Robotic extraperitoneal stoma closure with left hemicolectomy for descending colon cancer following abdominoperineal resection: A case report.

Extraperitoneal colostomy is often selected to reduce the risk of parastomal hernia. However, its closure surgery is rare and seldom reported. Here, we report our unique experience with robotic left hemicolectomy and extraperitoneal colostomy closure. An 83-year-old female was diagnosed with descending colon cancer with stenosis. She had previously undergone abdominoperineal resection with extraperitoneal colostomy. After improving the intestinal obstruction with a self-expanding stent, we performed robotic left hemicolectomy and extraperitoneal colostomy closure. Thanks to the multijoint function of the robot, which enables the forceps to be angled up to 90° in all directions, we could dissect the stoma from the abdominal wall up to just beneath the rectus abdominis in an intra-abdominal procedure without enlarging the skin incision. This case suggests that robotic surgery with the articulating function is beneficial for procedures near the abdominal wall ceiling and effective for extraperitoneal colostomy closure.

The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer.

BACKGROUND: Despite advances in the treatment of cancer, pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to the lack of effective therapies. Our previous study showed that Luteolin (Lut), a flavonoid, suppressed pancreatocarcinogenesis and reduced the expression of dihydropyrimidine dehydrogenase (DPYD), an enzyme that degrades pyrimidines such as 5-fluorouracil (5-FU), in PDACs. In this study, we investigated the role of DPYD and evaluated the therapeutic potential of combining 5-FU with Lut in PDACs. METHODS AND RESULTS: PDAC cells overexpressing DPYD showed increased proliferation, and invasiveness, adding to the resistance to 5-FU. The xenograft tumors of DPYD-overexpressing PDAC cells also exhibit enhanced growth and invasion compared to the control xenograft tumors. RNA-seq analysis of the DPYD-overexpressing PDAC xenograft tumors revealed an upregulation of genes associated with metallopeptidase activity-MMP9 and MEP1A. Furthermore, the overexpression of MEP1A in PDAC was associated with invasion. Next, we investigated the combined effects of Lut, a DPYD suppressor, and 5-FU on DPYD-overexpressing xenograft tumors and PDAC of Pdx1-Cre; LSL-KrasG12D/+; Trp53flox/flox(KPPC) mice. Neither single administration of 5-FU nor Lut showed significant inhibitory effects; however, the combined administration of 5-FU and Lut exhibited a significant tumor-suppressive effect in both the xenograft tumors and KPPC models. CONCLUSION: We have elucidated that DPYD expression contributes to proliferation, invasiveness, and 5-FU resistance, in PDACs. The combination therapy of Lut and 5-FU holds the potential for enhanced efficacy against PDACs.

Visualization of cecal tumor by near-infrared laparoscopy and intraoperative colonoscopy.

BACKGROUND: In laparoscopic colorectal surgery, accurate localization of a tumor is essential for ensuring an adequate ablative margin. Therefore, a new method, near-infrared laparoscopy combined with intraoperative colonoscopy, was developed for visualizing the contour of a cecal tumor from outside of the bowel. The method was used after it was verified on a model that employed a silicone tube. CASE PRESENTATION: The patient was a 77-year-old man with a cecal tumor near the appendiceal orifice. Laparoscopy was used to clamp of the terminal ileum, and a colonoscope was then inserted through the anus to the cecum. The laparoscope in the normal light mode could not be used to identify the cecal tumor. However, a laparoscope in the near-infrared ray mode could clearly visualize the contour of the cecal tumor from outside of the bowel, and the tumor could be safely resected by a stapler. The histopathological diagnosis of the resected specimen was adenocarcinoma with an invasion depth of M and a clear negative margin. CONCLUSIONS: This is the first report of the laparoscopic detection of the contour of a cecal tumor from outside the bowel. This technique is useful and safe for contouring tumors in laparoscopic colorectal surgery and can be used in various surgeries that combine endoscopy and laparoscopy.

