Treating and caring for an oncology patient should go beyond the knowledge of high complexity and evidence-based that is updated every day. A solid doctor-patient relationship with expectation management and a lot of trust is expected.

The situation I want to put here is that of a patient with cholestatic syndrome due to non-biopsied periampullary malignant neoplasia. He had a very good status, a totally independent athlete for daily activities and with little weight loss even in the presence of symptoms of food intolerance.

Not meeting criteria for neoadjuvant (borderline)¹ and without evidence of metastatic lesions in the staging performed, a resection was chosen as the first treatment (upfront) which took place about 1 month after the first contact with the surgeon.

I expose the intraoperative photo:

The subcentimetric lesion highlighted was resected and sent for freezing biopsy. The finding was malignant neoplasia in the sample sent.

There are several factors at this decision-making moment that induce us to proceed with the surgery: the fallibility of intraoperative freezing, the fact that this patient – the exception of most cases attended in this context – is so physically and nutritionally fit for surgery, the confidence and optimism transmitted in consultation to the patient and family in the face of the precocity of surgical treatment, the experience of previous cases that were “successful”.

For this reason, I share the following studies that aimed to define the real prognosis of this patient.

What do the studies say?

In the first² patients undergoing pancreatectomies associated with hepatic resections at an internationally renowned center were retrospectively analyzed.

The sample size (22 patients) is criticizable and is probably a consequence of high patient selection. This selection is also proven in the sample details: average size of the metastasis (0.6 cm), hepatic resections were mostly nodulectomies. In addition, all cases were similar to ours, an incidental intraoperative finding.

For control, two groups were designated: 1 – conventional resection with the same primary site without association with hepatic metastasis and 2 – palliative surgery performed in the face of hepatic metastasis (bili-digestive + food diversion). The comparison showed interesting but not unexpected results: at a cost of a higher rate of complications, bleeding and length of stay, there was no benefit in the survival of these patients in the long term compared to palliative surgery. It is worth noting that, as in our situation, we are comparing a group selected by optimism, by the expectation of better evolution compared to the usual.

I also highlight this more recent systematic review³ showing a similar survival between patients who underwent combined surgery in the proposed context and patients referred for palliative chemotherapy after metastasis detection in staging (not submitted to surgery). In selected patients, after chemotherapy and systemic control, the survival provided by the same surgery was 3 to 4 times greater.

Conclusion

As seen above, we are not lacking examples that in a few patients the surgery initially thought (resection of hepatic metastasis + duodenopancreatectomy) can bring benefit in survival⁴. However, at the time of surgery this individual has not yet gone through this selection of systemic treatment and, therefore, we do not yet know if he is – or better – will be one of these cases. Therefore, on that day, we proceeded with the bili-digestive diversion – thus solving the biliary obstruction – associated with food diversion due to the food symptoms alleged.

For those who would choose to proceed with the procedure, I invite you to reflect: no matter how optimistic our expectation, our intention and attitude remain subject to data and statistics. Our main function during our patient’s journey is to advise him to take the most advantageous path and not just hope for the best result.

After all, there are less risky surgeries that relieve symptoms and provide a systemic treatment without complications for our patient. In this way, in the light of current knowledge, he will remain with a higher quality of life and for a longer time outside the hospital environment. Remembering that definitive treatment will not cease to be an option if it proves adequate over its evolution.

Learn more about hepatic metastases. Click here

Synchronous colorectal hepatic metastasis – How to program treatment?

References

1. Isaji, S. et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology 18, 2–11 (2018).
2. Gleisner, A. L. et al. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer 110, 2484–2492 (2007).
3. Crippa, S. et al. A systematic review of surgical resection of liver-only synchronous metastases from pancreatic cancer in the era of multiagent chemotherapy. Updates Surg. 72, 39–45 (2020).
4. Nagai, M. et al. Oncologic resection of pancreatic cancer with isolated liver metastasis: Favorable outcomes in select patients. J. Hepatobiliary. Pancreat. Sci. 1–11 (2023) doi:10.1002/jhbp.1303.

