Clinical Significance of Body Weight Loss During Chemotherapy for Advanced Gastric Cancer Undergoing Conversion Surgery.

BACKGROUND/AIM: The purpose of the present study was to assess the clinical impact of body weight loss (BWL) during chemotherapy in patients with initially unresectable advanced gastric cancer who underwent conversion surgery. PATIENTS AND METHODS: This retrospective study included 61 patients with stage IV gastric cancer who underwent conversion surgery after chemotherapy, and body weight changes during chemotherapy were examined. Based on receiver operating characteristic (ROC) curve analysis of body weight change for disease recurrence, the cutoff value of BWL was determined. Based on the BWL cutoff value, patients were classified into two groups. RESULTS: Body weight change ranged from 28.2% to -21.8%. The cut-off value of BWL was set at 6% based on the ROC analysis. Of the 61 patients, 45 (74%) and 16 (26%) had <6% and ≥6% BWL, respectively. Patients with ≥6% BWL had peritoneal dissemination, pathological lymph node metastasis, residual tumor status of R1-2, and disease recurrence compared with those with <6% BWL (all p<0.05). The median survival times after conversion surgery were 21 and 63 months in the ≥6% and <6% BWL groups, respectively (p<0.01). Univariate analysis identified BWL as an independent prognostic factor (p=0.01), although histological response alone was significantly associated with survival in the multivariate analysis (p=0.02). CONCLUSION: Patients with severe BWL during chemotherapy may be excluded from the indication of conversion surgery.

Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report.

BACKGROUND: Conversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy. CASE PRESENTATION: An 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion's reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence. CONCLUSIONS: An sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy.

Comparison of the subtotal and narrow gastric conduit for cervical esophagogastrostomy after esophagectomy in esophageal cancer patients: a propensity score-matched analysis.

BACKGROUND: Several reports have compared narrow gastric conduit (NGC) with subtotal gastric conduit (SGC) for cervical esophagogastrostomy after esophagectomy; however, whether which one is more beneficial in terms of postoperative complications remains unclear. To determine the optimal gastric conduit type, we retrospectively investigated and compared the postoperative complications between NGC and SGC used in cervical circular-tapered esophagogastrostomy after esophagectomy through a propensity score-matched analysis. METHODS: Between 2008 and 2022, 577 consecutive esophageal cancer patients who underwent esophagectomy and cervical circular-stapled esophagogastrostomy were enrolled in this study. RESULTS: Of the 577 patients, 77 were included each in the SGC and NGC groups, after propensity score matching. Clinical characteristics did not differ between the two groups. The anastomotic leakage rate was significantly lower in the SGC group than in the NGC group (5% vs. 22%, p < 0.01). The anastomotic stenosis rate was significantly higher in the SGC group (16% vs. 5%, p = 0.03). Multivariate logistic analysis showed that NGC, subcutaneous route, and age were significant independent factors associated with anastomotic leakage (odds ratios, 8.58, 6.49, and 5.21; p < 0.01, < 0.01 and 0.03, respectively) and that SGC was a significant independent factor associated with anastomotic stricture (odds ratios, 4.91; p = 0.04). CONCLUSIONS: In cervical circular-stapled esophagogastrostomy after esophagectomy, SGC was superior to NGC in terms of reducing the risk of anastomotic leakage, although the risk of anastomotic stricture needs to be resolved.

Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Evaluation of Quality of Life and Prognosis of Gastric Cancer Patients After Laparoscopic Subtotal Gastrectomy.

BACKGROUND/AIM: The clinical significance of laparoscopic subtotal gastrectomy (LsTG) with a small remnant stomach remains unclear in patients with gastric cancer, including at an advanced stage. The present study assessed postoperative quality of life (QOL) and survival after LsTG compared with laparoscopic total gastrectomy (LTG). PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with gastric cancer who underwent LsTG (n=26) or LTG (n=26). Surgical outcome, postoperative nutritional status, QOL, and prognosis were compared between the LsTG and LTG groups. The Postgastrectomy Syndrome Assessment Scale was used to evaluate postoperative QOL. RESULTS: Operating time was significantly shorter (p<0.01) and postoperative morbidity was significantly lower (p=0.04) in the LsTG than in the LTG group. The reduction in body weight after surgery was significantly greater in the LTG than in the LsTG group (p<0.01). The Postgastrectomy Syndrome Assessment Scale revealed that, compared with LTG, LsTG significantly improved postoperative QOL (p<0.05). There was no significant difference in relapse-free survival and cancer-specific survival between the two groups. Three patients in the LTG group died of pneumonia and overall survival was significantly longer in the LsTG group (p=0.01). CONCLUSION: This study demonstrated the efficacy of LsTG with a small remnant stomach to prevent a decline in postoperative QOL and non-cancer-related death.

