A Prospective Cohort Study Exploring the Effect of Lenvatinib Planned Drug Holidays in Treatment of Differentiated Thyroid Cancer.

Background: Although lenvatinib is the preferred treatment for unresectable radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), this agent exerts considerable toxicities, which can lead to frequent dose interruptions and modifications. The adoption of planned drug holidays has been recently suggested as one means of minimizing or avoiding these severe adverse events. Our retrospective study demonstrated that planned drug holidays appear to be a promising strategy for continuing of lenvatinib. However, the benefits of planned drug holidays in a prospective study have yet to be clarified. Here, we investigated the impact of planned drug holidays on clinical outcomes in patients treated with lenvatinib in the COLLECT study. Methods: In COLLECT, a prospective observational study, patients with RR-DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities was permitted. Furthermore, planned drug holidays were allowed to avoid severe or intolerable toxicities. The present post hoc analysis focused on evaluating the impact of planned drug holidays on clinical outcomes, including overall survival (OS), time to treatment failure (TTF), time to failure strategy (TFS), and progression-free survival (PFS), in patients in the COLLECT study who were treated with lenvatinib. Results: In total, 262 patients were included. Of the 253 patients evaluable for efficacy, 73 undertook a planned drug holiday at the discretion of the attending physician. OS, TTF, TFS, and PFS were significantly longer in patients who used a planned drug holiday than in those who did not. The planned drug holiday group demonstrated notable clinical outcomes, with a 1-year OS of 95.8% and a 1-year PFS of 94.5%. Moreover, planned drug holidays demonstrated a clinically meaningful advantage in clinical outcomes. The planned drug holiday group had a significantly longer duration of administration at a dose of ≥10 mg. Conclusions: Planned drug holidays for lenvatinib were associated with significantly improved clinical outcomes compared to daily oral administration. Further investigation of the optimal treatment schedule for lenvatinib is warranted. Clinical Trial Registration: UMIN000022243.

[Questionnaire Survey on Oral Care and Oral Troubles for Patients with Gastric Cancer Received Chemotherapy].

BACKGROUND: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear. METHODS: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test. RESULTS: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia. CONCLUSIONS: Dysgeusia was the most frequent and severe oral trouble.

[Regimen Selection by Narrative Approach in Patients with Advanced Gastric Cancer-Paclitaxel or Nab-Paclitaxel?]

BACKGROUND: According to the sixth Gastric Cancer Treatment Guideline, the regimen included nab-paclitaxel(nab-PTX) is a conditional recommendation as second-line treatment for advanced gastric cancer. However, the selection criteria of nab-PTX is not clear. METHOD: Questionnaire survey as narrative approach on the problems of paclitaxel premedication, the symptoms due to paclitaxel containing alcohol, and infusion time was conducted for patients who had been treated with paclitaxel. RESULTS: Thirty-six patients answered the questionnaire. Nonelderly patients(<65 years)or patients without comorbid medications complained of dissatisfaction with the inconvenience due to premedication significantly more than elderly patients(≥65 years)or patients with comorbid medications. Females or nonelderly patients were significantly more troubled by sleepiness due to premedication than males or elderly patients. Eight out of 11 patients who had visited hospital by driving a car for first-line treatment were troubled by prohibition of driving on the day of treatment. Thirty out of 36 patients answered that they would feel benefits from 30-minutes shortening of infusion time. CONCLUSION: Questionnaire survey suggests that we may select the patients for nab-PTX properly by clarifying the inconvenience of daily life associated with premedication, the way of transportation for visiting hospital, and the benefits by shortening of infusion time.

[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.

Three-year progression-free survival of a patient with concomitant mucinous adenocarcinoma of the colon with peritoneal dissemination and multiple myeloma who received lenalidomide: a case report.

BACKGROUND: Concomitant multiple myeloma (MM) and other primary malignancies is rare. Therefore, the treatment outcomes of patients with these conditions have not been well discussed. Lenalidomide is an oral thalidomide analog drug used for MM. Recently, the antitumor effect of lenalidomide has been gaining attention, and lenalidomide has been applied for managing solid tumors. The current case showed the treatment course of a patient treated with lenalidomide for concomitant MM and colon cancer with peritoneal dissemination. CASE PRESENTATION: A 74-year-old female patient receiving treatment for MM was diagnosed with mucinous adenocarcinoma of the transverse colon. The patient was clinically diagnosed with stage IIIC T4aN2M0 disease. Subsequently, laparoscopic colectomy with lymph node dissection was planned. However, intraperitoneal observation revealed peritoneal dissemination that had sporadically and widely spread. Therefore, palliative partial colectomy was performed to prevent future hemorrhage or obstruction. The patient was discharged on the 10th postoperative day without postoperative complication. Based on the patient's preference, lenalidomide was continually administered for MM without systemic chemotherapy. The patient survived for > 36 months without any signs of tumor progression. CONCLUSION: The current case first showed the treatment course of concomitant MM and colon cancer. The antitumor effect of lenalidomide can possibly contribute to 3-year progression-free survival in patients with mucinous adenocarcinoma of the colon with peritoneal dissemination.

