Prognostic factors for gastric cancer patients aged ≥ 85 years.

BACKGROUND: As gastric cancer patients aged ≥ 85 years have a short life expectancy and often die from other diseases such as pneumonia, indications for surgery are controversial. In this study, we retrospectively analyzed the prognostic factors of elderly patients with gastric cancer who are candidates for curative gastrectomy. METHODS: Among 114 patients aged ≥ 85 years with gastric cancer at our hospital between 2010 and 2019, prognostic factors were examined using the Cox proportional hazards model in 76 patients excluding those with cStage IVB or endoscopic submucosal dissection. We also analyzed the factors of pneumonia death. RESULTS: cStage was I/IIA/IIB/III/IVA in 37/6/14/14/5 patients, respectively. Treatment included distal gastrectomy in 28 patients, total gastrectomy in 6, local resection in 9, others in 3, and no surgery in 30. In univariate analyses of overall survival, Eastern Cooperative Oncology Group Performance Status, physiological score of Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Onodera's prognostic nutritional index, cStage, and treatment were prognostic factors. In a multivariate analysis, POSSUM physiological score, cStage, treatment method {no surgery vs. distal gastrectomy: hazard ratio (HR) 5.78, 95% confidence interval (CI) 2.33-14.3}, (total gastrectomy vs. distal gastrectomy: HR 4.26, 95% CI 1.22-14.9) were independent prognostic factors. In univariate analyses of pneumonia-specific survival, treatment (total gastrectomy vs. distal gastrectomy: HR 6.98, 95% CI 1.18-41.3) was the only prognostic factor. CONCLUSIONS: The prognosis of distal gastrectomy was better than that of non-surgery even in patients aged ≥ 85 years. However, total gastrectomy was considered to be avoidable due to the high rate of postoperative pneumonia death.

[A Case of Stage â £c dMMR Transverse Colon Cancer with Complete Response to Combination Therapy with Immune Checkpoint Inhibitor in Stage â £B Lung Adenocarcinoma].

The patient is a 72-year-old man. He was diagnosed as a duplication of left upper lobe lung adenocarcinoma cStage ⅣB and transverse colon cancer cStage Ⅳc. Because he had symptoms of atelectasis and esophageal stricture due to the progression of lung cancer, we decided to precede immunochemotherapy(CBDCA plus PEM plus pembrolizumab)for lung cancer. After the start of treatment, both lung and colorectal cancer were shrinking, but after the 3 courses of treatment, he developed intestinal obstruction due to transverse colon cancer. Because generalized peritonitis due to perforation of the colon by endoscopic stenting for the obstruction and then emergency surgery was performed. The resected transverse colon lesion was diagnosed as pathologically complete response. Lung cancer was also diagnosed as clinically complete response. Since his ADL decreased postoperatively, he is under observation without reintroduction of immunochemotherapy. Fourteen months have passed since the last administration, and no progression has been observed in either lung nor colon cancers. Pembrolizumab is considered to be successful in the patient with dMMR colorectal cancer lacking MLH1 and PMS2.

End Sigmoid Colostomy Reconstruction Using Purse-string Subcutaneous Suture via Extraperitoneal Route at the Site of a Previous Transperitoneal Loop Stoma.

We previously experienced two cases of end sigmoid colostomy reconstruction via the extraperitoneal route at the same site as the transperitoneal loop stoma. For an anterior rectus fascia, the transperitoneal route used closed intraperitoneal interrupted sutures and continuous sutures with barbed sutures. A new extraperitoneal route was established through the sutured anterior rectus sheath. Before reconstructing the end stoma, a subcutaneous purse-string with monofilament absorbable sutures tied to create an approximately 2.5 cm diameter was used. There were no early complications associated with the stoma. One year after surgery, a parastomal hernia was not defined. Using the presented technique, two cases were successfully recreated extraperitoneally at the same site's end stoma.

