Pancreatic cancer with liver metastasis maintaining complete response with gemcitabine monotherapy: A case report.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for recurrent PDAC involves systemic chemotherapy, with gemcitabine (GEM) monotherapy historically serving as the standard of care. The present study describes the case of a patient with PDAC and postoperative liver metastases that maintained clinical complete remission (cCR) for >7 years following GEM monotherapy. A 63-year-old woman with upper abdominal pain was diagnosed with resectable PDAC and underwent pancreaticoduodenectomy. The patient was treated with GEM + S-1 as adjuvant chemotherapy for 6 months. Multiple liver metastases were detected 15 months post-operation and the patient was administered GEM alone. After 12 cycles, computed tomography showed cCR and GEM monotherapy was discontinued after 15 cycles. The patient has had no signs or symptoms of recurrence >7 years after the first recurrence. In addition, the present study analyzed PDAC resection specimens from four patients, including this case, to determine the expression levels of hENT1 protein in the tumor tissues. hENT1 is a transmembrane protein that acts as a nucleoside transporter and is a major mediator of GEM uptake into human cells. In the present case, hENT1 staining exhibited low frequency and weak positivity in the central region, whereas a strong positive reaction was observed in nearly all cell membranes at the invasive front of the cancer. The location, intensity, and frequency of hENT1 staining varied among cases. In conclusion, the efficacy of GEM may be predicted prior to treatment by evaluating hENT1 expression.

Preoperative CA19­9 level and dual time point FDG­PET/CT as strong biological indicators of borderline resectability in pancreatic cancer: A retrospective study.

Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability.

Impact of Preoperative Tumor Size on Prognosis of Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinomas.

BACKGROUND: Tumor size (TS) is a well-established prognostic factor of pancreatic ductal adenocarcinoma (PDAC). However, whether a uniform treatment strategy can be applied for all resectable PDACs (R-PDACs) and borderline resectable PDACs (BR-PDACs), regardless of TS, remains unclear. This study aimed to investigate the impact of preoperative TS on surgical outcomes of patients with R-PDACs and BR-PDACs. METHODS: Chart data from three institutions were reviewed to select patients who underwent pancreatectomy for R-PDACs and BR-PDACs between January 2006 and December 2020. The patients were divided into TSsmall and TSlarge groups according to a TS cutoff value determined for each of R- and BR-PDAC using the minimum P value approach for the risk of R1 resection. RESULTS: TS of 35 mm and 24 mm was the best cutoff value in R-PDAC and BR-PDAC, respectively. The R1 rate was higher in the TSlarge than TSsmall group, in both R- (n = 35, 37% versus n = 294, 19%; P = 0.011) and BR-PDAC (n = 89, 37% versus n = 27, 15%; P = 0.030). Overall survival was significantly better in the TSsmall than TSlarge group in R-PDAC (38.2 versus 12.1 months; P < 0.001), but comparable between the two groups in BR-DPAC (21.2 versus 22.7 months; P = 0.363). Multivariate analysis revealed TS > 35 mm as an independent predictor of worse survival in patients with R-PDAC. CONCLUSION: Larger TS was associated with a higher R1 rate and is a worse prognostic factor in patients with R-PDAC.

Prognosis of Pancreatic Cancer Based on Resectability: A Single Center Experience.

Although conversion surgery has increasingly been performed for initially unresectable advanced pancreatic ductal adenocarcinoma (PDAC), the rate of conversion, including that for patients who do not undergo resection, remains unclear. Patients with PDAC who were treated between January 2013 and December 2018 were classified into three groups: resectable (R), borderline resectable (BR), and unresectable (UR). We analyzed patient outcomes, including the rate of surgical resection and survival, in each of these groups. In total, 211 patients (R, 118; BR, 22; UR, 81) were selected. Among them, 117 (99%), 18 (82%), and 15 (19%) patients in the R, BR, and UR groups, respectively, underwent surgical resection. R0 resection rates were 88, 78, and 67%, whereas median overall survival (OS) from treatment initiation were 31, 18, and 11 months (p < 0.0001) in the R, BR, and UR groups, respectively. In patients who underwent surgical resection, relapse-free survival (RFS) and OS were similar among the three groups (R vs. BR vs. UR; median RFS (months), 17 vs. 13 vs. 11, p = 0.249; median OS (months), 31 vs. 26 vs. 32, p = 0.742). Lymph node metastases and incomplete adjuvant chemotherapy were identified as independent prognostic factors for OS. Although the surgical resection rate was low, particularly in the BR and UR groups, the prognosis of patients who underwent surgical resection was similar irrespective of the initial resectability status.

