The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative approaches. Current treatment costs amount to billions of dollars annually, combined with the risks and comorbidities associated with invasive surgery. This highlights the importance of less invasive alternatives with organ preservation being a central aspect of the treatment paradigm. The current standard of care typically involves neoadjuvant systemic therapy followed by surgical resection. There is a growing interest in organ preservation approaches by way of minimizing extensive surgical resections. Endoscopic ablation has proven to be useful in precursor lesions, as well as in palliative cases of unresectable disease. More recently, there has been an increase in reports on the utility of adjunct endoscopic ablative techniques for downstaging disease as well as contributing to non-surgical complete clinical response. This expansive field within endoscopic oncology holds great potential for advancing patient care. By addressing challenges, fostering collaboration, and embracing technological advancements, the gastrointestinal cancer treatment paradigm can shift towards a more sustainable and patient-centric future emphasizing organ and function preservation. This editorial examines the evolving landscape of endoscopic ablation strategies, emphasizing their potential to improve patient outcomes. We briefly review current applications of endoscopic ablation in the esophagus, stomach, duodenum, pancreas, bile ducts, and colon.

Endoscopic submucosal dissection allows for "en bloc" removal of early gastrointestinal neoplasms. However, it is technically demanding and time-consuming. Alternatives could rely on energy-based techniques. We aimed to evaluate a predictive numerical model of thermal damage to preoperatively define optimal laser settings allowing for a controlled ablation down to the submucosa, and the ability of confocal endomicroscopy to provide damage information.

A Nd:YAG laser was applied onto the gastric mucosa of 21 Wistar rats on 10 spots (total 210). Power settings ranging from 0.5 to 2.5W were applied during 1-12 s, with a consequent energy delivery varying from 0.5 to 30 J. Out of the 210 samples, a total of 1050 hematoxilin-eosin stained slides were obtained. To evaluate thermal injury, the ratio between the damage depth (DD) over the mucosa and the submucosa thickness (T) was calculated. Effective and safe ablation was considered for a DD/T ratio ≤ 1 (only mucosal and submucosal damage). Confocal endomicroscopy was performed before and after ablation. A numerical model, using human physical properties, was developed to predict thermal damage.

No full-thickness perforations were detected. On histology, the DD/T ratio at 0.5 J was 0.57 ± 0.21, significantly lower when compared to energies ranging from 15 J (a DD/T ratio = 1.2 ± 0.3; p < 0.001) until 30 J (a DD/T ratio = 1.33 ± 0.31; p < 0.001). Safe mucosal and submucosal ablations were achieved applying energy between 4 and 12 J, never impairing the muscularis propria. Confocal endomicroscopy showed a distorted gland architecture. The predicted damage depth demonstrated a significant positive linear correlation with the experimental data (Pearson's r 0.85; 95% CI 0.66-0.94).

Low-power settings achieved effective and safe mucosal and submucosal ablation. The numerical model allowed for an accurate prediction of the ablated layers. Confocal endomicroscopy provided real-time thermal damage visualization. Further studies on larger animal models are required.

Endoscopic submucosal dissection (ESD) is a minimally invasive technique allowing for the removal of early gastrointestinal (GI) tumors, widely considered as a valid alternative to conventional surgery. However, ESD is technically demanding, and potentially severe complications, such as bleeding and perforation, may occur. Energy-based techniques (e.g., radiofrequency ablation) might offer a potential alternative to ESD. However, their use mandates the ability to predict the damage induced and to identify a "signature" of the complete ablation, without the need for a physical specimen. Ideally, an energy-based procedure should be tunable in order to limit the ablation to the superficial layers, namely mucosa (M) and submucosa (SM), without injuring the muscularis propria (MP), thereby minimizing GI perforation. This experimental study aims to investigate thermal damage induced by Nd:YAG laser on the gastric wall, at different laser settings such as power (P) and time (t). Laser ablation was performed on the stomach wall of 6 Wistar rats. Two powers (2.5W and 1.0W) and 3 exposure times (12s, 6s and 2s) were tested, for a total of 30 ablations. Histological analysis allowed to assess thermal damage, in terms of damage depth (DD) and identification of involved layers. The ratio (R) between DD and the total depth (TD) of target layers (M+SM) was used as an index to evaluate the effectiveness of laser settings. At P=2.5W, MP was damaged (R>1) in the majority of cases (11/15). At P=1.0W, MP was preserved in all tests (R<;1), and rarely (4/15) did the damage reach the whole SM (R=1). Histopathological analysis evidenced that tissue damage was strongly related to the variable tissue thickness. These preliminary results seem to support the fact that endoscopic tunable laser ablation is feasible with a consistent damage/power correlation. Further tests are required to optimize the settings for applications on early GI tumors.