Transanal Total Mesorectal Excision Considering the Embryology Along the Fascia in Rectal Cancer Patients.

BACKGROUND/AIM: Transanal total mesorectal excision (TaTME) remains a challenging technique for rectal dissection. This study aimed to evaluate the clinical and oncological outcomes of TaTME, compared to those of the laparoscopic TME (LaTME) in rectal cancer. PATIENTS AND METHODS: Using propensity score-matched analyses, we analyzed retrospective data from 134 consecutive patients with rectal cancer who underwent TaTME or LaTME from January 2011 to June 2020 in our hospital. Clinical and oncological outcomes were evaluated. The primary endpoint was the 2-year local recurrence rate. RESULTS: Before data analysis, significant group-dependent differences were observed only in the tumor height (p<0.01). After analysis, preoperative patient demographics were similar between the TaTME and LaTME groups. The operative time was significantly shorter in the TaTME group (p=0.02), and the rates of hand-sewn anastomosis and protective loop ileostomy were significantly higher (p<0.01). The TaTME group showed a null conversion to open surgery compared to the LaTME group (5.9%). The postoperative complications, including anastomotic leak, were comparable between the two groups. However, the rate of Clavien-Dindo grade III tended to be lower in the TaTME group (p=0.07). There were no statistically significant differences in terms of pathological findings, and the 2-year local recurrence rate was similar between the two groups (both 5.9%). CONCLUSION: TaTME based on embryology along the fascia is feasible and seems a safe alternative to LaTME in selected patients with rectal cancer when considering the conversion rate and the operative time.

Clinical significance of intraperitoneal paclitaxel combined with systemic chemotherapy for gastric cancer with peritoneal metastasis.

BACKGROUND: Despite investigations of intraperitoneal paclitaxel as a personalized treatment for peritoneal metastasis of gastric cancer, few studies have evaluated its prognostic impact on conversion surgery for unresectable gastric cancer with peritoneal metastasis. Our study aimed to close this gap in knowledge. METHODS: We retrospectively enrolled 128 patients who underwent chemotherapy for peritoneal metastasis from gastric cancer and assigned them into intraperitoneal (IP) (n = 36) and non-IP (n = 92) groups, based on the use of intraperitoneal paclitaxel plus systemic chemotherapy. RESULTS: Disease control rates were 94% and 69% in the IP and non-IP groups, respectively, with the former having a significantly higher tumor response rate than the latter (p < 0.01). The median survival times in the IP and non-IP groups were 665 and 359 days, respectively, with the former having significantly better prognosis than the latter (p = 0.02). Fifteen (42%) and sixteen (17%) patients underwent conversion surgery after chemotherapy in the IP and non-IP groups, respectively, with the former having a significantly higher conversion surgery induction rate than the latter (p < 0.01). Although the prognosis of the conversion surgery group was significantly better than that of the non-conversion surgery group (p < 0.01), there was no significant difference in prognosis between patients in the IP and non-IP groups who underwent conversion surgery (p = 0.22). Multivariate analysis identified performance status and conversion surgery as independent prognostic factors (all p < 0.01). CONCLUSION: Our study demonstrated that the IP chemotherapy was one of important factors for conversion surgery induction, while it was not a risk factor for prognosis.

Modified pull-through coloanal anastomosis to avoid permanent stomas and reduce postoperative complications for lower rectal tumors.