Therapeutic efficacy of dose-reduced adjuvant chemotherapy with S-1 in patients with pancreatic cancer: a retrospective study.

BACKGROUND: S-1 adjuvant chemotherapy is the standard treatment in Asia for resectable pancreatic ductal adenocarcinoma. The relative dose intensity of adjuvant chemotherapy influences survival in pancreatic cancer but does not precisely reflect treatment schedule modifications. We investigated the effects of total dose intensity of S-1 adjuvant chemotherapy on the survival of patients with pancreatic cancer and the permissible dose reduction. METHODS: Patients who underwent surgical resection during 2011-2019 for pancreatic cancer were selected. We determined the total dose intensity cut-off value that predicted tumor recurrence within 2 years postoperatively using receiver operating characteristic curves and compared the outcomes between the high and low total dose intensity groups. RESULTS: Patients with total dose intensity ≥ 62.5% (n = 53) showed significantly better overall survival than those with total dose intensity < 62.5% (n = 16) (median survival time: 53.3 vs. 20.2 months, P < 0.001). The median survival of patients without adjuvant chemotherapy (total dose intensity = 0, n = 28) was 24.8 months. Univariate analysis identified lymphatic involvement (P = 0.035), lymph node metastasis (P = 0.034), and total dose intensity (P < 0.001) as factors affecting survival. On multivariate analysis, total dose intensity (P < 0.001) was an independent predictor of worse survival. CONCLUSIONS: Maintaining a total dose intensity of at least 60% in S-1 adjuvant chemotherapy seems important to achieve a long postoperative survival in patients with pancreatic cancer.

Clinical Impact of Dual Time Point 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Fusion Imaging in Pancreatic Cancer.

We examined the value of preoperative dual time point (DTP) 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (FDG PET/CT) as a predictor of early recurrence or the outcomes in patients with pancreatic cancer. Standardized uptake values (SUVs) in DTP FDG PET/CT were performed as preoperative staging. SUVmax1 and SUVmax2 were obtained in 60 min and 120 min, respectively. ΔSUVmax% was defined as (SUVmax2 − SUVmax1)/SUVmax1 × 100. The optimal cut-off values for SUVmax parameters were selected based on tumor relapse within 1 year of surgery. Optimal cut-off values for SUVmax1 and ΔSUVmax% were 7.18 and 24.25, respectively. The combination of SUVmax1 and ΔSUVmax% showed higher specificity and sensitivity, and higher positive and negative predictive values for tumor relapse within 1 year than SUVmax1 alone. Relapse-free survival (RFS) was significantly worse in the subgroups of high SUVmax1 and high ΔSUVmax% (median 7.0 months) than in the other subgroups (p < 0.0001). The multivariate Cox analysis of RFS identified high SUVmax1 and high ΔSUVmax% as independent prognostic factors (p = 0.0060). DTP FDG PET/CT may effectively predict relapse in patients with pancreatic cancer. The combination of SUVmax1 and ΔSUVmax% identified early recurrent patient groups more precisely than SUVmax1 alone.

Preoperative Rapid Weight Loss as a Prognostic Predictor After Surgical Resection for Pancreatic Cancer.