Poor Prognosis in Patients With Stage III Colorectal Cancer Receiving Adjuvant FOLFOX/CAPOX Therapy Is Predicted by the Presence of Many Poorly Differentiated Clusters.

BACKGROUND/AIM: Poorly differentiated clusters (PDCs) have been reported to be a useful grading system for predicting prognosis in patients with colorectal cancer (CRC). We investigated the association between the number of PDCs and prognosis in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. PATIENTS AND METHODS: This is a retrospective study of 49 patients with stage III CRC who underwent curative surgery followed by oxaliplatin-based adjuvant chemotherapy. PDC was defined as a cluster of ≥5 cancer cells without glandular structure at the invasive front of the primary tumor. RESULTS: During the observation period, 12 patients experienced relapse. The patients were divided into two groups (<7 and ≥7 PDC groups), and receiver operating characteristic (ROC) curves were calculated [area under the curve (AUC)=0.743]. Patients with ≥7 PDCs had a much shorter relapse-free survival (RFS) than those with <7 PDCs (p<0.0001). The overall survival (OS) was also significantly worse in patients with ≥7 PDCs than in those with <7 PDCs (p<0.0001). Multivariate analysis revealed that PDC was the only significant prognostic factor measured that could predict RFS (p=0.002) and OS (p=0.0047) in patients with stage III CRC treated with oxaliplatin-based adjuvant chemotherapy. CONCLUSION: In patients with stage III CRC treated with post-resection oxaliplatin-based adjuvant chemotherapeutic regimens, the presence of ≥7 PDCs at the invasive front of the primary tumor predicted unfavorable prognosis.

[A Curatively Resected Case of Recto-Sigmoidal Cancer with Massive Bladder Invasion after Multimodal Therapy Including Chemotherapy].

A 68-year-old male patient was referred to our hospital because of unfit to treat his recto-sigmoidal cancer massively invaded to bladder at the former hospital. During drug administration to treat heart failure, we could perform a transverse colostomy and initiated mFOLFOX plus Pmab. During chemotherapy, he improved malnutrition. After 7 courses, CT scan showed a marked reduction in tumor diameter, which was PR. Since his nutritional and heart status were improved, he underwent a high anterior resection with partial bladder resection. Pathological findings showed that a few cancer cells were remained at bladder and bowel wall. He was diagnosed as Stage Ⅱc. His postoperative course was almost uneventful. No symptom of recurrence has been observed at 9 months after surgery without adjuvant chemotherapy.

The comparison of prognoses between total and distal gastrectomy for gastric cancer in elderly patients ≥ 80 years old.

PURPOSE: In Japan, the number of distal gastrectomy for patients ≥ 80 years old is increasing, whereas that of total gastrectomy is decreasing. Surgeons seem to avoid total gastrectomy for elderly patients. Total gastrectomy is reported to have a poorer prognosis than distal gastrectomy, and postoperative pneumonia may be involved in the cause. METHODS: The medical records of 39 and 108 patients ≥ 80 years old who underwent total and distal gastrectomy, respectively, at 2 affiliated institutions between 2010 and 2019 were retrospectively reviewed. Prognoses were compared between the two groups, focusing on death from pneumonia. RESULTS: The median overall survival time after total and distal gastrectomy was 21.3 and 74.1 months, respectively, with a significantly poorer prognosis after total gastrectomy than after distal gastrectomy (p < 0.01, hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.37-3.53). The gastric cancer-specific survival time was significantly worse after total gastrectomy than after distal gastrectomy (p < 0.01, HR 2.73, 95% CI 1.29-5.79). The pneumonia-specific survival time was also significantly worse after total gastrectomy than after distal gastrectomy (p = 0.01, HR 3.44, 95% CI 1.25-9.48). CONCLUSIONS: Patients who underwent total gastrectomy had a poorer prognosis than those who underwent distal gastrectomy, because many patients died of pneumonia early after total gastrectomy.

[A Case of Liver Metastasis of Gastric Cancer Successfully Treated with SOX plus Nivolumab].

