Long-Term Survival Outcomes After Minimally Invasive Surgery for Ileal Neuroendocrine Tumors.

BACKGROUND: Ileal neuroendocrine tumors (i-NETs) are characterized by their multifocality and bulky mesenteric mass. Having shown that minimally invasive surgery (MIS) utilizing a hand-access port device has favorable short-term outcomes and achieves the goals of surgery for i-NETs, we sought to analyze long-term survival outcomes of MIS. METHODS: One hundred and sixty-eight patients who underwent resection of primary i-NETs at a single institution between January 2007 and February 2023 were retrospectively studied. Patients were categorized into the MIS or open surgery cohorts on an intention-to-treat basis. Open surgery was selected mainly based on the need for hepatectomy or bulky mesenteric mass resection. Overall survival was analyzed using log-rank tests with propensity score matching (PSM) and Cox proportional hazards regression. PSM was performed to reduce standardized mean differences of the variables to <0.2. RESULTS: Overall, 129 (77%) patients underwent MIS and 39 (23%) underwent open surgery. Twenty-seven MIS patients were converted to an open procedure. The median follow-up time was 49 months (interquartile range 23-87 months). In the PSM cohorts, overall survival did not differ significantly between the MIS and open surgery cohorts {median 99 months (95% confidence interval [CI] 91-not applicable [NA]) vs. 103 months (95% CI 86-NA), p = 0.77; hazard ratio 0.87 (95% CI 0.33-2.2), p = 0.77}. CONCLUSIONS: MIS is an alternative to open surgery for i-NETs, achieving similar short- and long-term oncological outcomes. Bulky mesenteric mass and a plan for concurrent liver resection are potential criteria for open surgery.

Traction-assisted endoscopic submucosal dissection for resection of ileocecal valve neoplasia: a French retrospective multicenter case series.

BACKGROUND: The ileocecal valve (ICV) is considered to be one of the most difficult locations for endoscopic submucosal dissection (ESD). The objective of this study was to evaluate the efficacy and safety of traction-assisted ESD in this situation. METHODS: All patients who underwent traction-assisted ESD for an ICV lesion at three centers were identified from a prospective ESD database. En bloc and R0 rates were evaluated. Factors associated with non-R0 resection were explored. RESULTS: 106 patients with an ICV lesion were included. The median lesion size was 50 mm (interquartile range 38-60) and 58.5% (62/106) invaded the terminal ileum. The en bloc and R0 resection rates were 94.3% and 76.4%, respectively. Factors associated with non-R0 resection were lesions covering ≥75% of the ICV (odds ratio [OR] 0.21. 95%CI 0.06-0.76; P=0.02), and involving the anal lip (OR 0.36, 95%CI 0.13-0.99; P=0.04) or more than two sites on the ICV (OR 0.27, 95%CI 0.07-0.99; P=0.03). CONCLUSION: Traction-assisted ESD for treatment of ICV lesions was a safe and feasible option. Large lesions and anal lip involvement appeared to be factors predictive of difficulty.

Tertiary lymphoid structures' pattern and prognostic value in primary adenocarcinoma of jejunum and ileum.

To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS < 1 group compared to PD-L1(22C3) score CPS ≥ 1 group (P = 0.071). TMB-H was significantly associated with MSI-H (P = 0.040). Univariate survival analysis demonstrated a correlation between high SFL-TLS group and prolonged disease free survival (DFS) (P = 0.047). There was also a trend towards prolonged DFS in the E-TLS-high group compared to the E-TLS-low group (P = 0.069). The peri-tumoral TLS (PT-TLS)-high group showed a trend of prolonged overall survival (OS) compared to the PT-TLS-low group (P = 0.090). In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.

Should we perform regular surveillance capsule endoscopies in patients following small-bowel adenocarcinoma resection? A case report and discussion.