BACKGROUND: We performed pull-through hand-sewn coloanal anastomosis immediately after sphincter-preserving ultralow anterior resection (ULAR) [pull-through ultra (PTU)] to avoid permanent stoma and reduce postoperative complications of lower rectal tumors. This study aimed to compare the clinical outcomes of PTU versus non-PTU (stapled or hand-sewn coloanal anastomosis with diverting stoma) after sphincter-preserving ULAR for lower rectal tumors. METHODS: This retrospective cohort study analyzed prospectively maintained data from 100 consecutive patients who underwent PTU (n = 29) or non-PTU (n = 71) after sphincter-preserving ULAR for rectal tumors between January 2011 and March 2023. In PTU, hand-sewn coloanal anastomosis was immediately performed using 16 stitches of 4-0 monofilament suture during primary surgery. The clinical outcomes were assessed. The primary outcomes were rates of permanent stomas and overall postoperative complications. RESULTS: The PTU group was significantly less likely to require a permanent stoma than the non-PTU group (P < 0.01). None of the patients in the PTU group required permanent stoma and the rate of overall complications was significantly lower in the PTU group (P = 0.01). The median operative time was comparable between the two groups (P = 0.33) but the median operative time during the second stage was significantly shorter in the PTU group (P < 0.01). The rates of anastomotic leakage and complications of Clavien-Dindo grade III were comparable between the two groups. Diverting ileostomy was performed in two patients with an anastomotic leak in the PTU group. The PTU group was significantly less likely to require a diverting ileostomy than those in the non-PTU group (P < 0.01). The composite length of hospital stay was significantly shorter in the PTU group (P < 0.01). CONCLUSIONS: PTU via immediate coloanal anastomosis for lower rectal tumors is a safe alternative to the current sphincter-preserving ULAR with diverting ileostomy for patients who wish to avoid a stoma.

Clinical Significance of Recurrence Risk Score for Conversion Surgery in Patients With Advanced Gastric Cancer.

BACKGROUND/AIM: To develop a recurrence risk score for determining the clinical indication for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer who underwent conversion surgery after chemotherapy. PATIENTS AND METHODS: A total of 65 patients with stage IV gastric cancer who underwent conversion surgery after chemotherapy were retrospectively enrolled. We established a risk score based on clinicopathological factors related to recurrence after conversion surgery. RESULTS: Out of 65 patients, 40 (62%) had recurrence after conversion surgery. The 5-year overall survival rates in patients with and without recurrence were 14.4% and 87.1%, respectively (p<0.01). Multivariate logistic regression analysis identified the depth of tumor invasion (pT2-4) and histological tumor response (grade 0-1a) as an independent risk factor for disease recurrence (p=0.033 and p=0.048, respectively). A scoring system determined by these two factors was created; total score ranged from 0 to 2 points, and patients were categorized into three groups (scores of 0 vs. 1 vs. 2 points). This scoring system showed that 12 (18%), 15 (23%), and 38 (58%) patients had recurrence risk scores of 0, 1, and 2 points, respectively. There was a close relationship between a high score and the presence of tumor recurrence (p<0.01). Moreover, our model system had a high sensitivity for the prediction of recurrence, compared with the pathological stage. CONCLUSION: Recurrence risk score is a promising tool for assessing the need for adjuvant chemotherapy in patients with initially unresectable advanced gastric cancer after conversion surgery.

Mucosectomy of the anal canal via transanal minimally invasive surgery combined with transanal total mesorectal excision for familial adenomatous polyposis: A technical note.

AIM: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment modality for familial adenomatous polyposis (FAP). It is challenging to perform proctectomy and preserve anal sphincter function. In this video, precise mucosectomy of the anal canal via transanal minimally invasive surgery (MAC-TAMIS) is reported. METHODS: An asymptomatic 35-year-old man was found to have a positive faecal occult blood test in routine screening examination and was diagnosed with FAP on colonoscopic examination. The patient was scheduled for total proctocolectomy with IPAA using the TAMIS approach combined with transanal total mesorectal excision. MAC-TAMIS was performed to preserve the internal anal sphincter during laparoscopy. RESULTS: The total duration of surgery was 543 min, blood loss was minimal, and the postoperative course was uneventful. The postoperative hospital stay was 12 days. The pathological findings demonstrated no evidence of malignancy. Gastrographic imaging from the ileostomy showed sufficient size of the J pouch and good tonus of the anus at 6 months after surgery. The Wexner scores at 1, 3 and 6 months after ileostomy closure were 5, 3 and 0, respectively. CONCLUSION: The MAC-TAMIS technique is safe and feasible during total proctocolectomy with IPAA in patients with FAP. This technique allows us to precisely preserve the internal anal sphincter using a laparoscopic approach.