An 82-year-old, male. He visited his local doctor with a chief complaint of dyspnea on exertion. Anemia was noted, and upper gastrointestinal endoscopy was performed, which revealed an ulcerative lesion in the gastric antrum. A biopsy revealed Group 5, tub2, and HER2 negative, with PD-L1≥5%. cT3N1H1(M1 HEP), cStage ⅣB was diagnosed based on CT scan showing enlarged #8 lymph node and a single liver metastasis in the 2 cm range in S6 of the liver. The patient was deemed unresectable and was started on SOX plus nivolumab therapy. On day 11 after initiation, the patient had Grade 3 diarrhea by CTCAE v5.0, and S-1 was withdrawn for 3 days, but was administered for 2 courses. CT and MRI after chemotherapy showed shrinkage of both the primary tumor and liver metastases; R0 resection was deemed possible, and pyloric gastrectomy, D2 lymph node dissection, and partial hepatic S6 resection were performed. The histological evaluation of response to treatment was Grade 1b, and the patient was in ypStage ⅠA. The patient has been alive without recurrence for 6 months postoperatively while receiving S-1 monotherapy on an outpatient basis.

Prognostic factors for elderly gastric cancer patients who underwent gastrectomy.

BACKGROUND: Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. METHODS: The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. RESULTS: In univariate analyses, age (≥ 90 vs. ≥ 80, < 85), performance status (3 vs. 0), American Society of Anesthesiologists physical status (ASA-PS) (3, 4 vs. 1, 2), Onodera's prognostic nutritional index (< 40 vs. ≥ 45), the physiological score of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) (≥ 40 vs. ≥ 20, ≤ 29), surgical approach (laparoscopic vs. open), extent of gastrectomy (total, proximal vs. distal), extent of lymphadenectomy (D1 vs. ≥ D2), pathological stage (II-IV vs. I), and residual tumor (R1 vs. R0) were significantly correlated with worse overall survival. Multivariate analysis revealed that ASA-PS [3, 4 vs. 1, 2, hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.24-4.24], extent of gastrectomy (total vs. distal, HR 2.17, 95% CI 1.10-4.31) (proximal vs. distal, HR 4.05, 95% CI 1.45-11.3), extent of lymphadenectomy (D0 vs. ≥ D2, HR 12.4, 95% CI 1.58-97.7), and pathological stage were independent risk factors for mortality. CONCLUSIONS: ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.

Survival analyses of elderly gastric cancer patients with or without surgery.

PURPOSE: Deciding whether or not surgery should be performed for elderly patients is sometimes difficult. This study examined the prognosis of patients ≥ 80 years old with gastric cancer who underwent surgery or not. METHODS: The medical records of 111 patients who underwent surgery (surgery group) and 35 who received best supportive care (BSC group) were retrospectively reviewed, excluding those with clinical stage IVB disease, those with a performance status of 4, and those who underwent endoscopic submucosal dissection. The overall survival was compared between the two groups. RESULTS: The patients in the BSC group were significantly older and had worse performance status scores, worse physiological scores, and lower prognostic nutritional indexes than those in the surgery group. The patients in the surgery group showed a significantly better survival than those in the BSC group (median survival time, 38.9 vs. 11.4 months; p = 0.01) even after propensity score matching. In the subgroups of patients ≥ 90 years old and those with a performance status of 3, no marked difference in the survival between the 2 groups was observed. CONCLUSIONS: Surgery imbued a survival benefit to elderly gastric cancer patients, except for those ≥ 90 years old and those with a performance status of ≥ 3. The surgical indication of patients ≥ 90 years old and those with a performance status of ≥ 3 requires careful deliberation.

[Long-Term Survival following Multidisciplinary Therapy for Unresectable Pancreatic Body Cancer].