How to cite this article

Magalhães DP. Periampullary neoplasia with isolated hepatic metastasis: what would you do? Gastropedia, vol. 2 Available at: gastropedia.com.br/cirurgia/neoplasia-periampular-com-metastase-hepatica-isolada-o-que-voce-faria/

Colorectal tumor has a major impact on global health and, according to INCA data, it ranked second in incidence in both sexes in our country in 2020. Complications resulting from colorectal tumor rank second in cancer mortality worldwide⁶. At diagnosis, about 20% of these patients already present with hepatic metastases.⁴

With the advancement of oncological treatments and better understanding of the disease, a greater number of treatments are available for these patients, including: surgery, chemotherapy, immunotherapy, radiotherapy and radio interventional treatments. Although patients with hepatic metastases are considered stage IV, they are still cases eligible for curative treatment.

Faced with several therapeutic options and with the increase in survival, complex cases have become more common, which requires us to have a deep knowledge of the different therapeutic options. Recognizing this difficulty, oncology hospitals organize specialized multidisciplinary committees that discuss the particularities of each patient with the intention of obtaining the best results. It is in these meetings that we outline the therapeutic planning and the best time for reassessment and action of each team.

Figure 1 – Performing radiofrequency ablation guided by simultaneous ultrasound to hepatic surgery for multimodal treatment of colorectal tumor metastases

Given the epidemiological importance of the diagnosis that frequently presents in clinics and in emergency situations – where we do not always have access to multidisciplinary opinion in a timely manner – this article aims to show the benefits and disadvantages of each available strategy to offer to the patient with colorectal tumor and synchronous hepatic metastasis.

The studies on hepatic metastases from colorectal tumors are numerous and there is often a regional difference in terminology on the subject. This article applies to patients with hepatic metastasis already existing or identified at the staging of the primary tumor.

Figure 2 – Magnetic resonance imaging showing synchronous hepatic metastasis (yellow arrow) to a right colon adenocarcinoma (blue arrow).

Patients with asymptomatic colorectal tumor and resectable hepatic metastases

Most clinical and surgical specialists recommend preoperative chemotherapy – for about 02 months – followed by surgical treatment if good response¹. Surgery can involve resection of the primary in association with hepatectomy as long as the surgeons are qualified for this and that both are medium-sized surgeries. Casuistics have already shown a higher rate of perioperative complications and mortality in cases of combined surgery involving major hepatectomies².

It is also possible to perform resection of the primary followed by chemotherapy in the interval between surgeries; with hepatic resection scheduled for after about 2 to 3 months. During the first surgery, the evaluation of hepatic disease and histopathological confirmation of metastases can be performed, if necessary.

Figure 3 – Intraoperative laparoscopic ultrasound. Valid resource in the identification and intraoperative planning of hepatic resections.

There was no difference in survival over a 5-year period when analyzing the options; however, we highlight that these are data from retrospective studies in which there may have been a bias in the indication of primary surgery for patients with better performance and less volume of oncological disease. Therefore, the consensus among specialized centers is to indicate chemotherapy as the first treatment¹.

Patients with asymptomatic colorectal tumor and unresectable hepatic metastases

It is common for cases of colorectal tumors in patients with good performance to undergo surgery as the first treatment regardless of the presence of hepatic metastases. However, it is observed that the limiting factor for the possible curative treatment of these patients is the systemic disease manifested in the liver³.

Therefore, it is recommended to perform chemotherapy as the first treatment, with reassessment of the response after 2 months and programming of the hepatectomy, if feasible. In 1996, Bismuth already demonstrated a conversion rate of unresectable hepatic metastases to resectable in 16% with impact on prognosis (survival rate of 40% in 05 years). More recent results show conversion rates of up to 30%².

The literature shows that the outcome of patients who, in the end, underwent both surgeries is similar whether for those who started treatment with chemotherapy, or for those who started with colectomy. This data gives us confidence to keep the primary lesion under treatment with chemotherapy and, at the same time, pursue the possibility of surgical treatment – simultaneous or in stages – of all lesions¹.

Figure 4 – In addition to the reduction in dimensions after chemotherapy, there is a change in signal (scar aspect) and better delimitation of the lesion limits; factors that favor the surgical procedure

Patients with symptomatic colorectal tumor and hepatic metastases

It is estimated that about 20% of colorectal tumor cases have their diagnosis and treatment started in an emergency.⁵ In this context, it is important to highlight the impact of complete staging in the face of clinical suspicion of colorectal tumor. If it is safe for the patient, performing contrast-enhanced abdominal and thoracic tomography and carcinoembryonic antigen dosage before a possible resection of the primary tumor will be fundamental during oncological therapeutic planning.

