[A Case of Lymphoepithelial Cyst of the Pancreas for Which Malignancy Could Not Be Ruled Out Difficult Preoperative Diagnosis].

Lymphoepithelial cyst(LEC)of the pancreas is a relatively rare benign cystic disease of the pancreas. In this report, we describe a case of LEC in which a malignant tumor could not be ruled out by preoperative diagnosis and surgery was performed. The patient was a 72-year-old man. A simple CT scan of the chest and abdomen performed as a follow-up for another disease incidentally revealed a mass in the pancreatic tail. Enhanced CT of the abdomen showed a tumor approximately 3 cm in size at the pancreatic tail with no contrast effect. MRCP showed moderate signal on T2WI, high signal on T1WI, and high signal on T2WI on some cysts inside the pancreas. PET-CT showed slight uptake of FDG. Both tumor markers CEA and CA19-9 were normal. Therefore, malignant disease such as pancreatic IPMC could not be ruled out, and laparoscopic distal pancreatectomy plus splenectomy was performed. The pathology results showed a diagnosis of pancreatic lymphoepithelial cyst with slight differentiation into sebaceous gland.

Prognostic Value of C-reactive Protein-to-albumin Ratio after Curative Resection in Patients with Colorectal Cancer.

Objectives: The current retrospective study aimed to evaluate the association between combined preoperative and postoperative C-reactive protein-to-albumin ratio, which is correlated with prognosis in different types of malignancies, and prognosis after curative resection in patients with colorectal cancer. Methods: This study enrolled 263 patients who underwent curative resection for stage II/III colorectal cancer. C-reactive protein-to-albumin ratio was calculated within 30 days before and 7 days after surgery. Receiver operating characteristic curve analyses were performed to determine the optimal cutoff values of preoperative and postoperative C-reactive protein-to-albumin ratio. The correlations between combined preoperative and postoperative C-reactive protein-to-albumin ratio and prognosis were analyzed. Results: The cutoff values of preoperative and postoperative C-reactive protein-to-albumin ratio were 0.223 and 0.813, respectively; higher ratios were significantly associated with poor overall survival, based on the Kaplan-Meier curves (p < 0.001, p = 0.003, respectively). Further, preoperative and postoperative C-reactive protein-to-albumin ratios were correlated with poor progression-free survival (p < 0.001, p = 0.064, respectively). In the multivariate analysis, combined preoperative and postoperative C-reactive protein-to-albumin ratio was an independent predictor of overall survival and progression-free survival (p = 0.012, p = 0.044, respectively). Compared with low preoperative and postoperative C-reactive protein-to-albumin ratio, high ratios of that were significantly associated with poor overall survival (hazard ratio = 3.897, p = 0.006) and progression-free survival (hazard ratio = 2.130, p = 0.029). Conclusions: Combined preoperative and postoperative C-reactive protein-to-albumin ratio, useful for prognostic prediction, can be a promising prognostic marker after curative resection in patients with colorectal cancer.

[A Case of Schwannoma in the Ascending Colon].

A 69-year-old man who was diagnosed with a submucosal tumor in the ascending colon by colonoscopy in X-7 year was presented. The endoscopic biopsy showed normal mucosa, and he had been followed up. During follow-up, computed tomography and colonoscopy performed in X year showed an enlargement of the tumor. Positron emission tomography-computed tomography showed intense FDG uptake. Malignant tumor was suspected, and laparoscopic-assisted right hemicolectomy was performed. The histopathological diagnosis showed spindle-shaped tumor cells proliferating in a fascicular manner. Immunohistochemical staining was positive for S-100 protein and negative for CD34, c-kit, and desmin, and schwannoma was diagnosed. Schwannomas are tumors derived from Schwann cells and therefore rarely develop in the gastrointestinal tract. Careful preoperative diagnosis is important because they do not normally metastasize or undergo malignant transformation.

[A Case of Retroperitoneal Leiomyosarcoma Treated with Repeated Surgical Resection].

A 55-year-old male revealed with a 5 cm-diameter mass in the lower abdomen on ultrasonography incidentally. Computed tomography showed a mass of 7 cm in size on the left side of the bladder. A malignant tumor was suspected, and surgically excised for purpose of diagnosis and treatment. Pathological examination confirmed retroperitoneal leiomyosarcoma, and the resection margins were negative. Follow-up computed tomography scan was performed every 3 months. Repeated resections were performed for twice recurrences within a year after surgery. A year after the first surgery, lung metastasis was detected and chemotherapy was started. Although retroperitoneal leiomyosarcoma is considered to have a poor prognosis, the present case had relatively good prognosis. This may be due to early detection and repeated surgical resection.