Because small-bowel tumors are rare, prospective data on the utility of video capsule endoscopy (VCE) for their detection are limited. Current guidelines do not advocate for surveillance VCEs in patients following small-bowel tumor resection, which is mostly due to a lack of data. Here, we report an 81-year-old male patient who had undergone curative segmental ileal adenocarcinoma resection 15 years ago and another segmental jejunal adenocarcinoma resection (TNM-Classification: pT2 pN0 (0/2) G2M0) 7 years ago. He now presents with melena, progressive dyspnea, and decreased hemoglobin levels. VCE revealed local intestinal recurrence of the previously resected jejunal adenocarcinoma, leading to a second segmental jejunal resection (TNM-Classification: pT3 L1 pN0 (0/5) G2 M0). We believe that regular surveillance VCEs after the first jejunal adenocarcinoma resection might have facilitated earlier detection of tumor recurrence in this patient's case. Therefore, we suggest considering regular surveillance VCEs, at least in patients with recurrent small-bowel malignancies. However, future prospective studies are warranted to validate our findings.

[Multiple ileal neuroendocrine tumors 10mm in diameter with lymph node metastasis detected on endoscopy:a case report].

A 53-year-old man with an abnormal routine physical examination was referred to our hospital. Colonoscopy showed a 5-mm submucosal tumor that was 7cm proximal to the ileocecal valve. It was identified as a neuroendocrine tumor (NET) on biopsy. Preoperatively, we conducted a double balloon endoscopy to examine the entire small intestine. Another 7-mm submucosal tumor was found on the ileocecal valve, which was missed during the first colonoscopy. A final diagnosis of multiple ileal NETs (<10mm in diameter) was made, and the patient underwent ileocecal resection with lymphadenectomy. Histopathological evaluation of the surgical specimen verified the diagnosis of NET Grade 1 with submucosal invasion. Metastasis to lymph node #202 was also detected. He remained relapse-free for 5 years and 5 months after the operation. In conclusion, this was a case of multiple ileal NETs (<10mm in diameter) with lymph node metastasis that could not be detected preoperatively on contrast-enhanced computed tomography. This case highlights the significance of detailed endoscopic observation of the terminal ileum.

[A Patient with Small Intestinal Leiomyosarcoma and Intussusception Who Underwent Single Port Surgery].

The patient was a 33-year-old female. She was referred to our hospital from a previous clinic with abdominal pain and vomiting. Contrast-enhanced abdominal CT revealed intussusception, leading to a diagnosis of intussusception with a small intestinal tumor as an advanced part. Intestinal obstruction symptoms were observed, and emergency surgery was performed on the same day. As a technique, single port surgery was selected, and laparoscopic reduction was attempted. However, it was ineffective. The site of intussusception was induced outside the body through a small laparotomy wound, and reduction was performed using Hutchinson's procedure. As an adjacent lymph node was markedly swollen, the mesentery involving this lymph node was dissected in a fan shape, and the tumor was extirpated. The tumor measured 40 mm in long diameter, being a hemicircular, protruding lesion. Histologically, disarray of short spindle tumor cells was observed. Immunostaining showed Kit- and DOG1-negtive reactions and partially α-SMA and desmin-positive reactions, suggesting leiomyosarcoma. With the establishment of an immunostaining-test-based classification, leiomyosarcoma is currently rare. In this study, we report a patient in whom single port surgery for intussusception related to small intestinal leiomyosarcoma was successful.

Unifocal versus Multiple Ileal Neuroendocrine Tumors Location: An Embryological Origin.

INTRODUCTION: Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET. PATIENTS AND METHODS: Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least 1 non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40 cm from the ileocecal valve), and unifocal ones on the right side. RESULTS: Ninety-four patients were included, 6 with unifocal jejunal-NET located 35 cm (range, 10-60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2-95), within a median small bowel segment of 105 cm (10-240). The median length between the proximal tumor and the DJA was 428 cm (300-635) and 540 cm (350-725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577 cm (305-820) from the DJA (p < 0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p < 0.001). CONCLUSION: Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.

How to Manage Small Intestine (Jejunal and Ileal) Neuroendocrine Neoplasms Presenting with Liver Metastases?

PURPOSE OF REVIEW: Small intestinal neuroendocrine neoplasms (siNENs) are slowly growing tumours with a low malignant potential. However, more than half of the patients present with distant metastases (stage IV) and nearly all with locoregional lymph node (LN) metastases at the time of surgery. The value of locoregional treatment is discussed controversially. RECENT FINDINGS: In stage I to III disease, locoregional surgery was currently shown to be curative prolonging survival. In stage IV disease, surgery may prolong survival in selected patients with the chance to cure locoregional disease besides radical/debulking liver surgery. It may improve the quality of life and may prevent severe local complications resulting in a state of chronic malnutrition and severe intestinal ischaemia or bowel obstruction. Locoregional tumour resection offers the opportunity to be curative or to focus therapeutically on liver metastasis, facilitating various other therapeutic modalities. Risks and benefits of the surgical intervention need to be balanced individually.

