A Single-Center Retrospective and Descriptive Study of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 Epidemic

Objective: In the battle against COVID-19, most medical resources in China have been directed to infected patients in Wuhan. Thus, patients with hepatobiliary pancreatic tumors who are not suffering from COVID-19 are often not given timely and effective anti-cancer treatments. In this study, we aimed to describe clinical characteristics, treatment, and outcomes of patients with hepatobiliary and pancreatic oncology from our department, which retained normal working during the COVID-19 epidemic. We also sought to formulate a set of standardized hospitalization and treatment processes. Methods: A retrospective and descriptive study was conducted involving patients hospitalized from February 1, 2020, to February 29, 2020 (Return to work after the Spring Festival), at our Department of Hepatobiliary and Pancreatic Surgical Oncology. Results: The study included 92 patients from 12 provinces in the north of China who underwent surgical resection at our Department of Hepatobiliary and Pancreatic Surgical Oncology during the COVID-19 epidemic. Robotic surgery was performed on 82% (75/92) of patients, while the rest underwent laparoscopic (2/92) and open surgery (15/92). Eighty-six patients had malignant tumor, and six had emergency benign diseases. Only ve patients had severe pancreatic stula, and three had biliary stula after operation. Conclusions: The standardized hospitalization and treatment processes described in this study could prevent cross-infection of patients and still ensure timely treatment of patients with hepatobiliary and pancreatic cancers. These study ndings will guide the management of surgical oncology departments and treatment of patients with hepatobiliary and pancreatic oncology during serious epidemics. Our hepatobiliary pancreatic surgical oncology department performed 92 operations in February 1–29, 2020, during the most serious stage of the epidemic. In this study, we summarized the process management of patients with hepatobiliary pancreatic tumors during the outbreak, and clinical and surgical characteristics and postoperative complications in 92 patients. We believe that our experience will help other clinicians working during the epidemic.


Introduction
Coronaviruses are enveloped, non-segmented, positive-sense RNA viruses broadly distributed in humans and other mammals. 1 Although most human coronavirus infections are mild, epidemics of the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) together caused more than 10,000 cases in the past two decades, with mortality rates of 10% for SARS-CoV and 37% for MERS-CoV. [2][3][4] Wuhan, the capital of Hubei province in China, is investigating an outbreak of atypical pneumonia caused by the zoonotic severe acute respiratory syndrome coronavirus 2 or the novel 2019 coronavirus . 5 In the early stages of this pneumonia, severe acute respiratory infection symptoms occur, with some patients rapidly developing acute respiratory distress syndrome, acute respiratory failure, and other serious complications. The National Health Commission of China has developed a case-de nition system to facilitate the classi cation of patients (panel). To mitigate the spread of the virus, the Chinese Government has progressively implemented metropolitan-wide quarantine of Wuhan and several nearby cities since Jan 24, 2020. 6 In the battle against COVID-19, most medical resources have been directed to infected patients in Wuhan, resulting in many hospitals being closed or open to emergencies only. Thus, many patients with malignancies were denied curative therapies, leading to an increase in non-infectious deaths during isolation at home. Patients with cancer who were not infected with COVID-19 were denied timely and effective anti-cancer treatments.
Hepatobiliary pancreatic tumors are one of the most common cancers and the leading cause of cancerrelated death worldwide. 7 Patients with liver, gallbladder, or pancreatic cancer have fast progression and poor prognosis. With recent improvements in surgical techniques (robotic and laparoscopic surgery), 8,9 medical care, and non-surgical treatment (radiotherapy, chemotherapy, and targeted therapy), treatment modalities in these patients vary greatly among different institutions. 10,11 Clearly, timely and effective treatments should be given to these patients. Therefore, in light of the COVID-19 epidemic, clinicians must consider how to reasonably allocate limited medical resources and establish a balanced medical security system to ensure that patients with hepatobiliary pancreatic tumor receive proper treatment.
Research has focused increasingly on patients infected with COVID-19, with the epidemiology and clinical features of patients with con rmed 2019 nCoV pneumonia being explored in depth. [12][13][14] However, few studies have investigated the clinical treatment and management of patients with hepatobiliary and pancreatic oncology during the COVID-19 epidemic and clinical approaches taken by departments of hepatobiliary and pancreatic surgical oncology. Therefore, we aimed to describe clinical, laboratory, and radiological characteristics, as well as treatment and outcomes of patients with hepatobiliary and pancreatic oncology treated in our department, which maintained normal working hours during the COVID-19 epidemic. In addition, as hepatobiliary surgeons, we performed timely treatment of patients with hepatobiliopancreatic tumors, avoiding cross-infection of patients and formulating a standardized treatment process. We hope our study ndings will guide the management of surgical oncology departments and treatment of patients with hepatobiliary and pancreatic oncology during serious epidemics.