Unanticipated pathological clearance in two cases of clinical T4b dMMR/MSI-h advanced colorectal cancer: the potential of immune checkpoint inhibitors despite positive positron-emission tomography results.

BACKGROUND: The standard treatment for colorectal cancer consists of surgery and chemotherapy, which can be combined to improve outcomes. Immune checkpoint inhibitors (ICI) are a significant advancement in the standard treatment of metastatic, unresectable colorectal cancer with deficient mismatch repair (dMMR). However, limited data are available about the use of ICI in the neoadjuvant and conversion settings. Here, we present two cases treated with ICI. CASE PRESENTATION: Case 1: A 75-year-old male with a large, borderline resectable rectal cancer diagnosed as cT4bN1bM0 who underwent neoadjuvant chemotherapy, followed by combination ICI consisting of ipilimumab and nivolumab. After four courses of ICI, the tumor significantly shrank, but positron emission tomography still showed a positive result and R0 resection was performed. Pathological analysis revealed no residual cancer cells. The patient has been monitored without adjuvant chemotherapy, and no recurrences have occurred after one year. Case 2: A 60-year-old male with locally advanced sigmoid colon cancer who received neoadjuvant treatment with pembrolizumab. The tumor partially shrank after three courses, and continued pembrolizumab monotherapy resulted in further tumor shrinkage which still showed positive positron emission tomography. Curative sigmoidectomy with partial resection of the ileum and bladder was performed, and the pathological outcome was pCR. There was no viable tumor in the specimen. The patient has been monitored without adjuvant chemotherapy for six months, and no recurrence has been observed. CONCLUSIONS: The present study reports two cases, including a large, borderline resectable rectal cancer after failure of chemotherapy followed by combination treatment with nivolumab and ipilimumab and one case of sigmoid colon cancer after pembrolizumab treatment, which resulted in pathological complete response. However, it remains unknown whether ICI therapy can replace surgery or diminish the optimal extent of resection, or whether adjuvant chemotherapy is needed after surgery in the case of achieving pCR after ICI therapy. Overall, this case report suggests that ICI before colorectal surgery can be effective and potentially a 'watch-and-wait" strategy could be used for cases in which ICI is effective.

Expression of ZKSCAN3 protein suppresses proliferation, migration, and invasion of pancreatic cancer through autophagy.

Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.

The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines.

We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.

Robotic resection for splenic artery aneurysm associated with neurofibromatosis type 1: a case report.

BACKGROUND: Neurofibromatosis type 1 is an autosomal-dominant disease characterized by café-au-lait spots and neurofibromas, as well as various other symptoms in the bones, eyes, and nervous system. Due to its connection with vascular fragility, neurofibromatosis type 1 has been reported to be associated with vascular lesions, such as aneurysms. However, there have been few reports of abdominal visceral aneurysms associated with neurofibromatosis type 1. Furthermore, there have been no reports of robotic treatment of aneurysms associated with neurofibromatosis type 1. In this report, we describe the case of a patient with neurofibromatosis type 1 with a splenic artery aneurysm who was successfully treated with robotic surgery. CASE PRESENTATION: This report describes a 41-year-old Asian woman with a history of neurofibromatosis type 1 who was referred to our hospital for evaluation of a 28 mm splenic artery aneurysm observed on abdominal ultrasound. The aneurysm was in the splenic hilum, and transcatheter arterial embolization was attempted; however, this was difficult due to the tortuosity of the splenic artery. Thus, we suggested minimally invasive robotic surgery for treatment and resection of the splenic artery aneurysm with preservation of the spleen. The postoperative course was uneventful, and the patient was discharged on the eighth day after surgery. At 1 year of follow-up, the patient was doing well, with no evidence of recurrence. CONCLUSION: We encountered a rare case of splenic artery aneurysm in a patient with neurofibromatosis type 1 who was successfully treated with robotic surgery. There is no consensus on treatment modalities for neurofibromatosis-related aneurysms, and endovascular treatment is considered safe and effective; however, surgery remains an important treatment modality. Especially in patients with stable hemodynamic status, robotic surgery may be considered as definitive treatment. To our knowledge, this is the first successfully treated case of a splenic artery aneurysm in a patient with neurofibromatosis type 1.