Plasma trough concentration of imatinib and its effect on therapeutic efficacy and adverse events in Japanese patients with GIST.

BACKGROUND: Imatinib mesylate (IM) is the standard chemotherapy for patients with gastrointestinal stromal tumors (GISTs) and has a favorable safety profile. Pharmacokinetics (PK), such as plasma trough concentration (Cmin), varies among patients, requiring the need for therapeutic drug monitoring (TDM) during IM administration. Despite some reports from overseas, the relationship between Cmin, adverse events (AEs), and treatment efficacy in Japanese patients with GIST has still been lacking. This study aimed to investigate the relationship between IM plasma concentration and AEs in Japanese patients with GISTs. METHODS: This retrospective study analyzed the data of 83 patients who underwent IM treatment for GISTs at our institution between May 2002 and September 2021. RESULTS: The IM Cmin was associated with any grade of AEs (with AEs vs. without AEs = 1294 (260-4075) vs. 857 (163-1886) ng/mL, P < 0.001), edema (with edema vs. without edema = 1278 (634-4075) vs. 1036 (163-4069) ng/mL, P = 0.017), and fatigue (with fatigue vs. without fatigue = 1373 (634-4069) vs. 1046 (163-4075) ng/mL, P = 0.044). Moreover, a Cmin ≥ 1283 ng/mL was a risk factor for severe AEs. The median progression-free survival (PFS) was 3.04 years in the lowest Cmin tertile (T1, < 917 ng/mL) compared with 5.90 years for T2 and T3 (P = 0.010). CONCLUSION: Edema and fatigue are potentially associated with IM plasma trough concentrations of ≥ 1283 ng/mL in Japanese patients with GISTs. Further, maintaining an IM plasma trough concentration above 917 ng/mL may improve PFS.

High Lymphocyte Count as a Significant Risk Factor for Incisional Hernia After Laparoscopic Colorectal Surgery.

BACKGROUND: In the era of laparoscopic surgery, incisional hernia (IH) remains a common complication of colorectal surgery. Various risk factors for IH have been evaluated to reduce the incidence, but the impact of nutrition on IH has not been well discussed. The aim of this study is to evaluate the relationship between nutritional status and the development of IH after laparoscopic colorectal surgery. MATERIALS AND METHODS: We retrospectively evaluated 342 colorectal cancer patients undergoing laparoscopic colectomy or proctectomy between January 2012 and December 2018. Postoperative computed tomography was used to diagnose the IH. Patient characteristics, including preoperative albumin and lymphocyte counts, were evaluated for the risk of development of IH. Further investigations were conducted regarding the impact of nutritional status on the development of IH in each patient of body mass index (BMI) under and over 25.0 kg/m 2 . RESULTS: IH was observed in 37 patients (10.8%), with a median follow-up period of 48.5 months. Female [odds ratio (OR)=3.43, P <0.01], BMI ≥25 kg/m 2 (OR=2.9, P <0.01), lymphocyte count ≥1798/µL (OR=3.37, P <0.01), and operative time ≥254 minutes (OR=3.90, P <0.01) had statistically significant relationships to IH in multivariate analysis. Low albumin was related to IH in BMI ≥25 kg/m 2 ( P =0.02), but was not in BMI<25 kg/m 2 ( P =0.21). On the other hand, a high lymphocyte count was related to IH regardless of BMI (BMI ≥25 kg/m 2 : P =0.01, BMI<25 kg/m 2 : P =0.04). CONCLUSIONS: A high preoperative lymphocyte count is an independent risk factor for IH, whereas a low albumin count is limited regarding predicting IH.

[Peritoneal Recurrence of Gastric Cancer Treated with Chemoradiotherapy-A Case Report].

A 76-year-old male patient underwent a distal gastrectomy for advanced gastric cancer. As the postoperative serum CA19-9 level was elevated, chemotherapy was initiated. Computed tomography(CT)detected a solitary peritoneal recurrence in the left subhepatic space 17 months later. Consequently, chemoradiotherapy(CRT)at a total dose of 60 Gy, combined with S-1 therapy, was administered for local tumor control. After CRT, CT scans revealed a remarkable reduction in the peritoneal recurrence. Presently, 8 months after CRT, the patient remains alive with no indications of regrowth. CRT could prove efficacious as a treatment for gastric cancer patients with localized peritoneal recurrences.