OBJECTIVE: The aim of the study is to evaluate the influence of cachexia at the time of diagnosis of pancreatic ductal adenocarcinoma (PDAC) on prognosis in patients undergoing surgical resection. METHODS: Patients with data on preoperative body weight (BW) change followed by surgical resection during 2008-2017 were selected. Large BW loss was defined as weight loss >5% or >2% in individuals with body mass index less than 20 kg/m2 within 1 year preoperatively. Influence of large BW loss, ΔBW defined as preoperative BW change (%) per month, prognostic nutrition index, and indices of sarcopenia. RESULTS: We evaluated 165 patients with PDAC. Preoperatively, 78 patients were categorized as having large BW loss. ΔBW was ≤ -1.34% per month (rapid) and > -1.34% per month (slow) in 95 and 70 patients, respectively. The median postoperative overall survival of rapid and slow ΔBW groups was 1.4 and 4.4 years, respectively (P < 0.001). In multivariate analyses rapid ΔBW (hazard ratio [HR], 3.88); intraoperative blood loss ≥430 mL (HR, 1.89); tumor size ≥2.9 cm (HR, 1.74); and R1/2 resection (HR, 1.77) were independent predictors of worse survival. CONCLUSIONS: Preoperative rapid BW loss ≥1.34% per month was an independent predictor of worse survival of patients with PDAC.

COVID-19 with essential thrombocythemia treated with apixaban for antithrombotic prophylaxis.

A 40-year-old man was admitted to our hospital for COVID-19. He had been treated for essential thrombocythemia (ET). He was diagnosed severe illness of COVID-19, oxygen therapy and dexamethasone were administered. There was a possibility of thromboembolic events in this case, apixaban for prophylaxis was added. With these treatments, the patient has made a good recovery, and he was discharged on hospital day 11. There is no standard strategy for prophylaxis of thrombosis in patients with ET, and apixaban could be a clinical benefit for these patients.

Co-expression of mesothelin and CA125/MUC16 is a prognostic factor for breast cancer, especially in luminal-type breast cancer patients.

The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the expression of mesothelin and CA125, and the clinicopathological meaning and prognosis of the co-expression of mesothelin and CA125 in breast cancer. Our results showed that among 478 patients, mesothelin and CA125 were co-expressed in 48 (10 %), mesothelin only in 75 (16 %), CA125 only in 217 (45 %), and neither in 234 (49 %). A high correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with poor patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox's multivariate analysis. In conclusion, this is the first to report the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of mesothelin and CA125 may be clinically useful for prognostication after surgical therapy in patients with breast cancer.

Impact of Lymph Node Metastases Around the Superior Mesenteric Artery on Postoperative Outcomes of Pancreatic Head Cancer.

BACKGROUND: The neural plexus and lymph nodes around the superior mesenteric artery (LN#14), are the most frequent sites involved by pancreatic head cancer. However the influence of metastases to LN#14 on patients' prognosis has rarely been evaluated. METHODS: The patients who underwent pancreatectomy for pancreatic head cancer between January 2010 and December 2018 were selected. The patients with nodal metastases were classified into an LN#14 + or LN#14-group according to LN#14 metastasis. Clinical and pathological characteristics and prognosis were compared between the two groups. RESULTS: In total, 99 patients underwent pancreatectomy. Ninety-four patients were positive for lymph node metastases and 14 and 80 were classified as LN#14 + and LN#14 - , respectively. Postoperative median overall survival (OS) of the LN#14 + and LN#14 - groups was 10.2 and 31.1 months, respectively (P < 0.001). Median OS of the LN#14 + group was worse than that of patients with ≥ 4 metastatic nodes in the LN#14 - group (n = 35, 24.7 months, P = 0.002). In multivariate analysis, LN#14 + (hazard ratio [HR] = 3.89, 95% confidence interval [CI], 1.64-8.86) was one of the independent predictors of worse OS. CONCLUSION: It might be feasible to recognize LN#14 metastases as an important prognostic factor independently from other regional lymph node metastases.

Erratum: Recurrent cholangiocarcinoma with long-term survival by multimodal treatment: A case report.

[This corrects the article DOI: 10.3892/mco.2021.2234.].

Different role of MSLN and CA125 co-expression as a prognostic predictor between perihilar and distal bile duct carcinoma.