Vascular endothelial growth factor inhibitors promote antitumor responses via tumor microenvironment immunosuppression in advanced colorectal cancer.

PURPOSE: This study aims to investigate changes in the tumor immune environment of patients who underwent therapy with a vascular endothelial growth factor (VEGF) inhibitor for advanced colorectal cancer. METHODS: Patients (n = 135) with T3 or T4 colorectal cancer were included in this retrospective study. They were classified as follows: patients who had not received preoperative treatment (UPFRONT group, n = 54), who had received FOLFOX as preoperative chemotherapy (FOLFOX group, n = 55), and who had undergone resection after combination FOLFOX and bevacizumab as unresectable colorectal cancer (B-MAB group, n = 26). The number of cytotoxic T lymphocytes (CTLs), FOXP3+ lymphocytes (including regulatory T cells (Tregs)), CD163+ monocytes (including M2-type tumor-associated macrophages (TAM-M2 type)), and programmed cell death 1 (PD-1)+ lymphocytes was evaluated immunohistochemically in the cancer cell area (CC) and stromal cell area (ST) of surgical specimens, and compared among the three groups. RESULTS: The CTL population did not differ among the three groups in both areas. In the B-MAB group, the numbers of PD-1+ cells in the ST, FOXP3+ lymphocytes in both areas, and CD163+monocytes in the ST was lower than that in the other two groups, and a correlation with the histological therapeutic effect was observed. CONCLUSIONS: In advanced colorectal cancer, VEGF inhibitors may decrease the number of PD-1+ cells and inhibit the infiltration of FOXP3+ lymphocytes and CD163+monocytes into the tumor environment.

[A Case of Curative Resection Following TNT for Locally Advanced Rectal Cancer with Liver Metastasis].

The standard treatment of locally advanced rectal cancer is preoperative chemoradiotherapy(CRT)in Europe and the United States, while that is surgical excision and lateral pelvic lymph node dissection followed by adjuvant chemotherapy in Japan. Recently, total neoadjuvant therapy(TNT), which combines neoadjuvant chemotherapy and preoperative CRT, have been popular. We performed curative excision for initially locally advanced rectal cancer with liver metastasis after TNT. A 61- year-old woman was diagnosed as having rectal cancer with liver metastasis and invasion of the uterus, vagina, bladder, and left ureter. The patient underwent 8 courses of FOLFOX plus bevacizumab, followed by radiotherapy, and totally pelvic excision for the primary tumor. Because of liver metastasis progression, hepatectomy was performed after 6 courses of FOLFIRI plus panitumumab. The patient has been cancer free for 20 months to date. TNT is considered to be an effective strategy for the treatment of large locally advanced rectal cancer.

Clinical Significance of Eligibility Criteria Determined by the SPIRITS Trial in Patients with Advanced Gastric Cancer.

INTRODUCTION: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. METHODS: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. RESULTS: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). CONCLUSION: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

A new overlapped delta-shaped anastomosis technique using linear staplers with reinforced bioabsorbable material for intracorporeal anastomosis during laparoscopic colectomy.

AIM: Totally laparoscopic colectomy with intracorporeal anastomosis (IA) is associated with less surgical trauma and wound related complications compared to laparoscopy-assisted colectomy with extracorporeal anastomosis. Delta shaped anastomosis is a widely popular IA technique. In this study, we discuss a construction technique for an overlapped delta-shaped anastomosis using a linear stapler with a reinforced bioabsorbable material. METHODS: We excised the bowel at a point 10 cm from the tumour on either sides and laid them in an overlapped fashion. The entry hole was created at a point 3 cm proximal to the right stump and 7 cm distal to the left stump on the antimesenteric side. Then, a 60-mm linear stapler with reinforced bioabsorbable material was inserted inside each lumen and fired. Finally, the common entry hole was fixed with a suture in the middle, the bowel was elevated holding the bioabsorbable material, and closed using the linear stapler in a delta-shaped manner. RESULTS: The technique was applied in five patients with tumours in the ascending, transverse, and descending colon. The median surgery time, anastomosis construction time and postoperative stay was 329 min (range 285-682 min), 19 min (range 14-29 min), and 12 days (range 9-15 days), respectively. There were no perioperative complications and only one postoperative complication. CONCLUSION: The overlapped delta-shaped anastomosis technique using linear staplers with reinforced bioabsorbable material appears to be both safe and feasible.