Admission process during COVID-19 epidemic
Our hospital did not completely halt services to some patients who needed to visit the Hepatobiliary and Pancreatic Surgical Oncology outpatient department during the COVID-19 outbreak, nor did we cease hepatobiliary and pancreatic surgery, although we did limit the department to emergency operations and elective surgeries for patients with hepatobiliary and pancreatic cancers. To meet the medical requirements and reduce the ow of patients to the hepatobiliary pancreatic surgery clinic, we began free online and telephone hepatobiliary and pancreatic consultation. Patients made an advanced appointment to receive this medical service. People entering the outpatient and inpatient buildings were required to wear masks and had their body temperature checked by professionals wearing tight protective clothing. At the entrance to the building, anyone with a fever (body temperature ≥ 37.3℃), a travel history to Hubei in the last 2 weeks, clear contact with Hubei residents in the last 2 weeks, or contact with people having fever were sent directly to the fever clinic for screening; those who had been exposed were quarantined for 2 weeks, while those with potential exposure were asked to quarantine themselves at home for 2 weeks. At the hepatobiliary pancreatic surgery clinic, patients were not allowed to take off their masks. Doctors were required to wear masks, surgical caps, protective suits, gloves, and goggles at work, and to take off their protective equipment only after their work in a designated disposal area.
All patients were rst isolated in the local community for 14 days. When they were admitted to the hospital, they made an appointment for medical treatment in the Department of Hepatobiliary and Pancreatic Surgical Oncology. A chest plain scan computed tomography (CT) was performed in the outpatient department. Those with normal inspection results were then issued a hospital admission form.
If the patients had fever symptoms, they were required to have a throat swab examination. After admission, they were isolated in the transitional ward for 3 days; they then underwent preoperative examination and surgery.

Study population
A retrospective study was conducted on patients hospitalized from February 1, 2020, to February 29, 2020 (Return to work after the Spring Festival), at the Department of Hepatobiliary and Pancreatic Surgical Oncology, during the COVID-19 epidemic. Clinical and pathological data of these patients were retrospectively analyzed. The present study was approved by our Institutional Ethics Committee. Informed consent was obtained from all patients for their data to be used for research. In addition, this study included patients' basic information gathered between 2017 and 2019.

Inclusion and exclusion criteria
The inclusion criteria were patients with hepatobiliary and pancreatic cancer with: (1) good basic state and liver function (Child-Pugh score of A or B7 ≤ 7); (2) complete preoperative serological data and contrast-enhanced CT or MRI of the abdomen; (3) surgical resection with no residual tumors left, based on both gross inspection and histological examination of the resection specimens; (4) histopathological diagnosis of hepatobiliary or pancreatic cancer; (5) no macrovascular invasion or extrahepatic metastasis; and (6) complete pathological and clinical data during follow-up. The exclusion criteria were: (1) a history of other cancers; and (2) incomplete clinical data.

Preoperative and postoperative investigations
Routine preoperative investigations included imaging and serological tests. All patients underwent a standard hepatobiliary and pancreatic surgery imaging protocol that included abdominal ultrasonography, contrast-enhanced MRI and/or CT scan of the abdomen, and plain radiography or noncontrast CT scan of the chest. All radiological examinations were reviewed by two experienced radiologists. Routine preoperative laboratory investigations included complete blood counts, liver and renal function tests, and tumor marker level. The coagulability state and infection index were obtained before surgery. Routine postoperative investigations included histopathology and immunohistochemical studies. Other pathological indexes used in this study included maximum tumor diameter, number of tumors, and tumor encapsulation. Histopathological evaluations were performed by two independent and experienced pathologists who were blinded to the clinical data. Treatment All patients were assessed by a multidisciplinary team of experienced liver surgeons, oncologists, radiologists, and hepatologists at our hospital. Surgical resection was the treatment of choice if the disease was resectable. Surgical procedures have been reported previously, including open surgery, laparoscopic surgery, and robotic surgery.