[A Case of Pathologic Complete Response Achieved with Preoperative Pembrolizumab Therapy for Transverse Colon Cancer].

A 77-year-old female patient presented with a medical history of 4 cancerous lesions, each with a surgical history. She was referred to our hospital due to anemia. Upon examination, she was diagnosed with transverse colon cancer. Duodenal invasion was suspected, which made performing R0 surgery difficult; therefore, the NAC approach was chosen. Three courses of CAPOX were administered, resulting in tumor obstruction, leading to the formation of an ileum stoma. MSI testing revealed MSI-H, and pembrolizumab treatment was initiated. CT scans showed tumor shrinkage, and PET scans indicated no accumulation, resulting in a cCR. Colon resection including the lesion suspected of stenosis was performed with a strong desire for stoma closure and the determination of potential curative resection. Additionally, a partial resection of the duodenum was performed. Pathological examination did not reveal any evident tumor cells, leading to the determination for a pCR. The patient has been under postoperative surveillance for 1 year without any recurrence.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

Correction: Lipolysis-stimulated lipoprotein receptor overexpression is a novel predictor of poor clinical prognosis and a potential therapeutic target in gastric cancer.

[This corrects the article DOI: 10.18632/oncotarget.25952.].

Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis.

BACKGROUND: Despite improvements in gastric cancer treatment, the mortality associated with advanced gastric cancer is still high. The activation of ß-adrenergic receptors by stress has been shown to accelerate the progression of several cancers. Accordingly, increasing evidence suggests that the blockade of ß-adrenergic signaling can inhibit tumor growth. However, the effect of ß-blockers, which target several signaling pathways, on gastric cancer remains to be elucidated. This study aimed to investigate the anti-tumor effects of propranolol, a non-selective ß-blocker, on gastric cancer. METHODS: We explored the effect of propranolol on the MKN45 and NUGC3 gastric cancer cell lines. Its efficacy and the mechanism by which it exerts anti-tumor effects were examined using several assays (e.g., cell proliferation, cell cycle, apoptosis, and wound healing) and a xenograft mouse model. RESULTS: We found that propranolol inhibited tumor growth and induced G1-phase cell cycle arrest and apoptosis in both cell lines. Propranolol also decreased the expression of phosphorylated CREB-ATF and MEK-ERK pathways; suppressed the expression of matrix metalloproteinase-2, 9 and vascular endothelial growth factor; and inhibited gastric cancer cell migration. In the xenograft mouse model, propranolol treatment significantly inhibited tumor growth, and immunohistochemistry revealed that propranolol led to the suppression of proliferation and induction of apoptosis. CONCLUSIONS: Propranolol inhibits the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis. These findings indicate that propranolol might have an opportunity as a new drug for gastric cancer.

Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors.

PURPOSE: Imatinib is the standard treatment for unresectable and metastatic GIST. In the late stages, patients undergoing imatinib show drug resistance. Surgical intervention has been occasionally performed for resistant lesions. However, the clinical significance of such intervention remains unclear. METHODS: Between 2006 and 2015, 37 patients were diagnosed with imatinib-resistant GISTs. We performed surgical intervention only for localized resistant lesions. We retrospectively investigated the background characteristics, data on surgical intervention and subsequent treatment, progression-free survival (PFS), and overall survival (OS). RESULTS: Eighteen patients diagnosed with localized resistance received surgical intervention (S-group) and 19 patients diagnosed with generalized resistance were received other TKIs (M-group). In S-group, no serious complications occurred, and all patients restarted imatinib after resection. The median PFS was 14.5 months. Five patients underwent surgical intervention multiple times followed by the continuation of imatinib, and the median duration of imatinib continuation was 22.2 months. Second-line TKIs were administered to 93% of the patients and the dose-intensity and outcome were similar in both groups. The median OS was 47.2 months after surgery. CONCLUSIONS: Surgical intervention could be performed safely and therefore could be followed by the continuation of TKI therapy. Surgical intervention based on the appropriate criteria of resistance might thus be useful for imatinib-resistant GISTs.

[A Case of Giant Intestinal GIST That Was Resected Just after TAE].