Implications of PD-1, Tim-3, and TIGIT Expression for Cancer Immunity and Pancreatic Cancer Prognosis.

BACKGROUND/AIM: The development and application of cancer immunotherapy to pancreatic cancer has not progressed because its efficacy has not been proven in clinical trials. In this study, we aimed to explore potential targets of immune checkpoint inhibitor therapy for pancreatic cancer treatment. MATERIALS AND METHODS: We collected resected specimens from 40 patients with pancreatic cancer who underwent resection at our Institution without any preoperative treatment. We evaluated the expression of molecules in the programmed death receptor-1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3)/Galectin-9, and CD155/T cell immunoreceptor with Ig and ITIM domains (TIGIT) pathways using immunohistochemical staining. The correlation between the expression pattern of these molecules and patient prognosis were assessed using Kaplan-Meier analysis. RESULTS: An increased number of CD8+ T cells in pancreatic cancer tissue was significantly associated with a better patient prognosis. Additionally, patients with a higher ratio of PD-1 expression to CD8+ T cells had a worse prognosis. We observed no correlation between the Tim-3/Galectin-9 and CD155/TIGIT pathways and patient prognosis. CONCLUSION: Modifications in the immune environment to increase T cell infiltration into tumors could result in the PD-1 pathway becoming a potential target to treat pancreatic cancer using immune checkpoint inhibition.

Clinical Outcome After Esophagectomy or Definitive Chemoradiotherapy in Elderly Patients (≥80 Years) With Esophageal Cancer.

BACKGROUND/AIM: Given the increased incidence of esophageal cancer (EC) in individuals over 80 years old, the optimum therapeutic strategy for elderly patients is needed to be established with scientific evidence. Here, we studied the short-term and long-term outcomes after treatment of patients aged 80 years old or older with EC. PATIENTS AND METHODS: Eighty patients with EC aged 80 years old or older, who underwent esophagectomy (n=23), definitive chemoradiotherapy (dCRT) (n=46) or best supportive care (n=11) between January 2010 and March 2019 were included in this study, and clinical data were compared among these groups. RESULTS: Surgery had a great benefit on the 3-year overall survival (OS) compared to dCRT (68.4% vs. 29.3%, p<0.01). The cure rates of treatment were 86.9% in surgery and 34.8% in dCRT. dCRT led to a better 3-year OS compared to BSC (29.3% vs. 0%, p<0.01); however, dCRT did not improved OS in patients with T4. Patients with T4 had high frequency of adverse events and treatment-related death in dCRT; CTCAE Grade 3-5 was observed in 100% of all T4 patients and Grade 5 in 57.1%. Multivariate analysis revealed that T4 was an independent risk factor of treatment-related death after dCRT (p<0.01). CONCLUSION: Surgery is the first treatment option for resectable EC even in elderly patients, and dCRT can be considered as an alternative. However, dCRT may induce severe toxicity especially in T4 EC patients.

Additional Effects of Docetaxel on Neoadjuvant Radiotherapy With Cisplatin/5-Fluorouracil for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: To further improve the prognosis of locally advanced esophageal cancer patients, investigating new perioperative treatment strategies is necessary. The current study aimed to retrospectively investigate neoadjuvant radiotherapy with cisplatin and 5-fluorouracil (CF-RT) and radiotherapy with docetaxel and CF (DCF-RT) and compare their treatment outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: We retrospectively reviewed 95 patients with ESCC who received CF-RT or DCF-RT followed by esophagectomy. The CF-RT group received chemotherapy consisting of two courses of CF repeated every 4 weeks. The DCF-RT group received chemotherapy consisting of two courses of DCF repeated every 2 weeks. A radiotherapy dose of 1.8-2 Gy was administered per session, up to a total of 40-41.4 Gy. Adverse events of neoadjuvant chemoradiotherapy, surgical outcomes, pathological responses, prognosis, and recurrence patterns were evaluated. RESULTS: Both the CF-RT and DCF-RT groups had equivalent pathological complete response rates of the primary tumor at 31.6% and 38.6%, respectively. However, the DCF-RT group had significantly better 5-year disease-free survival and 5-year overall survival than (HR=0.50, 95%CI=0.26-0.97, p=0.0392) than the CF-RT group. CONCLUSION: DCF-RT may be a candidate neoadjuvant therapy for locally advanced ESCC.