Follow-up
Patients who underwent surgery were followed up once every day. In particular, their body temperature, infection index, and surgical related complications were recorded. Surgical complications and death were recorded during the postoperative hospital stay. This study was censored on March 1, 2020.

Statistical analysis
To compare baseline variables, the Student's t-test was used for continuous variables and the χ2 test for categorical variables. Survival curves and univariate analyses were conducted using the Kaplan-Meier method, and differences were analyzed using the log-rank test. Prognostic factors that were signi cant on univariate analysis (P < 0.05) were subjected to multivariate analysis using the Cox proportional hazards regression model. All reported P-values were two-sided. A signi cance level of 0.05 was applied throughout. Statistical analyses were performed using the R statistical package, Version 3.4.3 (R Development Team, Vienna, Austria).

Changes of disease spectrum
Our hospital treated 92 patients from 12 provinces in the north of China during the COVID-19 epidemic (Fig. 1). In the time period from 2017 to 2020, the proportion of patients with malignant tumors increased signi cantly, even though the total number of surgical patients decreased (Fig. 2). During the COVID-19 epidemic, limited medical resources were directed to patients with malignant tumors. The use of robotic surgery also increased, which indicated that minimally invasive surgery can accelerate the recovery of patients after surgery (Fig. 3).

Patient characteristics
All 92 patients with hepatobiliary pancreatic diseases in this study were hospitalized during the outbreak from February 1, 2020, to February 29, 2020 (after the Spring Festival in China). They were divided into two groups according to their gender (66 men; 26 women). Baseline characteristics of all patients with hepatocellular carcinoma are detailed in Table 1. All patients had a normal body temperature (< 37.3℃) before surgery. Preoperative chest CT was normal in 90.2% of patients; 6.5% had cardiopulmonary changes, all of whom were elderly, and one patient had bacterial pneumonia, old tuberculosis, or solid pulmonary nodule. None of the variables listed above showed any signi cant difference between the groups, except for weight and height (Table 1). included partial hepatectomy, resection of hilar cholangiocarcinoma, pancreaticoduodenectomy, distal pancreatic resection, and others (including benign and malignant cholecystectomy). All details are shown in Table 2.  Table 3.

Postoperative complications
Major postoperative complications after hepatobiliary pancreatic surgery included pancreatic stula, biliary stula, and bleeding. Only ve patients had severe pancreatic stula after operation. Three cases of biliary stula occurred, one of which was severe. In addition, 2 of the 92 patients had postoperative bleeding and underwent emergency interventional embolization to return to stable condition. All details are shown in Table 4.

Discussion
In the space of just 3 months, a novel coronavirus-a family that historically was not viewed as a global health concern-has become daily headline news worldwide. Moreover, robotic surgery has a longer operating time, less intraoperative blood loss, and shorter LOS than open surgery, whereas it has a similar overall complication rate, perioperative mortality, and POPF rate. 25 Taken together, robotic surgery has some advantages in patients with hepatobiliary pancreatic tumor, especially during COVID-19 outbreak, in that it decreases LOS and enhances recovery after surgery.
The present study had some limitations. First, data came from a single center and were acquired retrospectively. Second, the study was descriptive, so it is unclear whether the results can be extrapolated to other public health events. Third, we only included patients who underwent emergency operations and elective surgeries for hepatobiliary and pancreatic cancers, so it remains to be con rmed whether the approach described is bene cial in patients with benign hepatobiliary and pancreatic diseases.
In conclusion, we performed surgical resection in 92 patients with hepatobiliary and pancreatic oncology in a department that maintained a normal working regimen during the COVID-19 epidemic. Our standardized hospitalization and treatment processes could prevent cross-infection of patients and still ensure the timely treatment of patients with hepatobiliary and pancreatic cancers. These ndings will guide the operation of surgical oncology departments and treatment of patients with hepatobiliary and pancreatic cancers during serious epidemics.  Trends in disease types from 2017 to 2020 in the same time period.

Figure 3
Trends in surgical procedures from 2017 to 2020 in the same time period.