Suctionable Gauze Ball Operated by the Console Surgeon Overcomes Wet Scenes during Robotic Rectal Surgery.

Although robotic rectal resections are now widely performed, there are few robotic suction tools that can be easily used by console surgeons. It can therefore be difficult to maintain a clear visual field in the pelvis when there is effusion and bleeding from either a highly advanced cancer or from preoperative cancer treatment. In this report, we introduce our unique surgical technique that uses a soft catheter with a small gauze ball attached, inserted through the assistant port. This simple and inexpensive "instrument" can be used by the console surgeon as a retractor as well as a reliable suction device to secure their view of the operative field in the pelvis. This technique can be used in a narrow surgical field and does not rely on an assistant surgeon, making it potentially applicable to all types of surgery.

Robotic distal gastrectomy plus spleen-preserving distal pancreatectomy: optimal resection for simultaneous gastric cancer and intraductal papillary mucinous neoplasm of the pancreatic body.

BACKGROUND: Organ-preserving surgery has recently gained increasing attention. However, performing the surgery for duplicated gastric and distal pancreatic tumors is difficult because of procedural complexity and concerns of remnant gastric necrosis. We present the first case of simultaneous robotic distal gastrectomy plus spleen-preserving distal pancreatectomy in a patient with overlapping gastric cancer and intraductal papillary mucinous neoplasm. CASE PRESENTATION: A 78-year-old man was diagnosed with gastric cancer in the middle stomach and intraductal papillary mucinous neoplasm of the pancreatic body. Radical cure surgery was performed using the da Vinci Xi robotic system. Conventional distal gastrectomy was initially completed using near-infrared ray guidance when transecting the stomach. After dividing the pancreas, the parenchyma of the distal pancreas was detached from the splenic artery and vein; multiple branches from these splenic vessels were dissected. Indocyanine green imaging confirmed sufficient blood flow in the splenic vessels and perfusion of the remnant stomach. Ultimately, gastrointestinal reconstruction was performed, and the postoperative course was uneventful. CONCLUSIONS: The robotic distal gastrectomy plus spleen-preserving distal pancreatectomy procedure was safely performed. Compared to the total gastrectomy plus distal pancreatectomy with splenectomy procedure, this technique may improve the quality of dietary life, reduce weight loss, and prevent complications associated with splenectomy.

Simultaneous presentation and resection of esophageal cancer and metastasis to the pancreas: Α case report and literature review.

The frequency of metastasis to the pancreas is limited, and the frequency of metastasis of a squamous cell carcinoma of the esophagus is limited even further. The curative resection of this type of metastatic lesion has been reported for some patients; however, the survival benefit that can be attributed to these procedures has not yet been clearly determined. The patient examined in the present study was a 54-year-old man who was diagnosed with a lower thoracic esophageal cancer. Computed tomography revealed a 2-cm tumor at the tail of the pancreas. Since no other obvious distal metastases were observed, the patient underwent simultaneous surgical procedures, excising the esophageal squamous cell carcinoma and the pancreatic metastasis. A histopathological examination confirmed squamous cell carcinoma in both specimens. The patient has been free of disease for 9 months since the resection. A literature review of all relevant cases to date also demonstrated that the primary tumor site in all cases of patients with esophageal cancer presenting with metastasis to the pancreas was the lower thoracic esophagus. Complete simultaneous resections of esophageal squamous cell carcinoma and a solitary metastasis to the pancreas is beneficial and may produce favorable outcomes. However, due to the reduced number of corresponding reports, further studies are required for the confirmation of the benefits of surgery.

[A Case of Transverse Colon Cancer with Gastrointestinal Amyloidosis Prevented from Anastomotic Leakage by Multidimensional Approach].