Conversion surgery for microsatellite instability-high gastric cancer with a complete pathological response to pembrolizumab: a case report.

BACKGROUND: Immune checkpoint inhibitors are reportedly effective in treating microsatellite instability (MSI)-high gastric cancer. There are a few case reports of conversion surgery (CS) with nivolumab but none with pembrolizumab. Herein, we describe a patient with MSI-high gastric cancer who was successfully treated with pembrolizumab and underwent CS with a pathological complete response. CASE PRESENTATION: A 69-year-old man was diagnosed with stage III gastric cancer (T3N2M0) based on contrast-enhanced computed tomography, which revealed a neoplastic lesion and enlarged perigastric lymph nodes in the gastric lesser curvature. The anterior superior lymph node of the common hepatic artery (CHA) was determined to be unresectable due to invasion of the pancreatic head and CHA. Histopathologically, the biopsied tissue showed moderately differentiated adenocarcinoma, then determined to be MSI-high. After three courses of mFOLFOX6 therapy, the patient was diagnosed with progressive disease. Since one course of paclitaxel plus ramucirumab therapy caused grade 3 fatigue, his second-line therapy was switched to pembrolizumab monotherapy. After three courses, the primary tumor and perigastric lymph nodes had shrunk, and it was determined as a partial response. The anterior superior lymph node of the CHA became resectable based on the improvement of infiltration of the pancreatic head and CHA due to shrinkage of the lymph node. Tumor markers remained low; hence, distal gastrectomy plus D2 lymphadenectomy was performed at the end of six courses. Anterior superior lymph node of the CHA was confirmed by intraoperative ultrasonography, and the resection was completed safely. The gross examination of the resected specimen revealed an ulcer scar at the primary tumor site. The histopathological examination showed no viable tumor cell remnants in the primary tumor, which had a grade 3 histological response, and resection margins were negative. The lymph nodes showed mucus retention only in the anterior superior lymph node of the CHA, indicating the presence of metastasis, but no viable tumor cells remained. The patient commenced 6 months of adjuvant pembrolizumab monotherapy 3 months after surgery. Twenty months after surgery, there was no evidence of recurrence. CONCLUSIONS: Conversion surgery following pembrolizumab monotherapy has a potential utility for the treatment of MSI-high gastric cancer.

A prognostic scoring system for conversion surgery after trastuzumab-based chemotherapy for human epidermal growth factor receptor 2-positive advanced gastric cancer.

PURPOSE: To investigate the clinical indications and prognostic significance of surgical interventions after chemotherapy using trastuzumab-containing regimens for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). METHODS: A total of 146 patients with AGC who underwent chemotherapy were enrolled in this retrospective study. Tumors with an immunohistochemistry (IHC) score of 3 + or an IHC score of 2 + plus fluorescence in situ hybridization positivity were defined as HER2-positive AGC. We devised a scoring system for predicting prognosis associated with conversion surgery. RESULTS: Thirty-three patients received trastuzumab-based chemotherapy for HER2-positive tumors. Multivariate analyses identified advanced age, peritoneal dissemination, histologically undifferentiated tumors, and tumor response of progressive disease as independent prognostic factors for a worse prognosis. Twelve patients with HER2-positive AGC underwent conversion surgery. The conversion surgery group of patients with HER2-positive AGC had a better prognosis than the chemotherapy-alone group. A prognostic scoring system based on age, peritoneal dissemination, and histological type was significantly correlated with the presence or absence of conversion surgery and the prognosis of patients with HER2-positive AGC. CONCLUSIONS: Our scoring system has the clinical potential to predict prognosis associated with conversion surgery after trastuzumab-containing chemotherapy for patients with HER2-positive AGC.