Recent studies have suggested that the interaction of mesothelin (MSLN) and cancer antigen 125 (CA125) enhances tumor metastases. The aim of the present study was to clarify the impact of MSLN and CA125 co-expression on the prognosis of patients with extrahepatic bile duct carcinoma (BDC). Tissue samples from patients who underwent surgical resection between 2007 and 2015 for perihilar or distal BDC were immunohistochemically examined. The expression levels of MSLN and CA125 in tumor cells were analyzed. The expression in <50% and ≥50% of the total tumor cells were defined as low- and high-level expression, respectively. Tissue samples were obtained from 31 patients with perihilar BDC and 43 patients with distal BDC. Lymph node metastases were associated with MSLN and CA125 co-expression in patients with perihilar BDC (P=0.002), while there was no association between lymph node metastasis and co-expression in patients with distal BDC (P=0.362). MSLN and CA125 co-expression was associated with a worse overall survival rate in patients with perihilar BDC (5-year overall survival rate, co-expression positive vs. negative, 24 vs. 63%; P=0.038). To the best of our knowledge, the present study is the first to report an association between co-expression of MSLN and CA125 with a poor prognosis in patients with perihilar BDC. The current findings suggested that the significance of co-expression differed according to the BDC location.

Recurrent cholangiocarcinoma with long-term survival by multimodal treatment: A case report.

Long-term outcomes after surgical resection of bile duct cancer remain unsatisfactory, and survival, particularly after tumor recurrence, is poor. Gemcitabine and cisplatin combination (GC) therapy is the standard first-line treatment; however, second-line approaches are yet to be established. Radiotherapy may prolong the survival of patients with advanced biliary tract cancer, and particle radiotherapy delivers a more concentrated dose than conventional radiotherapy to deeper tumors. The present report describes the long-term survival of a 65-year-old man with distal bile duct cancer of pathological stage IIA (T2N0M0; depth of invasion, 5.5 mm) following multimodal treatment. Following subtotal stomach-preserving pancreatoduodenectomy, multiple hepatic recurrences were identified 9 months later, and GC therapy was initiated. The tumors were no longer evident 18 months later, and GC therapy was discontinued at the patient's request. A computed tomography (CT) scan performed 30 months after surgery identified a new solitary hepatic recurrence and duke pancreatic monoclonal antigen type-2 (DUPAN-2) levels were increased. Further GC therapy was declined. Carbon ion radiotherapy (CIRT) at a dose of 60 Gy [relative biological effectiveness (RBE)-weighted absorbed dose] was then delivered in four fractions over 4 days [15 Gy (RBE)/day]. Tumor size decreased on CT, and fluorodeoxyglucose-positron emission tomography/CT revealed a decline in the standardized uptake value of the tumor after 2 months, with decreased DUPAN-2 levels. Following regrowth of the hepatic recurrence, CIRT was repeated at a dose of 66 Gy (RBE) in four fractions over 4 days [16.5 Gy (RBE)/day] and stable disease was maintained for 19 months. After 19 months, CT revealed tumor regrowth and another new metastatic lesion was identified in the left kidney. The patient received systematic chemotherapy again and died of the disease 81 months after the initial surgery. In conclusion, CIRT is a potential treatment option to control solitary recurrence of biliary tract cancer.

Destruction of a wandering accessory right hepatic artery in a patient with pancreatic body cancer: a case report.

Aberrant right hepatic arteries are sometimes involved in pancreatic head tumors or accidentally damaged during surgical procedures, which could result in postoperative complications. The risk of such injury has been discussed in patients undergoing pancreatoduodenectomy; however, no reports describe the influence of this anomaly in distal pancreatectomy. We report a patient with pancreatic body cancer with an accessory right hepatic artery following a very unique route. A 77-year-old man was referred to our hospital for the treatment of pancreatic cancer. Computed tomography revealed an anomaly in the hepatic artery, with an accessory right hepatic artery encased in the extensive tumor, which also involved the stomach, left gastric artery, and portal vein. Curative resection was achieved by distal pancreatectomy with wedge resection of the stomach and portal vein reconstruction. Both the accessory right hepatic artery and the left gastric artery were sacrificed after confirming intrahepatic arterial flow by intraoperative Doppler ultrasonography. The route of the accessory right hepatic artery in this patient was unique in that it did not run directly into the hepatic hilum but from behind the pancreatic body, where it was incorporated into the tumor. Accurate preoperative assessment and identification of arterial variations is mandatory in any type of pancreatectomy.

A rare case of isolated splenic sarcoidosis: A case report and literature review.