A 72-year-old woman underwent gastric endoscopic mucosal resection with a cap-fitted endoscope for an adenocarcinoma in situ. She was scheduled for endoscopic follow-up at 1 and 3 months after the procedure. By the third month of follow up, biopsies of a slightly depressed scar area showed an high grade epithelial dysplasia. For this reason a second endoscopic resection (ER) was performed using the oblique soft cap. A perforation in the site of endoscopic resection was immediately observed. The complication was treated successfully by the application of seven clips.

The objective of this study was to determine the efficacy and safety of endoscopic submucosal dissection for locally recurrent colorectal cancer after previous endoscopic mucosal resection.

A total of 16 patients with locally recurrent colorectal lesions were enrolled. A needle knife, an insulated-tip knife and a hook knife were used to resect the lesion along the submucosa. The rate of the curative resection, procedure time, and incidence of complications were evaluated.

Of 16 lesions, 15 were completely resected with endoscopic submucosal dissection, yielding an en bloc resection rate of 93.8 percent. Histologic examination confirmed that lateral and basal margins were cancer-free in 14 patients (87.5 percent). The average procedure time was 87.2 +/- 60.7 minutes. None of the patients had immediate or delayed bleeding during or after endoscopic submucosal dissection. Perforation in one patient (6.3 percent) was the only complication and was managed conservatively. The mean follow-up period was 15.5 +/- 6.8 months; none of the patients experienced lesion residue or recurrence.

Endoscopic submucosal dissection appears to be effective for locally recurrent colorectal cancer after previous endoscopic mucosal resection, making it possible to resect whole lesions and provide precise histologic information.

Gastric carcinomas have been classified into the differentiated and undifferentiated type, on the basis of its tendency to gland formation. As a result of recent advances in mucin histochemistry, mucin phenotypes of gastric carcinomas have been investigated. However, no consensus on the evaluation of the grade of malignancy of early gastric carcinomas regarding mucin phenotype expression has developed. To address this issue, we evaluated the lymph node metastasis rate and proliferative activity of a submucosal invasive (sm) gastric carcinoma according to mucin phenotype expression.

In resected surgical specimens from 108 patients with a single sm gastric carcinoma, the association between clinicopathological factors and lymph node metastasis was evaluated. In all cases, immunohistochemical staining with human gastric mucin, Muc-2, and CD10 and mucin histochemical staining by paradoxical concanavalin A staining were performed. The mucin phenotypes were classified into gastric-type (G-type), intestinal-type (I-type), mixed gastric and intestinal type (M-type), or a lack of mucin (LOM), using these as markers. To evaluate the cell proliferative activity of the gastric carcinoma, proliferating cell nuclear antigen (PCNA) staining was also performed.

The rate of lymph node metastasis was higher for G-type sm carcinomas. A multivariate analysis showed that the G-type and lymphatic invasion were independent factors of lymph node metastasis. However, the PCNA-labeling index (PCNA-LI) was low for G-type carcinomas irrespective of the presence or absence of lymph node metastasis. In I-type carcinomas, PCNA-LI was significantly higher in cases that were positive for lymph node metastasis than in negative cases.

G-type and lymphatic invasion are independent risk factors for lymph node metastasis of an sm gastric carcinoma, and proliferative activity may be a significant parameter for lymph node metastasis in cases with I-type carcinomas.