The patient was a 68-year-old woman who was on hemodialysis due to systemic amyloidosis and nephrotic syndrome. Biopsy revealed amyloid deposition in the stomach, duodenum, and colon. A transverse colon tumor was found on a follow- up CT after the aortic dissection surgery. We performed lower gastrointestinal endoscopy and contrast-enhanced CT and diagnosed transverse colon cancer with gastric wall infiltration(cStage Ⅲc). We considered that transverse colon resection was oncologically sufficient. However, due to concurrent gastrointestinal amyloidosis, which increased the risk of anastomotic leakage we performed laparoscopic extended right hemicolectomy to avoid colon-colon anastomosis with partial gastrectomy. Additionally intraoperative indocyanine green(ICG)fluorescence imaging showed that the fluorescence signal in the small intestinal wall was satisfactory, while it was weak in the colon wall. As a result, we suspected of impaired blood flow of colon wall due to an amyloidosis, so we additionally created a loop ileostomy. It is said that gastrointestinal amyloidosis raises the risk of anastomotic leakage. A case of transverse colon cancer complicated by gastrointestinal amyloidosis in which we successfully prevented anastomotic leakage through a multidimensional evaluation and approach is reported, along with a literature review.

Laparoscopic pancreas-preserving duodenectomy: Minimally invasive surgery for superficial nonampullary duodenal epithelial tumors.

No consensus exists regarding the optimal treatment for superficial nonampullary duodenal epithelial tumors. Herein, we describe a laparoscopic pancreas-preserving duodenectomy for the treatment of a 30-mm adenoma located in the third portion of the duodenum. The adenoma was located on the pancreatic side, further hindering safe endoscopic resection. Via laparoscopy, the jejunum was transected first. After releasing the third portion of the duodenum from the retroperitoneal space, the jejunum was pulled to the right side of the superior mesenteric artery and separated from the pancreas. Under endoscopic guidance, the duodenum was then transected and duodenojejunostomy performed intracorporeally. Laparoscopic pancreas-preserving duodenectomy can be considered minimally invasive, achieving tumor radicality while preserving organs and causing minimal destruction to the abdominal wall. In conclusion, although technically demanding, laparoscopic pancreas-preserving duodenectomy is a valuable treatment option for superficial nonampullary duodenal epithelial tumors.

"Role-sharing surgery": a new surgical education system that gives beginner surgeons more chances to operate while ensuring the surgical quality of robotic surgery.

It has been pointed out that robotic surgery is more time-consuming than laparoscopic surgery, and a major challenge for the future is educating young surgeons while maintaining the surgical quality. To solve these problems, we report a role-sharing surgery (RSS) approach in which the surgery is divided into several areas and timetabled, with roles shared by several operators. We performed RSS for 19 standard colorectal cancer surgeries. The surgery was completed within + 28 min of the scheduled operation time, and a beginner robotic surgeon (BRS) was able to perform approximately 66% of the total surgery. There were no statistically significant differences in the short-term outcomes between the RSS and conventional surgery groups. Based on these findings, RSS has the potential to be the best practice for educating BRSs in robotic surgery, the use of which is expected to increase steadily in the future.

Natural Products and Cancer.

Natural and dietary compounds are known to offer protection and affect the pathogeneses of numerous chronic diseases [...].

Dual role of autotaxin as novel biomarker and therapeutic target in pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (panNENs) are rare pancreatic neoplasms, and descriptions of treatment remain limited. Autotaxin (ATX) is a secreted autocrine motility factor involved in the production of lysophosphatidic acid (LPA), a lipid mediator that promotes the progression of various cancers. The aim of this study was to clarify the importance of the ATX-LPA axis in panNENs and to confirm its contribution to panNEN progression using clinical data, cell lines, and a mouse model. Serum ATX level was higher in patients with panNEN than in patients with other pancreatic diseases (chronic pancreatitis, pancreatic ductal adenocarcinoma [PDAC], intraductal papillary mucinous neoplasm, autoimmune pancreatitis) and healthy controls, and 61% of clinical specimens stained strongly for ATX. In a case we encountered, serum ATX level fluctuated with disease progression. An in vitro study showed higher ATX mRNA expression in panNEN cell lines than in PDAC cell lines. Cell proliferation and migration in panNEN cell lines were stimulated via the ATX-LPA axis and suppressed by RNA interference or inhibitors. An in vivo study showed that intraperitoneal injection of GLPG1690, an ATX inhibitor, suppressed tumor progression in a xenograft model. These findings revealed that ATX expression is significantly elevated in panNEN and is related to the progression of panNEN. We showed the potential of ATX as a novel biomarker and therapeutic target.