The main complications that lead the patient with colorectal tumor to emergency are intestinal obstruction, perforation or bleeding. Even in the face of a metastatic patient, we need to consider the patient as potentially treatable and, therefore, offer a surgery with oncological principles or a derivation that allows to delay the treatment with curative intentions¹.

There is consensus among specialists that during the symptomatic context with obstruction or perforation there is no room to involve any approach to hepatic metastases.¹

Bleeding in colorectal tumor rarely requires emergency surgery. In general, bleeding can be solved with transfusion therapy followed by early chemotherapy with good response. Once the bleeding is resolved, these patients can be managed according to the strategies above.

The different surgical treatment strategies

• Traditional

The strategy of the traditional approach consists in performing colectomy as the first treatment, followed by chemotherapy and hepatic surgery in 2-3 months². On the one hand, this path is safer with the reduction of the risk of complications of the primary tumor. On the other hand, it is important to pay attention to the risk of complication during the resection of the primary that can, and often exceeds, the risk of intercurrences if we keep it under chemotherapy treatment.

A perioperative complication will delay the treatment of the patient’s systemic metastases, which is what will actually define his prognosis. Therefore, in cases of unresectable hepatic lesion, strongly consider starting with chemotherapy that may provide the opportunity for a complete treatment¹.

• Simultaneous surgery

There are clear benefits to offering a combined treatment during just one surgical act. Being subjected to a single anesthetic act and a shorter hospital stay is an inviting possibility for the surgeon and the patient. However, prolonged operative time and a higher risk of perioperative complications are disadvantages already demonstrated and that, when they occur, nullify these benefits.

Currently, combined resection is reserved for cases of simple colectomy and minor hepatectomies that can be performed at the same surgical time by conventional or videolaparoscopic approach. The right subcostal incision of the hepatectomy allows the performance of oncological right colectomy, being this the most frequent indication. For cases of left colectomy, the laparoscopic approach with resection of smaller and peripheral nodules is the most used.

Increased mortality and morbidity have already been demonstrated in the association of large oncological colectomies (mesorectum approach or multivisceral) and/or major hepatectomies (resection of more than 3 segments); suggesting the limits of this type of strategy.⁵

Figure 5 – The simultaneous approach of primary tumor (right colon) and hepatic metastasis.

• Liver-first or Reverse Approach

Approach is increasingly used and reserved for cases where the complete oncological treatment will depend on a major hepatectomy and/or response of the lesions to chemotherapy.

Very applied in cases of medium/low rectal tumors where neoadjuvant chemotherapy and radiotherapy will be performed. In this interval, it is possible to start the treatment of hepatic disease over the time of response of the primary to chemoradiotherapy¹.

The disadvantage of this strategy is the attention and monitoring of the symptoms of the primary tumor or its complications, such as intestinal obstruction and perforation. Studies show that the incidence of these local complications in asymptomatic patients during chemotherapy is low, but not null.⁷

References

1. Adam, R. et al. Managing synchronous liver metastases from colorectal cancer: A multidisciplinary international consensus. 41, 729–741 (2022).
2. Lillemoe, H. A. & Vauthey, J. Surgical approach to synchronous colorectal liver metastases: staged, combined, or reverse strategy. 9, 25–34 (2020).
3. Siriwardena, A. K., Mason, J. M., Mullamitha, S. & Hancock, H. C. Management of colorectal cancer presenting with synchronous liver metastases. Nat. Publ. Gr. 11, 446–459 (2014).Borner MM. Neoadjuvant chemotherapy for unresectable liver metastases of colorectal cancer–too good to be true?. Ann Oncol. 10(6):623-626. (1999)
4. Reddy SK, Pawlik TM, Zorzi D, et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: A multi-institutional analysis. Ann Surg Oncol. 14:3481-91 (2007)
5. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 71(3):209-249. (2021)
6. Tebbutt NC, Norman AR, Cunningham D, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 52(4):568-573 (2003)

How to cite this article

Magalhães DP. Synchronous colorectal hepatic metastasis – How to program the treatment

Insulinoma is the most frequent functioning pancreatic neuroendocrine tumor (55%), with its peak occurrence in patients in their fifth decade of life (between 40 and 50 years) and a slight predominance among women (1.4:1)¹.