A 42-year-old woman visited our hospital complaining of fever and diarrhea. She had abdominal swelling and muscular defense. CT revealed a lobulated tumor occupying the lower abdomen. The tumor contained solid and cystic areas. The main artery vascularizing the tumor was the ileocecal artery, so we considered the tumor to be derived from the intestine or mesentery. We anticipated massive bleeding due to resection, and immediately after the embolization of the artery just before the operation. A vascular bundle from the terminal ileum and mesentery was found on the dorsal side of the tumor, and an outflow from the inferior mesenteric vein was also observed. We ligated each vessel and performed ileocecal resection. The operation lasted 4 hours and 18 minutes, with an estimated blood loss of 2,585 mL, requiring the transfusion of 6 units of concentrated red blood cells. According to histopathological findings, tumor cells with spindle-shaped to ellipsoidal nuclei proliferated in bundles and intricately, and immunostaining was positive for c-kit and DOG-1. We identified the tumor as high-risk GIST. The clinical course after the operation was uneventful. She continued to take imatinib for 3 years and is currently alive and without recurrence for 6 years after the operation.

A case of multiple serous cystadenoma of pancreas.

INTRODUCTION: Typically, SCN is single and doesn't invade around tissue. In our case, tumors were multiple and had gradually grown and caused vein stenosis. This is extremely rare and unique resected multiple SCN case. In addition, I report that it was thought to be educational that even benign tumors could cause such changes. PRESENTATION OF CASE: A 60-year-old female was diagnosed with 3 multilocular cystic tumors in distal pancreas by contrast enhanced computed tomography (CT) at the preoperative staging for rectal neoplasm. The diameters of cystic tumors were 22/23/29 mm. The CT showed that the tumors had multiple internal septa enhanced in the arterial phase and the second tumor contained internal calcifications located centrally. The main pancreatic duct was not dilated. Although SCN often occurred single and multiple SCN was very rare, we diagnosed that the tumors were suspected microcystic type SCN because they had typical image findings. So, we planned to follow up every six months after resection for rectal neoplasm. 2 years and half later, they had gradually grown, and splenic vein stenosis appeared. The pancreatic parenchyma atrophy and dilatation of the main pancreatic duct had been gradually progressing. We performed distal pancreatectomy because of possibility of malignancy. The histopathological findings showed that 2 cystic tumors the side of pancreatic head had a connection and had typical findings of SCA of pancreas. The other tumor was independent from two tumors. They had no malignant findings. DISCUSSION: At first, we expected tumor invasion had caused the changes. But tumors had no malignant findings, so we considered that compression from the tumor had caused stenosis, and obstructive pancreatitis had induced the pancreatic parenchyma atrophy. CONCLUSION: We learned from this case that not only invasion but also compression caused vein stenosis and pancreatic duct dilation.

[A Case of Early Rectal Cancer Accompanied by Multiple Liver Abscesses].

An 81-year-old female who suffered from headache and general fatigue was diagnosed multiple liver abscesses by abdominal computed tomography(CT). Antibiotics and percutaneous transhepatic abscess drainage(PTAD)were performed, liver abscesses were improved. During the treatment, followed abdominal CT indicated lower rectal tumor. An early rectal cancer accompanied by multiple liver abscesses was diagnosed and performed surgery. The histological diagnosis was Rb, type 1, tub2, pT1b(SM 8,000 µm), Ly0, V1a, pN0, pStage Ⅰ. After surgery, the patient remains free from liver abscess. We report early colorectal cancer with multiple liver abscesses in Japanese literature.

[A Case of Locally Advanced Appendiceal Cancer with Radical Resection after CAPOX plus Bevacizumab].

We report a case of a male in his sixties with appendiceal cancer who underwent radical resection following CAPOX plus bevacizumab neoadjuvant chemotherapy. The patient presented to our hospital with a chief complaint of chronic low abdominal pain. Contrast-enhanced CT before neoadjuvant chemotherapy revealed an inhomogeneous tumor in the ileocecal region. Invasion to the bladder and the sigmoid colon was also observed. A colonoscopy showed an elevated lesion, which was caused by extramural invasion to the sigmoid colon. Pathological examination of the sigmoid colon tumor revealed well differentiated tubular adenocarcinoma and KRAS codon13 G13D. Hence, we diagnosed the patient with locally advanced appendiceal cancer with invasion to the bladder and sigmoid colon. We administered CAPOX plus bevacizumab as neoadjuvant chemotherapy. Contrast-enhanced abdominal CT after neoadjuvant chemotherapy revealed shrinkage of the primary tumor and reduction in the invasion to the bladder and sigmoid colon. We performed ileocecal resection(+D3), a partial sigmoidectomy, and partial bladder resection on the 135th day from the diagnosis. The resected specimen showed an appendiceal tumor with invasion to the bladder and sigmoid colon. The pathological diagnosis was Ⅴ, yType 5, tub2>tub1, ypT4b, ypN0, ycH0, ycM0, ycPUL0, Ly1b, V1b(VB), Pn01b, pStage Ⅱa, and the histological treatment effect of preoperative therapy was Grade 1b. Our experience indicates that in patients with locally advanced appendiceal cancer, multimodal treatment with neoadjuvant chemotherapy is an effective option.