Bleeding Edge Therapy: Ileocolic Intussusception Due to Ileocecal Valve Adenocarcinoma and Its Management in an Adult Patient-Case Report and Literature Review.

Adenocarcinoma as the primary cause of bowel intussusception is uncommon. We describe the case of a 86-year-old patient admitted for ileocecal intussusception due to the presence of adenocarcinoma, located in the ileocecal valve and right colon. The etiologies of intussusception, its diagnosis, and conservative or surgical treatments are discussed, with attention placed on the indications for reduction of the invagination prior to surgical resection.

Gastrointestinal and oncologic outcomes of pediatric gastrointestinal lymphoma following upfront resection or biopsy of bowel masses.

PURPOSE: Complete upfront resection of pediatric gastrointestinal lymphomas is recommended over biopsy whenever feasible, but either approach may have adverse sequelae. We sought to compare gastrointestinal and oncological outcomes of pediatric gastrointestinal lymphomas who underwent attempted upfront resection or biopsy of the presenting bowel mass. METHODS: We retrospectively reviewed charts of children with gastrointestinal lymphomas treated on LMB89 and LMB96 protocols from 2000 to 2019 who underwent upfront gastrointestinal surgery, and compared resection and biopsy groups. RESULTS: Of 33 children with abdominal lymphomas, 20 had upfront gastrointestinal surgery-10 each had resection or biopsy. Patients with attempted upfront resections had fewer postoperative gastrointestinal complications compared to biopsies (10% vs. 60%, p = 0.057), but longer time to chemotherapy initiation (median 11.5 vs. 4.5 days, p < 0.001). Three resection patients were surgically down-staged. Second surgeries were required in 30% and 40% of resected and biopsied patients, respectively, at median 4.6 months. Survival was similar in both groups, but better in patients on LMB96 protocol and stage II/III disease. CONCLUSIONS: Children with upfront attempted resection had low rates of surgical down-staging, greater delay in chemotherapy initiation, but fewer gastrointestinal complications and subsequent surgeries than biopsies. Survival was similar regardless of upfront surgery, likely reflecting beneficial effects of newer protocols.

Patterns of chromosome 18 loss of heterozygosity in multifocal ileal neuroendocrine tumors.

Ileal neuroendocrine tumors (NETs) represent the most common neoplasm of the small intestine. Although up to 50% of patients with ileal NETs are diagnosed with multifocal disease, the mechanisms by which multifocal ileal NETs arise are not yet understood. In this study, we analyzed genome-wide sequencing data to examine patterns of copy number variation in 40 synchronous primary ileal NETs derived from three patients. Chromosome (chr) 18 loss of heterozygosity (LOH) was the most frequent copy number alteration identified; however, not all primary tumors from the same patient had evidence of this LOH. Our data revealed three distinct patterns of chr18 allelic loss, indicating that primary tumors from the same patient can present different LOH patterns including retention of either parental allele. In conclusion, our results are consistent with the model that multifocal ileal NETs originate independently. In addition, they suggest that there is no specific germline allele on chr18 that is the target of somatic LOH.

Ovarian metastases from ileum cancer in a patient with germline EPCAM gene deletion successfully treated with surgical resection and CAPOX chemotherapy: a case report.