The aim of the study was to compare the ability of endoscopic ultrasonography (EUS) in detecting lymph node metastases in differentiated and undifferentiated gastric adenocarcinoma. EUS was performed in 149 patients with differentiated or undifferentiated gastric cancer. Histopathological findings were compared with pre-operative EUS findings in a total of 2961 resected lymph nodes. The EUS detection rates of metastasis to individual nodes in relation to node size, the ratio of the metastasized area to the cross-sectional area of the node and to the depth of primary tumour invasion, were also investigated. The accuracy and negative predictive values of EUS for detecting metastatic lymphadenopathy in each patient were significantly higher for differentiated (87%, 94%) than for undifferentiated (71%, 71%) tumours. The detection rate of individual node metastasis was higher for differentiated (31%) than for undifferentiated (21%) tumours. For differentiated lesions, EUS detected more small nodal metastases (< 5 mm in diameter) (p < 0.01) and more nodes involved with a relatively small proportion of the metastasized area to the cross-sectional area of the node (< 1/3 involvement) (p < 0.05). In relatively superficial lesions, such as pT1 and pT2, the pre-operative EUS detection rate of metastatic nodes was higher for differentiated than for undifferentiated tumours. In conclusion, the ability of EUS to detect nodal metastases is related to the histological type of gastric cancer.

Endoscopic treatment of superficial gastric cancer has been reported to be effective by many Japanese teams. In this study, the Nd:YAG laser was used to treat superficial gastric carcinoma in inoperable Caucasian patients with the aim of obtaining a complete response, i.e., disappearance of the lesion endoscopically and biopsy specimens negative for cancer. Eighteen patients unsuitable for surgery with various endoscopic patterns of superficial gastric cancer were treated with the Nd:YAG laser. The endoscopic pattern was type I in 4 patients, type II in 10 (5 type IIa, 1 type IIb, 2 type IIc, 2 mixed IIa + IIc), and type III in 4. Staging by echoendoscopy was performed in 11 patients (T1N0). Nd:YAG laser destruction of the gastric tumor was performed in all cases, with a mean of 4.4 laser sessions per patient. Tumor response was assessed by endoscopy and biopsy. Follow-up averaged 33 +/- 23 (SD) months. Five patients died of diseases unrelated to gastric cancer. An initial complete response was obtained in 16 (89%) patients after a mean of 1.7 laser sessions; histologic evidence of cancer persisted in 2 patients during the entire follow-up period. Among patients with an initial complete response, recurrence was observed in 2. One of them was successfully re-treated. At the end of the follow-up period, 14 (77.7%) of the 18 patients had a complete tumoral response; only 4 patients had histologic evidence of cancer. In 3 of these 4 patients, pretherapeutic echoendoscopic staging had not been performed. Among the 14 patients exhibiting a complete response, 3 had negative biopsy results more than 5 years after diagnosis. No complications occurred. In gastric cancer classified as T1N0 on the basis of pretherapeutic echoendoscopy, a high tumor response rate and even 5-year disease-free survival can be obtained with endoscopic Nd:YAG laser treatment. Endoscopic laser destruction thus appears to be a valuable therapeutic alternative to surgery in inoperable patients with superficial gastric cancer.

Recently, endoscopic surgery for small superficial gastric carcinomas has become increasingly more challenging, and the treatment criteria remain controversial.

To examine the metastatic potential of intramucosal gastric cancers (IMGCs), IMGCs with regional lymph node involvement (NI) were compared with IMGCs without regional lymph NI clinicopathologically. To clarify the metastatic behavior of well differentiated adenocarcinoma (W-type), immunohistochemical staining using Ki-67 and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were performed.

Of the 943 lesions with IMGC, 21 (2.2%) were NI on histologic examination. There was no significant difference between the macroscopic classification and the incidence of NI. The sizes of the IMGCs with NI (median, 4.3 cm) were significantly larger than the IMGCs without NI (median, 2.4 cm). Among the histologic grades classified according to the predominant features, the incidence of NI in poorly differentiated adenocarcinoma (P-type) (12/304, 3.9%) was significantly higher than that in well differentiated (W-type) (6/489, 1.2%). Besides the 12 P-type IMGCs, 6 well and moderately differentiated type IMGCs contained some poorly differentiated components, totaling 18 IMGCs (86%) that were either mainly or partially P-type. Among the W-type IMGCs, the mean values of the Ki-67 and PCNA labeling indices (LI) for IMGCs with NI (Ki-67, 47.5%; PCNA, 58.3%) were higher than those of the 25 randomly selected IMGCs without NI (Ki-67, 39.2%; PCNA, 39.9%).

The potential for NI in IMGCs seems to be related closely to tumor size, the presence of poorly differentiated components, and, particularly in the W-type IMGC, the LI that are demonstrated immunohistochemically with Ki-67 and/or PCNA.