenuation hepatic lesion in the right hepatic lobe was further characterized with liver MRI, and ultimately US-guided biopsy confirmed metastatic adenocarcinoma. 

The SMA and SMV were not involved by the mass, but there was effacement of the splenic vein. 

CT scan after completion of neoadjuvant treatment prior to surgical resection over two years following initial diagnosis demonstrated a 1.2-cm x 0.5-cm hypodense focus in the body of the pancreas, which was unchanged from prior imaging studies with no ductal dilation but persistent atrophy of the pancreatic tail. Liver MRI no longer visualized what had become a subcentimeter hepatic lesion in the right lobe.

Options and Rationale for Treatment

Operative technique in distal pancreatectomy generally follows two models. One may approach the dissection in a medial-to-lateral fashion, first forming a tunnel under the pancreas and transecting the gland, extending the dissection towards the pancreatic tail and splenic hilum. Alternatively, the dissection may be initiated on the lateral aspect of the gland and carried medially. Our favored approach is the medial-to-lateral dissection, though an understanding and skillset involving both offers the surgeon alternative avenues when a difficult dissection may preclude one or the other approach.

Distal pancreatectomy may be performed with or without splenectomy. Surgical techniques for splenic preservation include meticulous dissection of the splenic vessels from the posterior of the pancreas, or preservation of the short gastric vessels, which provide blood supply to the spleen in the setting of ligation of the splenic vessels, first described by Warshaw et al. in 1988.⁷ In this case, we elected to perform a splenectomy given the nature of the patient's oncologic presentation, though preservation of the spleen does portend some clinical benefits, such as avoiding the risk of overwhelming postsplenectomy infection (OPSI). In patients undergoing splenectomy in conjunction with distal pancreatectomy, vaccines against encapsulated organisms must be administered to reduce the risk of OPSI. This includes vaccination against Neisseria meningitides, Streptococcus pneumoniae and Haemophilus influenzae. Patients are also routinely given an emergency supply of antibiotics in case of infection.

The goal of surgical treatment of pancreatic body and tail lesions with distal pancreatectomy and splenectomy is R0 resection with removal of all disease. This provides the patient with the only option for curative treatment. Though perioperative mortality rates are low in high-volume centers (1–2%), morbidity remains high (20–30%).⁸ This includes complications related to the operation, including pancreatic fistula, which is the most common, but also consequences, such as development of diabetes, which occurs in approximately 15–30% of patients.⁹ Thus, the risk of a relatively morbid operation must also be weighed against the potential benefits and likelihood of achieving an R0 resection, which is an individualized discussion to be had in multidisciplinary conferences and between the patient and surgeon alike.

Discussion

This case features a unique patient, initially presenting with metastatic disease, who demonstrated durable response to NAT for over two years prior to undergoing surgical resection, with a pathologic complete response. This remarkable course is an outlier, but provides significant hope for the future of treatment in PDAC, and highlights the power of NAT in potentially down-staging disease (a paradigm seen in other digestive tract cancers, including rectal cancer, in which complete pathologic response is often seen after NAT¹⁰). A few case reports in the literature describe similar patient responses.¹¹

Technical highlights of this case include a difficult retroperitoneal dissection with extensive fibrosis, as is often seen in patients after NAT. Frozen section was sent of fibrotic tissue overlying the hepatic artery and was negative for malignancy. The tumor was noted to be soft and pliant, which is a feature often seen in patients with good response to neoadjuvant treatment. Dissection of the major vascular structures around the body and tail of the pancreas including the PV and SMV, hepatic artery, renal vein and adrenal vein all proceeded without incident. The pancreas was transected with a stapler, utilizing a seam-guard staple load. One drain was left in place at the pancreatic transection margin, as is our protocol. Estimated blood loss was < 100 cc and the patient recovered without significant postoperative complications. Notably, final surgical pathology revealed no evidence of disease with a complete pathologic response. 

Modern treatment of pancreatic cancer depends on the stage at which the patient presents, and patients are treated with multimodality therapy including chemotherapy and radiation therapy.  Upfront resectable pancreatic cancer can be treated with surgery first, with an aim for attaining an R0 resection; however, there is increasing interest in offering NAT prior to surgery even in upfront resectable disease. As mentioned above, in locally advanced and borderline resectable disease, first-line treatment is NAT; if patients show no disease progression on NAT, surgical exploration is generally offered, as radiographic findings are often not predictive of resectability after NAT.

The benefits of NAT in resectable disease include allowing for earlier and faster treatment of microscopic disease, improved patient selection, as well as a higher likelihood for completion of the full regimen of treatment. Given the high rates of patients (up to 25%) found to have metastatic disease at the time of surgery, delivery of neoadjuvant treatment allows tumor biology to evolve and potentially self-select for patients most likely to benefit from a surgical procedure that puts a patient at risk for significant morbidity. An additional benefit is that the risk of pancreatic fistula decreases markedly after NAT.¹²

However, there are some downfalls of this approach. Forgoing NAT offers the opportunity to remove the tumor before any progression occurs, as surgical removal is the only chance at long term cure in PDAC. For patients with biliary obstruction undergoing NAT, biliary stenting needs to be performed, which carries its own accordant risks that have been chronicled in several studies.¹³

Advances in distal pancreatectomy include the use of minimally invasive techniques; both laparoscopic and robotic procedures are being performed across the country. Recently, the first randomized controlled clinical trials of minimally invasive versus open distal pancreatectomy were published.¹⁴ The LEOPARD trial is a multicenter patient-blinded RCT for patients with left-sided pancreatic tumors without vascular involvement. In this trial, minimally invasive distal pancreatectomy was associated with a reduced time to functional recovery; however, overall complication rate was not affected.¹⁵ The LAPOP trial is a prospective RCT that was nonblinded, evaluating the primary endpoint of length of postoperative hospital stay. This trial demonstrated a significant decrease in the length of hospital stay (5 days versus 6 days) and overall no change in complication rate.¹⁶ These data suggest that minimally invasive distal pancreatectomy may offer patients more expedient recovery. However, data is lacking with regards to oncologic outcomes when comparing open to minimally invasive procedures, and more work is needed in this area. In patients with NAT, particularly if radiation was a component, there can be marked fibrosis surrounding the major vessels making the dissection, though minimally invasive, more difficult.

In follow up, this patient was able to return to her normal activities of daily living. She reported significant weight loss of > 25 lbs and ongoing loose stool.  She was started on Creon for presumed pancreatic exocrine insufficiency. Most recent imaging at the writing of this article in February 2022 demonstrated no evidence of recurrent disease. The patient will continue to be followed by her medical oncology team with q3 month CT scans and tumor marker measurement. 

Disclosures

Nothing to disclose.

Statement of Consent

The patient referred to in this video article has given their informed consent to be filmed and is aware that information and images will be published online.