BACKGROUND: Despite recent findings that epithelial cell adhesion molecule (EPCAM) deletions can cause Lynch syndrome (LS), its clinical characteristics are still unknown. We present the first case of ileum cancer in a patient with germline EPCAM gene deletion, which was discovered during ovarian tumor surgery. CASE PRESENTATION: A 59-year-old woman presented with a history of colon cancer occurring at 38 and 55 years old. Five of her siblings had a history of colon cancer, and an elder sister had confirmed LS. As imaging examination revealed an ovarian tumor, and we performed hysterectomy and bilateral salpingo-oophorectomy. Careful observation during surgery revealed a cherry-sized tumor in the ileum, prompting partial ileal resection. Pathological examination showed the ovarian tumor to be a metastasis of ileum cancer. Genetic testing with blood-relative information using multiplex ligation-dependent probe amplification showed EPCAM exons 8 and 9 deletions, confirming LS. The patient received adjuvant chemotherapy with CAPOX (capecitabine and oxaliplatin) and has remained disease-free for 24 months. CONCLUSIONS: We were fortunate to identify ileum cancer that would have been difficult to find preoperatively through careful observation during ovarian tumor surgery and successfully treated the patient by using surgical resection and CAPOX chemotherapy. When treating patients with hereditary cancer syndromes including LS, we should keep all associated cancers in mind.

An isolated vaginal metastasis from intestinal signet ring cell carcinoma: a case report and literature review.

BACKGROUND: Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history. CASE PRESENTATION: We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes. CONCLUSIONS: We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.

Small Bowel Adenocarcinomas: Impact of Location on Survival.

BACKGROUND: Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS: Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS: Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS: Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.

A novel stratification of mesenteric mass involvement as a predictor of challenging mesenteric lymph node dissection by minimally invasive approach for ileal neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: We classified the extent of mesenteric mass (MM) involvement that predicts challenging mesenteric lymph node dissection (mLND) by minimally invasive surgery (MIS) for ileal neuroendocrine tumors (i-NETs). METHODS: Patients who underwent surgery for i-NETs were retrospectively reviewed. MM involvement was classified as region-0: no MM; region-1: >2 cm from the origins of the ileocolic artery/vein; region-2: ≤2 cm from the origins; and region-3: more proximal superior mesenteric artery/vein. Logistic regression analysis was used to evaluate the predictive value of MM regions for gross positive mesenteric margin (mR2) and/or conversion among the MIS cohort. The open surgery cohort was used as a reference for mR2 rates. RESULTS: Of 108 patients, 83 patients (77%) underwent MIS. MMs in region-2 and region-3 were independent risk factors for mR2 and/or conversion (odds ratio [95% confidence interval]: 4.25 [1.17-16.4] and 8.51 × 107 [11.0-], respectively, against regions-0 and 1]. mR2 rates of MIS and open surgery cohorts per region did not differ significantly (4% and 7% for regions-0 and 1; 17% and 25% for region-2; and 100% and 83% for region-3). CONCLUSIONS: The novel stratification of MM regions was predictive of challenging mLND by MIS. Surgeons should have a low threshold for conversion for MMs in proximal regions.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma.

Background: Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities. The association of PD-1/PD-L1 expression and its impact on patient prognosis with SBA is unclear. Material and methods: Seventy-five consecutive patients who underwent surgery for SBA were retrospectively analyzed and stained for PD-L1 expression in the tumour or the stroma. Analysis of mismatch repair genes was performed to determine microsatellite status. Kaplan-Meier estimate was used to analyze patient survival. Univariate and multivariable Cox regression-analyses were used to assess the impact of PD-L1 expression and microsatellite status on patient survival.Results: PD-L1 was weakly upregulated within the tumour or the stroma and associated with prolonged survival (p = .0071 and p = .0472, respectively). Fifty-one tumours (68%) revealed microsatellite stability (MSS) and 24 tumours (32%) were microsatellite instable (MSI) without correlating with patient survival (p = .611). Neither PD-L1 expression in the tumour nor in the stroma was identified as an independent risk factor influencing survival (p = .572 and p = .3055).Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival.

[Mucinous cystadenoma of the ileocecal valve. Uncommon intestinal tumor in a oneyear-old boy. Case report]. / Cistoadenoma mucinoso de la vá lvula ileocecal: tumoración intestinal infrecuente en un niñ o de 1 añ o. Reporte de caso.

Mucinous cystadenoma is usually found in the ovary, pancreas and appendix but its presentation in the intestine is extremely rare. In this case report we present an infant with partial intestinal occlusion due to a mucinous cystadenoma of the ileocecal valve. We performed an excision of the terminal ileum, ileocecal valve, cecum and appendix, followed by ileocolic anastomosis. The patient did well after the procedure and recovered uneventfully. To our knowledge, this is the first case report of this tumor in this location.