Girdin regulates both migration and angiogenesis in pancreatic cancer cell lines.

Girdin, an actin­binding protein, is reportedly involved in the invasion and angiogenesis of various cancers. It has been suggested that the flavonoid Scutellarin (SCU) inhibits Girdin signaling. In the present study, the function and therapeutic applications of Girdin in pancreatic cancer (PaCa) were investigated. Immunohistochemical staining of Girdin in resected PaCa specimens from the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science showed that high Girdin expression was associated with poor overall survival and relapse­free survival, as well as with T factor, indicating invasion into the surrounding tissues. On the other hand, Girdin was highly expressed in almost all PaCa cell lines, and the migration ability of Girdin­knockdown cell lines was decreased even under epidermal growth factor (EGF) stimulation. In addition, SCU suppressed PaCa cell migration by inhibiting the phosphorylation of Girdin. The expression and production of vascular endothelial growth factor A (VEGF­A) was significantly decreased in Girdin­knockdown cell lines. Furthermore, in Matrigel tube formation assays performed using culture supernatant, the lumen­forming ability of vascular endothelial cells was also decreased in Girdin­knockdown cell lines. However, SCU treatment did not significantly alter the expression or production of VEGF­A. These results suggested that Girdin is involved in EGF signaling­mediated migration of PaCa cells, that SCU inhibits PaCa invasion by suppressing Girdin activity, and that Girdin is also involved in angiogenesis via an activation pathway different from the action site of SCU. Girdin may be a prognostic biomarker, and the development of a novel molecular­targeted drugs for Girdin may improve the prognosis of PaCa in the future.

Glissonean Pedicle Isolation Focusing on the Laennec's Capsule for Minimally Invasive Anatomical Liver Resection.

Background: Inflow control is one of the most important procedures during anatomical liver resection (ALR), and Glissonean pedicle isolation (GPI) is one of the most efficacious methods used in laparoscopic anatomical liver resection (LALR). Recognition of the Laennec's capsule covering the liver parenchyma is essential for safe and precise GPI. The purpose of this study was to verify identification of the Laennec's capsule, to confirm the validity of GPI in minimally invasive surgery, and to demonstrate the value of GPI focusing on the Laennec's capsule using a robotic system that has been developed in recent years. Methods: We used a cadaveric model to simulate the Glissonean pedicle and the surrounding liver parenchyma for pathologic verification of the layers. We performed 60 LALRs and 39 robotic anatomical liver resections (RALRs) using an extrahepatic Glissonean approach, from April 2020 to April 2023, and verified the layers of the specimens removed during LALR and RALR based on pathologic examination. In addition, the surgical outcomes of LALR and RALR were compared. Results: Histologic examination facilitated by Elastica van Gieson staining revealed the presence of Laennec's capsule covering the liver parenchyma in a cadaveric model. Similar findings were obtained following LALR and RALR, thus confirming that the gap between the Glissonean pedicle and the Laennec's capsule can be dissected without injury to the parenchyma. The mean GPI time was 32.9 and 27.2 min in LALR and RALR, respectively. The mean blood loss was 289.7 and 131.6 mL in LALR and RALR, respectively. There was no significant difference in the incidence of Clavien-Dindo grade ≥III complications between the two groups. Conclusions: Laennec's capsule is the most important anatomical landmark in performing a safe and successful extrahepatic GPI. Based on this concept, it is possible for LALR and RALR to develop GPI focusing on the Laennec's capsule. Furthermore, a robotic system has the potential to increase the safety and decrease the difficulty of this challenging procedure.