[A Case of 30s Female with Advanced Anal Canal Adenocarcinoma Managed with Adolescent-And-Young-Adult Team].

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

[A Case of Diffuse Large B-Cell Lymphoma Which Was Diagnosed during the Best Supportive Care of Recurrent Ascending Colon Cancer].

A 70s male, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N3M0, Stage Ⅲc(without adjuvant chemotherapy), had enhanced-computed tomography(CT)for 3-month follow-up and a hepatic low-density area, an newly emergent nodule behind inferior vena cava and distal ileal tumor were found. Three months later, enhanced CT showed that the distal ileal tumor got exponentially larger and the diagnosis of"malignant lymphoma"was suspected. The patient became sepsis, so we planned and safely performed partial resection of the tumor. The pathological diagnosis was diffuse large B-cell lymphoma. Postoperative course was smooth except for the Clostridium difficile colitis and he was discharged on postoperative day 19. Although the regrowth of the remnant tumor was observed soon after surgery, partial response was confirmed after introduction of systemic chemotherapy. When we cope with malignant lymphoma of small intestine, we need to keep it in mind that surgery is an option for the prevention of perforation and bacterial translocation.

[A Case of Fibromatosis-Like Tumor Which Was Difficult to Differentiate from Local Recurrence of Ascending Colon Cancer].

A 60s female, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N1bM0, Stage Ⅲb, followed by adjuvant therapy with 8 courses CAPOX 2 years ago, had enhanced- computed tomography(CT)for follow-up and a 15-mm nodule near anastomotic site was found. 18F-fluorodeoxyglucose (FDG)-positron emission tomography(PET)CT revealed abnormal accumulation of 18F-FDG only to the lesion and diagnosis of"anastomotic recurrence"was made. We planned and safely performed resection of the anastomotic site and the nodule. The pathological diagnosis was fibromatosis-like tumor without evidence of recurrence, and margin was negative. Postoperative course was smooth and she was discharged on postoperative day 9. When we diagnose local recurrence, we need to keep it in mind that fibromatosis is one of the differential diagnoses, although its incidence rate is low.

Association between methicillin-resistant Staphylococcus aureus nasal carriage and infection after pancreatic surgery.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections after pancreatectomy are relatively rare; however, they can be fatal when associated with pseudoaneurysms. For the past 12 years, we have been investigating nasal MRSA carriage by polymerase chain reaction testing, postoperatively in patients admitted to the intensive care units, to prevent nosocomial infections. Here, we investigated the relationship between MRSA nasal carriage and postoperative MRSA infection at the surgical site, following pancreatectomy. METHODS: This single-center retrospective study analyzed 313 pancreatectomies (220 pancreaticoduodenectomies and 93 distal pancreatectomies), performed at our hospital between January 2011 and June 2022. The incidence of surgical site infection (SSI) and postoperative MRSA infection were compared between the nasal MRSA-positive and nasal MRSA-negative groups. RESULTS: MRSA nasal carriage was identified in 24 cases (7.6%), and the frequency of SSIs in the nasal MRSA-positive and MRSA-negative groups were 50% and 36.7%, respectively, with no significant difference (p = .273). However, the frequency of MRSA infection among the SSI cases was significantly higher in the nasal MRSA-positive group (16.7%) than in the nasal MRSA-negative group (1.7%) (p = .003). CONCLUSION: It should be noted that MRSA carriers have a significantly higher frequency of MRSA-positive SSIs.

Breast Cancers Secreting Sialyl-fibronectin Are Less Likely to Cause Epithelial-mesenchymal Transition and Have Good Prognoses.