The symptoms associated with the tumor are divided between adrenergic – anxiety, tremors and agitation – and neuroglycopenic such as disorientation, visual alterations and seizures². Due to frequent food intake to avoid severe hypoglycemia during fasting, it is common for patients to present with obesity/overweight at diagnosis.

In 1938, the Whipple triad was described: documented hypoglycemia (<50mg/dL), symptomatic and relieved after caloric intake. Currently, diagnostic confirmation is given with a clinical fasting test of 48 to 72 hours in which laboratory tests are collected periodically. The laboratory profile will show low blood sugar in opposition to high levels of insulin, pro-insulin and C-peptide³. It is essential for diagnosis to ensure that the patient does not use oral antidiabetics such as sulfonylureas or injectable insulin.

The relationship of insulinoma in endocrine syndromes (MEN-1 and tuberous sclerosis) is known and brings propaedeutic particularities due to a higher risk of multiple neuroendocrine tumors or malignant insulinomas⁴.

The recommended treatment is surgical excision of the tumor. Enucleation, as well as segmental pancreatectomies, are recognized treatments since the vast majority of tumors are benign. Thus, lymphadenectomy becomes less relevant than the preservation of pancreatic parenchyma in order to avoid exocrine or endocrine insufficiency¹.

Therefore, this article aims to bring an analysis of the different diagnostic tests used in insulinoma cases and their applications, in addition to a list of specific perioperative care for these patients.

Diagnostic methods by image

Axial methods with contrast are the most used for the anatomical study of the pancreas and its vascular relations. Among them, magnetic resonance, when available, has proven to be more sensitive to locate insulinomas that present as hypervascular nodules in the arterial phase, with hyperintensity in T2 and hypointensity in T1 in relation to the pancreatic parenchyma. Smaller lesions can be located more easily in diffusion phases⁵.

A specific exam for neuroendocrine tumors that uses their somatostatin receptors, the PET Gallium 68 can assist in cases of clinical suspicion without diagnosis by the methods above. It is an appropriate exam for the location of ectopic insulinomas that were not visualized in the upper abdomen⁵.

Invasive diagnostic methods

Echoendoscopy: Exam for evaluation of the pancreatic parenchyma in search of subcentimetric lesions, used by some authors as the first exam to locate the insulinoma. It offers even greater sensitivity in lesions of the head of the pancreas and uncinate process.

In the report of a suspected insulinoma, it is important to include, if possible, the measurement of the tumor, its location and the distance from relevant vascular structures (spleno-mesenteric junction), and the proximity of the main pancreatic duct (to assist the operative decision to enucleate the lesion).¹

Needle puncture is dispensable in the vast majority of cases. The symptomatic patient with sporadic lesion does not need histopathological confirmation for treatment. In endocrine syndromes, both functioning and non-functioning neuroendocrine tumors can express immunohistochemical markers for insulin. Thus, this exam is not suitable to differentiate them. ⁶

In non-peripheral or intrapancreatic lesions of difficult location, the surgeon may request a tattoo with methylene blue to facilitate intraoperative location.

Selective pancreatic arterial catheterization (SACS)

The exam consists of positioning a collector catheter in the right hepatic vein to collect the blood level of insulin after arterial stimuli.

Then, after selective arterial catheterization, calcium gluconate is injected into the peripancreatic arteries with the power to topograph the lesion if insulinemia doubles within 3 minutes after injection.

• Tumor in the body/tail of the pancreas: Positive after injection in the splenic artery
• Tumor in the pancreatic head or uncinate process: Positive after injection in the gastroduodenal or superior mesenteric artery
• Hidden hepatic metastasis: Positive after injection in the proper hepatic artery

The exam is used mainly in cases of endocrine syndromes and multiple neuroendocrine tumors in which it is desired to identify which lesion is metabolically active.¹

Surgical treatment

The definition of surgical route depends on the surgeon’s expertise. It is important to note that for laparoscopic access, especially for nodulectomies and distal pancreatectomies, a detailed planning of the location of the pancreatic section is necessary. Conversion to open surgery is justified in cases of imprecision.⁷

Intraoperative ultrasonography is an ally of the liver and pancreas surgeon and, in this context, certifies the tumor location and proximity to pancreatic ducts in cases where enucleation is considered. Thus, the exam provides greater safety to the procedure, reducing the risk of pancreatic fistula and allowing preservation of pancreatic parenchyma when possible.