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P H Sugarbaker

Publications and source records attributed to P H Sugarbaker.

At least 19 recordsLinked to original sources

A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma.

BACKGROUND: In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus indolent biologic behavior of the neoplasm. The overall median survival was approximately 1 year after systemic chemotherapy. Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established. PATIENTS AND METHODS: Searches for relevant studies published in peer-reviewed medical journals on CRS and PIC for DMPM before May 2006 were carried out on six databases. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. Expert academic surgeons in Washington, DC, USA were asked whether they knew about any important unpublished data. Two investigators independently evaluated each study according to predefined criteria. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Seven prospective observational studies from six tertiary institutions were available, allowing 240 DMPM patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. The perioperative morbidity varied from 25% to 40% and mortality ranged from 0% to 8%. CONCLUSIONS: This systematic review evaluated the current evidence for CRS and PIC for DMPM. Seven observational studies were available for assessment, which demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.

Antibiotics, Antineoplastic↗

Significance of lymph node metastasis in patients with diffuse malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and invariably fatal neoplasm. Some studies have shown that cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) achieved an improved survival, as compared to historical controls. However, the significance of lymph node involvement in this disease has never been well defined. METHODS: One hundred patients with DMPM underwent CRS and PIC at the Washington Hospital Center. The inclusion criteria for surgery consisted of histological diagnosis of DMPM, age <80 years and good performance status. All data were collected prospectively. Lymph node status, seven clinical variables and eight treatment-related prognostic factors were analyzed for survival. RESULTS: Seven patients were lymph node positive and they all died of their disease within 2 years after the surgery. The remaining 93 patients had 5- and 7-year survival of 50% and 43%, respectively. Univariate analysis showed that gender (p<0.001), peritoneal cancer index (p=0.009), lymph node status (p<0.001), extra-abdominal invasion (p=0.026), histological type (p<0.001), intraoperative blood loss (p=0.035), completeness of cytoreduction (p<0.001), intraperitoneal chemotherapy regimen (p=0.041), and redo cytoreductive surgery (p=0.022) were significant for survival. Multivariate analysis demonstrated that female gender, lymph node metastasis not detected, epithelial type, and adequate cytoreduction were independently associated with an improved survival. CONCLUSIONS: CRS and PIC showed an improved survival for DMPM, as compared to historical controls. Lymph node status along with three other prognostic variables was significant in the multivariate analysis.

Antineoplastic Combined Chemotherapy Protocols↗

Pseudomyxoma peritonei arising from colonic polyps.

AIMS: Pseudomyxoma peritonei may have as its primary site a mucinous gastrointestinal adenoma or carcinoma that gains access to the peritoneal cavity. This manuscript describes this disease arising from a benign or malignant colonic polyp. METHODS: From a database of over 1000 pseudomyxoma peritonei patients and colorectal carcinomatosis patients, three cases were identified in which the primary tumor site was a colonic polyp. The clinical history and course of these patients were studied. RESULTS: In a review of the clinical management of these patients, all three had an event whereby neoplastic cells from the surface of the colonic polyp could have gained access to the free peritoneal cavity. The patients developed the characteristic pseudomyxoma peritonei syndrome. All three patients were treated with cytoreductive surgery plus perioperative hyperthermic intraperitoneal chemotherapy. CONCLUSIONS: Colonic polyps can serve as a source of dysplastic cells whereby pseudomyxoma peritonei can result. Caution to prevent seeding to the free peritoneal cavity during surgery for colonic polyps should be observed. If pseudomyxoma peritonei develops, cytoreductive surgery and perioperative intraperitoneal chemotherapy should be considered for treatment.

Adenocarcinoma, Mucinous↗

The approval process for hyperthermic intraoperative intraperitoneal chemotherapy.

AIMS: To clarify the requirements for Food and Drug Administration approval in the United States for hyperthermic intraoperative intraperitoneal chemotherapy administration. Also, to review the status of the approval process in Europe. METHODS: The obstacles to be overcome for approval by the Food and Drug Administration for a new drug approval and for a new device approval were reviewed. Drugs approved in the past were examined for their potential for current application in this technology. RESULTS: The likelihood that the approval of a heater circulator along with the approval for specific chemotherapy agents for heated intraoperative intraperitoneal chemotherapy was judged to be remote. Rather, the continued use of "homemade heater circulators" and the off-label use of appropriate chemotherapy agents augmented by heat will continue to be the standard of care. The European community currently has several heater circulators approved for hyperthermic intraoperative intraperitoneal chemotherapy administration. These devices have been specifically approved for oncologic indications. CONCLUSIONS: Continued research and development of heated intraoperative intraperitoneal chemotherapy is necessary. As the requirement for prevention and treatment of the peritoneal surface component of gastrointestinal and gynecologic oncology expands, new investigations into the approval process in the United States will be necessary. Publication of results from institutions pioneering these new treatment strategies will, of necessity, continue.