Sarcoidosis is a multisystemic granulomatous disease. It is rarely isolated in the spleen. The present report describes a case of isolated splenic sarcoidosis that was diagnosed histologically following laparoscopic splenectomy. A 76-year-old woman, who underwent radical nephroureterectomy 7 years earlier for left renal pelvic cancer and mastectomy 6 years earlier for left breast cancer in another facility, was referred to our hospital for assessment of splenic tumors that were identified during a follow-up examination. The computed tomography scans revealed multiple nodules in the spleen, which had increased in size over 2 years. Positron emission tomography revealed accumulation of [18F]-fluorodeoxyglucose in the spleen. Laparoscopic splenectomy was performed and the diagnosis of sarcoidosis was confirmed histologically. A review of previous reports and the present case suggested that diagnosis of splenic sarcoidosis should be considered when the CT scans show multinodular splenic tumors, and sarcoidosis might be associated with malignant tumors.

Aromatherapies using Osmanthus fragrans oil and grapefruit oil are effective complementary treatments for anxious patients undergoing colonoscopy: A randomized controlled study.

BACKGROUND AND AIMS: Colonoscopy can be painful and uncomfortable. Aromatherapy is often used for the relief of anxiety or discomfort. Recently, it has been reported that olfactory stimulation induces various physiological effects. We investigated the effects of aromatherapy on anxiety and abdominal discomfort during colonoscopy. METHODS: The investigation was carried out using a randomized controlled study. Aromatherapy was performed by vapor diffusion, and each patient was given one of the following treatments: no inhalation (control group), essential-oil-less vapor (vehicle group), lavender oil (lavender group), grapefruit oil (grapefruit group), or Osmanthus fragrans oil (Osmanthus fragrans group). Following total colonoscopy procedures, each patient estimated their anxiety and abdominal discomfort using the Numeric Rating Scale. RESULTS: Total colonoscopy was performed on 361 patients. No complications caused by colonoscopy or aromatherapy were experienced. In the Osmanthus fragrans group, anxiety was significantly attenuated. The abdominal discomfort of patients who reported strong anxiety during colonoscopy was significantly attenuated in the grapefruit group and the Osmanthus fragrans group. CONCLUSION: Aromatherapies using Osmanthus fragrans oil and grapefruit oil are effective complementary treatments for anxious patients undergoing colonoscopy.

[A Curatively Resected Case of Lateral Lymph Node Metastasis Five-Years after Initial Surgery for Rectal Cancer].

A 74-year-old male had undergone laparoscopic abdominoperineal resection for lower rectal cancer in July 2009. The pathological diagnosis was T2, N0, M0, pStage I (TNM 7th). Because of pathological venous invasion, adjuvant chemotherapy with Tegafur-uracil(UFT)plus Leucovorin for a year was performed. A CT examination revealed slowly growing peripheral right internal iliaclymph node. PET-CT demonstrated a 20mm right lateral lymph node(LLN)metastasis without other distant metastases. On diagnosis of solitary LLN metastasis of rectal cancer, the patient underwent surgical lymph node resection in September 2014. The pathological diagnosis was lymph node metastasis from rectal cancer. Subsequently, the patient received mFOLFOX6 adjuvant chemotherapy for 6 months. The patient remains alive without any recurrence 31 months after the second surgical treatment. lt is important to consider that LLN metastasis of Stage I rectal cancer might still occur a long time after the curative operation.

Synchronous neuroendocrine tumors in both the pancreas and ileum: A case report.

INTRODUCTION: Although it is well-known that in multiple endocrine neoplasia type 1 (MEN 1) disease, multiple endocrine lesions frequently occur, synchronous or metachronous neuroendocrine tumors (NETs) in non-MEN 1 patients are extremely rare. PRESENTATION OF CASE: An asymptomatic 72-year-old woman with an ileal NET was referred to our hospital. Abdominal computed tomography revealed another circular tumor within the pancreatic head. She was classified as a non-MEN 1 patient. An operative procedure was performed with a preoperative diagnosis of synchronous NET, which was confirmed by pathological examination. DISCUSSION: Both morphologic and immunophenotypic findings were different between in the ileum and pancreas. Therefore, it was reasonable to consider that both tumors were primary tumors. The synchronous occurrence of these tumors is unusual, and it may be considered as a chance occurrence. CONCLUSION: We here report the first case of synchronous pancreatic NET and ileal NET in a non-MEN 1 patient.