A 57-year-old man was diagnosed with a tumor in the pancreatic body at a nearby hospital and consulted our hospital. Examinations revealed that carbohydrate antigen 19-9(CA19-9)levels were 1,765.0 U/mL. We confirmed metastatic liver tumors in S4 and S8 of the liver by EOB-MRI. We diagnosed unresectable pancreatic cancer(T3N0M1, cStage Ⅳ)and administered 10 courses of gemcitabine(GEM)plus nab-paclitaxel(nab-PTX)therapy. The main lesion and the lesion in S4 subsequently disappeared, and the lesion in S8 degenerated into a cyst. CA19-9 levels were 113 U/mL. Surgery was determined as the best course of action after normalizing CA19-9 levels. Therefore, we further administered 6 courses of FOLFIRINOX therapy and 4 courses of GEM plus nab-PTX therapy, but CA19-9 was not normalized. We decided that it would be difficult to normalize CA19-9, and thus proceeded with surgery. During the operation, cystic degenerative lesions were found in S8 and peritoneal dissemination was found in the transverse mesentery. Because the ascites cytopathology was negative, it was judged that the peritoneal dissemination was localized. We performed distal pancreatectomy(D2)plus partial hepatectomy(S8)plus peritoneal dissemination resection. On day 52 after surgery, we resumed GEM plus nab-PTX. The patient has survived without any recurrence for 3 years after the initial surgery.

[A Case of Pancreas Neuroendocrine Carcinoma Achieved Long-Term Survival by Carboplatin plus Etoposide Therapy].

A 70-year-old man with the history of diabetes mellitus complained of lower abdominal discomfort. Abdominal ultrasonography revealed a pancreatic mass. Contrast enhanced CT showed a 2.6 cm-enhanced tumor ventral to the pancreatic head. It was diagnosed with a pancreatic neuroendocrine carcinoma(PanNEC-G3)by EUS-FNA. The patient underwent pancreatoduodenectomy with the wedge resection of the portal vein and partial resection of the transverse colon. We administered 6 cycles of adjuvant therapy with CDDP plus CPT-11. With the presentation of lymph node metastases and the local recurrence in the anastomotic site of the transverse colon 15 months after surgery, the patient received carboplatin plus etoposide(CE)therapy. Although local recurrence completely responded to the CE therapy, bone metastases were detected 27 months after surgery. Metastatic lesion did not respond to systemic chemotherapy including gemcitabine plus nab-paclitaxel and nal-IRI plus 5-FU/LV, and the patient eventually died 37 months after the surgery. PanNECs represent for less than 1% of all pancreatic tumor. They are characterized by high malignant potential and short time survival with the reported OS of 8.5 to 21 months. This case served as an important reminder to consider multimodal treatment for PanNEC patients to obtain longer survival.

Current status and management of pancreatic trauma with main pancreatic duct injury: A multicenter nationwide survey in Japan.

BACKGROUND: Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment. METHODS: As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board-certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated. RESULTS: Sixty-four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0). CONCLUSIONS: Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics.

Successful treatment of gastric cancer after complete response of lung cancer by nivolumab: a case report.

BACKGROUND: Nivolumab is effective for gastric cancer and lung cancer, but complete response is rare. We experienced a case of synchronous gastric cancer and lung cancer who was treated by nivolumab and laparoscopic gastrectomy. CASE PRESENTATION: A 63-year-old male consulted our institution and was found to have gastric cancer cT1(SM)N0M0 Stage IA and lung cancer cT2N2M1(PUL) Stage IV. He received eight chemotherapy treatments plus radiation, but the lung disease remained progressive. Finally, he received nivolumab therapy and complete response of both cancers was obtained. The gastric cancer recurred, but was successfully treated by laparoscopic gastrectomy. The resected specimen revealed three lesions, each being pT1aN0M0 Stage IA. The primary gastric cancer seemed to have completely vanished without scarring. CONCLUSIONS: This was thought to be a rare case of gastric cancer recurrence after complete response of gastric cancer and lung cancer to nivolumab.

[Case of Intestinal GIST with Long-Term Survival after Multidisciplinary Treatment, Including Surgical Resection for Liver Metastasis].