Antineoplastic Agents↗

Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites.

AIM: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy (LIPHC) in the treatment of malignant ascites. METHODS: From September 2001 to December 2003, 14 patients between the age of 56 and 78years were treated. Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case). The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending on the type of primary tumor. The drains were left in situ after surgery and removed when perfuse drainage ceased. RESULTS: Ascites was controlled in all the treated cases. A CT scan performed in follow-up showed a small, clinically undetectable, fluid accumulation in the pelvis of one patient. CONCLUSIONS: This method resulted in benefit for those peritoneal carcinomatosis patients with debilitating malignant ascites who were excluded from cytoreductive surgery. Proficiency in laparoscopic staging procedures and experience in the management of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are required for the success of the procedure.

Aged↗

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

Adult↗

Comprehensive management of diffuse malignant peritoneal mesothelioma.

AIMS: In the past, diffuse malignant peritoneal mesothelioma (DMPM) has been regarded as a terminal condition. The length of the survival was dependent upon the aggressive versus indolent biology of the neoplasm, nevertheless cure was not considered as a reasonable expectation and the overall median survival was approximately one year. METHODS: A comprehensive literature review and a collection of pertinent data published on DMPM from the Washington Cancer Institute were used to construct this report. RESULTS: Recent publications from Bethesda MD, New York, Milan Italy, Lyon France and Washington DC have shown a remarkable prolongation in the median survival of this group of patients with approximately half the patients alive at 5 years. These prolonged survivors were treated with an intensive local-regional treatment strategy that included cytoreductive surgery (CRS) with peritonectomy and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) and some patients with early postoperative intraperitoneal chemotherapy (EPIC). As larger numbers of patients have been treated, clinical features by which to select patients most likely to benefit from this approach have been identified. Also, as the experience in the management of patients receiving these treatments has increased, the morbidity and mortality associated with their management is being reduced. CONCLUSIONS: A new standard of care involves surgical removal of large disease deposits combined with perioperative intraperitoneal chemotherapy. Knowledgeable management uses selection criteria and incurs low morbidity and mortality.

Antineoplastic Combined Chemotherapy Protocols↗

The natural history, gross pathology, and histopathology of appendiceal epithelial neoplasms.

AIM: To report the pathology of appendiceal epithelial neoplasms a review of the Washington Cancer Institute experience and a PubMed literature search was performed. FINDINGS: Epithelial appendiceal neoplasms present a significant oncologic challenge. The clinical and pathologic features are unusually varied as compared to other gastrointestinal cancers and require expert clinical judgment for proper management. CONCLUSIONS: Appendiceal epithelial neoplasms should be regarded as a distinct clinical entity with special clinical treatments used for optimal management.

Adenocarcinoma, Mucinous↗

Sex difference in diffuse malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is rare and in the past has proved an invariably fatal disease. Female patients have been reported to have an improved survival outcome for reasons that are not understood. METHODS: The survival of 34 men and 28 women who underwent cytoreduction and perioperative intraperitoneal chemotherapy for DMPM was compared. Twenty-five clinicopathological variables were subjected to univariate analysis. RESULTS: The women had a 5-year survival rate of 63 per cent and median survival was not reached. The men had a 5-year survival rate of 42 per cent, with a median survival of 32 months (P = 0.045). Women had undergone more extensive previous surgery and had less extensive peritoneal involvement at the time of cytoreduction. Tumours in women more frequently showed a small nuclear size (30 microm or less) and the chromatin pattern was more often granular than clear. CONCLUSION: Women with DMPM had better survival. This observation may be related to the favourable clinical and histopathological features associated with women.

Female↗

Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy.

Peritoneal surface malignancy usually results from implantation of gastrointestinal cancer. In the past, this clinical situation was treated with palliative intent. A definitive approach to peritoneal surface malignancy involves peritonectomy procedures, visceral resections, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The quantitative prognostic indicators necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 45% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. The definitive prognostic indicator was the complete cytoreduction. Oncologists must seek new knowledge regarding the management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies; in contrast all historical controls show 0% long-term survival. Additional adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.

Appendiceal Neoplasms↗

Lymph node metastasis in epithelial malignancies of the appendix with peritoneal dissemination does not reduce survival in patients treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy.