Background/Aim: Elevated blood fibronectin (FN) levels have been observed in various cancers; however, their significance is controversial. We measured sialyl-fibronectin (S-FN), a type of FN secreted by tumor cells in the blood, and investigated whether blood S-FN secretion is associated with cancer malignancy and recurrent metastases. Materials and Methods: We constructed an enzyme-linked immunosorbent assay (ELISA) system that recognizes S-FN as an antigen and measured the amount of S-FN secreted into the blood of 89 patients with breast tumors. The relationship between S-FN secretion and prognostic predictors was analyzed. Immunostaining was performed to identify the site of S-FN secretion in the breast tissue. Results: Among the 82 patients, 21 (25.6%, 21/82) and 61 (74.4%, 61/82) were blood S-FN-positive and S-FN-negative, respectively. Regarding prognostic predictors, blood S-FN-positive and S-FN-negative patients showed significant difference in locoregional recurrence (p=0.026), remote metastases (p=0.049), and histological margins (p=0.001). Locoregional recurrence was associated with positive histological margins in S-FN-positive patients. However, remote metastases were associated with N-factor and histological classification (HC) in S-FN-negative patients. Furthermore, S-FN particles were detected in the cytoplasm of breast cancer cells through immunostaining. After the onset of recurrent metastases, two S-FN-positive and six S-FN-negative patients received anticancer drug treatment; however, further progression was observed in five S-FN-negative patients. Conclusion: S-FN-positive patients are less likely to develop distant metastases, have a better prognosis, and may be less resistant to therapeutic agents than S-FN-negative patients, which contain many epithelial-mesenchymal transition cells.

The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity. CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately. TRAIL REGISTRATION: Retrospectively registered.

Genomic landscape and its prognostic significance in stage III colorectal cancer: JCOG1506A1, an ancillary of JCOG0910.

Large-scale genomic sequencing of colorectal cancers has been reported mainly for Western populations. Differences by stage and ethnicity in the genomic landscape and their prognostic impact remain poorly understood. We investigated 534 Japanese stage III colorectal cancer samples from the Phase III trial, JCOG0910. Targeted-capture sequencing of 171 potentially colorectal cancer-associated genes was performed, and somatic single-nucleotide variants and insertion-deletions were determined. Hypermutated tumors were defined as tumors with MSIsensor score >7 and ultra-mutated tumors with POLE mutations. Genes with alterations associated with relapse-free survival were analyzed using multivariable Cox regression models. In all patients (184 right-sided, 350 left-sided), mutation frequencies were TP53, 75.3%; APC, 75.1%; KRAS, 43.6%; PIK3CA, 19.7%; FBXW7, 18.5%; SOX9, 11.8%; COL6A3, 8.2%; NOTCH3, 4.5%; NRAS, 4.1%; and RNF43, 3.7%. Thirty-one tumors were hypermutated (5.8%; 14.1% right-sided, 1.4% left-sided). Modest associations were observed: poorer relapse-free survival was seen with mutant KRAS (hazard ratio 1.66; p = 0.011) and mutant RNF43 (2.17; p = 0.055), whereas better relapse-free survival was seen with mutant COL6A3 (0.35; p = 0.040) and mutant NOTCH3 (0.18; p = 0.093). Relapse-free survival tended to be better for hypermutated tumors (0.53; p = 0.229). In conclusion, the overall spectrum of mutations in our Japanese stage III colorectal cancer cohort was similar to that in Western populations, but the frequencies of mutation for TP53, SOX9, and FBXW7 were higher, and the proportion of hypermutated tumors was lower. Multiple gene mutations appeared to impact relapse-free survival, suggesting that tumor genomic profiling can support precision medicine for colorectal cancer.

Serum Sialyl Fibronectin Is an Indicator of Good Prognosis in Thyroid Cancer.

BACKGROUND/AIM: Sialyl-fibronectin (S-FN), a type of glycoprotein like Sialyl Lewisa and MAC1 thyroid cancer biomarkers, has been found to be expressed in thyroid cancer. In this study, we examined the usefulness of serum S-FN as a biomarker, as well as prognostic factor in various tumors including thyroid cancer. PATIENTS AND METHODS: Using the MoAb JT-95, an ELISA kit was created and S-FN levels in sera (blood S-FN) of a total of 182 cases were investigated. Analysis included 63 cases of thyroid cancer, 33 cases of thyroid benign tumors, 7 cases of parathyroid benign tumors, and 79 cases of breast cancer. RESULTS: The incidence of blood S-FN-positive cases was 24 (38.0%) in 63 examined patients with thyroid cancer. Out of 40 examined benign neck tumor cases, 16/40 (40%) were S-FN-positive. Out of 79 examined breast cancer cases, 20/79 (25.3%) were S-FN-positive, with significant differences between thyroid and breast cancer cases (p=0.007). Regarding the association of blood S-FN expression and prognosis in thyroid cancer, there was a significant difference between 39 blood S-FN-negative cases and 15 recurrent or metastatic cases in terms of progression and pathological factors: tumor size, lymph node metastasis, extra-membrane infiltration, and clinical stage. All 63 assessed thyroid cancer cases also had a significant difference in these factors. There were no significant differences between these factors in the 24 blood S-FN-positive thyroid cancer cases. In cases of recurrent metastasis, intravascular cells were observed in all recurrent metastasis patients of both groups. Regarding staining of intravascular infiltrating cells, recurrent metastasis appeared at a higher rate in cases with S-FN-negative infiltrating cells. CONCLUSION: S-FN presence in blood can be used as an indicator of good prognosis in thyroid cancer patients.