TAS-116 inhibits oncogenic KIT signalling on the Golgi in both imatinib-naïve and imatinib-resistant gastrointestinal stromal tumours.

BACKGROUND: Despite the effectiveness of imatinib mesylate (IM), most gastrointestinal stromal tumours (GISTs) develop IM resistance, mainly due to the additional kinase-domain mutations accompanied by concomitant reactivation of KIT tyrosine kinase. Heat-shock protein 90 (HSP90) is one of the chaperone molecules required for appropriate folding of proteins such as KIT. METHODS: We used a novel HSP90 inhibitor, TAS-116, which showed specific binding to HSP90α/ß with low toxicity in animal models. The efficacy and mechanism of TAS-116 against IM-resistant GIST were evaluated by using IM-naïve and IM-resistant GIST cell lines. We also evaluated the effects of TAS-116 on the other HSP90 client protein, EGFR, by using lung cell lines. RESULTS: TAS-116 inhibited growth and induced apoptosis in both IM-naïve and IM-resistant GIST cell lines with KIT activation. We found KIT was activated mainly in intracellular compartments, such as trans-Golgi cisternae, and TAS-116 reduced autophosphorylated KIT in the Golgi apparatus. In IM-resistant GISTs in xenograft mouse models, TAS-116 caused tumour growth inhibition. We found that TAS-116 decreased phosphorylated EGFR levels and inhibited the growth of EGFR-mutated lung cancer cell lines. CONCLUSION: TAS-116 may be a novel promising drug to overcome tyrosine kinase inhibitor-resistance in both GIST and EGFR-mutated lung cancer.

Lipolysis-stimulated lipoprotein receptor overexpression is a novel predictor of poor clinical prognosis and a potential therapeutic target in gastric cancer.

The prognosis of patients with advanced gastric cancer (GC) remains poor despite the recent advances in molecular targeted therapies, and the search for biomarkers that can predict prognosis and additional new agents with acceptable toxicity profiles are needed. Lipolysis-stimulated lipoprotein receptor (LSR) is a lipoprotein receptor that binds to triglyceride-rich lipoproteins and related to some malignancies. Herein, we examined the association between LSR expression and the prognosis of patients with GC, and investigated the antitumor effect of a previously developed anti-human LSR monoclonal antibody (#1-25). We first performed immunohistochemical analysis of LSR protein expression in GC and normal tissues, and then examined its association with the prognosis of 110 patients with GC. LSR was overexpressed in most of primary GC and metastatic tumors, but not in normal tissues. Patients with strong LSR expression (N = 80, 72.7%) had significantly poorer overall survival (OS) than those with weak expression (P = 0.017). Multivariate analysis identified strong LSR (as well as pT) as independent and significant prognostic factors for OS. Next, we demonstrated that very low density lipoprotein (VLDL) treatment increases cell proliferation in LSR-expressing GC cell lines in vitro; LSR inhibition using #1-25 inhibited VLDL-induced proliferation by suppressing JAK/STAT and PI3K signaling. In vivo, we demonstrated a marked antitumor effect of #1-25 in 2 distinct GC cell line xenograft mice models. Our findings suggest that LSR plays a key functional role in GC development, and that this antigen can be therapeutically targeted to improve GC treatment.

The feasibility and safety of single-incision totally extraperitoneal inguinal hernia repair after previous lower abdominal surgery: 350 procedures at a single center.

PURPOSE: To evaluate the feasibility and safety of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) with previous lower abdominal surgery (PLAS). METHODS: A retrospective analysis of 350 patients undergoing SILS-TEP for a primary inguinal hernia from January 2012 to December 2015 at Osaka Police Hospital was performed, and the outcomes of the patients with and without PLAS were compared. RESULTS: SILS-TEP was performed in 84 patients with PLAS and 266 patients without PLAS. Appendectomy was the most common previous operative procedure. There were more patients with an ASA score of ≥3 in the PLAS group than in the control group (p < 0.05). The mean operative time, and the rates of conversion and postoperative complications were comparable between the two groups. There were no cases of recurrence in either group. CONCLUSIONS: SILS-TEP could be safely performed in patients with PLAS and achieved better cosmetic outcomes than conventional laparoscopic surgery.