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Advances in molecular genetics have revolutionized our understanding of the pathogenesis, progression, and therapeutic options for treating gastrointestinal (GI) cancers. This chapter provides a comprehensive overview of the molecular landscape of GI cancers, focusing on key genetic alterations implicated in tumorigenesis across various anatomical sites including GIST, colon and rectum, and pancreas. Emphasis is placed on critical oncogenic pathways, such as mutations in tumor suppressor genes, oncogenes, chromosomal instability, microsatellite instability, and epigenetic modifications. The role of molecular biomarkers in predicting prognosis, guiding treatment decisions, and monitoring therapeutic response is discussed, highlighting the integration of genomic profiling into clinical practice. Finally, we address the evolving landscape of precision oncology in GI cancers, considering targeted therapies and immunotherapies., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Alterations in the DNA sequences of genes, or mutations, have traditionally been viewed as the primary factors driving tumor progression, however, epigenetic evidence would suggest that some heritable traits are mediated by changes in DNA expression that are not dependent upon alterations in the primary DNA sequence. Advances in the genetic understanding of cancer have, in some instances, allowed for more precise administration of anti-neoplastic therapy. Targeted therapies, the aim of which are to target specific cellular proteins or processes used by the cancer cells, have been advocated to avoid the adverse side effects attributable to a lack of cell specificity associated with traditional chemotherapy. Here we aim to describe the current state of understanding regarding the genetic related causes of cancers, the targeted therapies aimed at killing them and the inter-relationship between these two.

Background: The follow-up of patients with cutaneous melanoma is controversial. Current recommendations suggest routine history and physical examination every 3 to 6 months for the first 3 years and correlate studies including laboratory tests and radiographic imaging. However, the utility of these recommendations are unclear. The purpose of this study was to determine the impact of routine imaging on the method of detection of first recurrence in patients with stage II and sentinel lymph node-positive stage III melanoma., Methods: We analyzed a prospective database of all cutaneous melanoma patients treated at our institution from 1997 to 2005 who had at least 2 years of follow-up. The method of detection of initial recurrence was analyzed., Results: One hundred eighteen patients with stage II (n = 83) or III (n = 35) melanoma who were followed for at least 2 years were identified. Forty-three of these patients developed recurrence (median time to recurrence, 14 months). Site of first recurrence was as follows: 4 local, 17 in transit, 7 regional lymph node, and 15 distant. Twenty-nine recurrences (67%) were either patient detected or symptomatic. Eleven (26%) were detected by the physician at routine follow-up. Only three (7%) were identified by imaging (two chest X-ray and one brain magnetic resonance imaging) in an otherwise asymptomatic patient., Conclusions: Two-thirds of all initial recurrences of cutaneous melanoma were either detected by a patient or were symptomatic, with most of the remainder detected during routine physical examination. Routine imaging added little value in the detection of initial recurrence.

Background: Pancreaticoduodenectomy (PD) is the standard surgical management of invasive ampullary neoplasms. A rational plan to use ampullectomy (AMP) for lesions at this location requires careful analysis of preoperative clinical information (comorbidity, lesion size, and histopathology) and intraoperative data (frozen section pathology and clinical impression) to properly select patients for this treatment., Methods: We identified 140 consecutive cases of nonfamilial ampullary neoplasms from our prospective institutional database over a 7-year period (1996-2003). Preoperative and intraoperative factors were analyzed and related to outcomes., Results: AMP was planned for 37 patients with small lesions (median, 1.86 cm [range, 0-3 cm] vs. 2.6 cm [range, 0-8 cm] in PD). AMP was converted to PD because of the extent of disease in three and an intraoperative diagnosis of invasive cancer in five patients. Preoperative biopsy had a diagnostic accuracy of 79% (97 of 123) but missed 23 cancers. Intraoperative frozen section had a diagnostic accuracy of 84%; two cases of high-grade dysplasia and invasive cancer were missed. Patients with invasive cancer treated by AMP had a decreased recurrence-free and disease-specific survival compared with those treated by PD. Lymphatic spread of disease was associated with diminished long-term survival. Although both vascular invasion and tumor stage independently predicted lymphatic metastases, both were limited by their sensitivity., Conclusions: The reduced morbidity and mortality of AMP makes this the preferred treatment for benign lesions of the ampulla. Conversion to PD should be considered when intraoperative or final pathology identifies invasive adenocarcinoma. Refinement of clinicopathologic factors may reduce the occasional PD for benign disease and AMP for malignancy.

High-volume centers have low morbidity and mortality after pancreaticoduodenectomy (PD). Less is known about treatment pathways and their influence on intensive care unit (ICU) utilization. Patients who underwent PD at a tertiary cancer center during the five-year period between January 1998 and December 2003 were identified from a prospective database. Preoperative and intraoperative factors relating to ICU admission and outcome were analyzed. Five hundred ninety-one pancreaticoduodenectomies were performed during the study period. Of these, 536 patients had complete records for analysis. Of the 536 patients, 51 (10%) were admitted to the ICU after surgery. Admission to the ICU was associated with decreased overall survival (P < .0001). Of the preoperative predictors of ICU admission, serum creatinine, albumin, and increased body mass index (BMI) were associated with ICU admission (P = .02, .05, and .002, respectively). Age, blood glucose, diagnosis of diabetes mellitus, and chronic obstructive pulmonary disease were not predictive of ICU admission on univariate analysis. Of the intraoperative factors, longer operative time and estimated blood loss (EBL) correlated with ICU admission (P = .003 and .0001, respectively). On multivariate analysis, only preoperative BMI and intraoperative EBL were independent predictors of ICU admission (P = .03 and .003, respectively). Patients with a preoperative BMI greater than 30 had a substantially higher risk of ICU admission (relative risk 2.4). The majority of patients who undergo PD do not require admission to the ICU. Factors most associated with ICU admission after PD are increased preoperative BMI and intraoperative blood loss.

Background: Nearly half of patients with intra-abdominal (retroperitoneal, visceral, or pelvic) sarcoma undergo more than one operation. When the objective shifts from cure to palliation, the clinical quandary of doing no harm and maximizing benefit is magnified. Knowledge of the effectiveness of a procedure at achieving its palliative intent, as well as its attendant morbidity and mortality, is therefore paramount during this deliberation., Methods: A retrospective review was performed of all patients with a diagnosis of intra-abdominal sarcoma who underwent a palliative procedure between 1982 and 2003. A procedure was defined as palliative if it was explicitly performed to relieve symptoms., Results: Ten percent (112 of 1084) of patients with a diagnosis of intra-abdominal sarcoma underwent a total of 156 palliative procedures. The most frequent system for which a palliative procedure was performed was gastrointestinal (68 of 156; 44%). Overall, 71% of patients had improvement of symptoms 30 days after the operation, whereas only 54% of patients remained symptom free after 100 days. Although 54% of gastrointestinal tract obstructive symptoms were successfully relieved at 30 days, only 23% of patients remained symptom free at 100 days. The overall operative morbidity was 29%, and postoperative mortality was 12%. Patients undergoing procedures intended to palliate gastrointestinal obstruction encountered the greatest morbidity (19 of 40; 48%)., Conclusions: Successful palliation of many symptoms associated with advanced intra-abdominal sarcoma may be achieved. However, even in highly selected patients, the progressive and pervasive nature of the disease limits the opportunity to attain sustained relief for gastrointestinal obstructive symptoms.