A 54-year-old male underwent partial resection of the ileum for gastrointestinal stromal tumor(GIST). Although it was a high-risk GIST, he was followed-up without chemotherapy. Nineteen months after the initial operation, an EOB-MRI showed a mass in the liver(S8). As it had increased in size in 4 months of follow-up, 400mg/day of imatinib was started for the diagnosis of liver metastasis. The patient experienced PR 6 months after the initiation of chemotherapy and underwent partial hepatectomy. Imatinib 400mg/day was re-administered after hepatectomy, and the disease was well controlled for 16 months. Imatinib is acceptable as the first-line therapy for unresectable and metastatic GIST. The significance of surgical intervention remains unclear for liver metastasis in GIST; however, it could remain uncontrolled with surgery alone and requires concomitant imatinib therapy. On the other hand, imatinib could be beneficial and its life-long continuation is critical, but most patients eventually develop drug resistance. Complete resection of the metastatic site along with chemotherapy could lead to reduction of secondary resistance to imatinib and prolong the survival rate.

[Three Cases of Lower Advanced Rectal Cancer Involving Pathological Complete Response after Neoadjuvant Chemoradiotherapy].

Neoadjuvant chemoradiotherapy(NACRT)was administered at our hospital to 3 patients with lower advanced rectal cancer; NACRT resulted in pathological complete response(pCR). Case 1: A 65-year-old man was diagnosed with T4aN1M0, cStage Ⅲb disease; after chemoradiotherapy(CRT), the clinical stage improved to T4aN0M0, ycStage Ⅱb. Laparoscopic Hartmann's procedure and D3 lymph node dissection were performed 51 days after CRT. No recurrence was observed 31 months after surgery. Case 2: A 67-year-old man was diagnosed with T4aN2M0, cStage Ⅲb disease; after CRT, the clinical stage improved to T4aN1M0, ycStage Ⅲa. Laparoscopic abdominoperitoneal resection and D3 lymph node dissection were performed 57 days after CRT. No recurrence was observed 21 months after surgery. Case 3: An 83-year-old woman was diagnosed with T4aN2M0, cStage Ⅲb disease; after CRT, the clinical stage improved to T4aN0M0, ycStageⅡb. Laparoscopic abdominoperitoneal resection and D3 lymph node dissection were performed 64 days after CRT. No recurrence was observed 16 months after surgery. Here, we report 3 cases of lower advanced rectal cancer involving curative resection following CRT, and we provide a short literature review.

[A Case of Long-Term Survival with Far Advanced Gastric Cancer after Multidisciplinary Treatments, including Conversion Surgery].

An 82-year-old man with Stage Ⅳ advanced gastric cancer and multiple liver metastases was referred to our hospital. Chemotherapy using S-1 was administered, resulting in withdrawal from the usual course because of an adverse event of grade 4 anorexia. GIS and EOB-MRI showed a prominent tumor reduction in both lesions; however, despite this, distal gastrectomy, D2 lymph node dissection, liver biopsy for S3 lesion, partial liver resection for S6 lesion, and cholecystectomy were performed to obtain a therapeutic diagnosis. Pathology revealed that the tumor cells remained in the main liver metastatic lesions. Therapeutic effect was assessed as Grade 2. Although weekly paclitaxel followed by reduced S-1 dosage was introduced after surgery, the recurrent mass was observed in the para-aortic region after 2 years. Subsequently, para-aortic lymph node dissection was performed because no new lesion was detected. More than 10 years have passed without any recurrence since the first surgery. As part of a multidisciplinary treatment for far advanced gastric cancer with multiple liver metastases (Stage Ⅳ), conversion surgery might be considered effective.

[A Case of Esophageal Neuroendocrine Carcinoma(NEC)Treated with Collective Treatment].