Upregulation of integrin­linked kinase enhances tumor progression in gemcitabine­resistant pancreatic cancer.

Pancreatic cancer (PaCa) tends to be resistant to chemotherapy and is associated with a very poor prognosis. It has been previously reported by the authors that integrin­linked kinase (ILK) is a prognostic factor in PaCa. ILK expression was examined in a newly established gemcitabine (Gem)­resistant (Gem­R) PaCa cell line and it was demonstrated that ILK expression was upregulated compared with that in Gem­sensitive (Gem­S) cells. In the present study, the effects of increased ILK expression in Gem­R PaCa cells were evaluated and it was examined whether compound 22 (Cpd22), an ILK inhibitor, exerted antitumor effects not only in Gem­S cells but also in Gem­R cells. Reverse transcription­quantitative polymerase chain reaction and western blotting revealed that ILK expression was higher in Gem­R PaCa cells than in Gem­S PaCa cells. Cpd22 inhibited the growth of PaCa cells in a concentration­dependent manner. Cpd22 also inhibited the growth of Gem­R PaCa cells. The invasive and angiogenic potential of Gem­R PaCa cells was enhanced compared with that in Gem­S cells; however, ILK small interfering RNA and Cpd22 treatment suppressed this enhancement of invasive potential compared with that in Gem­S cells. The addition of Cpd22 to Gem also improved the sensitivity of Gem­R cell lines to Gem. Furthermore, enhanced Akt signaling was associated with increased malignancy in Gem­R cell lines. In conclusion, ILK was upregulated with resistance and may be involved in tumor angiogenesis, invasive potential, and chemotherapy resistance, which were all suppressed by Cpd22 treatment. Thus, Cpd22 may be a novel therapeutic agent for the treatment of PaCa.

Spontaneous regression of advanced transverse colon cancer with deficient mismatch repair: a case report.

BACKGROUND: Spontaneous regression (SR) of cancer occurs in 1 in 60,000-100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer. CASE PRESENTATION: A 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0-IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR. CONCLUSION: This study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

Elevated Preoperative Serum Vascular Endothelial Growth Factor Does Not Predict Poor Outcomes in Curatively Resected Non-metastatic Colorectal Cancer Treated Without Neoadjuvant Therapy.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) influences colorectal cancer (CRC) progression and is a key target in the treatment for metastatic CRC. However, the oncological impact of preoperative circulating VEGF in non-metastatic CRC (non-mCRC) has not been clearly elucidated. Herein, we have investigated the prognostic significance of elevated preoperative serum VEGF concentration in curatively resected non-mCRC without neoadjuvant therapy. PATIENTS AND METHODS: A total of 474 patients with pStage I-III CRC who underwent curative resection without neoadjuvant therapy were included. The relationship between preoperative serum VEGF concentration and clinicopathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were investigated. RESULTS: The median follow-up duration was 47.4 months. No significant relationship between preoperative VEGF and clinicopathologic characteristics including tumor markers, pStage, and lymphovascular invasion was identified; however, VEGF values were wide-ranged in every pStage. Patients were categorized into four groups as follows: VEGF < median, median to 75th percentile, 75th percentile to 90th percentile, and ≥90th percentile. A tendency for a difference in 5-year OS (p=0.064) and RFS (p=0.089) was observed among the groups; however, OS and RFS were not correlated with VEGF elevation. In multivariate analyses, VEGF ≥90th percentile was paradoxically associated with better RFS. CONCLUSION: Preoperative elevated serum VEGF concentration was associated with neither worse clinicopathological characteristics nor worse long-term outcomes in curatively resected non-mCRC. The prognostic value of preoperative circulating VEGF in initially resectable non-mCRC remains limited.