BACKGROUND: Peritoneal dissemination of appendiceal malignancy combined with regional lymph node metastasis is an unusual combination of patterns of cancer dissemination. METHODS: A database of 501 appendiceal malignancy patients, all with documented peritoneal seeding, was used to identify 25 patients with involvement of the regional lymph nodes. All patients were uniformly treated with cytoreductive surgery plus perioperative intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil. The clinical and pathologic features of the lymph node-positive patients were compared with those of the lymph node-negative patients. The effect of regional lymph node involvement on survival was determined. Within the group of lymph node-positive patients, clinical and pathologic features were tested for their effect on survival. RESULTS: When compared with patients with no apparent lymph node positivity, patients with positive lymph nodes were more likely to have an acute abdomen as the initial presentation (P < .001). The intestinal (nonmucinous) histological type was more common (P < .001), and the disseminated peritoneal adenomucinosis histology was less common (P < .001). Survival with the aggressive treatment strategy used in these patients was not different for lymph node-positive as compared with lymph node-negative patients (P = .15 by univariate and P = .38 by multivariate analysis). CONCLUSIONS: Appendiceal malignancy with dissemination to the lymph nodes has a more acute onset and a more frequent nonmucinous histology. With aggressive treatment strategies, lymph node-positive patients did not show a statistically significantly diminished survival.

Acute Disease↗

Regional lymph node metastasis from port site implants after laparoscopic surgery.

Although overall incidence of laparoscopic port site implants is decreasing, it remains problematic in patients with occult intraabdominal malignancy. Port-site metastases may themselves become the source of new metastases. A 42-year-old man underwent a laparoscopic cholecystectomy for cholelithiasis. One month later, he was diagnosed with a right colon cancer, for which a right colectomy was performed. Eleven months later, a CT scan showed nodules in the umbilicus (one of the original laparoscopic port sites) and behind the right rectus abdominis muscle, adjacent to the deep epigastric vessels. These sites were resected, and histopathology confirmed metastatic adenocarcinoma. The right deep epigastric nodule was reported to be lymph node-positive for metastatic adenocarcinoma. It is probable that dissemination of cancer cells to this lymph node occurred from the port site implants. Presence of metastasis in the lymph nodes draining the abdominal wall should be examined in all patients with port site implants.

Adult↗

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Adolescent↗

Hyperthermia modifies pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rat model.

BACKGROUND AND OBJECTIVES: Peritoneal surface malignancy is a common manifestation of failure of treatment for abdominal cancers. Best results of treatment have been achieved with complete cytoreduction followed by heated intraoperative chemotherapy. Melphalan is a chemotherapeutic agent that shows increased pharmacological activity with heat. But the combination of intraperitoneal administration and heat have never been tested for this drug. The purpose of this study was to evaluate the effect of hyperthermia on the pharmacokinetics and tissue distribution of intraperitoneal melphalan in a rodent model. METHODS: Melphalan was given by the intraperitoneal route to 20 Sprague-Dawley rats at a dose of 12 mg/kg over 90 min. Rats were randomized into two groups according to the temperature of the peritoneal perfusate: group NT received normothermic (33.5 degrees C) melphalan; group HT received hyperthermic (42 degrees C) melphalan. During the course of intraperitoneal chemotherapy, peritoneal fluid and blood were sampled at 5, 15, 30, 60 and 90 min. At the end of procedure, the rats were killed and tissues samples (heart, liver, ileum, jejunum, colon, omentum, and abdominal wall) were collected. Concentrations of melphalan were determined in peritoneal fluid, plasma, and tissues by high-performance liquid chromatography. RESULTS: The area under the curve (AUC) of peritoneal fluid melphalan was significantly lower in the HT group than in the NT group ( P=0.001), whereas no significant difference in plasma AUC was found. AUC ratios (AUC peritoneal fluid/AUC plasma) were 12.1 for the NT group and 12.3 for the HT group. The mean time to reach the plasma peak was shorter in the HT group than in the NT group ( P=0.004). The HT group exhibited increased melphalan concentrations in all intraabdominal tissues. These differences were significant for the ileum ( P=0.03) and jejunum ( P=0.04). CONCLUSION: Hyperthermia affected the pharmacokinetics of intraperitoneal melphalan by decreasing the AUC of peritoneal fluid melphalan without increasing the plasma AUC. It increased intraabdominal tissue concentrations.

Animals↗

Right hemicolectomy does not confer a survival advantage in patients with mucinous carcinoma of the appendix and peritoneal seeding.