A 68-year-old man presented to our hospital. An upper gastrointestinal tract endoscopy performed elsewhere revealed an elevated lesion with a circumferential esophageal cancer(identified as small cell carcinoma). Perthe treatment forsmall cell cancer and the standard treatment for esophageal neuroendocrine carcinoma, 7 courses of CBDCA(5mg/m2)plus ETP (100mg/m2)were administered. The lesion shrank and the lymph node swelling disappeared and the patient was deemed to be in partial remission. Nine months later, however, the primary tumor increased in size. A transthoracic subtotal esophagectomy( laparoscope-assisted), 2 area dissection, and gastric tube reconstruction(post-sternal)were performed at 2 years and 10 months afterdiagnosis.

Clinical significance of preoperative chemoradiotherapy for advanced esophageal cancer, evaluated by propensity score matching and weighting of inverse probability of treatment.

The present study used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to compare survival benefits among 112 patients with resectable, stage II-IV esophageal squamous cell carcinoma (SCC) treated between 1996 and 2016 with neoadjuvant chemoradiotherapy (NAC) plus surgery (Group A, n=55) or with surgery alone (Group B, n=57). Their propensity scores (PS) were calculated using a multivariable logistic regression model in which age, sex, cancer site, primary tumor length, cTNM stage, lymph node metastasis and depth of tumor invasion were the independent variables, and used to match Groups A and B according to the IPTW and matching method. After IPTW and PSM, univariate analysis was used to assess overall survival (OS) and disease-free survival (DFS), followed by Cox proportional hazard models for OS using IPTW between the two groups and the subgroups. After PSM, 5-year OS and DFS were significantly higher in Group A (OS: 65.2%, DFS: 65.2%) compared with Group B (OS: 31.2%, DFS: 20.87%). Similarly, after IPTW, OS and DFS were significantly higher in Group A compared with Group B patients. Five-year OS was 73.18% for Group A and 37.69% for Group B (hazard ratio: 0.2899, 95% confidence interval: 0.1167-0.7205). To conclude, treatment was more effective in Group A patients with clinical stage II, N0 and T3 disease involving the mid-esophagus. It was concluded that for patients with esophageal SCC, NAC plus esophagectomy exhibited improved survival compared with surgery alone, as demonstrated by use of IPTW and PSM methods.

[Three Cases of Decompression Failure in Colon Stent Placement for Obstructive Colorectal Cancer].

Forty-four patients underwent decompression using a self-expandable metallic stent for obstructive colorectal cancer as a bridge to surgery in our department. Three failure cases were examined. Case 1: A Rs, Ra type 2 cancer was treated with WallflexTM 60 mm. Enough decompression could not be obtained, and an additional stent was placed. Consequently, the patient underwent a transverse colostomy. Case 2: A Ra type 2 cancer was treated with Niti-S 60 mm. The patient's chief complaint was not improved due to the tumor ingrowth. Consequently, he underwent a transverse colostomy. Case 3: A sigmoid type 2 cancer was treated with Niti-S 80 mm. Decompression was successful. However, CT scan revealed another tumor in the descending colon. He underwent a transverse colostomy for further examination. The causes of the failure differed in each case. We gained many learning points from these cases that are useful for future treatment.

[A Resected Case of Rectal Metastasis from Gastric Cancer].

An 82-year-oldwoman previously underwent total gastrectomy for gastric cancer at the age of 75 years. After 7 years of follow-up, a colonoscopy was performedto investigate the cause of constipation, which revealedan irregularity in the rectal submucosa. A colonoscopy-guidedbiopsy showedpoorly differentiatedad enocarcinoma, andthe immunohistochemical staining pattern showedMUC2(-), MUC5AC(+), CDX2(+), andCA1 25(-). FDG-PET showedintense uptake only at the rectum. Thus, laparoscopic high anterior resection was performed. Pathological findings showed that poorly differentiated adenocarcinoma and signet-ring cell carcinoma hadd evelopedmainly in the submucosa. In comparison with the immunohistological features of the previous gastric cancer, the rectal tumor hadsimilar morphological characteristics. The definitive diagnosis was rectal metastasis from gastric cancer. She has remained recurrence-free in the 20 months since this operation.