Robot-assisted laparoscopic surgery with a fluorescent near-infrared ray ureteral catheter for a rectal cancer patient with pelvic kidney: A case report.

An 85-year-old woman presented with a stomachache after a meal and was admitted to the previous clinic. Multi-detector computed tomography (CT) of the abdomen showed wall thickening in the rectum and right ectopic pelvic kidney. Colonoscopy revealed a mass at the rectum, and a biopsy showed adenocarcinoma. CT showed no lymphadenopathy or distant metastasis. Hartmann's procedure with fluorescent near-infrared ray ureteral catheters was used to avoid causing urinary injury. Robotic surgery was performed while checking the route of the ureter in near-infrared mode. The patient was discharged on postoperative day 14 without specific complications. This case appears to be the first of robot-assisted laparoscopic surgery for a rectal cancer patient with pelvic kidney.

[Conversion Surgery Performed after SOX plus Nivolumab Therapy for Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis].

The patient was a 78-year-old woman. She presented with anemia and a positive fecal occult blood test. Endoscopic findings revealed type 3 advanced gastric cancer. As it had metastasized to the para-aortic lymph node(PALN: No. 16a2 lat), it was diagnosed as gastric cancer at cardia cT4aN1(No.1)M1(No.16a2 lat), cStage Ⅳ. She was administered S-1, oxaliplatin, and nivolumab(SOX plus Nivo)therapy as a first-line treatment. SOX plus Nivo resulted in a remarkable reduction of the lymph nodes, which were PR. After 3 courses of chemotherapy, a laparoscopic proximal gastrectomy was performed, with D2 plus No. 16a2 int/lat lymph nodes dissection as conversion surgery. Histopathological examination was pT3N0M0, and R0 resection was pStage ⅡA. She was discharged at POD21 and started S-1 from POD69. The patient is alive with no signs of recurrence 10 months postoperatively.

[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 Preoperative Chemotherapy for Advanced Gastric Cancer, Laparoscopic Total Gastrectomy, Pancreaticoduodenectomy, and Para-Aortic Lymph Node Dissection].

Bulky N+ gastric cancer has a poor prognosis. The results of JCOG0405 showed the efficacy of neoadjuvant chemotherapy with S-1 plus cisplatin combination therapy for Bulky N+ gastric cancer. JLSSG0901 demonstrated the safety and efficacy of laparoscopic surgery for advanced gastric cancer. But the safety of laparoscopic surgery for locally advanced and extensive nodal metastasis cancer(T4b, para-aortic lymph node metastasis)is not apparent. After DOS therapy, we performed total laparoscopic gastrectomy, DP(distal pancreatectomy), D2+ #16a2/b1 lat, and Roux-en-Y reconstruction, and histopathological results showed that the aortic lymph node metastasis disappeared. We controlled extensive lymph node metastasis using preoperative triplet chemotherapy. Laparoscopic surgery after preoperative chemotherapy for Bulky N+ gastric cancer can be a treatment option because we performed laparoscopic resection and para-aortic lymph node dissection with no complications, including pancreatic complications.

[Our Experience with Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma].

We report our experience with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. METHODS: Fourteen patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab at our department were retrospectively evaluated for antitumor efficacy and adverse events. RESULTS: Age ranged from 66-91 years(median 77.5 years), 11 males and 3 females, number of doses ranged from 2-26(median 13), and observation period ranged from 31-790 days (median 427 days). Antitumor efficacy was CR in 3 patients, PR in 3, SD in 6, and PD in 2. One patient with PD died 650 days after the start of treatment, but the others are still alive. Adverse events included proteinuria in 9 patients who discontinued bevacizumab, hypothyroidism requiring levothyroxine sodium hydrate in 7 patients, dermatitis in 2 patients, and colitis requiring hospitalization in 2 patients. DISCUSSION: Despite the small number of cases, a high antitumor effect was observed with a CR rate of 21%. Although proteinuria and hypothyroidism were observed relatively frequently as adverse events, they were easily controlled and did not pose a major clinical problem.