BACKGROUND: Traditionally epithelial malignancies of the appendix with or without carcinomatosis have been treated by right hemicolectomy. Recent accumulation of a large number of patients with this disease has enabled a re-evaluation of this surgical judgement. METHODS: Clinical data on 501 patients with epithelial malignancy of the appendix were collected prospectively. All patients had peritoneal seeding at the time of referral and were treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy. The main independent variable for statistical analysis was the surgical procedure used to resect the primary cancer (appendicectomy alone versus right hemicolectomy). Nineteen other clinical and pathological variables were considered as control variables. The endpoint for all analyses was survival. RESULTS: Median follow-up after the initial diagnosis was 4 years. The rate of regional lymph node positivity was 5.0 per cent. When the incidence of lymph node metastasis was determined by histological type, it was statistically significantly higher in intestinal (66.7 per cent) than in mucinous (4.2 per cent) tumours (P < 0.001). The presence of lymph node metastases had no influence on prognosis (P = 0.155). The surgical procedure (appendicectomy alone versus right hemicolectomy) had an influence on patient survival by univariate analysis (P < 0.001), but not by multivariate analysis (P = 0.258). CONCLUSION: Right hemicolectomy does not confer a survival advantage in patients with mucinous appendiceal tumours with peritoneal seeding. These data suggest that right hemicolectomy should be avoided unless metastatic involvement of the appendiceal or distal ileocolic lymph nodes is documented by biopsy, or the resection margin is inadequate.

Adenocarcinoma, Mucinous↗

Treatment of peritoneal carcinomatosis from adenocarcinoid of appendiceal origin.

BACKGROUND: Mucinous peritoneal carcinomatosis arising from appendiceal adenocarcinoid is uncommon and treatment options have been poorly defined. This study examined the effect of combined cytoreductive surgery and intraperitoneal chemotherapy on survival in these patients. METHODS: Of 810 patients with peritoneal malignancy of appendiceal origin treated by cytoreductive surgery and intraperitoneal chemotherapy, 22 patients (mean age 45 years; 17 women) had adenocarcinoid. RESULTS: The overall median survival was 18.5 (range 3.2-95.1) months, with 2- and 5-year survival rates of 39 and 25 per cent respectively. Survival after combined surgery and chemotherapy depended on the Peritoneal Cancer Index (P = 0.008) and the extent of cytoreduction (P = 0.007). CONCLUSION: Peritoneal carcinomatosis from adenocarcinoid of appendiceal origin is as invasive as peritoneal surface malignancy from colorectal adenocarcinoma. Patients in whom complete or near-complete surgical removal is possible should be considered for cytoreduction in combination with intraperitoneal chemotherapy.

Adenocarcinoma, Mucinous↗

The management of synchronous peritoneal carcinomatosis and hematogenous metastasis from colorectal cancer.

AIMS: Combined local and distant dissemination for colorectal cancer occurs especially in younger patients. New strategies combining maximal cytoreductive surgery with intraperitoneal and systemic chemotherapy have been used in an attempt to prolong survival with an acceptable morbidity and mortality. METHODS: Twenty-seven patients with histologically proven peritoneal carcinomatosis from colorectal cancer had distant metastases in addition to peritoneal carcinomatosis. The goal for treatment in all patients was complete local and distant cytoreduction. Aggressive intraperitoneal and systemic chemotherapy was used. The endpoint for all the analysis was survival from the time of definitive treatment at our Institution. RESULTS: In addition to peritoneal carcinomatosis, 16 patients had liver metastases, six patients had lung metastases, four had liver and lung metastases and one had supraclavicular lymph-node metastases. Median survival time (MST) for the entire group was 15.2 months. Patients that received a complete cytoreductive surgery had a MST of 20.6 months and patients with incomplete cytoreduction had a MST of 9.0 months (p= 0.0471). Post-operative morbidity and mortality was 14.8 and 0%, respectively. CONCLUSION: A group of carefully selected patients with peritoneal carcinomatosis and distant metastases from colorectal cancer may benefit from cytoreductive surgery and intraperitoneal chemotherapy.

Adult↗

Synchronous extraperitoneal and intraperitoneal dissemination of appendix cancer.

BACKGROUND: The aim of this study was to report the role of combined treatments, including cytoreductive surgery and perioperative regional chemotherapy, in patients with synchronous systemic and intraperitoneal dissemination of appendix cancer. METHODS: Patients with synchronous systemic and intraperitoneal dissemination of appendix cancer were treated with cytoreductive surgery and perioperative regional chemotherapy. Variables statistically analyzed with survival as an end point included demographic characteristics, prior surgical score (PSS), tumour marker levels, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). RESULTS: Mean follow up was 42.6 months, median survival time (MST) for 15 patients was 28 months and 5-year survival rate was 29.4%. Female patients had a longer MST than male patients (p=0.0199). Survival was better in patients with PSS 0 and 1 (p=0.0277). Patients with elevated CEA and CA 19-9 levels had a shorter MST (p=0.0083 and p=0.0193, respectively). PCI and CC comparisons did not show significant differences. Morbidity (n=2) and mortality (n=2) rates were 13.3% respectively. CONCLUSION: Acceptable morbidity and mortality and a 29.4% 5-year survival rate allows cytoreductive surgery and regional chemotherapy to be considered as a treatment option for selected patients with synchronous systemic and intraperitoneal dissemination of appendix cancer.

Adenocarcinoma, Mucinous↗